Dose-on-demand production of diverse 18F-radiotracers for preclinical applications using a continuous flow microfluidic system.

PubMed

Matesic, Lidia; Kallinen, Annukka; Greguric, Ivan; Pascali, Giancarlo

2017-09-01

The production of 18 F-radiotracers using continuous flow microfluidics is under-utilized due to perceived equipment limitations. We describe the dose-on-demand principle, whereby the back-to-back production of multiple, diverse 18 F-radiotracers can be prepared on the same day, on the same microfluidic system using the same batch of [ 18 F]fluoride, the same microreactor, the same HPLC column and SPE cartridge to obtain a useful production yield. [ 18 F]MEL050, [ 18 F]Fallypride and [ 18 F]PBR111 were radiolabeled with [ 18 F]fluoride using the Advion NanoTek Microfluidic Synthesis System. The outlet of the microreactor was connected to an automated HPLC injector and following the collection of the product, SPE reformulation produced the 18 F-radiotracer in <10% ethanolic saline. A thorough automated cleaning procedure was implemented to ensure no cross-contamination between radiotracer synthesis. The complete productions for [ 18 F]MEL050 and [ 18 F]Fallypride were performed at total flow rates of 20μL/min, resulting in 40±13% and 25±13% RCY respectively. [ 18 F]PBR111 was performed at 200μL/min to obtain 27±8% RCY. Molar activities for each 18 F-radiotracer were >100GBq/μmol and radiochemical purities were >97%, implying that the cleaning procedure was effective. Using the same initial solution of [ 18 F]fluoride, microreactor, HPLC column and SPE cartridge, three diverse 18 F-radiotracers could be produced in yields sufficient for preclinical studies in a back-to-back fashion using a microfluidic system with no detectable cross-contamination. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

The Heritage of Radiotracers for PET

DOE R&D Accomplishments Database

Fowler, J. S.; Wolf, A. P.

1988-05-01

The history of PET research clearly demonstrates that it is advances in chemistry coupled with a detailed examination of the biochemistry of new radiotracers which has allowed the PET method to be applied to new areas of biology and medicine. Radiotracers whose regional distribution reflects glucose metabolism, neutrotransmitter activity and enzyme activity have all required the development of rapid synthetic methods for the radiotracers themselves and the characterization of their biochemical behavior. This article traces some of the advances in the production of labeled precursors and in radiotracer synthesis and evaluation which have shaped the rapidly expanding application of PET to problems in the neurosciences, in cardiology and in oncology.

Methods to Increase the Metabolic Stability of (18)F-Radiotracers.

PubMed

Kuchar, Manuela; Mamat, Constantin

2015-09-03

The majority of pharmaceuticals and other organic compounds incorporating radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Metabolic degradation of these drugs is commonly caused by a system of enzymes of low substrate specificity requirement, which is present mainly in the liver, but drug metabolism may also take place in the kidneys or other organs. Thus, radiotracers and all other pharmaceuticals are faced with enormous challenges to maintain their stability in vivo highlighting the importance of their structure. Often in practice, such biologically active molecules exhibit these properties in vitro, but fail during in vivo studies due to obtaining an increased metabolism within minutes. Many pharmacologically and biologically interesting compounds never see application due to their lack of stability. One of the most important issues of radiotracers development based on fluorine-18 is the stability in vitro and in vivo. Sometimes, the metabolism of (18)F-radiotracers goes along with the cleavage of the C-F bond and with the rejection of [(18)F]fluoride mostly combined with high background and accumulation in the skeleton. This review deals with the impact of radiodefluorination and with approaches to stabilize the C-F bond to avoid the cleavage between fluorine and carbon.

Two signs indicative of successful access in nuclear medicine cerebrospinal fluid diversionary shunt studies.

PubMed

Bermo, Mohammed S; Khalatbari, Hedieh; Parisi, Marguerite T

2018-05-08

Successful shunt access is the first step in a properly performed nuclear medicine cerebrospinal fluid (CSF) shunt study. To determine the significance of the radiotracer configuration at the injection site during initial nuclear medicine CSF shunt imaging and the lack of early systemic radiotracer activity as predictors of successful shunt access. With Institutional Review Board approval, three nuclear medicine physicians performed a retrospective review of all consecutive CSF shunt studies performed in children at our institution in 2015. Antecedent nuclear medicine CSF shunt studies in these patients were also assessed and included in the review. The appearance of the reservoir site immediately after radiotracer injection was classified as either figure-of-eight or round/ovoid configuration. The presence or absence of early systemic distribution of the tracer on the 5-min static images was noted and separately evaluated. A total of 98 nuclear medicine ventriculoperitoneal CSF shunt studies were evaluated. Figure-of-eight configuration was identified in 87% of studies and, when present, had 93% sensitivity, 78% specificity, 92% accuracy, 98% positive predictive value (PPV) and 54% negative predictive value (NPV) as a predictor of successful shunt access. Early systemic activity was absent in 89 of 98 studies. Lack of early systemic distribution of the radiotracer had 98% sensitivity, 78% specificity, 96% accuracy, 98% PPV and 78% NPV as a predictor of successful shunt access. Figure-of-eight configuration in conjunction with the absence of early systemic tracer activity had 99% PPV for successful shunt access. Figure-of-eight configuration at the injection site or lack of early systemic radiotracer activity had moderate specificity for successful shunt access. Specificity and PPV significantly improved when both signs were combined in assessment.

Focal hot spot induced by a central subclavian line on bone scan.

PubMed

Moslehi, Masood; Cheki, Mohsen; Dehghani, Tohid; Eftekhari, Mansoureh

2014-01-01

The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these instrument-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants. We present a case of hot spot on the upper right chest in the region of right subclavicular region resulting from injection of radiotracer from central subclavian line. A 52-year-old woman with a history of left breast cancer and recent bone pain was referred to our nuclear medicine department for skeletal survey. Anterior views of chest show a focus of increased radiotracer uptake corresponding to anterior arch of one of the right second rib. The nuclear physician reported it as a focal rib bony lesion and recommended radiological evaluation. As technician later explained, physicians realized that injection site was a central subclavian line on the right side and hot spot on that region is due to injection site. The appearance of both skeletal and soft-tissue uptake depends heavily on imaging technique (such as the route of radiotracer administration) and the interpreting physicians should be aware of the impact of technical factors on image quality.

Nuclear emission-based imaging in the study of brain function

NASA Astrophysics Data System (ADS)

Sossi, Vesna

2016-09-01

Nuclear emission - based imaging has been used in medicine for decades either in the form of Single Photon Emission Computerized Tomography (SPECT) or Positron Emission Tomography (PET). Both techniques are based on radiolabelling molecules of biological interest (radiotracers) with either a gamma (SPECT) or a positron (PET) emitting radionuclide. By detecting radiation from the radiolabels and reconstructing the acquired data it is possible to form an image of the radiotracer distribution in the body and thus obtain information on the biological process that the radiotracer is tagging. While most of the clinical applications of PET are in oncology, where the glucose analogue 18F-flurodeoxyglocose (FDG) is the most commonly used radiotracer, the importance of PET imaging for brain applications is rapidly increasing. Numerous radiotracers exist that can tag different neurotransmitter systems as well as abnormal protein aggregations that are known to underlie several brain diseases: amyloid deposition, a characteristic of Alzheimer's, and, more recently, tau deposition, which is deemed abnormal not only in dementia, but also in Parkinson's syndrome and traumatic brain injury. Imaging has shown that may brain diseases start decades before clinical symptoms, in part explaining the difficulty of developing adequate treatments. This talk will briefly summarize the role of PET imaging in the study of neurodegeneration and discuss the upcoming hybrid PET/MRI imaging instrumentation. NSERC, CIHR, MJFF.

Long-Circulating and pH-Sensitive Liposome Preparation Trapping a Radiotracer for Inflammation Site Detection.

PubMed

Mota, Luciene Das Graças; de Barros, André Luís Branco; Fuscaldi, Leonardo Lima; de Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2015-06-01

Inflammatory and infectious diseases are one of the most common causes of mortality and morbidity. This paper aimed to prepare and to evaluate the ability of long-circulating and pH-sensitive liposomes, trapping a radiotracer, to identify inflamed focus. The physicochemical characterization of freeze-dried liposomes, using glucose as cryoprotectant, showed 80% of the vesicles with adequate mean diameter and good vesicle size homogeneity. Radiotracer encapsulation percentage in liposomes was 10.65%, of which 4.88% was adsorbed on the surface of the vesicles. Furthermore, liposomes presented positive zeta potential. Freeze-dried liposomes, stored for 180 days at 4 degrees C, did not show significant changes in the mean diameter, indicating good stability. Free radiotracer and radiolabeled liposomes were injected into inflammation focus-bearing rats, and ex-vivo biodistribution studies and scintigraphic images were performed. Results showed that radiopharmaceutical, free and encapsulated into liposomes, were able to identify the inflamed site. Target/non-target ratios, obtained by scintigraphic images, were greater than 1.5 at all investigated times. Data did not show significant differences between the free radiotracer and radiolabeled liposomes. Results suggest that this liposomal preparation could be employed as an alternative procedure for inflamed site detection by means of scintigraphic images. However, as the radiotracer is adsorbed onto the liposome surface by electrostatic forces, it is suggested that a neutral radiopharmaceutical be used to confirm the potential of this formulation as a scintigraphic probe for inflammation/infection detection.

The heritage of radiotracers for PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.S.; Wolf, A.P.

The history of PET research clearly demonstrates that it is advances in chemistry coupled with a detailed examination of the biochemistry of new radiotracers which has allowed the PET method to be applied to new areas of biology and medicine. Radiotracers whose regional distribution reflects glucose metabolism, neutrotransmitter activity and enzyme activity have all required the development of rapid synthetic methods for the radiotracers themselves and the characterization of their biochemical behavior. This article traces some of the advances in the production of labeled precursors and in radiotracer synthesis and evaluation which have shaped the rapidly expanding application of PETmore » to problems in the neurosciences, in cardiology and in oncology. 54 refs.« less

Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer's Disease with Positron Emission Tomography.

PubMed

Xie, Fang; Peng, Fangyu

2017-01-01

Aging is a risk factor for Alzheimer's disease (AD). There are changes of brain metabolism and biometal fluxes due to brain aging, which may play a role in pathogenesis of AD. Positron emission tomography (PET) is a versatile tool for tracking alteration of metabolism and biometal fluxes due to brain aging and AD. Age-dependent changes in cerebral glucose metabolism can be tracked with PET using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a radiolabeled glucose analogue, as a radiotracer. Based on different patterns of altered cerebral glucose metabolism, 18F-FDG PET was clinically used for differential diagnosis of AD and Frontotemporal dementia (FTD). There are continued efforts to develop additional radiopharmaceuticals or radiotracers for assessment of age-dependent changes of various metabolic pathways and biometal fluxes due to brain aging and AD with PET. Elucidation of age-dependent changes of brain metabolism and altered biometal fluxes is not only significant for a better mechanistic understanding of brain aging and the pathophysiology of AD, but also significant for identification of new targets for the prevention, early diagnosis, and treatment of AD.

A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats

NASA Astrophysics Data System (ADS)

Märk, J.; Benoit, D.; Balasse, L.; Benoit, M.; Clémens, J. C.; Fieux, S.; Fougeron, D.; Graber-Bolis, J.; Janvier, B.; Jevaud, M.; Genoux, A.; Gisquet-Verrier, P.; Menouni, M.; Pain, F.; Pinot, L.; Tourvielle, C.; Zimmer, L.; Morel, C.; Laniece, P.

2013-07-01

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.

Dual-radiotracer translational SPECT neuroimaging. Comparison of three methods for the simultaneous brain imaging of D2/3 and 5-HT2A receptors.

PubMed

Tsartsalis, Stergios; Tournier, Benjamin B; Habiby, Selim; Ben Hamadi, Meriem; Barca, Cristina; Ginovart, Nathalie; Millet, Philippe

2018-04-30

SPECT imaging with two radiotracers at the same time is feasible if two different radioisotopes are employed, given their distinct energy emission spectra. In the case of 123 I and 125 I, dual SPECT imaging is not straightforward: 123 I emits photons at a principal energy emission spectrum of 143.1-179.9 keV. However, it also emits at a secondary energy spectrum (15-45 keV) that overlaps with the one of 125 I and the resulting cross-talk of emissions impedes the accurate quantification of 125 I. In this paper, we describe three different methods for the correction of this cross-talk and the simultaneous in vivo [ 123 I]IBZM and [ 125 I]R91150 imaging of D 2/3 and 5-HT 2A receptors in the rat brain. Three methods were evaluated for the correction of the effect of cross-talk in a series of simultaneous, [ 123 I]IBZM and [ 125 I]R91150 in vivo and phantom SPECT scans. Method 1 employs a dual-energy window (DEW) approach, in which the cross-talk on 125 I is considered a stable fraction of the energy emitted from 123 I at the principal emission spectrum. The coefficient describing the relationship between the emission of 123 I at the principal and the secondary spectrum was estimated from a series of single-radiotracer [ 123 I]IBZM SPECT studies. In Method 2, spectral factor analysis (FA) is applied to separate the radioactivity from 123 I and 125 I on the basis of their distinct emission patterns across the energy spectrum. Method 3 uses a modified simplified reference tissue model (SRTM C ) to describe the kinetics of [ 125 I]R91150. It includes the coefficient describing the cross-talk on 125 I from 123 I in the model parameters. The results of the correction of cross-talk on [ 125 I]R91150 binding potential (BP ND ) with each of the three methods, using cerebellum as the reference region, were validated against the results of a series of single-radiotracer [ 123 I]R91150 SPECT studies. In addition, the DEW approach (Method 1), considered to be the most straightforward to apply of the three, was further applied in a dual-radiotracer SPECT study of the relationship between D 2/3 and 5-HT 2A receptor binding in the striatum, both at the voxel and at the regional level. Average regional BP ND values of [ 125 I]R91150, estimated on the cross-talk corrected dual-radiotracer SPECT studies provided satisfactory correlations with the BP ND values for [ 123 I]R91150 from single-radiotracer studies: r = 0.92, p < 0.001 for Method 1, r = 0.92, p < 0.001 for Method 2, r = 0.92, p < 0.001, for Method 3. The coefficient describing the ratio of the 123 I-emitted radioactivity at the 125 I-emission spectrum to the radioactivity that it emits at its principal emission spectrum was 0.34 in vivo. Dual-radiotracer in vivo SPECT studies corrected with Method 1 demonstrated a positive correlation between D 2/3 and 5-HT 2A receptor binding in the rat nucleus accumbens at the voxel level. At the VOI-level, a positive correlation was confirmed in the same region (r = 0.78, p < 0.01). Dual-radiotracer SPECT imaging using 123 I and 125 I-labeled radiotracers is feasible if the cross-talk of 123 I on the 125 I emission spectrum is properly corrected. The most straightforward approach is Method 1, in which a fraction (34%) of the radioactivity emitted from 123 I at its principal energy spectrum is subtracted from the measured radioactivity at the spectrum of 125 I. With this method, a positive correlation between the binding of [ 123 I]IBZM and [ 125 I]R91150 was demonstrated in the rat nucleus accumbens. This result highlights the interest of dual-radiotracer SPECT imaging to study multiple neurotransmitter systems at the same time and under the same biological conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

Radiosynthesis of carbon-11 and fluorine-18 labelled radiotracers to image the ionotropic and metabotropic glutamate receptors.

PubMed

Sobrio, Franck

2013-01-01

l-Glutamate is the major neurotransmitter in the central nervous system and activates both ionotropic and metabotropic receptors. Here the radiosynthesis of radiotracers developed for both types of receptors are reviewed with a highlight on the radiopharmaceuticals used or evaluated in humans. At first, radiotracers were developed for ionotropic N-methyl-d-aspartate receptors without any success to obtain radiopharmaceuticals useable for clinical or even preclinical positron emission tomography (PET) imaging purposes. Some compounds were radiolabelled and evaluated for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors without any successful results. The recent development of radiotracers for metabotropic glutamate receptors was more efficient because radiopharmaceuticals are currently evaluated or used in clinical trials to study the mGluR1, mGluR2 or mGluR5 receptors by PET. Although the majority of the radiotracers were classically labelled with carbon-11 by O- or N-[(11) C]-methylation or with fluorine-18 nucleophilic substitution of aromatic nitro or halogeno precursors using krypofix 2.2.2/potassium [(18) F]fluoride complex, some radiosyntheses were performed with recent radiolabelling reactions like the use of iodionium salt for [(18) F]-labelling. Copyright © 2013 John Wiley & Sons, Ltd.

Sodium-22-radiolabeled silica nanoparticles as new radiotracer for biomedical applications: in vivo positron emission tomography imaging, biodistribution, and biocompatibility

PubMed Central

Al Faraj, Achraf; Alotaibi, Basem; Shaik, Abjal Pasha; Shamma, Khaled Z; Al Jammaz, Ibrahim; Gerl, Jürgen

2015-01-01

Despite their advantageous chemical properties for nuclear imaging, radioactive sodium-22 (22Na) tracers have been excluded for biomedical applications because of their extremely long lifetime. In the current study, we proposed, for the first time, the use of 22Na radiotracers for pre-clinical applications by efficiently loading with silica nanoparticles (SiNPs) and thus offering a new life for this radiotracer. Crown-ether-conjugated SiNPs (300 nm; −0.18±0.1 mV) were successfully loaded with 22Na with a loading efficacy of 98.1%±1.4%. Noninvasive positron emission tomography imaging revealed a transient accumulation of 22Na-loaded SiNPs in the liver and to a lower extent in the spleen, kidneys, and lung. However, the signal gradually decreased in a time-dependent manner to become not detectable starting from 2 weeks postinjection. These observations were confirmed ex vivo by quantifying 22Na radioactivity using γ-counter and silicon content using inductively coupled plasma-mass spectrometry in the blood and the different organs of interest. Quantification of Si content in the urine and feces revealed that SiNPs accumulated in the organs were cleared from the body within a period of 2 weeks and completely in 1 month. Biocompatibility evaluations performed during the 1-month follow-up study to assess the possibility of synthesized nanocarriers to induce oxidative stress or DNA damage confirmed their safety for pre-clinical applications. 22Na-loaded nanocarriers can thus provide an innovative diagnostic agent allowing ultra-sensitive positron emission tomography imaging. On the other hand, with its long lifetime, onsite generators or cyclotrons will not be required as 22Na can be easily stored in the nuclear medicine department and be used on-demand. PMID:26504381

Cerenkov Luminescence Imaging as a Modality to Evaluate Antibody-Based PET Radiotracers

PubMed Central

D’Souza, Jimson W.; Hensley, Harvey; Doss, Mohan; Beigarten, Charles; Torgov, Michael; Olafsen, Tove; Yu, Jian Q.

2017-01-01

Antibodies, and engineered antibody fragments, labeled with radioisotopes are being developed as radiotracers for the detection and phenotyping of diseases such as cancer. The development of antibody-based radiotracers requires extensive characterization of their in vitro and in vivo properties, including their ability to target tumors in an antigen-selective manner. In this study, we investigated the use of Cerenkov luminescence imaging (CLI) as compared with PET as a modality for evaluating the in vivo behavior of antibody-based radiotracers. Methods: The anti–prostate-specific membrane antigen (PSMA) huJ591 antibody (IgG; 150 kDa) and its minibody (Mb; 80 kDa) format were functionalized with the chelator 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid (NODAGA) and radiolabeled with the positron-emitting radionuclide 64Cu (half-life, 12.7 h). Immunoreactive preparations of the radiolabeled antibodies were injected into NCr nu/nu mice harboring PSMA-positive CWR22Rv1 and PSMA-negative PC-3 tumor xenografts. Tumor targeting was evaluated by both PET and CLI. Results: 64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb retained the ability to bind cell surface PSMA, and both radiotracers exhibited selective uptake into PSMA-positive tumors. Under the experimental conditions used, PSMA-selective uptake of 64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb was observed by CLI as early as 3 h after injection, with tumor-to-background ratios peaking at 24 (IgG) and 16 (Mb) h after injection. Targeting data generated by CLI correlated with that generated by PET and necropsy. Conclusion: CLI provided a rapid and simple assessment of the targeting specificity and pharmacokinetics of the antibody-based PET radiotracers that correlated well with the behavior observed by standard PET imaging. Moreover, CLI provided clear discrimination between uptake kinetics of an intact IgG and its small-molecular-weight derivative Mb. These data support the use of CLI for the evaluation of radiotracer performance. PMID:27539844

The uses of radiotracers in the life sciences

NASA Astrophysics Data System (ADS)

Ruth, Thomas J.

2009-01-01

Radionuclides have been used to follow physical, chemical and biological processes almost from the time of their discovery. Probably the application with the biggest impact has been in the medical field where radionuclides have been incorporated into biologically active molecules and used to diagnose a wide variety of diseases and to treat many disorders. Other uses in the life sciences, in general, are related to using a radioactive isotope as marker for an existing species such as nitrogen-13 in plant studies or copper-67 to track copper catalysts in phytoplankton. This review describes in general terms these uses as well as providing the reader with the background related to the physical properties of radioactive decay, the concepts associated with the production of radionuclides using reactors or accelerators and the fundamentals of imaging radioactivity. The advances in imaging technology in recent years has had a profound impact on the use of radionuclides in positron emission tomography and the coupling of other imaging modalities to provide very precise insights into human disease. The variety of uses for radiotracers in science is almost boundless dependent only upon ones imagination.

Human brain imaging and radiation dosimetry of 11C-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein.

PubMed

Seneca, Nicholas; Zoghbi, Sami S; Liow, Jeih-San; Kreisl, William; Herscovitch, Peter; Jenko, Kimberly; Gladding, Robert L; Taku, Andrew; Pike, Victor W; Innis, Robert B

2009-05-01

P-glycoprotein (P-gp) is a membrane-bound efflux pump that limits the distribution of drugs to several organs of the body. At the blood-brain barrier, P-gp blocks the entry of both loperamide and its metabolite, N-desmethyl-loperamide (N-dLop), and thereby prevents central opiate effects. Animal studies have shown that (11)C-dLop, compared with (11)C-loperamide, is an especially promising radiotracer because it generates negligible radiometabolites that enter the brain. The purposes of this study were to determine whether (11)C-dLop is a substrate for P-gp at the blood-brain barrier in humans and to measure the distribution of radioactivity in the entire body to estimate radiation exposure. Brain PET scans were acquired in 4 healthy subjects for 90 min and included concurrent measurements of the plasma concentration of unchanged radiotracer. Time-activity data from the whole brain were quantified using a 1-tissue-compartment model to estimate the rate of entry (K(1)) of radiotracer into the brain. Whole-body PET scans were acquired in 8 healthy subjects for 120 min. For brain imaging, after the injection of (11)C-dLop the concentration of radioactivity in the brain was low (standardized uptake value, approximately 15%) and stable after approximately 20 min. In contrast, uptake of radioactivity in the pituitary was about 50-fold higher than that in the brain. The plasma concentration of (11)C-dLop declined rapidly, but the percentage composition of plasma was unusually stable, with the parent radiotracer constituting 85% of total radioactivity after approximately 5 min. The rate of brain entry was low (K(1) = 0.009 +/- 0.002 mL.cm(-3).min(-1); n = 4). For whole-body imaging, as a measure of radiation exposure to the entire body the effective dose of (11)C-dLop was 7.8 +/- 0.6 muSv/MBq (n = 8). The low brain uptake of radioactivity is consistent with (11)C-dLop being a substrate for P-gp in humans and confirms that this radiotracer generates negligible quantities of brain-penetrant radiometabolites. In addition, the low rate of K(1) is consistent with P-gp rapidly effluxing substrates while they transit through the lipid bilayer. The radiation exposure of (11)C-dLop is similar to that of many other (11)C-radiotracers. Thus, (11)C-dLop is a promising radiotracer to study the function of P-gp at the blood-brain barrier, at which impaired function would allow increased uptake into the brain.

Adenosine 2A receptor occupancy by tozadenant and preladenant in rhesus monkeys.

PubMed

Barret, Olivier; Hannestad, Jonas; Alagille, David; Vala, Christine; Tavares, Adriana; Papin, Caroline; Morley, Thomas; Fowles, Krista; Lee, Hsiaoju; Seibyl, John; Tytgat, Dominique; Laruelle, Marc; Tamagnan, Gilles

2014-10-01

Motor symptoms in Parkinson disease (PD) are caused by a loss of dopamine input from the substantia nigra to the striatum. Blockade of adenosine 2A (A(2A)) receptors facilitates dopamine D(2) receptor function. In phase 2 clinical trials, A(2A) antagonists (istradefylline, preladenant, and tozadenant) improved motor function in PD. We developed a new A(2A) PET radiotracer, (18)F-MNI-444, and used it to investigate the relationship between plasma levels and A(2A) occupancy by preladenant and tozadenant in nonhuman primates (NHP). A series of 20 PET experiments was conducted in 5 adult rhesus macaques. PET data were analyzed with both plasma-input (Logan graphical analysis) and reference-region-based (simplified reference tissue model and noninvasive Logan graphical analysis) methods. Whole-body PET images were acquired for radiation dosimetry estimates. Human pharmacokinetic parameters for tozadenant and preladenant were used to predict A(2A) occupancy in humans, based on median effective concentration (EC(50)) values estimated from the NHP PET measurements. (18)F-MNI-444 regional uptake was consistent with A(2A) receptor distribution in the brain. Selectivity was demonstrated by dose-dependent blocking by tozadenant and preladenant. The specific-to-nonspecific ratio was superior to that of other A(2A) PET radiotracers. Pharmacokinetic modeling predicted that tozadenant and preladenant may have different profiles of A(2A) receptor occupancy in humans. (18)F-MNI-444 appears to be a better PET radiotracer for A(2A) imaging than currently available radiotracers. Assuming that EC(50) in humans is similar to that in NHP, it appears that tozadenant will provide a more sustained A(2A) receptor occupancy than preladenant in humans at clinically tested doses. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Automatic delineation of brain regions on MRI and PET images from the pig.

PubMed

Villadsen, Jonas; Hansen, Hanne D; Jørgensen, Louise M; Keller, Sune H; Andersen, Flemming L; Petersen, Ida N; Knudsen, Gitte M; Svarer, Claus

2018-01-15

The increasing use of the pig as a research model in neuroimaging requires standardized processing tools. For example, extraction of regional dynamic time series from brain PET images requires parcellation procedures that benefit from being automated. Manual inter-modality spatial normalization to a MRI atlas is operator-dependent, time-consuming, and can be inaccurate with lack of cortical radiotracer binding or skull uptake. A parcellated PET template that allows for automatic spatial normalization to PET images of any radiotracer. MRI and [ 11 C]Cimbi-36 PET scans obtained in sixteen pigs made the basis for the atlas. The high resolution MRI scans allowed for creation of an accurately averaged MRI template. By aligning the within-subject PET scans to their MRI counterparts, an averaged PET template was created in the same space. We developed an automatic procedure for spatial normalization of the averaged PET template to new PET images and hereby facilitated transfer of the atlas regional parcellation. Evaluation of the automatic spatial normalization procedure found the median voxel displacement to be 0.22±0.08mm using the MRI template with individual MRI images and 0.92±0.26mm using the PET template with individual [ 11 C]Cimbi-36 PET images. We tested the automatic procedure by assessing eleven PET radiotracers with different kinetics and spatial distributions by using perfusion-weighted images of early PET time frames. We here present an automatic procedure for accurate and reproducible spatial normalization and parcellation of pig PET images of any radiotracer with reasonable blood-brain barrier penetration. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK-6577 in baboons.

PubMed

Zheng, Ming-Qiang; Lin, Shu-Fei; Holden, Daniel; Naganawa, Mika; Ropchan, Jim R; Najafzaden, Soheila; Kapinos, Michael; Tabriz, Mike; Carson, Richard E; Hamill, Terence G; Huang, Yiyun

2016-03-01

Glycine transporter type-1 (GlyT1) has been proposed as a target for drug development for schizophrenia. PET imaging with a GlyT1 specific radiotracer will allow for the measurement of target occupancy of GlyT1 inhibitors, and for in vivo investigation of GlyT1 alterations in schizophrenia. We conducted a comparative evaluation of two GlyT1 radiotracers, [(11) C]GSK931145, and [(18) F]MK-6577, in baboons. Two baboons were imaged with [(11) C]GSK931145 and [(18) F]MK-6577. Blocking studies with GSK931145 (0.3 or 0.2 mg/kg) were conducted to determine the level of tracer specific binding. [(11) C]GSK931145 and [(18) F]MK-6577 were synthesized in good yield and high specific activity. Moderately fast metabolism was observed for both tracers, with ∼ 30% of parent at 30 min post-injection. In the brain, both radiotracers showed good uptake and distribution profiles consistent with regional GlyT1 densities. [(18) F]MK-6577 displayed higher uptake and faster kinetics than [(11) C]GSK931145. Time activity curves were well described by the two-tissue compartment model. Regional volume of distribution (VT ) values were higher for [(18) F]MK-6577 than [(11) C]GSK931145. Pretreatment with GSK931145 reduced tracer uptake to a homogeneous level throughout the brain, indicating in vivo binding specificity and lack of a reference region for both radiotracers. Linear regression analysis of VT estimates between tracers indicated higher specific binding for [(18) F]MK-6577 than [(11) C]GSK931145, consistent with higher regional binding potential (BPND ) values of [(18) F]MK-6577 calculated using VT from the baseline scans and non-displaceable distribution volume (VND ) derived from blocking studies. [(18) F]MK-6577 appears to be a superior radiotracer with higher brain uptake, faster kinetics, and higher specific binding signals than [(11) C]GSK931145. © 2016 Wiley Periodicals, Inc.

EM reconstruction of dual isotope PET using staggered injections and prompt gamma positron emitters

PubMed Central

Andreyev, Andriy; Sitek, Arkadiusz; Celler, Anna

2014-01-01

Purpose: The aim of dual isotope positron emission tomography (DIPET) is to create two separate images of two coinjected PET radiotracers. DIPET shortens the duration of the study, reduces patient discomfort, and produces perfectly coregistered images compared to the case when two radiotracers would be imaged independently (sequential PET studies). Reconstruction of data from such simultaneous acquisition of two PET radiotracers is difficult because positron decay of any isotope creates only 511 keV photons; therefore, the isotopes cannot be differentiated based on the detected energy. Methods: Recently, the authors have proposed a DIPET technique that uses a combination of radiotracer A which is a pure positron emitter (such as 18F or 11C) and radiotracer B in which positron decay is accompanied by the emission of a high-energy (HE) prompt gamma (such as 38K or 60Cu). Events that are detected as triple coincidences of HE gammas with the corresponding two 511 keV photons allow the authors to identify the lines-of-response (LORs) of isotope B. These LORs are used to separate the two intertwined distributions, using a dedicated image reconstruction algorithm. In this work the authors propose a new version of the DIPET EM-based reconstruction algorithm that allows the authors to include an additional, independent estimate of radiotracer A distribution which may be obtained if radioisotopes are administered using a staggered injections method. In this work the method is tested on simple simulations of static PET acquisitions. Results: The authors’ experiments performed using Monte-Carlo simulations with static acquisitions demonstrate that the combined method provides better results (crosstalk errors decrease by up to 50%) than the positron-gamma DIPET method or staggered injections alone. Conclusions: The authors demonstrate that the authors’ new EM algorithm which combines information from triple coincidences with prompt gammas and staggered injections improves the accuracy of DIPET reconstructions for static acquisitions so they reach almost the benchmark level calculated for perfectly separated tracers. PMID:24506645

Synthesis of carbon-11, fluorine-18, and nitrogen-13 labeled radiotracers for biomedical applications. Nuclear Science Series: Nuclear Medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.S.; Wolf, A.P.

1982-09-01

Carbon 11, Fluorine 18, and Nitrogen 13-labeled radiotracers are reviewed from the standpoint of synthetic organic chemistry while keeping in perspective the necessity of integrating the organic chemistry with the design and ultimate application of the radiotracer. The reactions used, the principles used to adapt these reactions to labeling with short-lived radionuclides, and the concepts of chemical reactivity form the framework upon which synthetic strategies for short-lived radiotracers are developed. Potentially new routes are suggested which may be applied to problems in labeling organic molecules. (ACR)

Effects of flow changes on radiotracer binding: Simultaneous measurement of neuroreceptor binding and cerebral blood flow modulation.

PubMed

Sander, Christin Y; Mandeville, Joseph B; Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M; Rosen, Bruce R

2017-01-01

The potential effects of changes in blood flow on the delivery and washout of radiotracers has been an ongoing question in PET bolus injection studies. This study provides practical insight into this topic by experimentally measuring cerebral blood flow (CBF) and neuroreceptor binding using simultaneous PET/MRI. Hypercapnic challenges (7% CO 2 ) were administered to non-human primates in order to induce controlled increases in CBF, measured with pseudo-continuous arterial spin labeling. Simultaneously, dopamine D 2 /D 3 receptor binding of [ 11 C]raclopride or [ 18 F]fallypride was monitored with dynamic PET. Experiments showed that neither time activity curves nor quantification of binding through binding potentials ( BP ND ) were measurably affected by CBF increases, which were larger than two-fold. Simulations of experimental procedures showed that even large changes in CBF should have little effect on the time activity curves of radiotracers, given a set of realistic assumptions. The proposed method can be applied to experimentally assess the flow sensitivity of other radiotracers. Results demonstrate that CBF changes, which often occur due to behavioral tasks or pharmacological challenges, do not affect PET [ 11 C]raclopride or [ 18 F]fallypride binding studies and their quantification. The results from this study suggest flow effects may have limited impact on many PET neuroreceptor tracers with similar properties.

Radiotracers for PETT: new developments and perspectives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.S.; Wolf, A.P.

Radiotracer development with positron emitters has its major focus on problems in the neurosciences. Progress is reviewed for high-level isotope production and labelled precurser synthesis with the medical cyclotron. The study of regional brain glucose metabolism represented the first extension of one of the methods of neurochemical autoradiography to humans and the study of brain protein synthesis and neurotransmitter receptors followed. In a more general sense, one PETT instrumentation will provide resolution in the 5 mm range is already emerging. Research status is reviewed. 103 references. (PSB)

Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO).

PubMed

Yuan, Hong; Frank, Jonathan E; Merrill, Joseph R; Hillesheim, Daniel A; Khachaturian, Mark H; Anzellotti, Atilio I

2016-01-01

The hypoxia PET tracer, 1-[18F]fluoro-3-(2-nitro-1Himidazol- 1-yl)-propan-2-ol ([18F]FMISO) is the first radiotracer developed for hypoxia PET imaging and has shown promising for cancer diagnosis and prognosis. However, access to [18F]FMISO radiotracer is limited due to the needed cyclotron and radiochemistry expertise. The study aimed to develop the automated production method on the [18F]FMISO radiotracer with the novel fully automated platform of the BG75 system and validate its usage on animal tumor models. [18F]FMISO was produced with the dose synthesis cartridge automatically on the BG75 system. Validation of [18F]FMISO hypoxia imaging functionality was conducted on two tumor mouse models (FaDu/U87 tumor). The distribution of [18F]FMISO within tumor was further validated by the standard hypoxia marker EF5. The average radiochemical purity was (99±1) % and the average pH was 5.5±0.2 with other quality attributes passing standard criteria (n=12). Overall biodistribution for [18F]FMISO in both tumor models was consistent with reported studies where bladder and large intestines presented highest activity at 90 min post injection. High spatial correlation was found between [18F]FMISO autoradiography and EF5 hypoxia staining, indicating high hypoxia specificity of [18MF]FMISO. This study shows that qualified [18F]FMISO can be efficiently produced on the BG75 system in an automated "dose-on-demand" mode using single dose disposable cards. The possibilities of having a low-cost, automated system manufacturing ([18F]Fluoride production + synthesis + QC) different radiotracers will greatly enhance the potential for PET technology to reach new geographical areas and underserved patient populations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Radiotracer Dilution Method for Mercury Inventory Study in Electrolytic Cells

NASA Astrophysics Data System (ADS)

Sugiharto, Su'ud, Zaki; Kurniadi, Rizal; Waris, Abdul; Santoso, Sigit Budi; Abidin, Zainal; Santoso, Gatot Budi

2010-06-01

Purpose of the experiment is to demonstrate feasibility the use of radiotracer to measure weight of mercury in electrolytic cells of soda industry. The weight of mercury in each cell of the plant is designed approximately 1700 kg. Radiotracer is prepared by mixing 203 Hg radioactive mercury with 2400 g of inactive mercury in a bath. The respective precisely weighted mercury aliquots to be injected into the cells are prepared by pouring approximately 130 g of radioactive mercury taken from the bath into 13 standard vials, in accordance with the number of the cells tested. Four standard references prepared by further dilution of ±2 g active mercury taken from the bath to obtain the dilution factors range of 12,000 to 20,000 from which the calibration graph is constructed. The injection process is conducting by pouring the radioactive mercury from aliquots into the flowing mercury at the inlet side of the cell and allows them to mix thoroughly. It is assumed that the mass of the radiotracer injected into a closed system remains constant, at least during the period of the test. From this experiment it was observed that the mixing time is two days after injection of radioactive mercury. The inactive mercury in each electrolytic cell calculated by the radiotracer method is of the range 1351.529 kg to 1966.354 kg with maximum error (95% confidence) is 1.52 %. The accuracy of measurement of the present method is better than gravimetric one which accounts 4 % of error on average.

Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.

PubMed

Staley, J K; Van Dyck, C H; Tan, P Z; Al Tikriti, M; Ramsby, Q; Klump, H; Ng, C; Garg, P; Soufer, R; Baldwin, R M; Innis, R B

2001-04-01

The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical R(T) (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but was not altered by changes in endogenous 5-HT induced by fenfluramine. These findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.

Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers

NASA Astrophysics Data System (ADS)

Xie, Tianwu; Zaidi, Habib

2014-03-01

PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Optimization of integrated impeller mixer via radiotracer experiments.

PubMed

Othman, N; Kamarudin, S K; Takriff, M S; Rosli, M I; Engku Chik, E M F; Adnan, M A K

2014-01-01

Radiotracer experiments are carried out in order to determine the mean residence time (MRT) as well as percentage of dead zone, V dead (%), in an integrated mixer consisting of Rushton and pitched blade turbine (PBT). Conventionally, optimization was performed by varying one parameter and others were held constant (OFAT) which lead to enormous number of experiments. Thus, in this study, a 4-factor 3-level Taguchi L9 orthogonal array was introduced to obtain an accurate optimization of mixing efficiency with minimal number of experiments. This paper describes the optimal conditions of four process parameters, namely, impeller speed, impeller clearance, type of impeller, and sampling time, in obtaining MRT and V dead (%) using radiotracer experiments. The optimum conditions for the experiments were 100 rpm impeller speed, 50 mm impeller clearance, Type A mixer, and 900 s sampling time to reach optimization.

Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs.

PubMed

Schuster, David M; Nanni, Cristina; Fanti, Stefano

2016-10-01

Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids. The tumor imaging features of this last class of radiotracers mirror the upregulation of transmembrane amino acid transport that is necessary in carcinomas because of increased amino acid use for energy requirements and protein synthesis. Natural and synthetic amino acids radiolabeled for PET imaging have been investigated in prostate cancer patients. Early work with naturally occurring amino acid-derived radiotracers, such as l- 11 C-methionine and l-1- 11 C-5-hydroxytryptophan, demonstrated promising results, including greater sensitivity than 18 F-FDG for intraprostatic and extraprostatic cancer detection. However, limitations with naturally occurring amino acid-derived compounds, including metabolism of the radiotracer itself, led to the development of synthetic amino acid radiotracers, which are not metabolized and therefore more accurately reflect transmembrane amino acid transport. Of the synthetic amino acid-derived PET radiotracers, anti-1-amino-3- 18 F-fluorocyclobutane-1-carboxylic acid ( 18 F-FACBC or 18 F-fluciclovine) has undergone the most promising translation to human use, including the availability of simplified radiosynthesis. Several studies have indicated advantageous biodistribution in the abdomen and pelvis with little renal excretion and bladder activity-characteristics beneficial for prostate cancer imaging. Studies have demonstrated improved lesion detection and diagnostic performance of 18 F-fluciclovine in comparison with conventional imaging, especially for recurrent prostate cancer, although issues with nonspecific uptake limit the potential role of 18 F-fluciclovine in the diagnosis of primary prostate cancer. Although work is ongoing, recently published intrapatient comparisons of 18 F-fluciclovine with 11 C-choline reported higher overall diagnostic performance of the former, especially for the detection of disease relapse. This review is aimed at providing a detailed overview of amino acid-derived PET compounds that have been studied for use in prostate cancer imaging. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Radiotracer Technology in Mixing Processes for Industrial Applications

PubMed Central

Othman, N.; Kamarudin, S. K.

2014-01-01

Many problems associated with the mixing process remain unsolved and result in poor mixing performance. The residence time distribution (RTD) and the mixing time are the most important parameters that determine the homogenisation that is achieved in the mixing vessel and are discussed in detail in this paper. In addition, this paper reviews the current problems associated with conventional tracers, mathematical models, and computational fluid dynamics simulations involved in radiotracer experiments and hybrid of radiotracer. PMID:24616642

Investigation of flow behaviour of coal particles in a pilot-scale fluidized bed gasifier (FBG) using radiotracer technique.

PubMed

Pant, H J; Sharma, V K; Kamudu, M Vidya; Prakash, S G; Krishanamoorthy, S; Anandam, G; Rao, P Seshubabu; Ramani, N V S; Singh, Gursharan; Sonde, R R

2009-09-01

Knowledge of residence time distribution (RTD), mean residence time (MRT) and degree of axial mixing of solid phase is required for efficient operation of coal gasification process. Radiotracer technique was used to measure the RTD of coal particles in a pilot-scale fluidized bed gasifier (FBG). Two different radiotracers i.e. lanthanum-140 and gold-198 labeled coal particles (100 gm) were independently used as radiotracers. The radiotracer was instantaneously injected into the coal feed line and monitored at the ash extraction line at the bottom and gas outlet at the top of the gasifier using collimated scintillation detectors. The measured RTD data were treated and MRTs of coal/ash particles were determined. The treated data were simulated using tanks-in-series model. The simulation of RTD data indicated good degree of mixing with small fraction of the feed material bypassing/short-circuiting from the bottom of the gasifier. The results of the investigation were found useful for optimizing the design and operation of the FBG, and scale-up of the gasification process.

A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine Transmission as Assessed by [11 C]-(+)-PHNO.

PubMed

Thiruchselvam, Thulasi; Wilson, Alan A; Boileau, Isabelle; Le Foll, Bernard

2017-06-01

Previous positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D 2 /D 3 agonist radiotracer, [ 11 C]-(+)-propyl-hexahydro-naphtho-oxazin ([ 11 C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D 3 receptor also enables measuring changes in D 3 -rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [ 11 C]-(+)-PHNO binding in the striatum and in D 3 -rich extra-striatal areas. Eight healthy drinkers underwent 2 [ 11 C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [ 11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the 2 scans. Acute alcohol administration did not significantly reduce [ 11 C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15). Similarly, there were no changes in binding in the D 3 -rich areas of the ventral pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15). However, greater percent change in [ 11 C]-(+)-PHNO binding (ΔBP ND ) between scans was related to lower blood alcohol levels. Using the agonist radiotracer, [ 11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is not associated with robust changes in tracer binding in striatal or extra-striatal regions. However, we found that changes in [ 11 C]-(+)-PHNO binding following alcohol are dependent on blood alcohol levels suggesting that increases in DA may occur at lower stimulating doses. The effect of lower doses of alcohol on DA warrants further investigation in a larger study. Copyright © 2017 by the Research Society on Alcoholism.

Identifying novel radiotracers for PET imaging of the brain: application of LC-MS/MS to tracer identification.

PubMed

Barth, Vanessa; Need, Anne

2014-12-17

Nuclear medicine imaging biomarker applications are limited by the radiotracers available. Radiotracers enable the measurement of target engagement, or occupancy in relation to plasma exposure. These tracers can also be used as pharmacodynamic biomarkers to demonstrate functional consequences of binding a target. More recently, radiotracers have also been used for patient tailoring in Alzheimer's disease seen with amyloid imaging. Radiotracers for the central nervous system (CNS) are challenging to identify, as they require a unique intersection of multiple properties. Recent advances in tangential technologies, along with the use of iterative learning for the purposes of deriving in silico models, have opened up additional opportunities to identify radiotracers. Mass spectral technologies and in silico modeling have made it possible to measure and predict in vivo characteristics of molecules to indicate potential tracer performance. By analyzing these data alongside other measures, it is possible to delineate guidelines to increase the likelihood of selecting compounds that can perform as radiotracers or serve as the best starting point to develop a radiotracer following additional structural modification. The application of mass spectrometry based technologies is an efficient way to evaluate compounds as tracers in vivo, but more importantly enables the testing of potential tracers that have either no label site or complex labeling chemistry which may deter assessment by traditional means; therefore, use of this technology allows for more rapid iterative learning. The ability to differentially distribute toward target rich tissues versus tissue with no/less target present is a unique defining feature of a tracer. By testing nonlabeled compounds in vivo and analyzing tissue levels by LC-MS/MS, rapid assessment of a compound's ability to differentially distribute in a manner consistent with target expression biology guides the focus of chemistry resources for both designing and labeling tracer candidates. LC-MS/MS has only recently been used for de novo tracer identification; however, this connection of mass spectral technology to imaging has initiated engagement from a wider community that brings diverse backgrounds into the tracer discovery arena.

Converting energy to medical progress [nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2001-04-01

For over 50 years the Office of Biological and Environmental Research (BER) of the United States Department of Energy (DOE) has been investing to advance environmental and biomedical knowledge connected to energy. The BER Medical Sciences program fosters research to develop beneficial applications of nuclear technologies for medical diagnosis and treatment of many diseases. Today, nuclear medicine helps millions of patients annually in the United States. Nearly every nuclear medicine scan or test used today was made possible by past BER-funded research on radiotracers, radiation detection devices, gamma cameras, PET and SPECT scanners, and computer science. The heart of biologicalmore » research within BER has always been the pursuit of improved human health. The nuclear medicine of tomorrow will depend greatly on today's BER-supported research, particularly in the discovery of radiopharmaceuticals that seek specific molecular and genetic targets, the design of advanced scanners needed to create meaningful images with these future radiotracers, and the promise of new radiopharmaceutical treatments for cancers and genetic diseases.« less

Converting Energy to Medical Progress [Nuclear Medicine

DOE R&D Accomplishments Database

2001-04-01

For over 50 years the Office of Biological and Environmental Research (BER) of the United States Department of Energy (DOE) has been investing to advance environmental and biomedical knowledge connected to energy. The BER Medical Sciences program fosters research to develop beneficial applications of nuclear technologies for medical diagnosis and treatment of many diseases. Today, nuclear medicine helps millions of patients annually in the United States. Nearly every nuclear medicine scan or test used today was made possible by past BER-funded research on radiotracers, radiation detection devices, gamma cameras, PET and SPECT scanners, and computer science. The heart of biological research within BER has always been the pursuit of improved human health. The nuclear medicine of tomorrow will depend greatly on today's BER-supported research, particularly in the discovery of radiopharmaceuticals that seek specific molecular and genetic targets, the design of advanced scanners needed to create meaningful images with these future radiotracers, and the promise of new radiopharmaceutical treatments for cancers and genetic diseases.

Microleakage Evaluation at Implant-Abutment Interface Using Radiotracer Technique

PubMed Central

Siadat, Hakimeh; Arshad, Mahnaz; Mahgoli, Hossein-Ali; Fallahi, Babak

2016-01-01

Objectives: Microbial leakage through the implant-abutment (I-A) interface results in bacterial colonization in two-piece implants. The aim of this study was to compare microleakage rates in three types of Replace abutments namely Snappy, GoldAdapt, and customized ceramic using radiotracing. Materials and Methods: Three groups, one for each abutment type, of five implants and one positive and one negative control were considered (a total of 17 regular body implants). A torque of 35 N/cm was applied to the abutments. The samples were immersed in thallium 201 radioisotope solution for 24 hours to let the radiotracers leak through the I-A interface. Then, gamma photons received from the radiotracers were counted using a gamma counter device. In the next phase, cyclic fatigue loading process was applied followed by the same steps of immersion in the radioactive solution and photon counting. Results: Rate of microleakage significantly increased (P≤0.05) in all three types of abutments (i.e. Snappy, GoldAdapt, and ceramic) after cyclic loading. No statistically significant differences were observed between abutment types after cyclic loading. Conclusions: Microleakage significantly increases after cyclic loading in all three Replace abutments (GoldAdapt, Snappy, ceramic). Lowest microleakage before and after cyclic loading was observed in GoldAdapt followed by Snappy and ceramic. PMID:28392814

Micro-Dose Calibrator for Pre-clinical Radiotracer Assays | NCI Technology Transfer Center | TTC

Cancer.gov

Pre-clinical radiotracer biomedical research involves the use of compounds labeled with radioisotopes, including cell binding studies, immune cell labeling techniques, and radio-ligand bio-distribution studies. Before this Micro-Dose Calibrator, measurement of pre-clinical level dosage for small animal studies was inaccurate and unreliable. This dose calibrator is a prototype ready for manufacturing. It is designed to accurately measure radioactive doses in the range of 50 nCi (1.8 kBq) to 100 µCi (3.7 MBq) with 1% precision. The NCI seeks co-development or licensing to commercialize it. Alternative uses will be considered.

64Cu-Labeled Phosphonium Cations as PET Radiotracers for Tumor Imaging

PubMed Central

Zhou, Yang; Liu, Shuang

2011-01-01

Alteration in mitochondrial transmembrane potential (ΔΨm) is an important characteristic of cancer. The observation that the enhanced negative mitochondrial potential is prevalent in tumor cell phenotype provides a conceptual basis for development of mitochondrion-targeting therapeutic drugs and molecular imaging probes. Since plasma and mitochondrial potentials are negative, many delocalized organic cations, such as rhodamine-123 and 3H-tetraphenylphosphonium, are electrophoretically driven through these membranes, and able to localize in the energized mitochondria of tumor cells. Cationic radiotracers, such as 99mTc-Sestamibi and 99mTc-Tetrofosmin, have been clinically used for diagnosis of cancer by single photon emission computed tomography (SPECT) and noninvasive monitoring of the multidrug resistance (MDR) transport function in tumors of different origin. However, their diagnostic and prognostic values are often limited due to their insufficient tumor localization (low radiotracer tumor uptake) and high radioactivity accumulation in the chest and abdominal regions (low tumor selectivity). In contrast, the 64Cu-labeled phosphonium cations represent a new class of PET (positron emission tomography) radiotracers with good tumor uptake and high tumor selectivity. This review article will focus on our recent experiences in evaluation of 64Cu-labeled phosphonium cations as potential PET radiotracers. The main objective is to illustrate the impact of radiometal chelate on physical, chemical and biological properties of 64Cu radiotracers. It will also discuss some important issues related to their tumor selectivity and possible tumor localization mechanism. PMID:21696200

Preparation and comparative evaluation of 99m Tc-HYNIC-cNGR and 99m Tc-HYNIC-PEG2 -cNGR as tumor-targeting molecular imaging probes.

PubMed

Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Kumar, Chandan; Sarma, Haladhar Dev; Banerjee, Sharmila

2018-02-01

The tripeptide sequence asparagine-glycine-arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG 2 -c(NGR), were synthesized, radiolabeled with 99m Tc, and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being -2.33 ± 0.05 and -2.61 ± 0.08. The uptake of 2 radiotracers 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR) was similar in nude mice bearing human fibrosarcoma HT-1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99m Tc-labeled HYNIC peptide could not be modulated through introduction of PEG 2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention. Copyright © 2017 John Wiley & Sons, Ltd.

Radiolabeled Cyclic RGD Peptides as Radiotracers for Imaging Tumors and Thrombosis by SPECT

PubMed Central

Zhou, Yang; Chakraborty, Sudipta; Liu, Shuang

2011-01-01

The integrin family is a group of transmembrane glycoprotein comprised of 19 α- and 8 β-subunits that are expressed in 25 different α/β heterodimeric combinations on the cell surface. Integrins play critical roles in many physiological processes, including cell attachment, proliferation, bone remodeling, and wound healing. Integrins also contribute to pathological events such as thrombosis, atherosclerosis, tumor invasion, angiogenesis and metastasis, infection by pathogenic microorganisms, and immune dysfunction. Among 25 members of the integrin family, the αvβ3 is studied most extensively for its role of tumor growth, progression and angiogenesis. In contrast, the αIIbβ3 is expressed exclusively on platelets, facilitates the intercellular bidirectional signaling (“inside-out” and “outside-in”) and allows the aggregation of platelets during vascular injury. The αIIbβ3 plays an important role in thrombosis by its activation and binding to fibrinogen especially in arterial thrombosis due to the high blood flow rate. In the resting state, the αIIbβ3 on platelets does not bind to fibrinogen; on activation, the conformation of platelet is altered and the binding sites of αIIbβ3 are exposed for fibrinogen to crosslink platelets. Over the last two decades, integrins have been proposed as the molecular targets for diagnosis and therapy of cancer, thrombosis and other diseases. Several excellent review articles have appeared recently to cover a broad range of topics related to the integrin-targeted radiotracers and their nuclear medicine applications in tumor imaging by single photon emission computed tomography (SPECT) or a positron-emitting radionuclide for positron emission tomography (PET). This review will focus on recent developments of αvβ3-targeted radiotracers for imaging tumors and the use of αIIbβ3-targeted radiotracers for thrombosis imaging, and discuss different approaches to maximize the targeting capability of cyclic RGD peptides and improve the radiotracer excretion kinetics from non-cancerous organs. Improvement of target uptake and target-to-background ratios is critically important for target-specific radiotracers. PMID:21547153

[Pharmacokinetics of radiotracers in the ocular tissues exposed to infrasound and ultrasound phonophoreses].

PubMed

2006-01-01

The paper compares the efficiency of infrasound and ultrasound phonophoreses. The efficiency was evaluated on the basis of the rate of radiotracers within the eye after infrasound or ultrasound exposure of the eyeball. The exposure was made after preliminary putting the radiotracer-impregnated application into the bulbar conjunctiva of an animal. Radioactivity was recorded on a Siemens gamma camera in its lifetime. The time course of changes in the radioactivities measured 10, 30, and 60 minutes after termination of exposures strongly suggests its stable increase in the eye exposed to infrasound. At the same time 10 minutes after ultrasound exposure, the increased concentration of a radiotracer in the eye was less than that after infrasound exposure and then it progressively decreased. Thus, having a significant phoretic activity, infrasound, as ultrasound, creates more favorable conditions for long drug storage in the eye.

(18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization.

PubMed

Vallabhajosula, Shankar

2007-11-01

Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on regulatory compliance in addition to documentation of potential safety and efficacy by various investigators.

In vivo quantification of mouse autoimmune arthritis by PET/CT

PubMed Central

Kundu-Raychaudhuri, Smriti; Mitra, Anupam; Datta-Mitra, Ananya; Chaudhari, Abhijit J.; Raychaudhuri, Siba P.

2014-01-01

Aim To quantify the progression and severity of mouse collagen-induced arthritis (CIA) using an in vivo imaging tool, 18F-fluorodeoxyglucose (18F-FDG) PET/CT, and validate it against gold standard ‘histopathological’ evaluation. Method The PET radiotracer 18F-FDG, a marker for glucose metabolism, was injected in mice at different stages during the development of CIA and the radiotracer distribution was imaged using a PET scanner. A sequential CT scan provided correlated anatomy. Radiotracer concentration was derived from PET/CT images for individual limb joints and on a per-limb basis at different stages of the disease. The imaging outcomes were subjected to correlation analysis with concurrently-measured clinical and histological score. Results Clinical and histological score, and hence disease severity, showed a strong linear correlation (R2=0.71, p=0.001, and R2=0.87, p<0.001, respectively) with radiotracer concentration measured from PET/CT during the progression of CIA. Conclusions The strong positive correlation of the 18F-FDG PET/CT findings with the histopathological evaluation at different stages of the disease suggest the potential of this imaging tool for the non-invasive assessment of progression and severity in mouse autoimmune arthritis. Thus, 18F-FDG PET/CT can be considered as a non invasive tool in preclinical studies for development of novel therapies of inflammatory arthritis. PMID:24965561

Investigations of Au-198 as radiotracer in laboratory porous media using gamma camera: a preliminary study

NASA Astrophysics Data System (ADS)

Othman, N.; Kamal, W. H. B. Wan; Yusof, N. H.; Engku Chik, E. M. F.; Yunos, M. A. S.; Adnan, M. A. K.; Shari, M. R.

2018-01-01

Preliminary experiment has been carried out using irradiated Au-198 as radiotracer inside the laboratory porous media. The objectives are to check the compatibility of Au-198 as the radiotracer inside the porous media as well as to provide insights of fluid hydrodynamics inside the media using gamma camera.198Au is gamma emitter isotope with half-life of 2.7 days and energy of 0.41 MeV (99%). The porous media consists of fine sandstone with grain size 850μm, lubricant as the mimic of original oil in plant (OOIP) or trapped oil and a layer of cement on top of the rig as the bed rock. Gamma camera is arranged next to the porous media in order to capture the movement of radiotracer which has been set to 1minute per frame. Initially, the gold wire which has isotope of 197Au was irradiated inside the rotary rack of Reactor Triga PUSPATI (RTP) to produce 198Au. RTP is located in Nuclear Malaysia, Bangi has energy of 750kW and neutron flux of 5 × 102 n/cm2/s. 198Au, which is in liquid form, is injected inside the porous media and monitored and recorded by gamma camera. The gamma camera gives a quantitative determination of local fluid saturations over the area of observation.

Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies.

PubMed

Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Nariai, Tadashi; Ishiwata, Kiichi

2013-04-01

We investigated the whole-body biodistributions and radiation dosimetry of five (11)C-labeled and one (18)F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. The radiotracers investigated were (11)C-SA4503, (11)C-MPDX, (11)C-TMSX, (11)C-CHIBA-1001, (11)C-4DST, and (18)F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.

Radiosynthesis and radiopharmacological evaluation of [N-methyl-11C]Org 34850 as a glucocorticoid receptor (GR)-binding radiotracer.

PubMed

Wuest, Frank; Kniess, Torsten; Henry, Brian; Peeters, Bernardus W M M; Wiegerinck, Peter H G; Pietzsch, Jens; Bergmann, Ralf

2009-02-01

The radiosynthesis of [N-methyl-(11)C]Org 34850 as a potential brain glucocorticoid receptor (GR)-binding radiotracer is described. The radiosynthesis was accomplished via N-methylation of the corresponding desmethyl precursor with [(11)C]methyl triflate in a remotely controlled synthesis module to give the desired compound in a radiochemical yield of 23+/-5% (decay-corrected, based upon [(11)C]CO(2)) at a specific activity of 47+/-12 GBq/micromol (n=15) at the end-of-synthesis (EOS). The radiochemical purity after semi-preparative HPLC purification exceeded 95%. The total synthesis time was 35-40 min after end-of-bombardment (EOB). The radiotracer is rapidly metabolized in rat plasma leading to the formation of two more hydrophilic metabolites as the major metabolites. Radiopharmacological evaluation involving biodistribution and small animal PET imaging in normal Wistar rats showed that the compound [N-methyl-(11)C]Org 34850 is not able to sufficiently penetrate the blood-brain barrier. Therefore, compound [N-methyl-(11)C]Org 34850 seems not to be a suitable PET radiotracer for imaging rat brain GRs. However, involvement of Pgp or species differences requires further clarification to establish whether the radiotracer [N-methyl-(11)C]Org 34850 may still represent a suitable candidate for imaging GRs in humans.

{sup 18}F-desmethoxyfallypride: A fluorine-18 labeled radiotracer with properties similar to carbon-11 raclopride for PET imaging studies of dopamine D{sub 2} receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mukherjee, J.; Yang, Z.Y.; Brown, T.

1996-07-19

We have developed (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-{sup 18}F-fluoropropyl)-2-methoxybenzamide ({sup 18}F-desmethoxyfallypride) as a fluorine-18 radiotracer with properties analogous to that of {sup 11}C-raclopride. In vitro experiments in rat brain homogenates showed an association rate constant of 2.1X10{sup 8} M{sup -1} min{sup -1} and a dissociation rate constant of 0.073 min{sup -1}. High striatal uptake (up to 0.08% injected dose/cc) of {sup 18}F-desmethoxyfallypride in rhesus monkeys was observed in PET experiments. The radiotracer cleared from the striata with a dissociation rate of 1.80X10{sup -2} min{sup -1}. Striatum to cerebellum ratios peaked at 3.0 in 30 min after which they decreased steadily. Intravenously administered haloperidol displacedmore » specifically bound {sup 18}F-desmethoxyfallypride with a k{sub off} of 0.058 min{sup -1}. Synaptic dopamine released by the treatment of the monkeys with a d-amphetamine increased the dissociation rate of {sup 18}F-desmethoxyfallypride to 0.83 min{sup -1} thus reducing specifically bound {sup 18}F-desmethoxyfallypride by 56% over a period of 42 mins compared to a reduction of only 20% in controls during this time period. The sensitivity of {sup 18}F-desmethoxyfallypride towards competition with dopamine should make this radiotracer useful in PET studies to evaluate in vivo pharmacological effects of various agents that alter levels of endogenous dopamine. 27 refs., 8 figs.« less

Scintigraphic findings in ankylosing spondylitis.

PubMed

Lentle, B C; Russell, A S; Percy, J S; Jackson, F I

1977-06-01

A prospective study of bone scintigraphic findings has been carried out in 63 patients, firmly diagnosed as having ankylosing spondylitis. In addition to abnormal uptake of the radiotracer at the sacroiliac joints, a peripheral arthropathy has been a common finding, particularly in the proximal joints, occurring in up to 50% of patients. Increased uptake of radiotracer in the spine has also been found both diffusely and focally. Focal increases have been noted at the apophyseal joints in 40% of patients and in three patients with a sterile intervertebral diskitis, an unusual complication of this disease only diagnosed in two patients after bone scintigraphy.

Comparison of [11C]TZ1964B and [18F]MNI659 for PET imaging brain PDE10A in nonhuman primates.

PubMed

Liu, Hui; Jin, Hongjun; Yue, Xuyi; Han, Junbin; Yang, Hao; Flores, Hubert; Su, Yi; Alagille, David; Perlmutter, Joel S; Tamagnan, Gilles; Tu, Zhude

2016-10-01

Phosphodiesterase 10A (PDE10A) inhibitors show therapeutic effects for diseases with striatal pathology. PET radiotracers have been developed to quantify in vivo PDE10A levels and target engagement for therapeutic interventions. The aim of this study was to compare two potent and selective PDE10A radiotracers, [ 11 C]TZ1964B and [ 18 F]MNI659 in the nonhuman primate (NHP) brain. Double scans in the same cynomolgus monkey on the same day were performed after injection of [ 11 C]TZ1964B and [ 18 F]MNI659. Specific uptake was determined in two ways: nondisplaceable binding potential (BP ND ) was calculated using cerebellum as the reference region and the PDE-10A enriched striatum as the target region of interest (ROI); the area under the time-activity curve (AUC) for the striatum to cerebellum ratio was also calculated. High-performance liquid chromatography (HPLC) analysis of solvent-extracted NHP plasma identified the percentage of intact tracer versus radiolabeled metabolites samples post injection of each radiotracer. Both radiotracers showed high specific accumulation in NHP striatum. [ 11 C]TZ1964B has higher striatal retention and lower specific striatal uptake than [ 18 F]MNI659. The BP ND estimates of [ 11 C]TZ1964B were 3.72 by Logan Reference model (LoganREF) and 4.39 by simplified reference tissue model (SRTM); the BP ND estimates for [ 18 F]MNI659 were 5.08 (LoganREF) and 5.33 (SRTM). AUC ratios were 5.87 for [ 11 C]TZ1964B and 7.60 for [ 18 F]MNI659. Based on BP ND values in NHP striatum, coefficients of variation were ~10% for [ 11 C]TZ1964B and ~30% for [ 18 F]MNI659. Moreover, the metabolism study showed the percentage of parent compounds were ~70% for [ 11 C]TZ1964B and ~50% for [ 18 F]MNI659 60 min post injection. These data indicate that either [ 11 C]TZ1964B or [ 18 F]MNI659 could serve as suitable PDE10A PET radiotracers with distinguishing features for particular clinical application.

EM reconstruction of dual isotope PET using staggered injections and prompt gamma positron emitters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreyev, Andriy, E-mail: andriy.andreyev-1@philips.com; Sitek, Arkadiusz; Celler, Anna

2014-02-15

Purpose: The aim of dual isotope positron emission tomography (DIPET) is to create two separate images of two coinjected PET radiotracers. DIPET shortens the duration of the study, reduces patient discomfort, and produces perfectly coregistered images compared to the case when two radiotracers would be imaged independently (sequential PET studies). Reconstruction of data from such simultaneous acquisition of two PET radiotracers is difficult because positron decay of any isotope creates only 511 keV photons; therefore, the isotopes cannot be differentiated based on the detected energy. Methods: Recently, the authors have proposed a DIPET technique that uses a combination of radiotracermore » A which is a pure positron emitter (such as{sup 18}F or {sup 11}C) and radiotracer B in which positron decay is accompanied by the emission of a high-energy (HE) prompt gamma (such as {sup 38}K or {sup 60}Cu). Events that are detected as triple coincidences of HE gammas with the corresponding two 511 keV photons allow the authors to identify the lines-of-response (LORs) of isotope B. These LORs are used to separate the two intertwined distributions, using a dedicated image reconstruction algorithm. In this work the authors propose a new version of the DIPET EM-based reconstruction algorithm that allows the authors to include an additional, independent estimate of radiotracer A distribution which may be obtained if radioisotopes are administered using a staggered injections method. In this work the method is tested on simple simulations of static PET acquisitions. Results: The authors’ experiments performed using Monte-Carlo simulations with static acquisitions demonstrate that the combined method provides better results (crosstalk errors decrease by up to 50%) than the positron-gamma DIPET method or staggered injections alone. Conclusions: The authors demonstrate that the authors’ new EM algorithm which combines information from triple coincidences with prompt gammas and staggered injections improves the accuracy of DIPET reconstructions for static acquisitions so they reach almost the benchmark level calculated for perfectly separated tracers.« less

Development and Pre-Clinical Evaluation of a Novel Prostate-Restricted Replication Competent Adenovirus-AD-IU-1

DTIC Science & Technology

2006-05-01

CTCTGTTTGTGGA A A A TT TTA A A CTA CTGGTTTA A TTT CT TTA TTGGTTGTA A TA TGA CTA TTTTA CGTCA TA TA A CA A TTTTTA TT GTTTGT TA A A TGA CTTTA TTGTTTGTC A...radiotracer 1 was 0.8–1.2 Ci /mmol at end of synthesis (EOS). In comparison with the results reported in the literature,[15,25,33,34] several improvements in...99%, and the chemical purity of radiotracer 1 was 93%. The average (n ¼ 3–5) specific radio- activity of radiotracer 1 was 0.8–1.2 Ci /mmol at EOS

Radiotracers Used for the Scintigraphic Detection of Infection and Inflammation

PubMed Central

Tsopelas, Chris

2015-01-01

Over the last forty years, a small group of commercial radiopharmaceuticals have found their way into routine medical use, for the diagnostic imaging of patients with infection or inflammation. These molecular radiotracers usually participate in the immune response to an antigen, by tagging leukocytes or other molecules/cells that are endogenous to the process. Currently there is an advancing effort by researchers in the preclinical domain to design and develop new agents for this application. This review discusses radiopharmaceuticals used in the nuclear medicine clinic today, as well as those potential radiotracers that exploit an organism's defence mechanisms to an infectious or inflammatory event. PMID:25741532

Synthesis and comparative in vivo evaluation of 99m Tc(CO)3 -labeled PEGylated and non-PEGylated cRGDfK peptide monomers.

PubMed

Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Sarma, Haladhar D; Banerjee, Sharmila

2017-03-01

This work aimed at studying the effect of insertion of medium PEG (PEG 7 ) on the pharmacokinetic behavior of cRGDfK peptide in comparison with the non-PEGylated analogue. The cRGDfK peptide has thus been derivatized at ε-amino group of lysine by conjugation with N 3 -PEG 7 -COOH/N 3 -CH 2 -COOH to prepare a PEGylated and a non-PEGylated analogue of cRGDfK. A tridentate chelator was then incorporated by click chemistry conjugation of the two peptide azides for radiolabeling with [ 99m Tc(CO) 3 (H 2 O) 3 ] + precursor. Comparative in vivo evaluation of the two 99m Tc(CO) 3 -labeled radiotracers, 99m Tc(CO) 3 -Pra-Tz-CH 2 -cRGDfK 5 and 99m Tc(CO) 3 -Pra-Tz-PEG 7 -cRGDfK 6, was carried out in C57BL/6 mice bearing α v β 3 -positive melanoma tumors to determine their potential toward targeting integrin α v β 3 receptors. The radiotracers exhibited excellent stability in saline as well as in serum. Maximum tumor uptake for the two radiotracers was observed at 30 min p.i. (5: 3.0 ± 0.7% ID/g; 6: 4.1 ± 0.5% ID/g). The two neutral 99m Tc(CO) 3 radiotracers prepared exhibited receptor-mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG 7 unit was accompanied by slower clearance from other organs which resulted in decreased target-to-background ratios. The in vivo kinetics of 99m Tc(CO) 3 -labeled radiotracer, 99m Tc(CO) 3 -Pra-Tz-CH 2 -cRGDfK 5 with only methylene unit as the spacer, was found to be more favorable due to higher tumor/blood, tumor/liver, tumor/kidney, and tumor/lung ratios. © 2016 John Wiley & Sons A/S.

SU-E-T-507: Internal Dosimetry in Nuclear Medicine Using GATE and XCAT Phantom: A Simulation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fallahpoor, M; Abbasi, M; Sen, A

Purpose Monte Carlo simulations are routinely used for internal dosimetry studies. These studies are conducted with humanoid phantoms such as the XCAT phantom. In this abstract we present the absorbed doses for various pairs of source and target organs using three common radiotracers in nuclear medicine. Methods The GATE software package is used for the Monte Carlo simulations. A typical female XCAT phantom is used as the input. Three radiotracers 153Sm, 131I and 99mTc are studied. The Specific Absorbed Fraction (SAF) for gamma rays (99mTc, 153Sm and 131I) and Specific Fraction (SF) for beta particles (153Sm and 131I) are calculatedmore » for all 100 pairs of source target organs including brain, liver, lung, pancreas, kidney, adrenal, spleen, rib bone, bladder and ovaries. Results The source organs themselves gain the highest absorbed dose as compared to other organs. The dose is found to be inversely proportional to distance from the source organ. In SAF results of 153Sm, when the source organ is lung, the rib bone, gain 0.0730 (Kg-1) that is more than lung itself. Conclusion The absorbed dose for various organs was studied in terms of SAF and SF. Such studies hold importance for future therapeutic procedures and optimization of induced radiotracer.« less

In vivo metabolism and partitioning of 6-[18F]fluoro-L-meta-tyrosine in whole blood: a unified compartment model

NASA Astrophysics Data System (ADS)

Asselin, Marie-Claude; Wahl, Lindi M.; Cunningham, Vincent J.; Amano, Shigeko; Nahmias, Claude

2002-06-01

Physiological quantification of dynamic PET data requires the determination of an input function, preferably from plasma. A compartmental model relating a parent radiotracer, its radiolabelled metabolites and their exchange between plasma and erythrocytes is presented. This model allows for the time course of radioactivity measured in whole blood to be transformed into the time course of the radiotracer in plasma. The utility of this approach is illustrated with blood data collected on 30 human subjects injected with 6-[18F]fluoro-L-meta-tyrosine (FmT), a pre-synaptic dopaminergic radiotracer. A three-compartment four-parameter model is shown to yield significantly better fits to the blood data than related lower and higher order models. This model is found to be robust to measurement noise, and yet sensitive to metabolic changes induced by pretreatment with carbidopa. For FmT, the between-subject variations are shown to be small enough to warrant the use of a population-based correction;; tissue time-activity curves were simulated to verify that this correction does not significantly affect the precision and accuracy of the derived rate constants. The unified blood model can be adapted for radiotracers other than FmT as long as the blood partition ratio of the parent radiotracer differs from that of its metabolites and/or the rate at which they equilibrate between plasma and erythrocytes is different.

Evaluation of Fluorine-18-Labeled α1(I)-N-Telopeptide Analogs as Substrate-Based Radiotracers for PET Imaging of Melanoma-Associated Lysyl Oxidase.

PubMed

Kuchar, Manuela; Neuber, Christin; Belter, Birgit; Bergmann, Ralf; Lenk, Jens; Wodtke, Robert; Kniess, Torsten; Steinbach, Jörg; Pietzsch, Jens; Löser, Reik

2018-01-01

Accumulating evidence suggests an unequivocal role of lysyl oxidases as key players of tumor progression and metastasis, which renders this enzyme family highly attractive for targeted non-invasive functional imaging of tumors. Considering their function in matrix remodeling, malignant melanoma appears as particularly interesting neoplasia in this respect. For the development of radiotracers that enable PET imaging of the melanoma-associated lysyl oxidase activity, substrates derived from the type I collagen α1 N-telopeptide were labeled with fluorine-18 using N -succinimidyl 4-[ 18 F]fluorobenzoate ([ 18 F]SFB) as prosthetic reagent. With regards to potential crosslinking to tumor-associated collagen in vivo , their interaction with triple-helical type I collagen was studied by SPR. A mouse model of human melanoma was established on the basis of the A375 cell line, for which the expression of the oncologically relevant lysyl oxidase isoforms LOX and LOXL2 was demonstrated in Western blot and immunohistochemical experiments. The radiopharmacological profiles of the peptidic radiotracers were evaluated in normal rats and A375 melanoma-bearing mice by ex vivo metabolite analysis, whole-body biodistribution studies and dynamic PET imaging. Out of three 18 F-labeled telopeptide analogs, the one with the most favorable substrate properties has shown favorable tumor uptake and tumor-to-muscle ratio. Lysyl oxidase-mediated tumor uptake was proven by pharmacological inhibition using β-aminopropionitrile and by employing negative-control analogs of impeded or abolished targeting capability. The latter were obtained by substituting the lysine residue by ornithine and norleucine, respectively. Comparing the tumor uptake of the lysine-containing peptide with that of the non-functional analogs indicate the feasibility of lysyl oxidase imaging in melanoma using substrate-based radiotracers.

Evaluation of Fluorine-18-Labeled α1(I)-N-Telopeptide Analogs as Substrate-Based Radiotracers for PET Imaging of Melanoma-Associated Lysyl Oxidase

PubMed Central

Kuchar, Manuela; Neuber, Christin; Belter, Birgit; Bergmann, Ralf; Lenk, Jens; Wodtke, Robert; Kniess, Torsten; Steinbach, Jörg; Pietzsch, Jens; Löser, Reik

2018-01-01

Accumulating evidence suggests an unequivocal role of lysyl oxidases as key players of tumor progression and metastasis, which renders this enzyme family highly attractive for targeted non-invasive functional imaging of tumors. Considering their function in matrix remodeling, malignant melanoma appears as particularly interesting neoplasia in this respect. For the development of radiotracers that enable PET imaging of the melanoma-associated lysyl oxidase activity, substrates derived from the type I collagen α1 N-telopeptide were labeled with fluorine-18 using N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) as prosthetic reagent. With regards to potential crosslinking to tumor-associated collagen in vivo, their interaction with triple-helical type I collagen was studied by SPR. A mouse model of human melanoma was established on the basis of the A375 cell line, for which the expression of the oncologically relevant lysyl oxidase isoforms LOX and LOXL2 was demonstrated in Western blot and immunohistochemical experiments. The radiopharmacological profiles of the peptidic radiotracers were evaluated in normal rats and A375 melanoma-bearing mice by ex vivo metabolite analysis, whole-body biodistribution studies and dynamic PET imaging. Out of three 18F-labeled telopeptide analogs, the one with the most favorable substrate properties has shown favorable tumor uptake and tumor-to-muscle ratio. Lysyl oxidase-mediated tumor uptake was proven by pharmacological inhibition using β-aminopropionitrile and by employing negative-control analogs of impeded or abolished targeting capability. The latter were obtained by substituting the lysine residue by ornithine and norleucine, respectively. Comparing the tumor uptake of the lysine-containing peptide with that of the non-functional analogs indicate the feasibility of lysyl oxidase imaging in melanoma using substrate-based radiotracers.

Formation of nonextractable soil residues: A stable isotope approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richnow, H.H.; Eschenback, A.; Mahro, B.

1999-11-01

Stable carbon isotopic measurements were employed to characterize the transformation of a {sup 13}C-labeled polycyclic aromatic hydrocarbon (PAH), anthracene, in a closed soil bioreactor system. The {sup 13}C-label was used to calculate a carbon mass balance including mineralization and the formation of nonextractable soil-bound residues. Similar results were obtained from {sup 13}C-labeled carbon and {sup 14}C-labeled carbon mass balance calculations for separate batch experiments with labeled anthracene. In concentration ranges typical for real PAH-contaminated sites, the sensitivity of the {sup 13}C tracer method meets the requirements of classical radiotracer experiments. Therefore, the authors balancing method based on stable isotope-labeled chemicalsmore » may supplement or substitute radiotracer experiments under many circumstances. One major advantage of using stable isotope-labeled tracers is the possible application in transformation studies where the use of radioactive substances is of environmental concern. The transformation of {sup 13}C-labeled PAH into nonextractable residues clearly depends on the metabolic activity of the soil microflora and occurs during an early phase of biodegradation. Successive contamination of the soil by anthracene leads to a progressive adaptation of the microflora to a complete mineralization of anthracene in the soil. The extent of residue formation is controlled by the capability of the microflora to degrade the contaminant. Results of long-term experiments indicate that nonextractable residues are relatively stable over time.« less

Flow dependence of forearm noradrenaline overflow, as assessed during mental stress and sodium nitroprusside infusion.

PubMed

Lindqvist, M; Melcher, A; Hjemdahl, P

1999-01-01

To evaluate the influence of blood flow on measurements of regional sympathetic nerve activity by radiotracer methodology ([3H]noradrenaline). Ten healthy men were studied under two conditions of elevated forearm blood flow: mental stress (Stroop colour word conflict test) and an intra-arterial infusion of sodium nitroprusside. Arterial blood pressure was measured invasively and forearm blood flow with strain-gauge plethysmography. Arterial and venous plasma adrenaline and noradrenaline were measured with high-performance liquid chromatography, and regional and total noradrenaline spillover were calculated. During mental stress, mean arterial pressure increased by 17%, heart rate by 16 beats/min, forearm blood flow by 117%, while forearm vascular resistance decreased by 44% (P < 0.001 for all). Sodium nitroprusside increased forearm blood flow dose-dependently, but elicited only minor effects on systemic haemodynamics. Mental stress increased arterial plasma noradrenaline by 52% (P < 0.001), and total body noradrenaline spillover by 75% (P < 0.001). During sodium nitroprusside infusion, arterial plasma noradrenaline increased only slightly and total body noradrenaline spillover was unaffected Forearm noradrenaline overflow increased from 5.4 +/- 0.9 to 16.9 +/- 2.6 pmol/min per I (P < 0.001) during mental stress and from 6.6 +/- 0.8 to 16.9 +/- 3.7 pmol/min per I (P < 0.001) during the second dose-step of sodium nitroprusside infusion. By intra-individual comparisons of forearm noradrenaline overflow increases during mental stress and during sodium nitroprusside infusion, with similar forearm blood flow increases, the flow dependence of forearm noradrenaline overflow was estimated. During mental stress, about 60% (median value, range 29-112%) of the increase in forearm noradrenaline overflow was attributed to the increase in forearm blood flow, whereas 40% was considered to reflect increased sympathetic nerve activity. There seems to be a considerable flow dependence of the regional overflow of noradrenaline, that is, a component of simple wash-out of noradrenaline from the forearm tissues during vasodilation. However, the present results still indicate that sympathetic nerve activity in the forearm is increased during mental stress, justifying the radiotracer technique for semiquantitative measurements, also during vasodilation.

Distributed Microprocessor Automation Network for Synthesizing Radiotracers Used in Positron Emission Tomography [PET

DOE R&D Accomplishments Database

Russell, J. A. G.; Alexoff, D. L.; Wolf, A. P.

1984-09-01

This presentation describes an evolving distributed microprocessor network for automating the routine production synthesis of radiotracers used in Positron Emission Tomography. We first present a brief overview of the PET method for measuring biological function, and then outline the general procedure for producing a radiotracer. The paper identifies several reasons for our automating the syntheses of these compounds. There is a description of the distributed microprocessor network architecture chosen and the rationale for that choice. Finally, we speculate about how this network may be exploited to extend the power of the PET method from the large university or National Laboratory to the biomedical research and clinical community at large. (DT)

An Investigation of the Effectiveness of Radiotracer Techniques for Instruction in Microbiology.

ERIC Educational Resources Information Center

Hurlburt, Evelyn McClelland

Students in a junior college microbiology course were randomly assigned to one of two laboratory treatments: one using radiotracer techniques to investigate aspects of microbial metabolism, and the other using conventional techniques to investigate the same metabolic features. An achievement test administered at the completion of the unit and six…

Radionuclides, radiotracers and radiopharmaceuticals for in vivo diagnosis

NASA Astrophysics Data System (ADS)

Wiebe, Leonard I.

Radioactive tracers for in vivo clinical diagnosis fall within a narrow, strictly-defined set of specifications in respect of their physical properties, chemical and biochemical characteristics, and (approved) medical applications. The type of radioactive decay and physical half-life of the radionuclide are immutable properties which, along with the demands of production and supply, limit the choice of radionuclides used in medicine to only a small fraction of those known to exist. In use, the biochemical and physiological properties of a radiotracer are dictated by the chemical form of the radionuclide. This chemical form may range from elemental, molecular or ionic, to complex compounds formed by coordinate or covalent bonding of the radionuclide to either simple organic or inorganic molecules, or complex macromolecules. Few of the radiotracers which are tested in model systems ever become radiopharmaceuticals in the strictest sense. Radionuclides, radiotracers and radiopharmaceuticals in use are reviewed. Drug legislation and regulations concerning drug manufacture, as well as hospital ethical constraints and legislation concerning unsealed sources of radiation must all be satisfied in order to translate a radiopharmaceutical from the laboratory to clinical use.

Preclinical evaluation of melanocortin-1 receptor (MC1-R) specific 68Ga- and 44Sc-labeled DOTA-NAPamide in melanoma imaging.

PubMed

Nagy, Gábor; Dénes, Noémi; Kis, Adrienn; Szabó, Judit P; Berényi, Ervin; Garai, Ildikó; Bai, Péter; Hajdu, István; Szikra, Dezső; Trencsényi, György

2017-08-30

Alpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET). In this present study the MC1-R selectivity of the newly developed Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using melanoma tumors. DOTA-NAPamide was labeled with Ga-68 and Sc-44 radionuclides. The MC1-R specificity of Ga-68- and Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using MC1-R positive (B16-F10) and negative (A375) melanoma cell lines. For in vivo imaging studies B16-F10 and A375 tumor-bearing mice were injected with 44 Sc/ 68 Ga-DOTA-NAPamide (in blocking studies with α-MSH) and whole body PET/MRI scans were acquired. Radiotracer uptake was expressed in terms of standardized uptake values (SUVs). 44 Sc/ 68 Ga-labeled DOTA-NAPamide were produced with high specific activity (approx. 19 GBq/μmol) and with excellent radiochemical purity (99%<). MC1-R positive B16-F10 cells showed significantly (p≤0.01) higher in vitro radiotracer accumulation than that of receptor negative A375 melanoma cells. In animal experiments, also significantly (p≤0.01) higher Ga-68-DOTA-NAPamide (SUVmean: 0.38±0.02), and Sc-44-DOTA-NAPamide (SUVmean: 0.52±0.13) uptake was observed in subcutaneously growing B16-F10 tumors, than in receptor negative A375 tumors, where the SUVmean values of Ga-68-DOTA-NAPamide and Sc-44-DOTA-NAPamide were 0.04±0.01 and 0.07±0.01, respectively. Tumor-to-muscle (T/M SUVmean) ratios were approximately 15-fold higher in B16-F10 tumor-bearing mice, than that of A375 tumors, and this difference was also significant (p≤0.01) using both radiotracers after 60 min incubation time. Our newly synthesized 44 Sc-labeled DOTA-NAPamide probe showed excellent binding properties to melanocortin-1 receptor (MC1-R) positive melanoma cell and tumors. Due to its high specificity and sensitivity 44 Sc-DOTA-NAPamide is a promising radiotracer in molecular imaging of malignant melanoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

DOE PAGES

Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; ...

2015-10-09

Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variationmore » of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. We find these results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Finally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.« less

Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

NASA Astrophysics Data System (ADS)

Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

2015-11-01

Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.

Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.

Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variationmore » of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. We find these results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Finally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.« less

Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration.

PubMed

Shrestha, Uttam M; Seo, Youngho; Botvinick, Elias H; Gullberg, Grant T

2015-11-07

Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.

Plan for radionuclide tracer studies of the residence time distribution in the Wilsonville dissolver and preheater

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jolley, R.L.; Begovich, J.M.; Brashear, H.R.

1983-12-01

Stimulus-response measurements using radiotracers to measure residence time distribution (RTD) and hydrodynamic parameters for the preheaters and dissolvers at the Ft. Lewis Solvent Refined Coal (SRC) and the Exxon Donor Solvent (EDS) coal conversion pilot plants are reviewed. A plan is also presented for a series of radioactive tracer studies proposed for the Advanced Coal Liquefaction Facility at Wilsonville, Alabama, to measure the RTD for the preheater and dissolvers in the SRC-I mode. The tracer for the gas phase will be /sup 133/Xe, and /sup 198/Au (on carbonized resin or as an aqueous colloidal suspension) will be used as themore » slurry tracer. Four experimental phases are recommended for the RTD tracer studies: (1) preheater; (2) dissolver with 100% takeoff; (3) dissolver with 100% takeoff and solids withdrawal; and (4) dissolver with 50% takeoff. Eighteen gas-tracer and 22 liquid-tracer injections are projected to accomplish the four experimental phases. Two to four tracer injections are projected for preliminary tests to ensure the capability of safe injection of the radiotracers and the collection of statistically significant data. A complete projected cost and time schedule is provided, including procurement of necessary components, preparation of the radiotracers, assembly and testing of tracer injection apparatus and detection systems, onsite work and tracer injections, laboratory experimentation, data analysis, and report writing.« less

Biodistribution of meglumine antimoniate in healthy and Leishmania (Leishmania) infantum chagasi-infected BALB/c mice.

PubMed

Borborema, Samanta Etel Treiger; Osso, João Alberto; Andrade, Heitor Franco de; Nascimento, Nanci do

2013-08-01

Pentavalent antimonials such as meglumine antimoniate (MA) are the primary treatments for leishmaniasis, a complex disease caused by protozoan parasites of the genus Leishmania . Despite over 70 years of clinical use, their mechanisms of action, toxicity and pharmacokinetics have not been fully elucidated. Radiotracer studies performed on animals have the potential to play a major role in pharmaceutical development. The aims of this study were to prepare an antimony radiotracer by neutron irradiation of MA and to determine the biodistribution of MA in healthy and Leishmania (Leishmania) infantum chagasi-infected mice. MA (Glucantime®) was neutron irradiated inside the IEA-R1 nuclear reactor, producing two radioisotopes, ¹²²Sb and ¹²⁴Sb, with high radionuclidic purity and good specific activity. This irradiated compound presented anti-leishmanial activity similar to that of non-irradiated MA in both in vitro and in vivo evaluations. In the biodistribution studies, healthy mice showed higher uptake of antimony in the liver than infected mice and elimination occurred primarily through biliary excretion, with a small proportion of the drug excreted by the kidneys. The serum kinetic curve was bi-exponential, with two compartments: the central compartment and another compartment associated with drug excretion. Radiotracers, which can be easily produced by neutron irradiation, were demonstrated to be an interesting tool for answering several questions regarding antimonial pharmacokinetics and chemotherapy.

Cerenkov luminescence endoscopy: Improved molecular sensitivity with β --emitting radiotracers

DOE PAGES

Carpenter, Colin M.; Ma, Xiaowei; Liu, Hongguang; ...

2014-10-09

Cerenkov luminescence endoscopy (CLE) is an optical technique that captures the Cerenkov photons emitted from highly energetic moving charged particles (β + or β $-$) and can be used to monitor the distribution of many clinically available radioactive probes. A main limitation of CLE is its limited sensitivity to small concentrations of radiotracer, especially when used with a light guide. We investigated the improvement in the sensitivity of CLE brought about by using a β $-$ radiotracer that improved Cerenkov signal due to both higher β-particle energy and lower γ noise in the imaging optics because of the lack ofmore » positron annihilation. Here, the signal-to-noise ratio (SNR) of 90Y was compared with that of 18F in both phantoms and small-animal tumor models. Sensitivity and noise characteristics were demonstrated using vials of activity both at the surface and beneath 1 cm of tissue. Rodent U87MG glioma xenograft models were imaged with radiotracers bound to arginine-glycine-aspartate (RGD) peptides to determine the SNR. As a result, γ noise from 18F was demonstrated by both an observed blurring across the field of view and a more pronounced fall-off with distance. A decreased γ background and increased energy of the β particles resulted in a 207-fold improvement in the sensitivity of 90Y compared with 18F in phantoms. 90Y-bound RGD peptide produced a higher tumor-to-background SNR than 18F in a mouse model. In conclusion, the use of 90Y for Cerenkov endoscopic imaging enabled superior results compared with an 18F radiotracer.« less

Identification of averantin as an aflatoxin B1 precursor: placement in the biosynthetic pathway.

PubMed Central

Bennett, J W; Lee, L S; Shoss, S M; Boudreaux, G H

1980-01-01

A new blocked mutant of Aspergillus parasiticus produces no detectable aflatoxin B1, but accumulates several polyhydroxyanthraquinones. One of these pigments was identified as averantin. This is the first report of its formation by A. parasiticus. Radiotracer studies with [14C]averantin showed that 15.3% of label from averantin was incorporated into aflatoxin B1. This incorporation was blocked by dichlorvos. With radiotracers and other mutants, averantin was placed after norsolorinic acid and before averufin in the biosynthetic pathway in which the general steps are norsolorinic acid leads to averantin leads to averufin leads to versiconal hemiacetal acetate leads to versicolorin A leads to sterigmatocystin leads to aflatoxin B1. PMID:7377778

Validation of Non-Invasive Tracer Kinetic Analysis of 18F-Florbetaben PET Using a Dual Time-Window Acquisition Protocol.

PubMed

Bullich, Santiago; Barthel, Henryk; Koglin, Norman; Becker, Georg A; De Santi, Susan; Jovalekic, Aleksandar; Stephens, Andrew W; Sabri, Osama

2017-11-24

Accurate amyloid PET quantification is necessary for monitoring amyloid-beta accumulation and response to therapy. Currently, most of the studies are analyzed using the static standardized uptake value ratio (SUVR) approach because of its simplicity. However, this approach may be influenced by changes in cerebral blood flow (CBF) or radiotracer clearance. Full tracer kinetic models require arterial blood sampling and dynamic image acquisition. The objectives of this work were: (1) to validate a non-invasive kinetic modeling approach for 18 F-florbetaben PET using an acquisition protocol with the best compromise between quantification accuracy and simplicity and (2) to assess the impact of CBF changes and radiotracer clearance on SUVRs and non-invasive kinetic modeling data in 18 F-florbetaben PET. Methods: Data from twenty subjects (10 patients with probable Alzheimer's dementia/ 10 healthy volunteers) were used to compare the binding potential (BP ND ) obtained from the full kinetic analysis to the SUVR and to non-invasive tracer kinetic methods (simplified reference tissue model (SRTM), and multilinear reference tissue model 2 (MRTM2)). Different approaches using shortened or interrupted acquisitions were compared to the results of the full acquisition (0-140 min). Simulations were carried out to assess the effect of CBF and radiotracer clearance changes on SUVRs and non-invasive kinetic modeling outputs. Results: A 0-30 and 120-140 min dual time-window acquisition protocol using appropriate interpolation of the missing time points provided the best compromise between patient comfort and quantification accuracy. Excellent agreement was found between BP ND obtained using full and dual time-window (2TW) acquisition protocols (BP ND,2TW =0.01+ 1.00 BP ND,FULL , R2=0.97 (MRTM2); BP ND,2TW = 0.05+ 0.92·BP ND,FULL , R2=0.93 (SRTM)). Simulations showed a limited impact of CBF and radiotracer clearance changes on MRTM parameters and SUVRs. Conclusion: This study demonstrates accurate non-invasive kinetic modeling of 18 F-florbetaben PET data using a dual time-window acquisition protocol, thus providing a good compromise between quantification accuracy, scan duration and patient burden. The influence of CBF and radiotracer clearance changes on amyloid-beta load estimates was small. For most clinical research applications, the SUVR approach is appropriate. However, for longitudinal studies in which a maximum quantification accuracy is desired, this non-invasive dual time-window acquisition protocol and kinetic analysis is recommended. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6'-[18F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia.

PubMed

Wanek, Thomas; Kreis, Katharina; Križková, Petra; Schweifer, Anna; Denk, Christoph; Stanek, Johann; Mairinger, Severin; Filip, Thomas; Sauberer, Michael; Edelhofer, Patricia; Traxl, Alexander; Muchitsch, Viktoria E; Mereiter, Kurt; Hammerschmidt, Friedrich; Cass, Carol E; Damaraju, Vijaya L; Langer, Oliver; Kuntner, Claudia

2016-11-01

Positron emission tomography (PET) using fluorine-18 ( 18 F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6'-deoxy-6'-[ 18 F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[ 18 F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [ 18 F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12±8% (n=10, based on [ 18 F]fluoride starting activity) in a total synthesis time of 60min with a specific activity at end of synthesis of 218±58GBq/μmol (n=10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[ 18 F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[ 18 F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13±0.22 (n=4) at 2h after administration of β-[ 18 F]1. In ex vivo autoradiography experiments β-[ 18 F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[ 18 F]1 shows potential as PET hypoxia radiotracer which merits further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates.

PubMed

Lin, Shu-Fei; Bois, Frederic; Holden, Daniel; Nabulsi, Nabeel; Pracitto, Richard; Gao, Hong; Kapinos, Michael; Teng, Jo-Ku; Shirali, Anupama; Ropchan, Jim; Carson, Richard E; Elmore, Charles S; Vasdev, Neil; Huang, Yiyun

2017-01-01

The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABA A , GABA B , and GABA C groups. The various GABA A subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α 1 subunit, and the α 2 and α 3 subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships. The goal of this work was to characterize, in nonhuman primates, the in vivo binding profile of a novel positron emission tomography (PET) radiotracer, [ 11 C]ADO, which has been indicated to have functional selectivity for the GABA A α 2 /α 3 subunits. High specific activity [ 11 C]ADO was administrated to 3 rhesus monkeys, and PET scans of 120-minute duration were performed on the Focus-220 scanner. In the blood, [ 11 C]ADO metabolized at a fairly rapid rate, with ∼36% of the parent tracer remaining at 30 minutes postinjection. Uptake levels of [ 11 C]ADO in the brain were high (peak standardized uptake value of ∼3.0) and consistent with GABA A distribution, with highest activity levels in cortical areas, intermediate levels in cerebellum and thalamus, and lowest uptake in striatal regions and amygdala. Tissue kinetics was fast, with peak uptake in all brain regions within 20 minutes of tracer injection. The one-tissue compartment model provided good fits to regional time-activity curves and reliable measurement of kinetic parameters. The absolute test-retest variability of regional distribution volumes ( V T ) was low, ranging from 4.5% to 8.7%. Pretreatment with flumazenil (a subtype nonselective ligand, 0.2 mg/kg, intravenous [IV], n = 1), Ro15-4513 (an α 5 -selective ligand, 0.03 mg/kg, IV, n = 2), and zolpidem (an α 1 -selective ligand, 1.7 mg/kg, IV, n = 1) led to blockade of [ 11 C]ADO binding by 96.5%, 52.5%, and 76.5%, respectively, indicating the in vivo binding specificity of the radiotracer. Using the nondisplaceable volume of distribution ( V ND ) determined from the blocking studies, specific binding signals, as measured by values of regional binding potential ( BP ND ), ranged from 0.6 to 4.4, which are comparable to those of [ 11 C]flumazenil. In conclusion, [ 11 C]ADO was demonstrated to be a specific radiotracer for the GABA A receptors with several favorable properties: high brain uptake, fast tissue kinetics, and high levels of specific binding in nonhuman primates. However, subtype selectivity in vivo is not obvious for the radiotracer, and thus, the search for subtype-selective GABA A radiotracers continues.

Residence time distribution measurements in a pilot-scale poison tank using radiotracer technique.

PubMed

Pant, H J; Goswami, Sunil; Samantray, J S; Sharma, V K; Maheshwari, N K

2015-09-01

Various types of systems are used to control the reactivity and shutting down of a nuclear reactor during emergency and routine shutdown operations. Injection of boron solution (borated water) into the core of a reactor is one of the commonly used methods during emergency operation. A pilot-scale poison tank was designed and fabricated to simulate injection of boron poison into the core of a reactor along with coolant water. In order to design a full-scale poison tank, it was desired to characterize flow of liquid from the tank. Residence time distribution (RTD) measurement and analysis was adopted to characterize the flow dynamics. Radiotracer technique was applied to measure RTD of aqueous phase in the tank using Bromine-82 as a radiotracer. RTD measurements were carried out with two different modes of operation of the tank and at different flow rates. In Mode-1, the radiotracer was instantaneously injected at the inlet and monitored at the outlet, whereas in Mode-2, the tank was filled with radiotracer and its concentration was measured at the outlet. From the measured RTD curves, mean residence times (MRTs), dead volume and fraction of liquid pumped in with time were determined. The treated RTD curves were modeled using suitable mathematical models. An axial dispersion model with high degree of backmixing was found suitable to describe flow when operated in Mode-1, whereas a tanks-in-series model with backmixing was found suitable to describe flow of the poison in the tank when operated in Mode-2. The results were utilized to scale-up and design a full-scale poison tank for a nuclear reactor. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vivo imaging of reactive oxygen species in mouse brain by using [3H]Hydromethidine as a potential radical trapping radiotracer

PubMed Central

Abe, Kohji; Takai, Nozomi; Fukumoto, Kazumi; Imamoto, Natsumi; Tonomura, Misato; Ito, Miwa; Kanegawa, Naoki; Sakai, Katsunori; Morimoto, Kenji; Todoroki, Kenichiro; Inoue, Osamu

2014-01-01

To assess reactive oxygen species (ROS) production by detecting the fluorescent oxidation product, hydroethidine has been used extensively. The present study was undertaken to evaluate the potential of the hydroethidine derivative as a radiotracer to measure in vivo brain ROS production. [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]Hydromethidine) was synthesized, and evaluated using in vitro radical-induced oxidization and in vivo brain ROS production model. In vitro studies have indicated that [3H]Hydromethidine is converted to oxidized products by a superoxide radical (O2•−) and a hydroxyl radical (OH•−) but not hydrogen peroxide (H2O2). In vivo whole-body distribution study showed that [3H]Hydromethidine rapidly penetrated the brain and then was washed out in normal mice. Microinjection of sodium nitroprusside (SNP) into the brain was performed to produce ROS such as OH•− via Fenton reaction. A significant accumulation of radioactivity immediately after [3H]Hydromethidine injection was seen in the side of the brain treated with SNP (5 and 20 nmol) compared with that in the contralateral side. These results indicated that [3H]Hydromethidine freely penetrated into the brain where it was rapidly converted to oxidized forms, which were trapped there in response to the production of ROS. Thus, [3H]Hydromethidine should be useful as a radical trapping radiotracer in the brain. PMID:25227606

Nuclear cardiology: Part 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berger, H.J.; Zaret, B.L.

1981-10-01

A review of recent developments and future directions in nuclear cardiology is presented. Myocardial perfusion imaging is discussed with special emphasis on thallium-201 methods. Infarct-avid imaging is also discussed with emphasis on technetium-99m labelled in diagnosis, and emission computed tomography is briefly reviewed. In addition, new biologically based radiotracers such as indium-111-labeled blood cells, gallium-67 citrate, and new positron- and gamma-emittng radiotracers are reviewed.

Imaging of Nonprostate Cancers Using PSMA-Targeted Radiotracers: Rationale, Current State of the Field, and a Call to Arms.

PubMed

Salas Fragomeni, Roberto A; Amir, Tali; Sheikhbahaei, Sara; Harvey, Susan C; Javadi, Mehrbod S; Solnes, Lilja B; Kiess, Ana P; Allaf, Mohamad E; Pomper, Martin G; Gorin, Michael A; Rowe, Steven P

2018-06-01

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is highly overexpressed on prostate cancer epithelial cells and for which there is a growing body of literature examining the role of small-molecule and antibody radiotracers targeted against this protein for prostate cancer detection and therapy. Despite its name, PSMA is also expressed, to varying degrees, in the neovasculature of a wide variety of nonprostate cancers; indeed, the pathology literature is replete with promising immunohistochemistry findings. Several groups have begun to correlate those pathology-level results with in vivo imaging and therapy in nonprostate cancers using the same PSMA-targeted agents that have been so successful in prostate cancer. The potential to leverage radiotracers targeted to PSMA beyond prostate cancer is a promising approach for many cancers, and PSMA-targeted agents may be able to supplement or fill gaps left by other agents. However, to date, most of the reported findings with PSMA-targeted radiotracers in nonprostate malignancies have been in case reports and small case series, and the field must adopt a more thorough approach to the design and execution of larger prospective trials to realize the potential of these promising agents outside prostate cancer. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Phosphorus cycling and partitioning in an oligotrophic Everglades wetland ecosystem: A radioisotope tracing study

USGS Publications Warehouse

Noe, G.B.; Scinto, L.J.; Taylor, J.; Childers, D.L.; Jones, R.D.

2003-01-01

1. Our goal was to quantify short-term phosphorus (P) partitioning and identify the ecosystem components important to P cycling in wetland ecosystems. To do this, we added P radiotracer to oligotrophic, P-limited Everglades marshes. 32PO4 was added to the water column in six 1-m2 enclosed mesocosms located in long-hydroperiod marshes of Shark River Slough, Everglades National Park. Ecosystem components were then repeatedly sampled over 18 days. 2. Water column particulates (>0.45 ??m) incorporated radiotracer within the first minute after dosing and stored 95-99% of total water column 32P activity throughout the study. Soluble (<0.45 ??m) 32P in the water column, in contrast, was always <5% of the 32P in surface water. Periphyton, both floating and attached to emergent macrophytes, had the highest specific activity of 32P (Bq g-131P) among the different ecosystem components. Fish and aquatic macroinvertebrates also had high affinity for P, whereas emergent macrophytes, soil and flocculent detrital organic matter (floc) had the lowest specific activities of radiotracer. 3. Within the calcareous, floating periphyton mats, 81% of the initial 32P uptake was associated with Ca, but most of this 32P entered and remained within the organic pool (Ca-associated = 14% of total) after 1 day. In the floc layer, 32P rapidly entered the microbial pool and the labile fraction was negligible for most of the study. 4. Budgeting of the radiotracer indicated that 32P moved from particulates in the water column to periphyton and floc and then to the floc and soil over the course of the 18 days incubations. Floc (35% of total) and soil (27%) dominated 32P storage after 18 days, with floating periphyton (12%) and surface water (10%) holding smaller proportions of total ecosystem 32P. 5. To summarise, oligotrophic Everglades marshes exhibited rapid uptake and retention of labile 32P. Components dominated by microbes appear to control short-term P cycling in this oligotrophic ecosystem.

The Role of Chemistry in Positron Emission Tomography.

ERIC Educational Resources Information Center

Feliu, Anthony L.

1988-01-01

Investigates use of positron emission tomography (PET) to study in-vivo metabolic processes. Discusses methodology of PET and medical uses. Outlines the production of different radioisotopes used in PET radiotracers. Includes selected bibliography. (ML)

Development and performance test of an online blood sampling system for determination of the arterial input function in rats.

PubMed

Roehrbacher, Friedrich; Bankstahl, Jens P; Bankstahl, Marion; Wanek, Thomas; Stanek, Johann; Sauberer, Michael; Muellauer, Julia; Schroettner, Thales; Langer, Oliver; Kuntner, Claudia

2015-12-01

For positron emission tomography (PET) kinetic modelling, an accurate determination of the arterial input function is required. In this study, a blood sampling system was developed and tested using different radiotracers in rats. The detector consists of pairs of lutetium yttrium oxyorthosilicate (LYSO) detectors, photomultiplier tubes and lead shield assembled within a steel casing working in coincidence mode. Rats were cannulated with microtubes in the femoral artery and vein for arterial blood sampling as well as administration of the PET tracers. Connected PTFE microtubes were centred between the LYSO crystals using a special holder. To enhance sensitivity, three layers with two coils were used. A flexible tube pump was used to ensure a constant blood flow. Performance of the detector was assessed with [(18)F]fludeoxyglucose (FDG), [(18)F]ciprofloxacin, (R)-[(11)C]verapamil, [(11)C]tariquidar, [(11)C]mephobarbital and [(11)C]MC113. Obtained input function curves were compared with manual samples drawn every 5 s during the first 3 min and further on at 5, 10, 20, 30, 40, 50 and 60 min after radiotracer injection. After manual sampling, an arterio/venous shunt was established. Shape and area-under-the-curve (AUC; Bq/μl*h) of the input functions were evaluated. The developed detector system provided an absolute sensitivity of 6.5%. Maximum peak values agreed well between manual samples and the detector with a mean difference of -0.4% ± 7.0% (max 12.0%, min -9.9%). AUC values also exhibited an excellent correlation (R = 0.996) between manual sampling and detector measurements with a mean difference of 9.3% ± 9.7% (max 24.1%, min -3.2%). The system was able to measure peak blood activity concentration levels of 110 to 2,000 Bq/μl which corresponds to injected activities from 5.5 to 100 MBq depending on the used radiotracer, applied volume and weight of the animal. This study demonstrates that the developed blood sampling system can be used for in vivo small animal PET studies in rats in a reliable way. The usage of the systems enhances the accuracy of the input curve as handling of small blood samples especially with low activity (as for C-11) is prone to measurement errors. Additionally, the radiation dose of the experimenters can be reduced, as it is not required anymore to continuously draw samples where the personal is in close contact to the radioactive animals and blood.

Development of Tyrosine-Based Radiotracer 99mTc-N4-Tyrosine for Breast Cancer Imaging

PubMed Central

Kong, Fan-Lin; Ali, Mohammad S.; Rollo, Alex; Smith, Daniel L.; Zhang, Yinhan; Yu, Dong-Fang; Yang, David J.

2012-01-01

The purpose of this study was to develop an efficient way to synthesize 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine (99mTc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled with 99mTc with high radiochemical purity (>95%). Cellular uptake of 99mTc-N4-Tyrosine was much higher than that of 99mTc-N4 and the clinical gold standard 18F-2-deoxy-2-fluoro-glucose (18F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that 99mTc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although 99mTc-N4-Tyrosine appeared to be inferior to 18F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. 99mTc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging. PMID:22496612

16-Cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid: synthesis and evaluation of fatty acid metabolism in mouse myocardium.

PubMed

Lee, Byung Chul; Kim, Dong Hyun; Lee, Iljung; Choe, Yearn Seong; Chi, Dae Yoon; Lee, Kyung-Han; Choi, Yong; Kim, Byung-Tae

2008-06-26

We synthesized 16-cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid (99mTc-CpTT-16-oxo-HDA, 1) and investigated its potential as a radiotracer for evaluating fatty acid metabolism in myocardium. Radiotracer 1 was synthesized in 22.6 +/- 6.3% decay-corrected yield by a double ligand transfer reaction between the ferrocene adduct of methyl hexadecanoate ( 2) and Na99mTcO 4 in the presence of Cr(CO)6 and CrCl3, followed by hydrolysis of the methyl ester group. Radiotracer 1 was found to be chemically stable (99% at 6 h) when incubated in human serum. A tissue distribution study in mice showed that high radioactivity accumulated in heart (9.03%ID/g at 1 min and 5.41%ID/g at 5 min postinjection) with rapid clearance and that heart to blood uptake ratios increased with time (2.13 at 5 min and 3.76 at 30 min postinjection). Metabolite analysis of the heart tissues using a simple extraction method showed that 99mTc-CpTT-4-oxo-butyric acid was detected as the major radioactive metabolite by HPLC, suggesting that 1 is metabolized to 99mTc-CpTT-4-oxo-butyric acid via beta-oxidation in myocardium.

Comparison of In Vitro Assays in Selecting Radiotracers for In Vivo P-Glycoprotein PET Imaging

PubMed Central

Savolainen, Heli; Cantore, Mariangela; van de Steeg, Evita; Colabufo, Nicola A.; Elsinga, Philip H.; Windhorst, Albert D.

2017-01-01

Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer´s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized, are usually performed at micromolar concentration, causing often discrepant in vivo and in vitro data. We had in vivo rodent PET data of [11C]verapamil, (R)-N-[18F]fluoroethylverapamil, (R)-O-[18F]fluoroethyl-norverapamil, [18F]MC225 and [18F]MC224 and we included also two new molecules [18F]MC198 and [18F]KE64 in this study. To improve the predictive value of in vitro assays, we labeled all the tracers with tritium and performed bidirectional substrate transport assay in MDCKII-MDR1 cells at three different concentrations (0.01, 1 and 50 µM) and also inhibition assay with P-gp inhibitors. As a comparison, we used non-radioactive molecules in transport assay in Caco-2 cells at a concentration of 10 µM and in calcein-AM inhibition assay in MDCKII-MDR1 cells. All the P-gp substrates were transported dose-dependently. At the highest concentration (50 µM), P-gp was saturated in a similar way as after treatment with P-gp inhibitors. Best in vivo correlation was obtained with the bidirectional transport assay at a concentration of 0.01 µM. One micromolar concentration in a transport assay or calcein-AM assay alone is not sufficient for correct in vivo prediction of substrate P-gp PET ligands. PMID:29036881

Quantification of Viral and Prokaryotic Production Rates in Benthic Ecosystems: A Methods Comparison

PubMed Central

Rastelli, Eugenio; Dell’Anno, Antonio; Corinaldesi, Cinzia; Middelboe, Mathias; Noble, Rachel T.; Danovaro, Roberto

2016-01-01

Viruses profoundly influence benthic marine ecosystems by infecting and subsequently killing their prokaryotic hosts, thereby impacting the cycling of carbon and nutrients. Previously conducted studies, based on different methodologies, have provided widely differing estimates of the relevance of viruses on benthic prokaryotes. There has been no attempt so far to compare these independent approaches, including contextual comparisons among different approaches for sample manipulation (i.e., dilution or not of the sediments during incubations), between methods based on epifluorescence microscopy (EFM) or radiotracers, and between the use of different radiotracers. Therefore, it has been difficult to identify the most suitable methodologies and protocols to be used as standard approaches for the quantification of viral infections of prokaryotes. Here, we compared for the first time different methods for determining viral and prokaryotic production rates in marine sediments collected at two benthic sites, differing in depth and environmental conditions. We used a highly replicated experimental design, testing the potential biases associated to the incubation of sediments as diluted or undiluted. In parallel, we also compared EFM counts with the 3H-thymidine incubations for the determination of viral production rates, and the use of 3H-thymidine versus 3H-leucine radiotracers for the determination of prokaryotic production. We show here that, independent from sediment dilution, EFM-based values of viral production ranged from 1.4 to 4.6 × 107 viruses g-1 h-1, and were similar but overall less variable compared to those obtained by the 3H-thymidine method (0.3 to 9.0 × 107 viruses g-1h-1). In addition, the prokaryotic production rates were not affected by sediment dilution, and the use of different radiotracers provided very consistent estimates (10.3–35.1 and 9.3–34.6 ngC g-1h-1 using the 3H-thymidine or 3H-leucine method, respectively). These results indicated that viral lysis was responsible for the abatement of 55–81% of the prokaryotic heterotrophic production, corroborating previous findings of the major role of viruses in benthic deep-sea ecosystems. Moreover, our methodological comparison for the analysis of viral production in marine sediments suggests that microscopy-based approaches are simpler and more cost-effective than those based on radiotracers. These approaches also reduce time to results and overcome issues related to generation of radioactive waste. PMID:27713739

Design, Synthesis, and Biological Evaluation of 68Ga-DOTA-PA1 for Lung Cancer: A Novel PET Tracer for Multiple Somatostatin Receptor Imaging.

PubMed

Liu, Fei; Liu, Teli; Xu, Xiaoxia; Guo, Xiaoyi; Li, Nan; Xiong, Chiyi; Li, Chun; Zhu, Hua; Yang, Zhi

2018-02-05

Most of the radiolabeled somatostatin analogues (SSAs) are specific for subtype somatostatin receptor 2 (SSTR 2 ). Lack of ligands targeting other subtypes of SSTRs, especially SSTR 1, SSTR 3 , and SSTR 5 , limited their applications in tumors of low SSTR 2 expression, including lung tumor. In this study, we aimed to design and synthesize a positron emission tomography (PET) radiotracer targeting multi-subtypes of SSTRs for PET imaging. PA1 peptide and its conjugate with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator or fluorescein isothiocyanate (FITC) at the N-terminal of the lysine position were synthesized. 68 Ga was chelated to DOTA-PA1 to obtain 68 Ga-DOTA-PA1 radiotracer. The stability, lipophilicity, binding affinity, and binding specificity of 68 Ga-DOTA-PA1 and FITC-PA1 were evaluated by various in vitro experiments. Micro-PET imaging of 68 Ga-DOTA-PA1 was performed in nude mice bearing A549 lung adenocarcinoma, as compared with 68 Ga-DOTA-(Tyr3)-octreotate ( 68 Ga-DOTA-TATE). Histological analysis of SSTR expression in A549 tumor tissues and human tumor tissues was conducted using immunofluorescence staining and immunohistochemical assay. 68 Ga-DOTA-PA1 had high radiochemical yield and radiochemical purity of over 95% and 99%, respectively. The radiotracer was stable in vitro in different buffers over a 2 h incubation period. Cell uptake of 68 Ga-DOTA-PA1 was 1.31-, 1.33-, and 1.90-fold that of 68 Ga-DOTA-TATE, which has high binding affinity only for SSTR 2 , after 2 h incubation in H520, PG, and A549 lung cancer cell lines, respectively. Micro-PET images of 68 Ga-DOTA-PA1 showed that the PET imaging signal correlated with the total expression of SSTRs, instead of SSTR 2 only, which was measured by Western blotting and immunofluorescence analysis in mice bearing A549 tumors. In summary, a novel PET radiotracer, 68 Ga-DOTA-PA1, targeting multi-subtypes of SSTRs, was successfully synthesized and was confirmed to be useful for PET imaging. It may have potential as a noninvasive PET radiotracer for imaging SSTR-positive tumors.

Synthesis of carbon-11, fluorine-18, and nitrogen-13 labeled radiotracers for biomedical applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.S.; Wolf, A.P.

A number of reviews, many of them recent, have appeared on various aspects of /sup 11/C, /sup 18/F and /sup 13/N-labeled radiotracers. This monograph treats the topic principally from the standpoint of synthetic organic chemistry while keeping in perspective the necessity of integrating the organic chemistry with the design and ultimate application of the radiotracer. Where possible, recent examples from the literature of organic synthesis are introduced to suggest potentially new routes which may be applied to problems in labeling organic molecules with the short-lived positron emitters, carbon-11, fluorine-18, and nitrogen-13. The literature survey of carbon-11, fluorine-18 and nitrogen-13 labeledmore » compounds presented are of particular value to scientists working in this field. Two appendices are also included to provide supplementary general references. A subject index concludes this volume.« less

Addiction Studies with Positron Emission Tomography

ScienceCinema

Joanna Fowler

2017-12-09

Brookhaven scientist Joanna Fowler describes Positron Emission Technology (PET) research at BNL which for the past 30 years has focused in the integration of basic research in radiotracer chemistry with the tools of neuroscience to develop new scientific

Addiction Studies with Positron Emission Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joanna Fowler

Brookhaven scientist Joanna Fowler describes Positron Emission Technology (PET) research at BNL which for the past 30 years has focused in the integration of basic research in radiotracer chemistry with the tools of neuroscience to develop new scientific

Validation and quantification of [18F]altanserin binding in the rat brain using blood input and reference tissue modeling

PubMed Central

Riss, Patrick J; Hong, Young T; Williamson, David; Caprioli, Daniele; Sitnikov, Sergey; Ferrari, Valentina; Sawiak, Steve J; Baron, Jean-Claude; Dalley, Jeffrey W; Fryer, Tim D; Aigbirhio, Franklin I

2011-01-01

The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats. PMID:21750562

Preclinical Comparative Study of (68)Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA.

PubMed

Ray Banerjee, Sangeeta; Chen, Zhengping; Pullambhatla, Mrudula; Lisok, Ala; Chen, Jian; Mease, Ronnie C; Pomper, Martin G

2016-06-15

(68)Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: (68)Ga-1, using DOTA-monoamide as the chelating agent; (68)Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and (68)Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). (68)Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to (68)Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. (68)Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation (68)Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging.

A Profilometry-Based Dentifrice Abrasion Method for V8 Brushing Machines Part II: Comparison of RDA-PE and Radiotracer RDA Measures.

PubMed

Schneiderman, Eva; Colón, Ellen; White, Donald J; St John, Samuel

2015-01-01

The purpose of this study was to compare the abrasivity of commercial dentifrices by two techniques: the conventional gold standard radiotracer-based Radioactive Dentin Abrasivity (RDA) method; and a newly validated technique based on V8 brushing that included a profilometry-based evaluation of dentin wear. This profilometry-based method is referred to as RDA-Profilometry Equivalent, or RDA-PE. A total of 36 dentifrices were sourced from four global dentifrice markets (Asia Pacific [including China], Europe, Latin America, and North America) and tested blindly using both the standard radiotracer (RDA) method and the new profilometry method (RDA-PE), taking care to follow specific details related to specimen preparation and treatment. Commercial dentifrices tested exhibited a wide range of abrasivity, with virtually all falling well under the industry accepted upper limit of 250; that is, 2.5 times the level of abrasion measured using an ISO 11609 abrasivity reference calcium pyrophosphate as the reference control. RDA and RDA-PE comparisons were linear across the entire range of abrasivity (r2 = 0.7102) and both measures exhibited similar reproducibility with replicate assessments. RDA-PE assessments were not just linearly correlated, but were also proportional to conventional RDA measures. The linearity and proportionality of the results of the current study support that both methods (RDA or RDA-PE) provide similar results and justify a rationale for making the upper abrasivity limit of 250 apply to both RDA and RDA-PE.

64Cu-Labeled Lissamine Rhodamine B: A Promising PET Radiotracer Targeting Tumor Mitochondria

PubMed Central

Zhou, Yang; Kim, Young-Seung; Yan, Xin; Jacobson, Orit; Chen, Xiaoyuan; Liu, Shuang

2011-01-01

The enhanced mitochondrial potential in carcinoma cells is an important characteristic of cancer. It is of great current interest to develop a radiotracer that is sensitive to the mitochondrial potential changes at the early stage of tumor growth. In this report, we present the synthesis and evaluation of 64Cu-labeled Lissamine Rhodamine B (LRB), 64Cu(DOTA-LRB) (DOTA-LRB = 2-(6-(diethylamino)-3-(diethyliminio)-3H-xanthen-9-yl)-5-(N-(2-(2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclo-dodecan-1-yl)acetamido)ethyl)-sulfamoyl)benzenesulfonate), as a new radiotracer for imaging tumors in athymic nude mice bearing U87MG human glioma xenografts by positron emission tomography (PET). We also explored its localization mechanism using Cu(DOTA-LRB) as the fluorescent probe in both U87MG human glioma cell line and the cultured primary U87MG glioma cells. It was found that 64Cu(DOTA-LRB) had the highest tumor uptake (6.54 ± 1.50, 6.91 ± 1.26, 5.68 ± 1.13, 7.58 ± 1.96, and 5.14 ± 1.50 %ID/g at 0.5, 1, 2, 4 and 24 h post-injection, respectively) among many 64Cu-labeled organic cations evaluated in the same animal model. The cellular staining study indicated that Cu(DOTA-LRB) was able to localize in mitochondria of U87MG glioma cells due to the enhanced negative mitochondrial potential. This statement is completely supported by the results from decoupling experiment with carbonylcyanide-m-chlorophenylhydrazone (CCCP). MicroPET data showed that the U87MG glioma tumors were clearly visualized as early as 30 min post-injection with 64Cu(DOTA-LRB). 64Cu(DOTA-LRB) remained stable during renal excretion, but underwent extensive degradation during hepatobiliary excretion. On the basis of the results from this study, it was concluded that 64Cu(DOTA-LRB) represents a new class of promising PET radiotracers for noninvasive imaging of the MDR-negative tumors. PMID:21545131

Comparison of Biological Properties of 99mTc-Labeled Cyclic RGD Peptide Trimer and Dimer Useful as SPECT Radiotracers for Tumor Imaging

PubMed Central

Zhao, Zuo-Quan; Yang, Yong; Fang, Wei; Liu, Shuang

2016-01-01

Introduction This study sought to evaluate a 99mTc-labeled trimeric cyclic RGD peptide (99mTc-4P-RGD3) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of 99mTc-3P-RGD2 in the same animal model. Methods HYNIC-4P-RGD3 was prepared by reacting 4P-RGD3 with excess HYNIC-OSu in the presence of diisopropylethylamine. 99mTc-4P-RGD3 was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose, 99mTc-3P-RGD2 (a αvβ3-targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the αvβ3 specificity of 99mTc-4P-RGD3. Results 99mTc-4P-RGD3 was prepared with >95% RCP and high specific activity (~200 GBq/µmol). 99mTc-4P-RGD3 and 99mTc-3P-RGD2 shared almost identical tumor uptake and similar biodistribution properties. 99mTc-4P-RGD3 had higher uptake than 99mTc-3P-RGD2 in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with 99mTc-4P-RGD3 and 99mTc-3P-RGD2. Conclusion Increasing peptide multiplicity from 3P-RGD2 to 4P-RGD3 offers no advantages with respect to the tumor-targeting capability. 99mTc-4P-RGD3 is as good a SPECT radiotracer as 99mTc-3P-RGD2 for imaging αvβ3-positive tumors. PMID:27556955

Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging.

PubMed

Stammes, Marieke A; Knol-Blankevoort, Vicky T; Cruz, Luis J; Feitsma, Hans R I J; Mezzanotte, Laura; Cordfunke, Robert A; Sinisi, Riccardo; Dubikovskaya, Elena A; Maeda, Azusa; DaCosta, Ralph S; Bierau, Katja; Chan, Alan; Kaijzel, Eric L; Snoeks, Thomas J A; van Beek, Ermond R; Löwik, Clemens W G M

2016-12-01

Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with 111 indium, via the chelate diethylene triamine pentaacetic acid (DTPA). The necrosis avid properties of the radiotracer [ 111 In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo. Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [ 111 In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis. The radiotracer [ 111 In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy.

Methods for the correction of vascular artifacts in PET O-15 water brain-mapping studies

NASA Astrophysics Data System (ADS)

Chen, Kewei; Reiman, E. M.; Lawson, M.; Yun, Lang-sheng; Bandy, D.; Palant, A.

1996-12-01

While positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) can be used to map brain regions that are involved in normal and pathological human behaviors, measurements in the anteromedial temporal lobe can be confounded by the combined effects of radiotracer activity in neighboring arteries and partial-volume averaging. The authors now describe two simple methods to address this vascular artifact. One method utilizes the early frames of a dynamic PET study, while the other method utilizes a coregistered magnetic resonance image (MRI) to characterize the vascular region of interest (VROI). Both methods subsequently assign a common value to each pixel in the VROI for the control (baseline) scan and the activation scan. To study the vascular artifact and to demonstrate the ability of the proposed methods correcting the vascular artifact, four dynamic PET scans were performed in a single subject during the same behavioral state. For each of the four scans, a vascular scan containing vascular activity was computed as the summation of the images acquired 0-60 s after radiotracer administration, and a control scan containing minimal vascular activity was computed as the summation of the images acquired 20-80 s after radiotracer administration. t-score maps calculated from the four pairs of vascular and control scans were used to characterize regional blood flow differences related to vascular activity before and after the application of each vascular artifact correction method. Both methods eliminated the observed differences in vascular activity, as well as the vascular artifact observed in the anteromedial temporal lobes. Using PET data from a study of normal human emotion, these methods permitted the authors to identify rCBF increases in the anteromedial temporal lobe free from the potentially confounding, combined effects of vascular activity and partial-volume averaging.

Fluorine-18 patents (2009–2015). Part 2: new radiochemistry

PubMed Central

Mossine, Andrew V; Thompson, Stephen; Brooks, Allen F; Sowa, Alexandra R; Miller, Jason M; Scott, Peter JH

2016-01-01

Fluorine-18 (18F) is one of the most common positron-emitting radionuclides used in the synthesis of positron emission tomography radiotracers due to its ready availability, convenient half-life and outstanding imaging properties. In Part 1 of this review, we presented the first analysis of patents issued for novel radiotracers labeled with fluorine-18. In Part 2, we follow-up with a focus on patents issued for new radiochemistry methodology using fluorine-18 issued between January 2009 and December 2015. PMID:27610753

Ibuprofen induces reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA uptake in severe epithelial breast hyperplasia without atypia.

PubMed

Papantoniou, Vassilios; Tsaroucha, Angeliki; Valsamaki, Pipitsa; Tsiouris, Spyridon; Sotiropoulou, Evangelia; Karianos, Theodore; Marinopoulos, Spyridon; Fothiadaki, Athina; Sotiropoulou, Maria; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Dimitrakakis, Konstantinos; Antsaklis, Aris

2010-10-01

The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m-pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n  =  4) and without atypia (n  =  4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p  =  .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p  =  .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

Discharge rate measurements in a canal using radiotracer methods.

PubMed

Pant, H J; Goswami, Sunil; Biswal, Jayashree; Samantray, J S; Sharma, V K

2016-06-01

Discharge rates of water were measured in a canal using radiotracer methods with an objective to validate the efficacy of Concrete Volute Pumps (CVPs) installed at various pumping stations along the canal. Pulse velocity and dilution methods were applied to measure the discharge rates using Iodine-131 as a radiotracer. The discharge rate measured in one of the sections of the canal using the pulse velocity method was found to be 22.5m(3)/s, whereas the discharge rates measured using the dilution method in four different sections of the canal varied from 20.27 to 20.62m(3)/s with single CVP in operation. The standard error in discharge rate measurements using dilution method ranged from ±1.1 to ±1.8%. The experimentally measured values of the discharge rate were in good agreement with the design value of the discharge rate (20m(3)/s) thus validating the performance of the CVPs used in the canal. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optical reaction cell and light source for ›18F! fluoride radiotracer synthesis

DOEpatents

Ferrieri, Richard A.; Schlyer, David; Becker, Richard J.

1998-09-15

Apparatus for performing organic synthetic reactions, particularly no-carrier-added nucleophilic radiofluorination reactions for PET radiotracer production. The apparatus includes an optical reaction cell and a source of broadband infrared radiant energy, which permits direct coupling of the emitted radiant energy with the reaction medium to heat the reaction medium. Preferably, the apparatus includes means for focusing the emitted radiant energy into the reaction cell, and the reaction cell itself is preferably configured to reflect transmitted radiant energy back into the reaction medium to further improve the efficiency of the apparatus. The apparatus is well suited to the production of high-yield syntheses of 2-›.sup.18 F!fluoro-2-deoxy-D-glucose. Also provided is a method for performing organic synthetic reactions, including the manufacture of ›.sup.18 F!-labeled compounds useful as PET radiotracers, and particularly for the preparation of 2-›.sup.18 F!fluoro-2-deoxy-D-glucose in higher yields than previously possible.

Optical reaction cell and light source for [18F] fluoride radiotracer synthesis

DOEpatents

Ferrieri, R.A.; Schlyer, D.; Becker, R.J.

1998-09-15

An apparatus is disclosed for performing organic synthetic reactions, particularly no-carrier-added nucleophilic radiofluorination reactions for PET radiotracer production. The apparatus includes an optical reaction cell and a source of broadband infrared radiant energy, which permits direct coupling of the emitted radiant energy with the reaction medium to heat the reaction medium. Preferably, the apparatus includes means for focusing the emitted radiant energy into the reaction cell, and the reaction cell itself is preferably configured to reflect transmitted radiant energy back into the reaction medium to further improve the efficiency of the apparatus. The apparatus is well suited to the production of high-yield syntheses of 2-[{sup 18}F]fluoro-2-deoxy-Dglucose. Also provided is a method for performing organic synthetic reactions, including the manufacture of [{sup 18}F]-labeled compounds useful as PET radiotracers, and particularly for the preparation of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose in higher yields than previously possible. 4 figs.

Molecular neuroimaging in degenerative dementias.

PubMed

Jiménez Bonilla, J F; Carril Carril, J M

2013-01-01

In the context of the limitations of structural imaging, brain perfusion and metabolism using SPECT and PET have provided relevant information for the study of cognitive decline. The introduction of the radiotracers for cerebral amyloid imaging has changed the diagnostic strategy regarding Alzheimer's disease, which is currently considered to be a "continuum." According to this new paradigm, the increasing amyloid load would be associated to the preclinical phase and mild cognitive impairment. It has been possible to observe "in vivo" images using 11C-PIB and PET scans. The characteristics of the 11C-PIB image include specific high brain cortical area retention in the positive cases with typical distribution pattern and no retention in the negative cases. This, in combination with 18F-FDG PET, is the basis of molecular neuroimaging as a biomarker. At present, its prognostic value is being evaluated in longitudinal studies. 11C-PIB-PET has become the reference radiotracer to evaluate the presence of cerebral amyloid. However, its availability is limited due to the need for a nearby cyclotron. Therefore, 18F labeled radiotracers are being introduced. Our experience in the last two years with 11C-PIB, first in the research phase and then as being clinically applied, has shown the utility of the technique in the clinical field, either alone or in combination with FDG. Thus, amyloid image is a useful tool for the differential diagnosis of dementia and it is a potentially useful method for early diagnosis and evaluation of future treatments. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Study of axial mixing, holdup and slip velocity of dispersed phase in a pulsed sieve plate extraction column using radiotracer technique.

PubMed

Ghiyas Ud Din; Imran Rafiq Chughtai; Hameed Inayat, Mansoor; Hussain Khan, Iqbal

2009-01-01

Axial mixing, holdup and slip velocity of dispersed phase which are parameters of fundamental importance in the design and operation of liquid-liquid extraction pulsed sieve plate columns have been investigated. Experiments for residence time distribution (RTD) analysis have been carried out for a range of pulsation frequency and amplitude in a liquid-liquid extraction pulsed sieve plate column with water as dispersed and kerosene as continuous phase using radiotracer technique. The column was operated in emulsion region and (99m)Tc in the form of sodium pertechnetate eluted from a (99)Mo/(99m)Tc generator was used to trace the dispersed phase. Axial dispersed plug flow model with open-open boundary condition and two points measurement method was used to simulate the hydrodynamics of dispersed phase. It has been observed that the axial mixing and holdup of dispersed phase increases with increase in pulsation frequency and amplitude until a maximum value is achieved while slip velocity decreases with increase in pulsation frequency and amplitude until it approaches a minimum value. Short lived and low energy radiotracer (99m)Tc in the form of sodium pertechnetate was found to be a good water tracer to study the hydrodynamics of a liquid-liquid extraction pulsed sieve plate column operating with two immiscible liquids, water and kerosene. Axial dispersed plug flow model with open-open boundary condition was found to be a suitable model to describe the hydrodynamics of dispersed phase in the pulsed sieve plate extraction column.

Lymphatic mapping and sentinel node biopsy in ovarian tumors: a study using intra-operative Tc-99m-Phytate and lymphoscintigraphy imaging.

PubMed

Hassanzadeh, Malihe; Hosseini Farahabadi, Elham; Yousefi, Zohreh; Kadkhodayan, Sima; Zarifmahmoudi, Leili; Sadeghi, Ramin

2016-09-07

Experience on sentinel node mapping in ovarian tumors is very limited. We evaluated the sentinel node concept in ovarian tumors using intra-operativeTc-99m-Phytate injection and lymphoscintigraphy imaging. Thirty-five patients with a pelvic mass due to an ovarian pathology were included in the study. The radiotracer was injected just after laparotomy and before removal of the tumor either beneath the normal cortex (10 patients) or in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum two injections of the radiotracer (25 patients). For malignant masses, the sentinel nodes were identified using a hand held gamma probe. Then standard pelvic and para-aortic lymphadenectomy was performed. In case of benign pathologies or borderline ovarian tumors on frozen section, lymphadenectomy was not performed. The morning after surgery, all patients were sent for lymphoscintigraphy imaging of the abdomen and pelvis. Sentinel node was identified only in 4 patients of the cortical injection group. At least one sentinel node could be identified in 21 patients of the sub-peritoneal group. Sentinel nodes were identified only in the para-aortic area in 21, pelvic/para-aortic areas in 2, and pelvic only area in 2 patients. Three patients had lymph node involvement and all had involved sentinel nodes (no false negative case). Sentinel node mapping using intra-operative injection of the radiotracer (in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum) is feasible in ovarian tumors. Technical aspects of this method should be explored in larger multicenter studies in the future.

PET AND SPECT STUDIES IN CHILDREN WITH HEMISPHERIC LOW-GRADE GLIOMAS

PubMed Central

Juhász, Csaba; Bosnyák, Edit

2016-01-01

Molecular imaging is playing an increasing role in the pre-treatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting and improved detection of tumor recurrence. This review provides a brief overview of single photon emission computed tomography (SPECT) studies followed by a more detailed review of clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pre- and post-treatment evaluation of pediatric brain tumors. PMID:27659825

Dynamic cardiac PET imaging: extraction of time-activity curves using ICA and a generalized Gaussian distribution model.

PubMed

Mabrouk, Rostom; Dubeau, François; Bentabet, Layachi

2013-01-01

Kinetic modeling of metabolic and physiologic cardiac processes in small animals requires an input function (IF) and a tissue time-activity curves (TACs). In this paper, we present a mathematical method based on independent component analysis (ICA) to extract the IF and the myocardium's TACs directly from dynamic positron emission tomography (PET) images. The method assumes a super-Gaussian distribution model for the blood activity, and a sub-Gaussian distribution model for the tissue activity. Our appreach was applied on 22 PET measurement sets of small animals, which were obtained from the three most frequently used cardiac radiotracers, namely: desoxy-fluoro-glucose ((18)F-FDG), [(13)N]-ammonia, and [(11)C]-acetate. Our study was extended to PET human measurements obtained with the Rubidium-82 ((82) Rb) radiotracer. The resolved mathematical IF values compare favorably to those derived from curves extracted from regions of interest (ROI), suggesting that the procedure presents a reliable alternative to serial blood sampling for small-animal cardiac PET studies.

PET and SPECT studies in children with hemispheric low-grade gliomas.

PubMed

Juhász, Csaba; Bosnyák, Edit

2016-10-01

Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single-photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors.

Nurse exposure doses resulted from bone scintigraphy patient

NASA Astrophysics Data System (ADS)

Tunçman, Duygu; Kovan, Bilal; Poyraz, Leyla; ćapali, Veli; Demir, Bayram; Türkmen, Cüneyt

2016-03-01

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It's general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget's disease, investigation of loosening and infection in orthopedic implants. It is applied with using 99mTc labeled radiopharmaceuticals (e.g 99m Tc MDP,99mTc HEDP and 99mTc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. When some patient's situation is not good, patients are hospitalized until the scanning because of patients' close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse's exposure radiations from patient's routine treatment, examination and emergency station.

DNA double-strand breaks in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy.

PubMed

Rief, Matthias; Hartmann, Lisa; Geisel, Dominik; Richter, Felicitas; Brenner, Winfried; Dewey, Marc

2018-07-01

To investigate DNA double-strand breaks (DSBs) in blood lymphocytes induced by two-day 99m Tc-MIBI myocardial perfusion scintigraphy (MPS) using y-H2AX immunofluorescence microscopy and to correlate the results with 99m Tc activity in blood samples. Eleven patients who underwent two-day MPS were included. DSB blood sampling was performed before and 5min, 1h and 24h after the first and second radiotracer injections. 99m Tc activity was measured in each blood sample. For immunofluorescence microscopy, distinct foci representing DSBs were quantified in lymphocytes after staining for the phosphorylated histone variant y-H2AX. The 99m Tc-MIBI activity measured on days one and two was similar (254±25 and 258±27 MBq; p=0.594). Compared with baseline DSB foci (0.09±0.05/cell), a significant increase was found at 5min (0.19±0.04/cell) and 1h (0.18±0.04/cell) after the first injection and at 5min and 1h after the second injection (0.21±0.03 and 0.19±0.04/cell, respectively; p=0.003 for both). At 24h after the first and second injections, the number of DSB foci had returned to baseline (0.06±0.02 and 0.12±0.05/cell, respectively). 99m Tc activity levels in peripheral blood samples correlated well with DSB counts (r=0.451). DSB counts reflect 99m Tc-MIBI activity after injection for two-day MPS, and might allow individual monitoring of biological effects of cardiac nuclear imaging. • Myocardial perfusion scintigraphy using 99m Tc induces time-dependent double-strand breaks (DSBs) • γ-H2AX immunofluorescence microscopy shows DSB as an early response to radiotracer injection • Activity measurements of 99m Tc correlate well with detected DSB • DSB foci induced by 99m Tc return to baseline 24h after radiotracer injection.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of macrophages in large vessel vasculitis: Current status and future prospects.

PubMed

Jiemy, William Febry; Heeringa, Peter; Kamps, Jan A A M; van der Laken, Conny J; Slart, Riemer H J A; Brouwer, Elisabeth

2018-05-03

Macrophages are key players in the pathogenesis of large-vessel vasculitis (LVV) and may serve as a target for diagnostic imaging of LVV. The radiotracer, 18 F-FDG has proven to be useful in the diagnosis of giant cell arteritis (GCA), a form of LVV. Although uptake of 18 F-FDG is high in activated macrophages, it is not a specific radiotracer as its uptake is high in any proliferating cell and other activated immune cells resulting in high non-specific background radioactivity especially in aging and atherosclerotic vessels which dramatically lowers the diagnostic accuracy. Evidence also exists that the sensitivity of 18 F-FDG PET drops in patients upon glucocorticoid treatment. Therefore, there is a clinical need for more specific radiotracers in imaging GCA to improve diagnostic accuracy. Numerous clinically established and newly developed macrophage targeted radiotracers for oncological and inflammatory diseases can potentially be utilized for LVV imaging. These tracers are more target specific and therefore may provide lower background radioactivity, higher diagnostic accuracy and the ability to assess treatment effectiveness. However, current knowledge regarding macrophage subsets in LVV lesions is limited. Further understanding regarding macrophage subsets in vasculitis lesion is needed for better selection of tracers and new targets for tracer development. This review summarizes the development of macrophage targeted tracers in the last decade and the potential application of macrophage targeted tracers currently used in other inflammatory diseases in imaging LVV. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Novel Approach to Prepare {sup 99m}Tc-Based Multivalent RGD Peptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shuang Liu

2012-10-24

This project presents a novel approach to prepare the {sup 99m}Tc-bridged multivalent RGD (arginine-glycine-aspartate) peptides. This project will focus on fundamentals of {sup 99m}Tc radiochemistry. The main objective of this project is to demonstrate the proof-of-principle for the proposed radiotracers. Once a kit formulation is developed for preparation of the {sup 99m}Tc-bridged multivalent RGD peptides, various tumor-bearing animal models will be used to evaluate their potential for SPECT (single photon-emission computed tomography) imaging of cancer. We have demonstrated that (1) multimerization of cyclic RGD peptides enhances the integrin {alpha}{sub v}{beta}{sub 3} bonding affinity and radiotracer tumor uptake; (2) addition ofmore » G{sub 3} or PEG{sub 4} linkers makes it possible for two RGD motifs in 3P-RGD{sub 2} and 3G-RGD{sub 2} to achieve simultaneous integrin {alpha}{sub v}{beta}{sub 3} binding; and (3) multimers are actually bivalent (not multivalent), the presence of extra RGD motifs can enhance the tumor retention time of the radiotracer.« less

Technetium-99m colloidal bismuth subcitrate: A novel method for the evaluation of peptic ulcer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vasquez, T.E.; Lyons, K.P.; Raiszadeh, M.

1984-01-01

The therapeutic agent colloidal bismuth subcitrate (CBS) selectively binds to peptic ulcers. The authors have developed a method for labeling this agent with Tc-99m. Chromatographic quality control studies of the agent on silica gel coated strips (ITLC-SG) showed that more than 97% of Tc-99m was bound to CBS. During in-vitro stability testing, the radio-label was stable for a minimum of 6 hours. The chromatographic findings are in agreement with the in-vivo distribution of the agent which showed no significant radioactivity in thyroid, kidneys, liver, or bladder. The resulting Tc-99m-CBS solution is administered orally in drinking water. Preliminary animal studies havemore » been conducted on 5 adult 3 kg New Zealand rabbits sedated with 50 mg Ketamine I.M. The rabbits were intubated with I.V. tubing advanced to the stomach. They were given a gastric erosive suspension of 600-1000 mg/kg of pulverized ASA in 10 cc tap water. Four hours later they were given 3-4 mCi of the radiotracer in a 5 cc volume of water. Serial in-vivo images were obtained for 2 hours which included thyroid, abdomen, and urinary bladder. Next the stomachs were excised, opened along the greater curvature, imaged, vigorously washed and reimaged. All 5 rabbits showed avid localized binding of radiotracer which remained fixed even with vigorous washing. Areas of normal appearing mucosa were relatively devoid of radiotracer. This new compound may have significant clinical usefulness in the detection of peptic ulcer disease. In addition, such a non-invasive technique, carrying none of the risks or discomfort of endoscopy could also find application in the evaluation of the response to therapy.« less

Synthesis and Initial in Vivo Studies with [11C]SB-216763: The First Radiolabeled Brain Penetrative Inhibitor of GSK-3

PubMed Central

2015-01-01

Quantifying glycogen synthase kinase-3 (GSK-3) activity in vivo using positron emission tomography (PET) imaging is of interest because dysregulation of GSK-3 is implicated in numerous diseases and neurological disorders for which GSK-3 inhibitors are being considered as therapeutic strategies. Previous PET radiotracers for GSK-3 have been reported, but none of the published examples cross the blood–brain barrier. Therefore, we have an ongoing interest in developing a brain penetrating radiotracer for GSK-3. To this end, we were interested in synthesis and preclinical evaluation of [11C]SB-216763, a high-affinity inhibitor of GSK-3 (Ki = 9 nM; IC50 = 34 nM). Initial radiosyntheses of [11C]SB-216763 proved ineffective in our hands because of competing [3 + 3] sigmatropic shifts. Therefore, we have developed a novel one-pot two-step synthesis of [11C]SB-216763 from a 2,4-dimethoxybenzyl-protected maleimide precursor, which provided high specific activity [11C]SB-216763 in 1% noncorrected radiochemical yield (based upon [11C]CH3I) and 97–100% radiochemical purity (n = 7). Initial preclinical evaluation in rodent and nonhuman primate PET imaging studies revealed high initial brain uptake (peak rodent SUV = 2.5 @ 3 min postinjection; peak nonhuman primate SUV = 1.9 @ 5 min postinjection) followed by washout. Brain uptake was highest in thalamus, striatum, cortex, and cerebellum, areas known to be rich in GSK-3. These results make the arylindolemaleimide skeleton our lead scaffold for developing a PET radiotracer for quantification of GSK-3 density in vivo and ultimately translating it into clinical use. PMID:26005531

Evaluation of [11C]metergoline as a PET radiotracer for 5HTR in nonhuman primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooker, J.M.; Hooker, J.M.; Kim, S.W.

2010-04-20

Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.

Refraction-compensated motion tracking of unrestrained small animals in positron emission tomography.

PubMed

Kyme, Andre; Meikle, Steven; Baldock, Clive; Fulton, Roger

2012-08-01

Motion-compensated radiotracer imaging of fully conscious rodents represents an important paradigm shift for preclinical investigations. In such studies, if motion tracking is performed through a transparent enclosure containing the awake animal, light refraction at the interface will introduce errors in stereo pose estimation. We have performed a thorough investigation of how this impacts the accuracy of pose estimates and the resulting motion correction, and developed an efficient method to predict and correct for refraction-based error. The refraction model underlying this study was validated using a state-of-the-art motion tracking system. Refraction-based error was shown to be dependent on tracking marker size, working distance, and interface thickness and tilt. Correcting for refraction error improved the spatial resolution and quantitative accuracy of motion-corrected positron emission tomography images. Since the methods are general, they may also be useful in other contexts where data are corrupted by refraction effects. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Development of Gamma-Emitting Receptor Binding Radiopharmace

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reba, Richard

2003-02-20

The long-term objective is to develop blood-brain barrier (BBB) permeable m2-selective (relative to m1, m3, and m4) receptor-binding radiotracers and utilize these radiotracers for quantifying receptor concentrations obtained from PET or SPECT images of human brain. In initial studies, we concluded that the lipophilicity and high affinity prevented (R,S)-I-QNB from reaching a flow-independent and receptor-dependent state in a reasonable time. Thus, it was clear that (R,S)-I-QNB should be modified. Therefore, during the last portion of this funded research, we proposed that more polar heterocycles should help accomplish that. Since reports of others concluded that radiobromination and radiofluorination of the unactivatedmore » phenyl ring is not feasible (Newkome et al,,1982), we, therefore, explored during this grant period a series of analogues of (R)-QNB in which one or both of the six-membered phenyl rings is replaced by a five-membered thienyl (Boulay et al., 1995), or furyl ring. The chemistry specific aims were to synthesize novel compounds designed to be m2-selective mAChR ligands capable of penetrating into the CNS, and develop methods for efficient radiolabeling of promising m2-selective muscarinic ligands. The pharmacology specific aims were to determine the affinity and subtype-selectivity of the novel compounds using competition binding studies with membranes from cells that express each of the five muscarinic receptor subtypes, to determine the ability of the promising non-radioactive compounds and radiolabeled novel compounds to cross the BBB, to determine the biodistribution, in-vivo pharmacokinetics, and in-vitm kinetics of promising m2-selective radioligands and to determine the distribution of receptors for the novel m2-selective radioligands using quantitative autoradiography of rat brain, and compare this distribution to the distribution of known m2-selective compounds.« less

Small-animal PET of tumor damage induced by photothermal ablation with 64Cu-bis-DOTA-hypericin.

PubMed

Song, Shaoli; Xiong, Chiyi; Zhou, Min; Lu, Wei; Huang, Qian; Ku, Geng; Zhao, Jun; Flores, Leo G; Ni, Yicheng; Li, Chun

2011-05-01

The purpose of this study was to investigate the potential application of small-molecular-weight (64)Cu-labeled bis-DOTA-hypericin in the noninvasive assessment of response to photothermal ablation therapy. Bis-DOTA-hypericin was labeled with (64)Cu with high efficiency (>95% without purification). Nine mice bearing subcutaneous human mammary BT474 tumors were used. Five mice were injected intratumorally with semiconductor CuS nanoparticles, followed by near-infrared laser irradiation 24 h later (12 W/cm(2) for 3 min), and 4 mice were not treated (control group). All mice were intravenously injected with (64)Cu-bis-DOTA-hypericin (24 h after laser treatment in treated mice). Small-animal PET images were acquired at 2, 6, and 24 h after radiotracer injection. All mice were killed immediately after the imaging session for biodistribution and histology study. In vitro cell uptake and surface plasmon resonance studies were performed to validate the small-animal PET results. (64)Cu-bis-DOTA-hypericin uptake was significantly higher in the treatment group than in the control group. The percentage injected dose per gram of tissue in the treated and control groups was 1.72 ± 0.43 and 0.76 ± 0.19, respectively (P = 0.017), at 24 h after injection. Autoradiography and histology results were consistent with selective uptake of the radiotracer in the necrotic zone of the tumor induced by photothermal ablation therapy. In vitro results showed that treated BT474 cells had a higher uptake of (64)Cu-bis-DOTA-hypericin than nontreated cells. Surface plasmon resonance study showed that bis-DOTA-hypericin had higher binding affinity to phosphatidylserine and phosphatidylethanolamine than to phosphatidylcholine. (64)Cu-bis-DOTA-hypericin has a potential to image thermal therapy-induced tumor cell damage. The affinity of (64)Cu-bis-DOTA-hypericin for injured tissues may be attributed to the breakdown of the cell membrane and exposure of phosphatidylserine or phosphatidylethanolamine to the radiotracer, which binds selectively to these phospholipids.

Evaluation of [11C]TAZA for amyloid β plaque imaging in postmortem human Alzheimer's disease brain region and whole body distribution in rodent PET/CT.

PubMed

Pan, Min-Liang; Mukherjee, Meenakshi T; Patel, Himika H; Patel, Bhavin; Constantinescu, Cristian C; Mirbolooki, M Reza; Liang, Christopher; Mukherjee, Jogeshwar

2016-04-01

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11)C]TAZA), for binding to Aβ plaques in postmortem human brain (AD and normal control (NC)). Radiosyntheses of [(11)C]TAZA, related [(11)C]Dalene ((11)C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11)C]PIB were carried out using [(11)C]methyltriflate prepared from [(11) C]CO(2) and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Aβ plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/μmol. TAZA had an affinity, K(i) = 0.84 nM and was five times more potent than PIB. [(11)C]TAZA bound specifically to Aβ plaques present in AD brains with gray matter to white matter ratios >20. [(11)C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11)C]TAZA and [(11)C]PIB. [(11)C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. [(11)C]TAZA exhibited high binding to Aβ plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated. © 2016 Wiley Periodicals, Inc.

Applications of Beta Particle Detection for Synthesis and Usage of Radiotracers Developed for Positron Emission Tomography

NASA Astrophysics Data System (ADS)

Dooraghi, Alex Abreu

Positron Emission Tomography (PET) is a noninvasive molecular imaging tool that requires the use of a radioactive compound or radiotracer which targets a molecular pathway of interest. We have developed and employed three beta particle radiation detection systems to advance PET. Specifically, the goals of these systems are to: 1. Automate dispensing of solutions containing a positron emitting isotope. 2. Monitor radioactivity on-chip during synthesis of a positron emitting radiotracer. 3. Assay cellular uptake on-chip of a positron emitting radiotracer. Automated protocols for measuring and dispensing solutions containing radioisotopes are essential not only for providing an optimum environment for radiation workers, but also to ensure a quantitatively accurate workflow. For the first project, we describe the development and performance of a system for automated radioactivity distribution of beta particle emitting radioisotopes such as fluorine-18 (F-18). Key to the system is a radiation detector in-line with a peristaltic pump. The system demonstrates volume accuracy within 5 % for volumes of 20 muL or greater. When considering volumes of 20 muL or greater, delivered radioactivity is in agreement with the requested radioactivity as measured with the dose calibrator. The integration of the detector and pump leads to a flexible system that can accurately dispense solutions containing F-18 in radioactivity concentrations directly produced from a cyclotron (~ 0.1-1 mCi/muL), to low activity concentrations intended for preclinical mouse scans (~ 1-10 muCi/muL), and anywhere in between. Electrowetting on dielectric (EWOD) is an attractive microfluidic platform for batch synthesis of PET radiotracers. Visualization of radioisotopes on-chip is critical for synthesis optimization and technological development. For the second project, we describe the development and performance of a Cerenkov/real-time imaging system for PET radiotracer synthesis on EWOD. We also investigate fundamental physical characteristics of Cerenkov photon yield at different stages of [F-18]FDG synthesis on the EWOD platform. We are able to use this imaging system to optimize the mixing protocol as well as identify and correct for loss of radioactivity due to the migration of radioactive vapor outside of the EWOD heater, enabling an overall increase in the crude radiochemical yield from 50 +/- 3% (n = 3) to 72 +/- 13% (n = 5). Clinical use of PET has proven to be a critical tool for monitoring cancer treatment response. For the third project, we describe the redesign and performance of Betabox, a specialized device that incorporates PET radiotracers in an assay that gives clinicians and researchers the ability to assess the effectiveness of a drug therapy in-vitro by isolating small samples of patient tumor cells incubated in a polydimethylsiloxane (PDMS) microfluidic chip. We find that Betabox is a high sensitivity and low noise charged particle imaging system that can operate without significant impairment of its performance at both room and at elevated temperatures, such as those suitable for cell culture. The dark count rate is within range of the expected signal from cosmic rays, dictating a low detection limit that allows quantitative imaging of very small amounts of radioactivity. This system demonstrates the potential of direct cellular radioassay of small samples of cells (~100 cells per measurement).

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

PubMed

Buda, Alessandro; Crivellaro, Cinzia; Elisei, Federica; Di Martino, Giampaolo; Guerra, Luca; De Ponti, Elena; Cuzzocrea, Marco; Giuliani, Daniela; Sina, Federica; Magni, Sonia; Landoni, Claudio; Milani, Rodolfo

2016-07-01

To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid ((99m)Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with (99m)Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard (99m)Tc radiotracer with blue dye, or blue dye alone. SLN mapping with (99m)Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for (99m)Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with (99m)Tc with blue dye (p = 0.003) and the 54 % for blue dye (p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to (99m)Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment.

Automated cGMP-compliant radiosynthesis of [18 F]-(E)-PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5.

PubMed

Park, Jun Young; Son, Jeongmin; Yun, Mijin; Ametamey, Simon M; Chun, Joong-Hyun

2018-01-01

(E)-3-(Pyridin-2-yl ethynyl)cyclohex-2-enone O-(3-(2-[ 18 F]-fluoroethoxy)propyl) oxime ([ 18 F]-(E)-PSS232, [ 18 F]2a) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu 5 ) in vivo. The mGlu 5 has become an attractive therapeutic and diagnostic target owing to its role in many neuropsychiatric disorders. Several carbon-11-labeled and fluorine-18-labeled radiotracers have been developed to measure mGlu 5 receptor occupancy in the human brain. The radiotracer [ 18 F]2a, which is used as an analogue for [ 11 C]ABP688 ([ 11 C]1) and has a longer physical half-life, is a selective radiotracer that exhibits high binding affinity for mGlu 5 . Herein, we report the fully automated radiosynthesis of [ 18 F]2a using a commercial GE TRACERlab™ FX- FN synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron-produced [ 18 F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high-performance liquid chromatography (HPLC) purification and formulation, readily provided [ 18 F]2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [ 18 F]-(E)-conformer was greater than 95%. Molar activity was determined to be 63.6 ± 9.6 GBq/μmol (n = 5), and the overall synthesis time was 70 minutes. Copyright © 2017 John Wiley & Sons, Ltd.

In vivo evaluation of radiotracers targeting the melanin-concentrating hormone receptor 1: [11C]SNAP-7941 and [18F]FE@SNAP reveal specific uptake in the ventricular system.

PubMed

Zeilinger, Markus; Dumanic, Monika; Pichler, Florian; Budinsky, Lubos; Wadsak, Wolfgang; Pallitsch, Katharina; Spreitzer, Helmut; Lanzenberger, Rupert; Hacker, Marcus; Mitterhauser, Markus; Philippe, Cécile

2017-08-14

The MCHR1 is involved in the regulation of energy homeostasis and changes of the expression are linked to a variety of associated diseases, such as diabetes and adiposity. The study aimed at the in vitro and in vivo evaluation of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP as potential PET-tracers for the MCHR1. Competitive binding studies with non-radioactive derivatives and small-animal PET/CT and MRI brain studies were performed under baseline conditions and tracer displacement with the unlabelled MCHR1 antagonist (±)-SNAP-7941. Binding studies evinced high binding affinity of the non-radioactive derivatives. Small-animal imaging of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP evinced high tracer uptake in MCHR1-rich regions of the ventricular system. Quantitative analysis depicted a significant tracer reduction after displacement with (±)-SNAP-7941. Due to the high binding affinity of the non-labelled derivatives and the high specific tracer uptake of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP, there is strong evidence that both radiotracers may serve as highly suitable agents for specific MCHR1 imaging.

2-Deoxy-2-fluoro-d-glucose metabolism in Arabidopsis thaliana

PubMed Central

Fatangare, Amol; Paetz, Christian; Saluz, Hanspeter; Svatoš, Aleš

2015-01-01

2-Deoxy-2-fluoro-d-glucose (FDG) is glucose analog routinely used in clinical and animal radiotracer studies to trace glucose uptake but it has rarely been used in plants. Previous studies analyzed FDG translocation and distribution pattern in plants and proposed that FDG could be used as a tracer for photoassimilates in plants. Elucidating FDG metabolism in plants is a crucial aspect for establishing its application as a radiotracer in plant imaging. Here, we describe the metabolic fate of FDG in the model plant species Arabidopsis thaliana. We fed FDG to leaf tissue and analyzed leaf extracts using MS and NMR. On the basis of exact mono-isotopic masses, MS/MS fragmentation, and NMR data, we identified 2-deoxy-2-fluoro-gluconic acid, FDG-6-phosphate, 2-deoxy-2-fluoro-maltose, and uridine-diphosphate-FDG as four major end products of FDG metabolism. Glycolysis and starch degradation seemed to be the important pathways for FDG metabolism. We showed that FDG metabolism in plants is considerably different than animal cells and goes beyond FDG-phosphate as previously presumed. PMID:26579178

68Ga-PSMA Expression in Pseudoangiomatous Stromal Hyperplasia of the Breast.

PubMed

Malik, Dharmender; Basher, Rajender K; Mittal, Bhagwant Rai; Jain, Tarun Kumar; Bal, Amanjit; Singh, Shrawan Kumar

2017-01-01

Ga-labeled prostate-specific membrane antigen ligand PET-CT has emerged as a promising technique to evaluate the extent of disease in patients with prostate carcinoma. We are reporting a 63-year-old man with prostatic carcinoma subjected to Ga-prostate-specific membrane antigen ligand PET-CT for initial staging. In addition to the radiotracer uptake in known primary site (prostate), focal increased radiotracer uptake was also noticed in the left breast. Subsequent biopsy of the breast lesion revealed PASH (pseudoangiomatous stromal hyperplasia), which is a benign mesenchymal proliferative lesion that may present clinically as palpable mass requiring further evaluation to rule out malignancy.

No-carrier-added [1.sup.11 c]putrescine

DOEpatents

McPherson, Daniel W.; Fowler, Joanna S.; Wolf, Alfred P.

1989-01-01

The invention relates to a new radiolabeled imaging agent, no-carrier-added [1-.sup.11 C]putrescine, and to the use of this very pure material as a radiotracer with positron emission tomography for imaging brain tumors. The invention further relates to the synthesis of no-carrier-added [1-.sup.11 C]putrescine based on the Michael addition of potassium .sup.11 C-labeled cyanide to acrylonitrile followed by reduction of the .sup.11 C-labeled dinitrile. The new method is rapid and efficient and provides radiotracer with a specific activity greater than 1.4 curies per millimol and in a purity greater than 95%.

Measurements of liquid phase residence time distributions in a pilot-scale continuous leaching reactor using radiotracer technique.

PubMed

Pant, H J; Sharma, V K; Shenoy, K T; Sreenivas, T

2015-03-01

An alkaline based continuous leaching process is commonly used for extraction of uranium from uranium ore. The reactor in which the leaching process is carried out is called a continuous leaching reactor (CLR) and is expected to behave as a continuously stirred tank reactor (CSTR) for the liquid phase. A pilot-scale CLR used in a Technology Demonstration Pilot Plant (TDPP) was designed, installed and operated; and thus needed to be tested for its hydrodynamic behavior. A radiotracer investigation was carried out in the CLR for measurement of residence time distribution (RTD) of liquid phase with specific objectives to characterize the flow behavior of the reactor and validate its design. Bromine-82 as ammonium bromide was used as a radiotracer and about 40-60MBq activity was used in each run. The measured RTD curves were treated and mean residence times were determined and simulated using a tanks-in-series model. The result of simulation indicated no flow abnormality and the reactor behaved as an ideal CSTR for the range of the operating conditions used in the investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sentinel lymph nodes in endometrial cancer: is hysteroscopic injection valid?

PubMed

Clement, D; Bats, A S; Ghazzar-Pierquet, N; Le Frere Belda, M A; Larousserie, F; Nos, C; Lecuru, F

2008-01-01

We aimed to describe hysteroscopic peritumoral tracer injection for detecting sentinel lymph nodes (SLNs) in patients with endometrial cancer and to evaluate tolerance of the procedure, detection rate and location of SLNs. Five patients with early endometrial cancer underwent hysteroscopic radiotracer injection followed by lymphoscintigraphy, then by surgery with hysteroscopic peritumoral blue dye injection, and radioactivity measurement using an endoscopic handheld gamma probe. SLNs and other nodes were sent separately to the pathology laboratory. SLNs were evaluated by hematoxylin-eosin-saffron staining and, when negative, by immunohistochemistry. Tolerance of the injection by the patients was poor (mean visual analog scale score, 8/10). SLNs were detected in only two patients (external iliac and common iliac+paraaortic, respectively). Detection rates were 1/5 by radiotracer, 1/5 by dye, and 2/5 by the combined method. One SLN was involved in a patient whose other nodes were negative. In three patients no SLNs were found by radiotracer or blue dye. Of the 83 non sentinel nodes removed from these patients, none was involved. Hysteroscopic peritumoral injection may be more difficult than cervical injection and, in our experience, carries a lower SLN detection rate.

In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [11C]DPA-713 PET and analysis of CSF and plasma

PubMed Central

Coughlin, J M; Wang, Y; Ambinder, E B; Ward, R E; Minn, I; Vranesic, M; Kim, P K; Ford, C N; Higgs, C; Hayes, L N; Schretlen, D J; Dannals, R F; Kassiou, M; Sawa, A; Pomper, M G

2016-01-01

Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [11C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [11C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease. PMID:27070405

Potentially conflicting metabolic demands of diving and exercise in seals.

PubMed

Castellini, M A; Murphy, B J; Fedak, M; Ronald, K; Gofton, N; Hochachka, P W

1985-02-01

Metabolic replacement rates (Ra) for glucose and free fatty acids (FFA) were determined during rest, exercise, and diving conditions in the gray seal using bolus injections of radiotracers. In the exercise experiments the seal swam at a metabolic rate elevated twofold over resting Ra for glucose and FFA while resting were similar to values found in terrestrial mammals and other marine mammal species. During exercise periods glucose turnover increased slightly while FFA turnover changes were variable. However, the energetic demands of exercise could not be met by the increase in the replacement rates of glucose or FFA even if both were completely oxidized. Under diving conditions the tracer pool displayed radically different specific activity curves indicative of the changes in perfusion and metabolic rate associated with a strong dive response. Since the radiotracer curves during exercise and diving differed qualitatively and quantitatively, it is possible that similar studies on freely diving animals can be used to assess the role of the diving response during underwater swimming in nature.

Nurse exposure doses resulted from bone scintigraphy patient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tunçman, Duygu, E-mail: duygutuncman@gmail.com; Demir, Bayram; Kovan, Bilal

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It’s general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget’s disease, investigation of loosening and infection in orthopedic implants. It is applied with using {sup 99m}Tc labeled radiopharmaceuticals (e.g {sup 99m} Tc MDP,{sup 99m}Tc HEDP and {sup 99m}Tc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. Whenmore » some patient’s situation is not good, patients are hospitalized until the scanning because of patients’ close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse’s exposure radiations from patient’s routine treatment, examination and emergency station.« less

Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography.

PubMed

Fresneau, Nathalie; Dumas, Noé; Tournier, Benjamin B; Fossey, Christine; Ballandonne, Céline; Lesnard, Aurélien; Millet, Philippe; Charnay, Yves; Cailly, Thomas; Bouillon, Jean-Philippe; Fabis, Frédéric

2015-04-13

With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to favour brain penetration, and which demonstrated specific binding to the target of interest. Adding additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific binding, we were able to design a radioiodinated compound [(125)I]14. This compound exhibited a binding affinity value of 0.094 nM toward human 5-HT4R and a high selectivity over other serotonin receptor subtypes (5-HTR). In vivo SPECT imaging studies and competition experiments demonstrated that the decreased lipophilicity (in comparison with our previously reported compounds 4 and 5) allowed a more specific labelling of the 5-HT4R brain-containing regions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Target foil rupture scenario and provision for handling different models of medical cyclotrons used in India

PubMed Central

Shaiju, V. S.; Sharma, S. D.; Kumar, Rajesh; Sarin, B.

2009-01-01

Medical cyclotron is a particle accelerator used in producing short lived radiotracers such as 18F, 11C, 15O, 13N etc. These radiotracers are labeled with suitable pharmaceuticals for use to gather information related to metabolic activity of the cell using Positron Emission Tomography (PET) scan. Target foil rupture is considered one of the major emergency situations during medical cyclotron operations because there is a potential of over exposure to the working personnel. Radiation protection survey of a self-shielded medical cyclotron installation was carried out during normal and emergency conditions. It is found that the induced activity in the target foil increases with its successive usages. As a case study, we have evaluated the emergency handling procedures of GE PETtrace-6 medical cyclotron. Recommendations have also been made to reduce personal exposure while handling the target foil rupture condition such as the use of L-Bench near the target area and participation of experienced personnel. PMID:20098564

Improving cancer treatment with cyclotron produced radionuclides. Comprehensive progress report, February 1, 1992--July 15, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1995-07-17

This research continues the long term goals of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. This program fits into the nuclear medicine component of DOE`s mission, which is aimed at enhancing the beneficial applications of radiation, radionuclides, and stable isotopes in the diagnosis, study and treatment of human diseases. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology/Immunology; and Imaging Physics. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Section under the DOE grant during the 1992--1995more » will be employed in the Pharmacology/Immunology component in the period 1996--1999. Imaging Physics resolves relevant imaging related physics issues that arise during the experimentation that results. In addition to the basic research mission, this project also provides a basis for training of research scientists in radiochemistry, immunology, bioengineering and imaging physics.« less

Applications of 2-deoxy-2-fluoro-D-glucose (FDG) in Plant Imaging: Past, Present, and Future

PubMed Central

Fatangare, Amol; Svatoš, Aleš

2016-01-01

The aim of this review article is to explore and establish the current status of 2-deoxy-2-fluoro-D-glucose (FDG) applications in plant imaging. In the present article, we review the previous literature on its experimental merits to formulate a consistent and inclusive picture of FDG applications in plant-imaging research. 2-deoxy-2-fluoro-D-glucose is a [18F]fluorine-labeled glucose analog in which C-2 hydroxyl group has been replaced by a positron-emitting [18F] radioisotope. As FDG is a positron-emitting radiotracer, it could be used in in vivo imaging studies. FDG mimics glucose chemically and structurally. Its uptake and distribution are found to be similar to those of glucose in animal models. FDG is commonly used as a radiotracer for glucose in medical diagnostics and in vivo animal imaging studies but rarely in plant imaging. Tsuji et al. (2002) first reported FDG uptake and distribution in tomato plants. Later, Hattori et al. (2008) described FDG translocation in intact sorghum plants and suggested that it could be used as a tracer for photoassimilate translocation in plants. These findings raised interest among other plant scientists, which has resulted in a recent surge of articles involving the use of FDG as a tracer in plants. There have been seven studies describing FDG-imaging applications in plants. These studies describe FDG applications ranging from monitoring radiotracer translocation to analyzing solute transport, root uptake, photoassimilate tracing, carbon allocation, and glycoside biosynthesis. Fatangare et al. (2015) recently characterized FDG metabolism in plants; such knowledge is crucial to understanding and validating the application of FDG in plant imaging research. Recent FDG studies significantly advance our understanding of FDG translocation and metabolism in plants but also raise new questions. Here, we take a look at all the previous results to form a comprehensive picture of FDG translocation, metabolism, and applications in plants. In conclusion, we summarize current knowledge, discuss possible implications and limitations of previous studies, point to open questions in the field, and comment on the outlook for FDG applications in plant imaging. PMID:27242806

Applications of 2-deoxy-2-fluoro-D-glucose (FDG) in Plant Imaging: Past, Present, and Future.

PubMed

Fatangare, Amol; Svatoš, Aleš

2016-01-01

The aim of this review article is to explore and establish the current status of 2-deoxy-2-fluoro-D-glucose (FDG) applications in plant imaging. In the present article, we review the previous literature on its experimental merits to formulate a consistent and inclusive picture of FDG applications in plant-imaging research. 2-deoxy-2-fluoro-D-glucose is a [(18)F]fluorine-labeled glucose analog in which C-2 hydroxyl group has been replaced by a positron-emitting [(18)F] radioisotope. As FDG is a positron-emitting radiotracer, it could be used in in vivo imaging studies. FDG mimics glucose chemically and structurally. Its uptake and distribution are found to be similar to those of glucose in animal models. FDG is commonly used as a radiotracer for glucose in medical diagnostics and in vivo animal imaging studies but rarely in plant imaging. Tsuji et al. (2002) first reported FDG uptake and distribution in tomato plants. Later, Hattori et al. (2008) described FDG translocation in intact sorghum plants and suggested that it could be used as a tracer for photoassimilate translocation in plants. These findings raised interest among other plant scientists, which has resulted in a recent surge of articles involving the use of FDG as a tracer in plants. There have been seven studies describing FDG-imaging applications in plants. These studies describe FDG applications ranging from monitoring radiotracer translocation to analyzing solute transport, root uptake, photoassimilate tracing, carbon allocation, and glycoside biosynthesis. Fatangare et al. (2015) recently characterized FDG metabolism in plants; such knowledge is crucial to understanding and validating the application of FDG in plant imaging research. Recent FDG studies significantly advance our understanding of FDG translocation and metabolism in plants but also raise new questions. Here, we take a look at all the previous results to form a comprehensive picture of FDG translocation, metabolism, and applications in plants. In conclusion, we summarize current knowledge, discuss possible implications and limitations of previous studies, point to open questions in the field, and comment on the outlook for FDG applications in plant imaging.

Targeting Prostate-Specific Membrane Antigen (PSMA) with F-18-Labeled Compounds: the Influence of Prosthetic Groups on Tumor Uptake and Clearance Profile.

PubMed

Bouvet, Vincent; Wuest, Melinda; Bailey, Justin J; Bergman, Cody; Janzen, Nancy; Valliant, John F; Wuest, Frank

2017-12-01

Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in the majority of prostate cancers. The favorable positron emission tomography (PET) imaging profile of the PSMA imaging agent 2-(3-(1-carboxy-5-[(6-[ 18 F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentane-dioic acid [ 18 F]DCFPyL in preclinical prostate cancer models and in prostate cancer patients stimulated the development and validation of other fluorine-containing PSMA inhibitors to further enhance pharmacokinetics and simplify production methods. Here, we describe the synthesis and radiopharmacological evaluation of various F-18-labeled PSMA inhibitors which were prepared through different prosthetic group chemistry strategies. Prosthetic groups N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB), 4-[ 18 F]fluorobenzaldehyde, and 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) were used for bioconjugation reactions to PSMA-binding lysine-urea-glutamate scaffold via acylation and oxime formation. All fluorine-containing PSMA inhibitors were tested for their PSMA inhibitory potency in an in vitro competitive binding assay in comparison to an established reference compound [ 125 I]TAAG-PSMA. Tumor uptake and clearance profiles of three F-18-labeled PSMA inhibitors ([ 18 F]4, [ 18 F]7, and [ 18 F]8) were studied with dynamic PET imaging using LNCaP tumor-bearing mice. F-18-labeled PSMA inhibitors were synthesized in 32-69 % radiochemical yields using (1) acylation reaction at the primary amino group of the lysine residue with [ 18 F]SFB and (2) oxime formation with 4-[ 18 F]fluorobenzaldehyde and [ 18 F]FDG using the respective aminooxy-functionalized lysine residue. Compound 7 displayed an IC 50 value of 6 nM reflecting very high affinity for PSMA. Compounds 4 and 8 showed IC 50 values of 13 and 62 nM, respectively. The IC 50 value of reference compound DCFPyL was 13 nM. Dynamic PET imaging revealed the following SUV 60min for radiotracer uptake in PSMA(+) LNCaP tumors: 0.98 ([ 18 F]DCFPyL), 2.11 ([ 18 F]7), 0.40 ([ 18 F]4), and 0.19 ([ 18 F]8). The observed tumor uptake and clearance profiles demonstrate the importance of the selected prosthetic group on the pharmacokinetic profile of analyzed PSMA-targeting radiotracers. Radiotracer [ 18 F]7 displayed the highest uptake and retention in LNCaP tumors, which exceeded uptake values of reference compound [ 18 F]DCFPyL by more than 100 %. Despite the higher kidney and liver uptake and retention of compound [ 18 F]7, the simple radiosynthesis and the exceptionally high tumor uptake (SUV 60min 2.11) and retention make radiotracer [ 18 F]7 an interesting alternative to radiotracer [ 18 F]DCFPyL for PET imaging of PSMA in prostate cancer.

PSMA-Based [(18)F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer.

PubMed

Rowe, Steven P; Macura, Katarzyna J; Mena, Esther; Blackford, Amanda L; Nadal, Rosa; Antonarakis, Emmanuel S; Eisenberger, Mario; Carducci, Michael; Fan, Hong; Dannals, Robert F; Chen, Ying; Mease, Ronnie C; Szabo, Zsolt; Pomper, Martin G; Cho, Steve Y

2016-06-01

Current standard of care conventional imaging modalities (CIM) such as X-ray computed tomography (CT) and bone scan can be limited for detection of metastatic prostate cancer and therefore improved imaging methods are an unmet clinical need. We evaluated the utility of a novel second-generation low molecular weight radiofluorinated prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer, [(18)F]DCFPyL, in patients with metastatic prostate cancer. Nine patients with suspected prostate cancer recurrence, eight with CIM evidence of metastatic prostate cancer and one with biochemical recurrence, were imaged with [(18)F]DCFPyL PET/CT. Eight of the patients had contemporaneous CIM for comparison. A lesion-by-lesion comparison of the detection of suspected sites of metastatic prostate cancer was carried out between PET and CIM. Statistical analysis for estimated proportions of inter-modality agreement for detection of metastatic disease was calculated accounting for intra-patient correlation using general estimating equation (GEE) intercept-only regression models. One hundred thirty-nine sites of PET positive [(18)F]DCFPyL uptake (138 definite, 1 equivocal) for metastatic disease were detected in the eight patients with available comparison CIM. By contrast, only 45 lesions were identified on CIM (30 definite, 15 equivocal). When lesions were negative or equivocal on CIM, it was estimated that a large portion of these lesions or 0.72 (95 % confidence interval (CI) 0.55-0.84) would be positive on [(18)F]DCFPyL PET. Conversely, of those lesions negative or equivocal on [(18)F]DCFPyL PET, it was estimated that only a very small proportion or 0.03 (95 % CI 0.01-0.07) would be positive on CIM. Delayed 2-h-post-injection time point PET yielded higher tumor radiotracer uptake and higher tumor-to-background ratios than an earlier 1-h-post-injection time point. A novel PSMA-targeted PET radiotracer, [(18)F]DCFPyL, was able to a large number of suspected sites of prostate cancer, many of which were occult or equivocal by CIM. This study provides strong preliminary evidence for the use of this second-generation PSMA-targeted PET radiotracer for detection of metastatic prostate cancer and lends further support for the importance of PSMA-targeted PET imaging in prostate cancer.

Tau and Amyloid Positron Emission Tomography Imaging Predict Driving Performance Among Older Adults with and without Preclinical Alzheimer's Disease.

PubMed

Roe, Catherine M; Babulal, Ganesh M; Mishra, Shruti; Gordon, Brian A; Stout, Sarah H; Ott, Brian R; Carr, David B; Ances, Beau M; Morris, John C; Benzinger, Tammie L S

2018-01-01

Abnormal levels of Alzheimer's disease (AD) biomarkers, measured by positron emission tomography imaging using amyloid-based radiotracers and cerebrospinal fluid, are associated with impaired driving performance in older adults. We examined whether preclinical AD staging, defined using amyloid imaging and tau imaging using the radiotracer T807 (AKA flortaucipir or AV-1451), was associated with receiving a marginal/fail rating on a standardized road test (n = 42). Participants at Stage 2 (positive amyloid and tau scans) of preclinical AD were more likely to receive a marginal/fail rating compared to participants at Stage 0 or 1. Stage 2 preclinical AD may manifest in worse driving performance.

Improving cancer treatment with cyclotron produced radionuclides. Progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1993-11-01

This report describes our continuing long term goal of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The program includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Cyclotron section will be employed in the Pharmacology and Immunology sections during the next year. The development of novel radionuclides and tracers is of course useful in and of itself, but their utility is greatly enhanced by the interaction with the immunologymore » and pharmacology components of the program.« less

The 124Sb activity standardization by gamma spectrometry for medical applications

NASA Astrophysics Data System (ADS)

de Almeida, M. C. M.; Iwahara, A.; Delgado, J. U.; Poledna, R.; da Silva, R. L.

2010-07-01

This work describes a metrological activity determination of 124Sb, which can be used as radiotracer, applying gamma spectrometry methods with hyper pure germanium detector and efficiency curves. This isotope with good activity and high radionuclidic purity is employed in the form of meglumine antimoniate (Glucantime) or sodium stibogluconate (Pentostam) to treat leishmaniasis. 124Sb is also applied in animal organ distribution studies to solve some questions in pharmacology. 124Sb decays by β-emission and it produces several photons (X and gamma rays) with energy varying from 27 to 2700 keV. Efficiency curves to measure point 124Sb solid sources were obtained from a 166mHo standard that is a multi-gamma reference source. These curves depend on radiation energy, sample geometry, photon attenuation, dead time and sample-detector position. Results for activity determination of 124Sb samples using efficiency curves and a high purity coaxial germanium detector were consistent in different counting geometries. Also uncertainties of about 2% ( k=2) were obtained.

myo-Inositol and Phytate Are Toxic to Formosan Subterranean Termites (Isoptera: Rhinotermitidae).

PubMed

Veillon, Lucas; Bourgeois, Jared; Leblanc, Amanda; Henderson, Gregg; Marx, Brian D; Muniruzzaman, Syed; Laine, Roger A

2014-10-01

Several rare and common monosaccharides were screened for toxic effects on the Formosan subterranean termite, Coptotermes formosanus Shiraki, with the aim of identifying environmentally friendly termiticides. myo-Inositol and phytic acid, which are nontoxic to mammals, were identified as potential termite control compounds. Feeding bioassays with termite workers, where both compounds were supplied on filter paper in concentrations from 160.2 to 1,281.7 μg/mm(3), showed concentration-dependent toxicity within 2 wk. Interestingly myo-inositol was nontoxic when administered to termites in agar (40 mg/ml) in the absence of a cellulosic food source, an unexplained phenomenon. In addition, decreased populations of termite hindgut protozoa were observed upon feeding on myo-inositol but not phytate-spiked filter paper. Radiotracer feeding studies using myo-inositol-[2-(3)H] with worker termites showed no metabolism after ingestion over a 2-d feeding period, ruling out metabolites responsible for the selective toxicity. © 2014 Entomological Society of America.

Synthesis of Radioisotope Mn-56@SiO2, Sm-153@SiO2, and Dy-165@SiO2 Hybrid Nanoparticles for Use as Radiotracer.

PubMed

Seo, Sang-Ei; Kang, Yun Ok; Jung, Sung-Hee; Choi, Seong-Ho

2015-09-01

Radioisotope hybrid nanoparticles (NPs) of Mn-56@SiO2, Sm-153@SiO2, and Dy-165@SiO2 were synthesized by neutron irradiation of Mn-55@SiO2, Sm-150@SiO2, and Dy-163@SiO2 NPs respectively using the HANARO research reactor. The Mn-55@SiO2, Sm-150@SiO2, and Dy-163@SiO2 NPs were synthesized by calcination in air flow at 500 degrees C for 8 h of the hybrid NPs that has been prepared by the sol-gel reaction of tetraethyl silicate in the presence of the complex precursors. Mn-55, Sm-150, and Dy-163 were selected for use as radiotracers were selected because these elements can be easily gamma-activated by neutrons (activation limits: 1 picogram (Dy), 1-10 picogram (Mn), 10-100 picogram (Sm)). The successful synthesis of the radioisotope hybrid NPs was confirmed by Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Spectrometry (EDS), Scanning Electron Microscopy (SEM), and Gamma Spectroscopy analysis. The synthesized the radioisotope hybrid NPs could be used as radiotracers in the scientific, environmental, engineering, and industrial fields.

Radiochemistry Research and Training, UC Davis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutcliffe, Julie

2012-08-01

The report contains a summary of the accomplishments made during the R2@UCDavis proposal. In brief we proposed to develop new and highly innovative radiotracer methods and to enhance training opportunities to ensure the future availability of human resources for highly specialized fields of radiotracer development chemistry and clinical nuclear medicine research and allied disciplines. The overall scientific objectives of this proposal were to utilize “click” chemistry to facilitate fast and site-specific radiolabeling. Progress was made on all initial goals presented. This funding has to date resulted in publications in high impact journals such as Acta Biomaterialia, Molecular Imaging and Biology,more » Nuclear Medicine and Biology and most recently Environmental Science and technology, and it is anticipated that through the collaborations established during the time course of this funding that future research will be published in clinically relevant journals such as Science Translational Medicine and the Journal of Nuclear Medicine. Trainees involved in this proposal have gone on to further their careers in both academia, industry and the private sector. The collaborative forums established during the time course of this funding will ensure the future availability of human resources for highly specialized fields of radiotracer development chemistry and clinical nuclear medicine research and allied disciplines.« less

Effects of body habitus on internal radiation dose calculations using the 5-year-old anthropomorphic male models.

PubMed

Xie, Tianwu; Kuster, Niels; Zaidi, Habib

2017-07-13

Computational phantoms are commonly used in internal radiation dosimetry to assess the amount and distribution pattern of energy deposited in various parts of the human body from different internal radiation sources. Radiation dose assessments are commonly performed on predetermined reference computational phantoms while the argument for individualized patient-specific radiation dosimetry exists. This study aims to evaluate the influence of body habitus on internal dosimetry and to quantify the uncertainties in dose estimation correlated with the use of fixed reference models. The 5-year-old IT'IS male phantom was modified to match target anthropometric parameters, including body weight, body height and sitting height/stature ratio (SSR), determined from reference databases, thus enabling the creation of 125 5-year-old habitus-dependent male phantoms with 10th, 25th, 50th, 75th and 90th percentile body morphometries. We evaluated the absorbed fractions and the mean absorbed dose to the target region per unit cumulative activity in the source region (S-values) of F-18 in 46 source regions for the generated 125 anthropomorphic 5-year-old hybrid male phantoms using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code and calculated the absorbed dose and effective dose of five 18 F-labelled radiotracers for children of various habitus. For most organs, the S-value of F-18 presents stronger statistical correlations with body weight, standing height and sitting height than BMI and SSR. The self-absorbed fraction and self-absorbed S-values of F-18 and the absorbed dose and effective dose of 18 F-labelled radiotracers present with the strongest statistical correlations with body weight. For 18 F-Amino acids, 18 F-Brain receptor substances, 18 F-FDG, 18 F-L-DOPA and 18 F-FBPA, the mean absolute effective dose differences between phantoms of different habitus and fixed reference models are 11.4%, 11.3%, 10.8%, 13.3% and 11.4%, respectively. Total body weight, standing height and sitting height have considerable effects on human internal dosimetry. Radiation dose calculations for individual subjects using the most closely matched habitus-dependent computational phantom should be considered as an alternative to improve the accuracy of the estimates.

Effects of body habitus on internal radiation dose calculations using the 5-year-old anthropomorphic male models

NASA Astrophysics Data System (ADS)

Xie, Tianwu; Kuster, Niels; Zaidi, Habib

2017-08-01

Computational phantoms are commonly used in internal radiation dosimetry to assess the amount and distribution pattern of energy deposited in various parts of the human body from different internal radiation sources. Radiation dose assessments are commonly performed on predetermined reference computational phantoms while the argument for individualized patient-specific radiation dosimetry exists. This study aims to evaluate the influence of body habitus on internal dosimetry and to quantify the uncertainties in dose estimation correlated with the use of fixed reference models. The 5-year-old IT’IS male phantom was modified to match target anthropometric parameters, including body weight, body height and sitting height/stature ratio (SSR), determined from reference databases, thus enabling the creation of 125 5-year-old habitus-dependent male phantoms with 10th, 25th, 50th, 75th and 90th percentile body morphometries. We evaluated the absorbed fractions and the mean absorbed dose to the target region per unit cumulative activity in the source region (S-values) of F-18 in 46 source regions for the generated 125 anthropomorphic 5-year-old hybrid male phantoms using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code and calculated the absorbed dose and effective dose of five 18F-labelled radiotracers for children of various habitus. For most organs, the S-value of F-18 presents stronger statistical correlations with body weight, standing height and sitting height than BMI and SSR. The self-absorbed fraction and self-absorbed S-values of F-18 and the absorbed dose and effective dose of 18F-labelled radiotracers present with the strongest statistical correlations with body weight. For 18F-Amino acids, 18F-Brain receptor substances, 18F-FDG, 18F-L-DOPA and 18F-FBPA, the mean absolute effective dose differences between phantoms of different habitus and fixed reference models are 11.4%, 11.3%, 10.8%, 13.3% and 11.4%, respectively. Total body weight, standing height and sitting height have considerable effects on human internal dosimetry. Radiation dose calculations for individual subjects using the most closely matched habitus-dependent computational phantom should be considered as an alternative to improve the accuracy of the estimates.

Mathematical modeling of positron emission tomography (PET) data to assess radiofluoride transport in living plants following petiolar administration

DOE PAGES

Converse, Alexander K.; Ahlers, Elizabeth O.; Bryan, Tom W.; ...

2015-03-15

Background: Ion transport is a fundamental physiological process that can be studied non-invasively in living plants with radiotracer imaging methods. Fluoride is a known phytotoxic pollutant and understanding its transport in plants after leaf absorption is of interest to those in agricultural areas near industrial sources of airborne fluoride. Here we report the novel use of a commercial, high-resolution, animal positron emission tomography (PET) scanner to trace a bolus of [¹⁸F]fluoride administered via bisected petioles of Brassica oleracea, an established model species, to simulate whole plant uptake of atmospheric fluoride. This methodology allows for the first time mathematical compartmental modelingmore » of fluoride transport in the living plant. Radiotracer kinetics in the stem were described with a single-parameter free- and trapped-compartment model and mean arrival times at different stem positions were calculated from the free-compartment time-activity curves. Results: After initiation of administration at the bisected leaf stalk, [¹⁸F] radioactivity climbed for approximately 10 minutes followed by rapid washout from the stem and equilibration within leaves. Kinetic modeling of transport in the stem yielded a trapping rate of 1.5 +/- 0.3%/min (mean +/- s.d., n = 3), velocity of 2.2 +/- 1.1 cm/min, and trapping fraction of 0.8 +/- 0.5%/cm. Conclusion: Quantitative assessment of physiologically meaningful transport parameters of fluoride in living plants is possible using standard positron emission tomography in combination with petiolar radiotracer administration. Movement of free fluoride was observed to be consistent with bulk flow in xylem, namely a rapid and linear change in position with respect to time. Trapping, likely in the apoplast, was observed. Future applications of the methods described here include studies of transport of other ions and molecules of interest in plant physiology.« less

Mathematical modeling of positron emission tomography (PET) data to assess radiofluoride transport in living plants following petiolar administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Converse, Alexander K.; Ahlers, Elizabeth O.; Bryan, Tom W.

Background: Ion transport is a fundamental physiological process that can be studied non-invasively in living plants with radiotracer imaging methods. Fluoride is a known phytotoxic pollutant and understanding its transport in plants after leaf absorption is of interest to those in agricultural areas near industrial sources of airborne fluoride. Here we report the novel use of a commercial, high-resolution, animal positron emission tomography (PET) scanner to trace a bolus of [¹⁸F]fluoride administered via bisected petioles of Brassica oleracea, an established model species, to simulate whole plant uptake of atmospheric fluoride. This methodology allows for the first time mathematical compartmental modelingmore » of fluoride transport in the living plant. Radiotracer kinetics in the stem were described with a single-parameter free- and trapped-compartment model and mean arrival times at different stem positions were calculated from the free-compartment time-activity curves. Results: After initiation of administration at the bisected leaf stalk, [¹⁸F] radioactivity climbed for approximately 10 minutes followed by rapid washout from the stem and equilibration within leaves. Kinetic modeling of transport in the stem yielded a trapping rate of 1.5 +/- 0.3%/min (mean +/- s.d., n = 3), velocity of 2.2 +/- 1.1 cm/min, and trapping fraction of 0.8 +/- 0.5%/cm. Conclusion: Quantitative assessment of physiologically meaningful transport parameters of fluoride in living plants is possible using standard positron emission tomography in combination with petiolar radiotracer administration. Movement of free fluoride was observed to be consistent with bulk flow in xylem, namely a rapid and linear change in position with respect to time. Trapping, likely in the apoplast, was observed. Future applications of the methods described here include studies of transport of other ions and molecules of interest in plant physiology.« less

Synthesis and preliminary biological evaluation of 3-[(18)F]fluoro-5-(2-pyridinylethynyl)benzonitrile as a PET radiotracer for imaging metabotropic glutamate receptor subtype 5.

PubMed

Wang, Ji-Quan; Tueckmantel, Werner; Zhu, Aijun; Pellegrino, Daniela; Brownell, Anna-Liisa

2007-12-01

The metabotropic glutamate receptor subtype 5 (mGluR5) has been reported to be implicated in various neurological disorders in the central nervous system. To investigate physiological and pathological functions of mGluR5, noninvasive imaging in a living body with PET technology and an mGluR5-specific radiotracer is urgently needed. Here, we report the synthesis of 3-[(18)F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([(18)F]FPEB) through a convenient thermal reaction as a highly specific PET radiotracer for mGluR5. The precursor and standard compounds were prepared by a coupling reaction catalyzed by palladium. Radiosynthesis of [(18)F]FPEB was performed using nitro as a leaving group replaced by [(18)F]fluoride under conventional heating condition. Biodistribution, metabolite, and microPET studies were performed using Sprague-Dawley rats. Upto 30 mCi of [(18)F]FPEB was obtained with a radiochemical yield of 5% and a specific activity of 1900 +/- 200 mCi/mumol at the end of syntheses. Biodistribution showed rapid clearance from the blood pool and fast and steady accumulation of radioactivity into the brain. Metabolite studies indicated that only 22% of [(18)F]FPEB remained in the blood system 10 min after administration, and that a metabolite existed which was much more polar than the parent tracer. MicroPET studies demonstrated that [(18)F]FPEB accumulated specifically in mGluR5-rich regions of the brain such as striatum and hippocampus, and that blockade with 2-methyl-6-(2-phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) substantially reduced the activity uptake in these regions. Selectivity was investigated by blockage with 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-caroxamide (YM-298198), a specific antagonist for mGluR1. [(18)F]FPEB was prepared conveniently and showed high specificity and selectivity toward mGluR5. It possesses the potential to be used in human studies to evaluate mGluR5 functions in various neurological disorders. (c) 2007 Wiley-Liss, Inc.

In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA).

PubMed

Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P; Kovács, Tünde; Bai, Péter; Trencsényi, György

2017-01-01

The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68 Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 ( 68 Ga-NODAGA-PCA). The melanin specificity of 68 Ga-NODAGA-PCA was tested in vitro , ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68 Ga-NODAGA-PCA and 18 FDG tracers. 68 Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68 Ga-NODAGA-PCA uptake of B16-F10 cells was significantly ( p ≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly ( p ≤0.01) higher 68 Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18 FDG and 68 Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly ( p ≤0.05 and p ≤0.01) higher using 68 Ga-NODAGA-PCA than the 18 FDG accumulation. Our novel radiotracer 68 Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68 Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo .

In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA)

PubMed Central

Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P.; Kovács, Tünde; Bai, Péter; Trencsényi, György

2017-01-01

Purpose: The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Methods: Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 (68Ga-NODAGA-PCA). The melanin specificity of 68Ga-NODAGA-PCA was tested in vitro, ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68Ga-NODAGA-PCA and 18FDG tracers. Results: 68Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly (p≤0.01) higher 68Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18FDG and 68Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly (p≤0.05 and p≤0.01) higher using 68Ga-NODAGA-PCA than the 18FDG accumulation. Conclusion: Our novel radiotracer 68Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo. PMID:28382139

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies.

PubMed

Convert, Laurence; Lebel, Réjean; Gascon, Suzanne; Fontaine, Réjean; Pratte, Jean-François; Charette, Paul; Aimez, Vincent; Lecomte, Roger

2016-09-01

Small-animal nuclear imaging modalities have become essential tools in the development process of new drugs, diagnostic procedures, and therapies. Quantification of metabolic or physiologic parameters is based on pharmacokinetic modeling of radiotracer biodistribution, which requires the blood input function in addition to tissue images. Such measurements are challenging in small animals because of their small blood volume. In this work, we propose a microfluidic counting system to monitor rodent blood radioactivity in real time, with high efficiency and small detection volume (∼1 μL). A microfluidic channel is built directly above unpackaged p-i-n photodiodes to detect β-particles with maximum efficiency. The device is embedded in a compact system comprising dedicated electronics, shielding, and pumping unit controlled by custom firmware to enable measurements next to small-animal scanners. Data corrections required to use the input function in pharmacokinetic models were established using calibrated solutions of the most common PET and SPECT radiotracers. Sensitivity, dead time, propagation delay, dispersion, background sensitivity, and the effect of sample temperature were characterized. The system was tested for pharmacokinetic studies in mice by quantifying myocardial perfusion and oxygen consumption with (11)C-acetate (PET) and by measuring the arterial input function using (99m)TcO4 (-) (SPECT). Sensitivity for PET isotopes reached 20%-47%, a 2- to 10-fold improvement relative to conventional catheter-based geometries. Furthermore, the system detected (99m)Tc-based SPECT tracers with an efficiency of 4%, an outcome not possible through a catheter. Correction for dead time was found to be unnecessary for small-animal experiments, whereas propagation delay and dispersion within the microfluidic channel were accurately corrected. Background activity and sample temperature were shown to have no influence on measurements. Finally, the system was successfully used in animal studies. A fully operational microfluidic blood-counting system for preclinical pharmacokinetic studies was developed. Microfluidics enabled reliable and high-efficiency measurement of the blood concentration of most common PET and SPECT radiotracers with high temporal resolution in small blood volume. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Indepth diagnosis of a secondary clarifier by the application of radiotracer technique and numerical modeling.

PubMed

Kim, H S; Shin, M S; Jang, D S; Jung, S H

2006-01-01

To make an indepth diagnosis of a full-scale rectangular secondary clarifier, an experimental and numerical study has been performed in a wastewater treatment facility. Calculation results by the numerical model with the adoption of the SIMPLE algorithm of Patankar are validated with radiotracer experiments. Emphasis is given to the prediction of residence time distribution (RTD) curves. The predicted RTD profiles are in good agreement with the experimental RTD curves at the upstream and center sections except for the withdrawal zone of the complex effluent weir structure. The simulation results predict successfully the well-known flow characteristics of each stage such as the waterfall phenomenon at the front of the clarifier, the bottom density current and the surface return flow in the settling zone, and the upward flow in the exit zone. The detailed effects of density current are thoroughly investigated in terms of high SS loading and temperature difference between influent and ambient fluid. The program developed in this study shows the high potential to assist in the design and determination of optimal operating conditions to improve effluent quality in a full-scale secondary clarifier.

Novel 18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates.

PubMed

Li, Songye; Cai, Zhengxin; Zheng, Ming-Qiang; Holden, Daniel; Naganawa, Mika; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Kapinos, Michael; Lara-Jaime, Teresa; Navarro, Antonio; Huang, Yiyun

2018-01-01

The κ-opioid receptor (KOR) has been implicated in depression, addictions, and other central nervous system disorders and, thus, is an important target for drug development. We previously developed several 11 C-labeled PET radiotracers for KOR imaging in humans. Here we report the synthesis and evaluation of 18 F-LY2459989 as the first 18 F-labeled KOR antagonist radiotracer in nonhuman primates and its comparison with 11 C-LY2459989. Methods: The novel radioligand 18 F-LY2459989 was synthesized by 18 F displacement of a nitro group or an iodonium ylide. PET scans in rhesus monkeys were obtained on a small-animal scanner to assess the pharmacokinetic and in vivo binding properties of the ligand. Metabolite-corrected arterial activity curves were measured and used as input functions in the analysis of brain time-activity curves and the calculation of binding parameters. Results: With the iodonium ylide precursor, 18 F-LY2459989 was prepared at high radiochemical yield (36% ± 7% [mean ± SD]), radiochemical purity (>99%), and mean molar activity (1,175 GBq/μmol; n = 6). In monkeys, 18 F-LY2459989 was metabolized at a moderate rate, with a parent fraction of approximately 35% at 30 min after injection. Fast and reversible kinetics were observed, with a regional peak uptake time of less than 20 min. Pretreatment with the selective KOR antagonist LY2456302 (0.1 mg/kg) decreased the activity level in regions with high levels of binding to that in the cerebellum, thus demonstrating the binding specificity and selectivity of 18 F-LY2459989 in vivo. Regional time-activity curves were well fitted by the multilinear analysis 1 kinetic model to derive reliable estimates of regional distribution volumes. With the cerebellum as the reference region, regional binding potentials were calculated and ranked as follows: cingulate cortex > insula > caudate/putamen > frontal cortex > temporal cortex > thalamus, consistent with the reported KOR distribution in the monkey brain. Conclusion: The evaluation of 18 F-LY2459989 in nonhuman primates demonstrated many attractive imaging properties: fast tissue kinetics, specific and selective binding to the KOR, and high specific binding signals. A side-by-side comparison of 18 F-LY2459989 and 11 C-LY2459989 indicated similar kinetic and binding profiles for the 2 radiotracers. Taken together, the results indicated that 18 F-LY2459989 appears to be an excellent PET radiotracer for the imaging and quantification of the KOR in vivo. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

The effect of bi-terminal PEGylation of an integrin  α vβ 6-targeted 18F peptide on pharmacokinetics and tumor uptake

DOE PAGES

Hausner, Sven H.; Bauer, Nadine; Hu, Lina Y.; ...

2015-03-26

Radiotracers based on the peptide A20FMDV2 selectively target the cell surface receptor integrin α vβ 6. This integrin has been identified as a prognostic indicator correlating with the severity of disease for several challenging malignancies. In previous studies of A20FMDV2 peptides labeled with 4- 18F-fluorobenzoic acid ( 18F-FBA), we have shown that the introduction of poly(ethylene glycol) (PEG) improves pharmacokinetics, including increased uptake in α vβ 6-expressing tumors. The present study evaluated the effect of site-specific C-terminal or dual (N- and C-terminal) PEGylation, yielding 18F-FBA-A20FMDV2-PEG 28 (4) and 18F-FBA-PEG 28-A20FMDV2-PEG 28 (5), on α vβ 6-targeted tumor uptake and pharmacokinetics.more » The results are compared with 18F-FBA–labeled A20FMDV2 radiotracers (1–3) bearing either no PEG or different PEG units at the N terminus. The radiotracers were prepared and radiolabeled on solid phase. Using 3 cell lines, DX3puroβ6 (α vβ 6+), DX3puro (α vβ 6–), and BxPC-3 (α vβ 6+), we evaluated the radiotracers in vitro (serum stability; cell binding and internalization) and in vivo in mouse models bearing paired DX3puroβ6–DX3puro and, for 5, BxPC-3 xenografts. Here, the size and location of the PEG units significantly affected α vβ 6 targeting and pharmacokinetics. Although the C-terminally PEGylated 4 showed some improvements over the un-PEGylated 18F-FBA-A20FMDV2 (1), it was the bi-terminally PEGylated 5 that displayed the more favorable combination of high α vβ 6 affinity, selectivity, and pharmacokinetic profile. In vitro, 5 bound to α vβ 6-expressing DX3puroβ6 and BxPC-3 cells with 60.5% ± 3.3% and 48.8% ± 8.3%, respectively, with a significant fraction of internalization (37.2% ± 4.0% and 37.6% ± 4.1% of total radioactivity, respectively). By comparison, in the DX3puro control 5 showed only 3.0% ± 0.5% binding and 0.9% ± 0.2% internalization. In vivo, 5 maintained high, α vβ 6-directed binding in the paired DX3puroβ6–DX3puro model (1 h: DX3puroβ6, 2.3 ± 0.2 percentage injected dose per gram [%ID/g]; DX3puroβ6/DX3puro ratio, 6.5:1; 4 h: 10.7:1). In the pancreatic BxPC-3 model, uptake was 4.7 ± 0.9 %ID/g (1 h) despite small tumor sizes (20–80 mg). In conclusion, the bi-PEGylated radiotracer 5 showed a greatly improved pharmacokinetic profile, beyond what was predicted from individual N- or C-terminal PEGylation. It appears that the 2 PEG units acted synergistically to result in an improved metabolic profile including high α vβ 6+ tumor uptake and retention.« less

The effect of bi-terminal PEGylation of an integrin  α vβ 6-targeted 18F peptide on pharmacokinetics and tumor uptake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hausner, Sven H.; Bauer, Nadine; Hu, Lina Y.

Radiotracers based on the peptide A20FMDV2 selectively target the cell surface receptor integrin α vβ 6. This integrin has been identified as a prognostic indicator correlating with the severity of disease for several challenging malignancies. In previous studies of A20FMDV2 peptides labeled with 4- 18F-fluorobenzoic acid ( 18F-FBA), we have shown that the introduction of poly(ethylene glycol) (PEG) improves pharmacokinetics, including increased uptake in α vβ 6-expressing tumors. The present study evaluated the effect of site-specific C-terminal or dual (N- and C-terminal) PEGylation, yielding 18F-FBA-A20FMDV2-PEG 28 (4) and 18F-FBA-PEG 28-A20FMDV2-PEG 28 (5), on α vβ 6-targeted tumor uptake and pharmacokinetics.more » The results are compared with 18F-FBA–labeled A20FMDV2 radiotracers (1–3) bearing either no PEG or different PEG units at the N terminus. The radiotracers were prepared and radiolabeled on solid phase. Using 3 cell lines, DX3puroβ6 (α vβ 6+), DX3puro (α vβ 6–), and BxPC-3 (α vβ 6+), we evaluated the radiotracers in vitro (serum stability; cell binding and internalization) and in vivo in mouse models bearing paired DX3puroβ6–DX3puro and, for 5, BxPC-3 xenografts. Here, the size and location of the PEG units significantly affected α vβ 6 targeting and pharmacokinetics. Although the C-terminally PEGylated 4 showed some improvements over the un-PEGylated 18F-FBA-A20FMDV2 (1), it was the bi-terminally PEGylated 5 that displayed the more favorable combination of high α vβ 6 affinity, selectivity, and pharmacokinetic profile. In vitro, 5 bound to α vβ 6-expressing DX3puroβ6 and BxPC-3 cells with 60.5% ± 3.3% and 48.8% ± 8.3%, respectively, with a significant fraction of internalization (37.2% ± 4.0% and 37.6% ± 4.1% of total radioactivity, respectively). By comparison, in the DX3puro control 5 showed only 3.0% ± 0.5% binding and 0.9% ± 0.2% internalization. In vivo, 5 maintained high, α vβ 6-directed binding in the paired DX3puroβ6–DX3puro model (1 h: DX3puroβ6, 2.3 ± 0.2 percentage injected dose per gram [%ID/g]; DX3puroβ6/DX3puro ratio, 6.5:1; 4 h: 10.7:1). In the pancreatic BxPC-3 model, uptake was 4.7 ± 0.9 %ID/g (1 h) despite small tumor sizes (20–80 mg). In conclusion, the bi-PEGylated radiotracer 5 showed a greatly improved pharmacokinetic profile, beyond what was predicted from individual N- or C-terminal PEGylation. It appears that the 2 PEG units acted synergistically to result in an improved metabolic profile including high α vβ 6+ tumor uptake and retention.« less

Analysis of position-dependent Compton scatter in scintimammography with mild compression

NASA Astrophysics Data System (ADS)

Williams, M. B.; Narayanan, D.; More, M. J.; Goodale, P. J.; Majewski, S.; Kieper, D. A.

2003-10-01

In breast scintigraphy using /sup 99m/Tc-sestamibi the relatively low radiotracer uptake in the breast compared to that in other organs such as the heart results in a large fraction of the detected events being Compton scattered gamma-rays. In this study, our goal was to determine whether generalized conclusions regarding scatter-to-primary ratios at various locations within the breast image are possible, and if so, to use them to make explicit scatter corrections to the breast scintigrams. Energy spectra were obtained from patient scans for contiguous regions of interest (ROIs) centered left to right within the image of the breast, and extending from the chest wall edge of the image to the anterior edge. An anthropomorphic torso phantom with fillable internal organs and a compressed-shape breast containing water only was used to obtain realistic position-dependent scatter-only spectra. For each ROI, the measured patient energy spectrum was fitted with a linear combination of the scatter-only spectrum from the anthropomorphic phantom and the scatter-free spectrum from a point source. We found that although there is a very strong dependence on location within the breast of the scatter-to-primary ratio, the spectra are well modeled by a linear combination of position-dependent scatter-only spectra and a position-independent scatter-free spectrum, resulting in a set of position-dependent correction factors. These correction factors can be used along with measured emission spectra from a given breast to correct for the Compton scatter in the scintigrams. However, the large variation among patients in the magnitude of the position-dependent scatter makes the success of universal correction approaches unlikely.

Method of using 5,10,15,20-tetrakis(carboxyphenyl)porphine for detecting cancers of the lung

DOEpatents

Cole, Dean A.; Moody, III, David C.; Ellinwood, L. Edward; Klein, M. Gerard

1992-01-01

Method using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with .sup.67 Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the situs thereof by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the .sup.67 Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques cna be used to locate the malignant tissue mass.

Method using 5,10,15,20-tetrakis(4-carboxyphenyl)porphine for treating cancers of the lung

DOEpatents

Cole, Dean A.; Moody, III, David C.; Ellinwood, L. Edward; Klein, M. Gerard

1995-01-01

Method using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with .sup.67 Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the situs thereof by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the .sup.67 Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques can be used to locate the malignant tissue mass.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parra, Pamela Ochoa, E-mail: lapochoap@unal.edu.co; Veloza, Stella

The radiotracer called {sup 68}Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) is a novel radiophar-maceutical for the detection of prostate cancer lesions by positron emission tomography (PET) imaging. Setting up a cost-effective manual synthesis of this radiotracer and making its clinical translation in Colombia will require two important elements: the evaluation of the procedure to yield a consistent product, meeting standards of radio-chemical purity and low toxicity and then, the evaluation of the radiation dosimetry. In this paper a protocol to extrapolate the biokinetic model made in normal mice to humans by using the computer software for internal dose assessment OLINDA/EXM® is presented asmore » an accurate and standardized method for the calculation of radiation dosimetry estimates.« less

Imaging Prostate Cancer With Prostate-Specific Membrane Antigen PET/CT and PET/MRI: Current and Future Applications.

PubMed

Hope, Thomas A; Afshar-Oromieh, Ali; Eiber, Matthias; Emmett, Louise; Fendler, Wolfgang P; Lawhn-Heath, Courtney; Rowe, Steven P

2018-06-27

The purpose of this article is to describe the large number of radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET, which is becoming a central tool in the staging of prostate cancer. PSMA PET is a highly promising modality for the staging of prostate cancer because of its higher detection rate compared with that of conventional imaging. Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET findings frequently lead to changes in management. It is imperative that subsequent treatment changes be evaluated to show improved outcomes. PSMA PET also has potential applications, including patient selection for PSMA-based radioligand therapy and evaluation of treatment response.

A novel radioguided surgery technique exploiting β- decays

NASA Astrophysics Data System (ADS)

Camillocci, E. Solfaroli; Baroni, G.; Bellini, F.; Bocci, V.; Collamati, F.; Cremonesi, M.; De Lucia, E.; Ferroli, P.; Fiore, S.; Grana, C. M.; Marafini, M.; Mattei, I.; Morganti, S.; Paganelli, G.; Patera, V.; Piersanti, L.; Recchia, L.; Russomando, A.; Schiariti, M.; Sarti, A.; Sciubba, A.; Voena, C.; Faccini, R.

2014-03-01

The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with β+-emitting radio-tracers has been suggested in literature. Here we propose the use of β--emitting radio-tracers and β- probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a β- probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.

A Novel Way To Radiolabel Human Butyrylcholinesterase for Positron Emission Tomography through Irreversible Transfer of the Radiolabeled Moiety.

PubMed

Sawatzky, Edgar; Al-Momani, Ehab; Kobayashi, Ryohei; Higuchi, Takahiro; Samnick, Samuel; Decker, Michael

2016-07-19

The enzyme butyrylcholinesterase (BChE) is known to be involved in the detoxification of xenobiotics in blood plasma and is associated with the progress of neurodegenerative disorders, diabetes type 2, obesity, and diseases of the cardiovascular system. In the present study, we developed carbamate-based inhibitors serving as positron emission tomography (PET) radiotracers with (18) F and (11) C as radioisotopes to visualize BChE distribution. These inhibitors are radiolabeled at the carbamate site and transfer this moiety onto BChE, which thus results in covalent and permanent radiolabeling of the enzyme. There are no comparable radiotracers for cholinesterases described to date. By ex vivo autoradiography experiments on mice brain slices and kinetic investigations, selective and covalent transfer of the radiolabeled carbamate moiety onto BChE was proven. These tracers might provide high resolution of BChE distribution in vivo to enable investigations into the pathophysiological mechanisms of diseases associated with alterations in BChE occurrence. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel radioguided surgery technique exploiting β(-) decays.

PubMed

Camillocci, E Solfaroli; Baroni, G; Bellini, F; Bocci, V; Collamati, F; Cremonesi, M; De Lucia, E; Ferroli, P; Fiore, S; Grana, C M; Marafini, M; Mattei, I; Morganti, S; Paganelli, G; Patera, V; Piersanti, L; Recchia, L; Russomando, A; Schiariti, M; Sarti, A; Sciubba, A; Voena, C; Faccini, R

2014-03-20

The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with β(+)-emitting radio-tracers has been suggested in literature. Here we propose the use of β(-)-emitting radio-tracers and β(-) probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a β(-) probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.

Single photon emission computed tomography/positron emission tomography imaging and targeted radionuclide therapy of melanoma: new multimodal fluorinated and iodinated radiotracers.

PubMed

Maisonial, Aurélie; Kuhnast, Bertrand; Papon, Janine; Boisgard, Raphaël; Bayle, Martine; Vidal, Aurélien; Auzeloux, Philippe; Rbah, Latifa; Bonnet-Duquennoy, Mathilde; Miot-Noirault, Elisabeth; Galmier, Marie-Josèphe; Borel, Michèle; Askienazy, Serge; Dollé, Frédéric; Tavitian, Bertrand; Madelmont, Jean-Claude; Moins, Nicole; Chezal, Jean-Michel

2011-04-28

This study reports a series of 14 new iodinated and fluorinated compounds offering both early imaging ((123)I, (124)I, (18)F) and systemic treatment ((131)I) of melanoma potentialities. The biodistribution of each (125)I-labeled tracer was evaluated in a model of melanoma B16F0-bearing mice, using in vivo serial γ scintigraphic imaging. Among this series, [(125)I]56 emerged as the most promising compound in terms of specific tumoral uptake and in vivo kinetic profile. To validate our multimodality concept, the radiosynthesis of [(18)F]56 was then optimized and this radiotracer has been successfully investigated for in vivo PET imaging of melanoma in B16F0- and B16F10-bearing mouse model. The therapeutic efficacy of [(131)I]56 was then evaluated in mice bearing subcutaneous B16F0 melanoma, and a significant slow down in tumoral growth was demonstrated. These data support further development of 56 for PET imaging ((18)F, (124)I) and targeted radionuclide therapy ((131)I) of melanoma using a single chemical structure.

Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

PubMed

Joice, Gregory A; Rowe, Steven P; Pienta, Kenneth J; Gorin, Michael A

2017-11-01

The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

A novel radioguided surgery technique exploiting β− decays

PubMed Central

Camillocci, E. Solfaroli; Baroni, G.; Bellini, F.; Bocci, V.; Collamati, F.; Cremonesi, M.; De Lucia, E.; Ferroli, P.; Fiore, S.; Grana, C. M.; Marafini, M.; Mattei, I.; Morganti, S.; Paganelli, G.; Patera, V.; Piersanti, L.; Recchia, L.; Russomando, A.; Schiariti, M.; Sarti, A.; Sciubba, A.; Voena, C.; Faccini, R.

2014-01-01

The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with β+-emitting radio-tracers has been suggested in literature. Here we propose the use of β−-emitting radio-tracers and β− probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a β− probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible. PMID:24646766

Uptake of 18F-DCFPyL in Paget's Disease of Bone, an Important Potential Pitfall in Clinical Interpretation of PSMA PET Studies.

PubMed

Rowe, Steven P; Deville, Curtiland; Paller, Channing; Cho, Steve Y; Fishman, Elliot K; Pomper, Martin G; Ross, Ashley E; Gorin, Michael A

2015-12-01

Prostate-specific membrane antigen (PSMA)-targeted PET imaging is an emerging technique for evaluating patients with prostate cancer (PCa) in a variety of clinical contexts. As with any new imaging modality, there are interpretive pitfalls that are beginning to be recognized. In this image report, we describe the findings in a 63-year-old male with biochemically recurrent PCa after radical prostatectomy who was imaged with 18 F-DCFPyL, a small molecule inhibitor of PSMA. Diffuse radiotracer uptake was noted throughout the sacrum, corresponding to imaging findings on contrast-enhanced CT, bone scan, and pelvic MRI consistent with Paget's disease of bone. The uptake of 18 F-DCFPyL in Paget's disease is most likely due to hyperemia and increased radiotracer delivery. In light of the overlap in patients affected by PCa and Paget's, it is important for nuclear medicine physicians and radiologists interpreting PSMA PET/CT scans to be aware of the potential for this diagnostic pitfall. Correlation to findings on conventional imaging such as diagnostic CT and bone scan can help confirm the diagnosis.

Radio-methyl vorozole and methods for making and using the same

DOEpatents

Kim, Sung Won; Biegon, Anat; Fowler, Joanna S.

2014-08-12

Radiotracer vorozole compounds for in vivo and in vitro assaying, studying and imaging cytochrome P450 aromatase enzymes in humans, animals, and tissues and methods for making and using the same are provided. [N-radio-methyl] vorozole substantially separated from an N-3 radio-methyl isomer of vorozole is provided. Separation is accomplished through use of chromatography resins providing multiple mechanisms of selectivity.

Radio-methyl vorozole and methods for making and using the same

DOEpatents

Kim, Sung Won; Biegon, Anat; Fowler, Joanna S.

2014-08-05

Radiotracer vorozole compounds for in vivo and in vitro assaying, studying and imaging cytochrome P450 aromatase enzymes in humans, animals, and tissues and methods for making and using the same are provided. [N-radio-methyl] vorozole substantially separated from an N-3 radio-methyl isomer of vorozole is provided. Separation is accomplished through use of chromatography resins providing multiple mechanisms of selectivity.

Comparative evaluation of p5+14 with SAP and peptide p5 by dual-energy SPECT imaging of mice with AA amyloidosis.

PubMed

Martin, Emily B; Williams, Angela; Richey, Tina; Stuckey, Alan; Heidel, R Eric; Kennel, Stephen J; Wall, Jonathan S

2016-03-03

Amyloidosis is a protein-misfolding disorder characterized by the extracellular deposition of amyloid, a complex matrix composed of protein fibrils, hyper-sulphated glycosaminoglycans and serum amyloid P component (SAP). Accumulation of amyloid in visceral organs results in the destruction of tissue architecture leading to organ dysfunction and failure. Early differential diagnosis and disease monitoring are critical for improving patient outcomes; thus, whole body amyloid imaging would be beneficial in this regard. Non-invasive molecular imaging of systemic amyloid is performed in Europe by using iodine-123-labelled SAP; however, this tracer is not available in the US. Therefore, we evaluated synthetic, poly-basic peptides, designated p5 and p5+14, as alternative radiotracers for detecting systemic amyloidosis. Herein, we perform a comparative effectiveness evaluation of radiolabelled peptide p5+14 with p5 and SAP, in amyloid-laden mice, using dual-energy SPECT imaging and tissue biodistribution measurements. All three radiotracers selectively bound amyloid in vivo; however, p5+14 was significantly more effective as compared to p5 in certain organs. Moreover, SAP bound principally to hepatosplenic amyloid, whereas p5+14 was broadly distributed in numerous amyloid-laden anatomic sites, including the spleen, liver, pancreas, intestines and heart. These data support clinical validation of p5+14 as an amyloid radiotracer for patients in the US.

Advances in PET myocardial perfusion imaging: F-18 labeled tracers.

PubMed

Rischpler, Christoph; Park, Min-Jae; Fung, George S K; Javadi, Mehrbod; Tsui, Benjamin M W; Higuchi, Takahiro

2012-01-01

Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI.

Free Radical Polymerization of Styrene: A Radiotracer Experiment

ERIC Educational Resources Information Center

Mazza, R. J.

1975-01-01

Describes an experiment designed to acquaint the chemistry student with polymerization reactions, vacuum techniques, liquid scintillation counting, gas-liquid chromatography, and the handling of radioactive materials. (MLH)

Molt-related susceptibility and regenerative limb growth as sensitive indicators of aquatic pollutant toxicity to crustaceans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, K.R.; Conklin, P.J.

1986-01-01

The study evaluated the comparative toxicity of various pollutants to intermolt and molting grass shrimp (Palaemonetes pugio). Most of the tested materials (pentachlorophenol, tetrachlorophenols, trichlorophenols, methylenebis dichlorophenol, dibutyl phthalate, chromium, and drilling mud) were more toxic to molting shrimp than to intermolt shrimp. Radio-tracer studies with 2,4,5-trichlorophenol and pentachlorophenol indicated that the increased susceptibility of newly molted shrimp is linked to increased pollutant uptake.

Application of Timepix3 based CdTe spectral sensitive photon counting detector for PET imaging

NASA Astrophysics Data System (ADS)

Turecek, Daniel; Jakubek, Jan; Trojanova, Eliska; Sefc, Ludek; Kolarova, Vera

2018-07-01

Positron emission tomography (PET) is a nuclear medicine functional imaging technique. It is used in clinical oncology (medical imaging of tumors and the search for metastases), and pre-clinical studies using animals. PET uses small amounts of radioactive materials (radiotracers) and a special photon sensitive camera. Most of these cameras use scintillators with photomultipliers as detectors. However, these detectors have limited energy sensitivity and large pixels. Therefore, the false signal caused by a scattering poses a significant problem. In this work we study properties of position, energy and time sensitive semiconductor detector of Timepix3 type and its applicability for PET measurements. This work presents an initial study and evaluation of two Timepix3 detectors with 2 mm thick CdTe sensors used in simplified geometry for PET imaging. The study is performed on 2 samples - a capillary tube and a cylindrical plexiglass phantom with cavities. Both samples are filled with fluodeoxyglucose (FDG) solution that is used as a radiotracer. The Timepix3 offers better properties compared to conventional detectors - high granularity (55 μm pixel pitch), good energy resolution (1 keV at 60 keV) and sufficient time resolution (1.6 ns). The spectral sensitivity of Timepix3 together with coincidence/anticoincidence technique allows for significant reduction of background signal caused by Compton scattering and internal X-ray fluorescence of Cd and Te.

Method of using 5,10,15,20-tetrakis(carboxyphenyl)porphine for detecting cancers of the lung

DOEpatents

Cole, D.A.; Moody, D.C. III; Ellinwood, L.E.; Klein, M.G.

1992-11-10

A method is described for using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with [sup 67]Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the lungs by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the [sup 67]Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques can be used to locate the malignant tissue mass. 1 figure.

Improving cancer treatment with cyclotron produced radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M. Finn, R.D.

1992-08-04

This report describes the author's continuing long term goal of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The program has 3 interactive components: Radiochemistry /Cyclotron; Pharmacology; and Immunology. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Cyclotron section under the DOE grant during the 1989--1992 grant period, will be employed in the Pharmacology and Immunology sections of the DOE grant during the 1992--1995 grant period. The development of novel radionuclides and tracers is of course usefulmore » in and of itself, but their utility is greatly enhanced by the interaction with the immunology and pharmacology components of the program.« less

Nanoparticles and Radiotracers: Advances toward Radio-Nanomedicine

PubMed Central

Pratt, Edwin C.; Shaffer, Travis M.; Grimm, Jan

2016-01-01

Here, we cover the convergence of radiochemistry for imaging and therapy with advances in nanoparticle (NP) design for biomedical applications. We first explore NP properties relevant for therapy and theranostics and emphasize the need for biocompatibility. We then explore radionuclide-imaging modalities such as Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Cerenkov Luminescence (CL) with examples utilizing radiolabeled NP for imaging. PET and SPECT have served as diagnostic workhorses in the clinic, while preclinical NP design examples of multimodal imaging with radiotracers show promise in imaging and therapy. CL expands the types of radionuclides beyond PET and SPECT tracers to include high-energy electrons (β−) for imaging purposes. These advances in radionanomedicine will be discussed, showing the potential for radiolabeled NPs as theranostic agents. PMID:27006133

Application of Palladium-Mediated 18F-Fluorination to PET Radiotracer Development: Overcoming Hurdles to Translation

PubMed Central

Kamlet, Adam S.; Neumann, Constanze N.; Lee, Eunsung; Carlin, Stephen M.; Moseley, Christian K.; Stephenson, Nickeisha; Hooker, Jacob M.; Ritter, Tobias

2013-01-01

New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging–an important milestone on the path to human PET imaging. The method, which transforms [18F]fluoride into an electrophilic fluorination reagent, provides access to aryl–18F bonds that would be challenging to synthesize via conventional radiochemistry methods. PMID:23554994

18F-labeled norepinephrine transporter tracer [18F]NS12137: radiosynthesis and preclinical evaluation.

PubMed

Kirjavainen, Anna K; Forsback, Sarita; López-Picón, Francisco R; Marjamäki, Päivi; Takkinen, Jatta; Haaparanta-Solin, Merja; Peters, Dan; Solin, Olof

2018-01-01

Several psychiatric and neurodegenerative diseases are associated with malfunction of brain norepinephrine transporter (NET). However, current clinical evaluations of NET function are limited by the lack of sufficiently sensitive methods of detection. To this end, we have synthesized exo-3-[(6-[ 18 F]fluoro-2-pyridyl)oxy]-8-azabicyclo[3.2.1]-octane ([ 18 F]NS12137) as a radiotracer for positron emission tomography (PET) and have demonstrated that it is highly specific for in vivo detection of NET-rich regions of rat brain tissue. We applied two methods of electrophilic, aromatic radiofluorination of the precursor molecule, exo-3-[(6-trimethylstannyl-2-pyridyl)oxy]-8-azabicyclo-[3.2.1]octane-8-carboxylate: (1) direct labeling with [ 18 F]F 2 , and (2) labeling with [ 18 F]Selectfluor, a derivative of [ 18 F]F 2 , using post-target produced [ 18 F]F 2 . The time-dependent distribution of [ 18 F]NS12137 in brain tissue of healthy, adult Sprague-Dawley rats was determined by ex vivo autoradiography. The specificity of [ 18 F]NS12137 binding was demonstrated on the basis of competitive binding by nisoxetine, a known NET antagonist of high specificity. [ 18 F]NS12137 was successfully synthesized with radiochemical yields of 3.9% ± 0.3% when labeled with [ 18 F]F 2 and 10.2% ± 2.7% when labeled with [ 18 F]Selectfluor. The molar activity of radiotracer was 8.8 ± 0.7 GBq/μmol with [ 18 F]F 2 labeling and 6.9 ± 0.4 GBq/μmol with [ 18 F]Selectfluor labeling at the end of synthesis of [ 18 F]NS12137. Uptake of [ 18 F]NS12137 in NET-rich areas in rat brain was demonstrated with the locus coeruleus (LCoe) having the highest regional uptake. Prior treatment of rats with nisoxetine showed no detectable [ 18 F]NS12137 in the LCoe. Analyses of whole brain samples for radiometabolites showed only the parent compound [ 18 F]NS12137. Uptake of 18 F-radioactivity in bone increased with time. The two electrophilic 18 F-labeling methods proved to be suitable for synthesis of [ 18 F]NS12137 with the [ 18 F]Selectfluor method providing an approximate three-fold higher yield than the [ 18 F]F 2 method. As an electrostatically neutral radiotracer [ 18 F]NS12137 crosses the blood-brain barrier and enabled specific labeling of NET-rich regions of rat brain tissue with the highest concentration in the LCoe. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiosynthesis and in Vivo Evaluation of [11C]A1070722, a High Affinity GSK-3 PET Tracer in Primate Brain.

PubMed

Prabhakaran, Jaya; Zanderigo, Francesca; Sai, Kiran Kumar Solingapuram; Rubin-Falcone, Harry; Jorgensen, Matthew J; Kaplan, Jay R; Mintz, Akiva; Mann, J John; Kumar, J S Dileep

2017-08-16

Dysfunction of glycogen synthase kinase 3 (GSK-3) is implicated in the etiology of Alzheimer's disease, Parkinson's disease, diabetes, pain, and cancer. A radiotracer for functional positron emission tomography (PET) imaging could be used to study the kinase in brain disorders and to facilitate the development of small molecule inhibitors of GSK-3 for treatment. At present, there is no target-specific or validated PET tracer available for the in vivo monitoring of GSK-3. We radiolabeled the small molecule inhibitor [ 11 C]1-(7-methoxy- quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)urea ([ 11 C]A1070722) with high affinity to GSK-3 (K i = 0.6 nM) in excellent radiochemical yield. PET imaging experiments in anesthetized vervet/African green monkey exhibited that [ 11 C]A1070722 penetrated the blood-brain barrier (BBB) and accumulated in brain regions, with highest radioactivity binding in frontal cortex followed by parietal cortex and anterior cingulate, and with the lowest bindings found in caudate, putamen, and thalamus, similarly to the known distribution of GSK-3 in human brain. Our studies suggest that [ 11 C]A1070722 can be a potential PET radiotracer for the in vivo quantification of GSK-3 in brain.

Effects of targeting moiety, linker, bifunctional chelator, and molecular charge on biological properties of 64Cu-labeled triphenylphosphonium cations.

PubMed

Kim, Young-Seung; Yang, Chang-Tong; Wang, Jianjun; Wang, Lijun; Li, Zi-Bo; Chen, Xiaoyuan; Liu, Shuang

2008-05-22

In this report, we present the synthesis and evaluation of six new 64Cu-labeled triphenylphosphonium (TPP) cations. Biodistribution studies were performed using the athymic nude mice bearing U87MG human glioma xenografts to explore the impact of TPP moieties, linkers, bifunctional chelators (BFCs), and molecular charge on biological properties of 64Cu radiotracers. On the basis of the results from this study, it is concluded that (1) mTPP (tris(4-methoxyphenyl)phosphonium) is a better mitochondrion-targeting molecule than TPP and 3mTPP (tris(2,4,6-trimethoxyphenyl)phosphonium); (2) DO3A (1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid) and DO2A (1,4,7,10-tetraazacyclododecane-4,7-diacetic acid) are suitable BFCs for the 64Cu-labeling of TPP cations; (3) NOTA-Bn ( S-2-(4-thioureidobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid) has a significant adverse effect on the radiotracer tumor uptake and tumor-to-background ratios; and (4) monoanionic BFCs should be avoided to ensure that 64Cu chelate has a neutral or negative charge. Considering the tumor uptake and tumor/liver ratios, 64Cu(DO2A-xy-TPP)+ is the best candidate for more extensive evaluations in different tumor-bearing animal models.

The uterine blush. A potential false-positive in Meckel's scan interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fink-Bennett, D.

To determine the presence, prevalence, and clinical importance of /sup 99m/Tc pertechnetate uterine uptake, this retrospective analysis of 71 Meckel's scans was undertaken. Specifically, each study was evaluated for the presence of a focal accumulation of radiotracer cephalad to the bladder. Patients received an intravenous dose of 150 microCi/kg of /sup 99m/Tc pertechnetate. Each study consisted of 15 one minute anterior serial gamma camera images, and a 15, 30, and 60 minute anterior, right lateral and posterior scintiscan. Menstrual histories were obtained from all patients except two. No males (33/33), nor premenstrual (13/13), menopausal (4/4) or posthysterectomy (2/2) patients revealedmore » a uterine blush. Eleven of 15 patients (73%) with regular menses demonstrated a uterine blush. They were in the menstrual or secretory phases of their cycle. Four demonstrated no uterine uptake, had regular periods, but were in the proliferative phase of their cycle. Two with irregular periods, and one with no recorded menstrual history, manifested the blush. Radiotracer should be expected in the uterus during the menstrual and secretory phases of the menstrual cycle. It is a manifestation of a normal physiologic phenomenon, and must be recognized to prevent false-positive Meckel's scan interpretations.« less

A comparison of image contrast with 64Cu-labeled long circulating liposomes and 18F-FDG in a murine model of mammary carcinoma

PubMed Central

Wong, Andrew W; Ormsby, Eleanor; Zhang, Hua; Seo, Jai Woong; Mahakian, Lisa M; Caskey, Charles F; Ferrara, Katherine W

2013-01-01

Conjugation of the 64Cu PET radioisotope (t1/2 = 12.7 hours) to long circulating liposomes enables long term liposome tracking. To evaluate the potential clinical utility of this radiotracer in diagnosis and therapeutic guidance, we compare image contrast, tumor volume, and biodistribution of 64Cu-liposomes to metrics obtained with the dominant clinical tracer, 18F-FDG. Twenty four female FVB mice with MET1 mammary carcinoma tumor grafts were examined. First, serial PET images were obtained with the 18F-FDG radiotracer at 0.5 hours after injection and with the 64Cu-liposome radiotracer at 6, 18, 24, and 48 hours after injection (n = 8). Next, paired imaging and histology were obtained at four time points: 0.5 hours after 18F-FDG injection and 6, 24, and 48 hours after 64Cu-liposome injection (n = 16). Tissue biodistribution was assessed with gamma counting following necropsy and tumors were paraffin embedded, sectioned, and stained with hematoxylin and eosin. The contrast ratio of images obtained using 18F-FDG was 0.88 ± 0.01 (0.5 hours after injection), whereas with the 64Cu-liposome radiotracer the contrast ratio was 0.78 ± 0.01, 0.89 ± 0.01, 0.88 ± 0.01, and 0.94 ± 0.01 at 6, 18, 24, and 48 hours, respectively. Estimates of tumor diameter were comparable between 64Cu-liposomes and 18F-FDG, 64Cu-liposomes and necropsy, and 64Cu-liposomes and ultrasound with Pearson’s r-squared values of 0.79, 0.79, and 0.80, respectively. Heterogeneity of tumor tracer uptake was observed with both tracers, correlating with regions of necrosis on histology. The average tumor volume of 0.41 ± 0.05 cc measured with 64Cu-liposomes was larger than that estimated with 18F-FDG (0.28 ± 0.04 cc), with this difference apparently resulting primarily from accumulation of the radiolabeled particles in the pro-angiogenic tumor rim. The imaging of radiolabeled nanoparticles can facilitate tumor detection, identification of tumor margins, therapeutic evaluation and interventional guidance. PMID:23342299

Your Radiologist Explains Nuclear Medicine

MedlinePlus Videos and Cool Tools

... into the bloodstream, inhaled or swallowed. The radiotracer travels through the area being examined and gives off ... Radiology Info dot org. Thank you for your time! Spotlight Recently posted: Pancreatic Cancer The Limitations of ...

Development of Liposome Encapsulated Hemoglobin (LEH) and Studies of Hemorrhagic Shock by Use of Imaging Studies with Oxygen-15 and Other Radiotracers

DTIC Science & Technology

2004-09-01

hemoglobin in the oxy-hemoglobin state [Stratton 1988; Takeoka 1997]. 3) Decreased Vasoactivity. Because LEH has physical properties closer to red cells...in rabbit arterial segments. J Appl Physiol 82:1826-1835. [21] Sakai H, Horinouchi H, Masada Y, Takeoka S, Ikeda E, Takaori M, Kobayashi K and...4317-4325. [22] Sakai H, Horinouchi H, Tomiyama K, Ikeda E, Takeoka S, Kobayashi K and Tsuchida E (2001) Hemoglobin-vesicles as oxygen carriers

High efficiency microfluidic beta detector for pharmacokinetic studies in small animals

NASA Astrophysics Data System (ADS)

Convert, Laurence; Girard-Baril, Frédérique; Renaudin, Alan; Grondin, Étienne; Jaouad, Abdelatif; Aimez, Vincent; Charette, Paul; Lecomte, Roger

2011-10-01

New radiotracers are continuously being developed to improve diagnostic efficiency using Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). The characterization of their pharmacokinetics requires blood radioactivity monitoring over time during the scan and is very challenging in small animals because of the low volume of blood available. In this work, a prototype microfluidic blood counter made of a microchannel atop a silicon substrate containing PIN photodiodes is proposed to improve beta detection efficiency in a small volume by eliminating unnecessary interfaces between fluid and detector. A flat rectangular-shaped epoxy channel, 36 μm×1.26 mm cross section and 31.5 mm in length, was microfabricated over a die containing an array of 2×2 mm 2 PIN photodiodes, leaving only a few micrometers of epoxy floor layer between the fluid and the photodiode sensitive surface. This geometry leads to a quasi 2D source, optimizing geometrical detection efficiency that was estimated at 41% using solid angle calculation. CV- IV measurements were made at each fabrication step to confirm that the microchannel components had no significant effects on the diodes' electrical characteristics. The chip was wire-bonded to a PCB and connected to charge sensitive preamplifier and amplifier modules for pulse shaping. Energy spectra recorded for different isotopes showed continuous beta distribution for PET isotopes and monoenergetic conversion electron peaks for 99mTc. Absolute sensitivity was determined for the most popular PET and SPECT radioisotopes and ranged from 26% to 33% for PET tracers ( 18F, 13N, 11C, 68Ga) and more than 2% for 99mTc. Input functions were successfully simulated with 18F, confirming the setup's suitability for pharmacokinetic modeling of PET and SPECT radiotracers in animal experiments. By using standard materials and procedures, the fabrication process is well suited to on-chip microfluidic functionality, allowing full characterization of new radiotracers.

Initial in vivo PET imaging of 5-HT1A receptors with 3-[18F]mefway

PubMed Central

Wooten, Dustin W; Hillmer, Ansel T; Murali, Dhanabalan; Barnhart, Todd E; Thio, Joanne P; Bajwa, Alisha K; Bonab, Ali A; Normandin, Marc D; Schneider, Mary L; Mukherjee, Jogeshwar; Christian, Bradley T

2014-01-01

4-trans-[18F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[18F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[18F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[18F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[18F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[18F]mefway to 4-trans-[18F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[18F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[18F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[18F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[18F]mefway suggests the lower BPND of 3-[18F]mefway is due to a lower affinity. The lower affinity of 3-[18F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained. PMID:25143866

Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis

PubMed Central

Schiper, Luis; Faintuch, Bluma Linkowski; da Silva Badaró, Roberto José; de Oliveira, Erica Aparecida; Chavez, Victor E. Arana; Chinen, Elisangela; Faintuch, Joel

2016-01-01

OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications. PMID:27759852

Copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) Pharmacokinetics in FaDu Xenograft Tumors and Correlation With Microscopic Markers of Hypoxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCall, Keisha C.; Humm, John L.; Bartlett, Rachel

Purpose: The behavior of copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) ({sup 64}Cu-ATSM) in hypoxic tumors was examined through a combination of in vivo dynamic positron emission tomography (PET) and ex vivo autoradiographic and histologic evaluation using a xenograft model of head-and-neck squamous cell carcinoma. Methods and Materials: {sup 64}Cu-ATSM was administered during dynamic PET imaging, and temporal changes in {sup 64}Cu-ATSM distribution within tumors were evaluated for at least 1 hour and up to 18 hours. Animals were sacrificed at either 1 hour (cohort A) or after 18 hours (cohort B) postinjection of radiotracer and autoradiography performed. Ex vivo analysis of microenvironment subregions was conductedmore » by immunohistochemical staining for markers of hypoxia (pimonidazole hydrochloride) and blood flow (Hoechst-33342). Results: Kinetic analysis revealed rapid uptake of radiotracer by tumors. The net influx (K{sub i}) constant was 12-fold that of muscle, whereas the distribution volume (V{sub d}) was 5-fold. PET images showed large tumor-to-muscle ratios, which continually increased over the entire 18-hour course of imaging. However, no spatial changes in {sup 64}Cu-ATSM distribution occurred in PET imaging at 20 minutes postinjection. Microscopic intratumoral distribution of {sup 64}Cu-ATSM and pimonidazole were not correlated at 1 hour or after 18 hours postinjection, nor was {sup 64}Cu-ATSM and Hoechst-33342. Conclusions: The oxygen partial pressures at which {sup 64}Cu-ATSM and pimonidazole are reduced and bound in cells are theorized to be distinct and separable. However, this study demonstrated that microscopic distributions of these tracers within tumors are independent. Researchers have shown {sup 64}Cu-ATSM uptake to be specific to malignant expression, and this work has also demonstrated clear tumor targeting by the radiotracer.« less

In vivo PET/CT in a human glioblastoma chicken chorioallantoic membrane model: a new tool for oncology and radiotracer development.

PubMed

Warnock, Geoff; Turtoi, Andrei; Blomme, Arnaud; Bretin, Florian; Bahri, Mohamed Ali; Lemaire, Christian; Libert, Lionel Cyrille; Seret, Alain E J J; Luxen, André; Castronovo, Vincenzo; Plenevaux, Alain R E G

2013-10-01

For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more rapid, low cost, and ethically sustainable alternative. For the first time, to our knowledge, we demonstrate the feasibility of in vivo PET and CT imaging in a U87 glioblastoma tumor model on chicken CAM, with the aim of applying this model for screening of novel PET tracers. U87 glioblastoma cells were implanted on the CAM at day 11 after fertilization and imaged at day 18. A small-animal imaging cell was used to maintain incubation and allow anesthesia using isoflurane. Radiotracers were injected directly into the exposed CAM vasculature. Sodium (18)F-fluoride was used to validate the imaging protocol, demonstrating that image-degrading motion can be removed with anesthesia. Tumor glucose metabolism was imaged using (18)F-FDG, and tumor protein synthesis was imaged using 2-(18)F-fluoro-l-tyrosine. Anatomic images were obtained by contrast-enhanced CT, facilitating clear delineation of the tumor, delineation of tracer uptake in tumor versus embryo, and accurate volume measurements. PET imaging of tumor glucose metabolism and protein synthesis was successfully demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood vessels facilitated dynamic imaging of glucose metabolism with (18)F-FDG and demonstrated the ability to study PET tracer uptake over time in individual tumors, and CT imaging improved the accuracy of tumor volume measurements. We describe the novel application of PET/CT in the CAM tumor model, with optimization of typical imaging protocols. PET imaging in this valuable tumor model could prove particularly useful for rapid, high-throughput screening of novel radiotracers.

Trichloroethylene Biodegradation by a Methane-Oxidizing Bacterium †

PubMed Central

Little, C. Deane; Palumbo, Anthony V.; Herbes, Stephen E.; Lidstrom, Mary E.; Tyndall, Richard L.; Gilmer, Penny J.

1988-01-01

Trichloroethylene (TCE), a common groundwater contaminant, is a suspected carcinogen that is highly resistant to aerobic biodegradation. An aerobic, methane-oxidizing bacterium was isolated that degrades TCE in pure culture at concentrations commonly observed in contaminated groundwater. Strain 46-1, a type I methanotrophic bacterium, degraded TCE if grown on methane or methanol, producing CO2 and water-soluble products. Gas chromatography and 14C radiotracer techniques were used to determine the rate, methane dependence, and mechanism of TCE biodegradation. TCE biodegradation by strain 46-1 appears to be a cometabolic process that occurs when the organism is actively metabolizing a suitable growth substrate such as methane or methanol. It is proposed that TCE biodegradation by methanotrophs occurs by formation of TCE epoxide, which breaks down spontaneously in water to form dichloroacetic and glyoxylic acids and one-carbon products. Images PMID:16347616

Toward radioguided surgery with β- decays: uptake of a somatostatin analogue, DOTATOC, in meningioma and high-grade glioma.

PubMed

Collamati, Francesco; Pepe, Alessandra; Bellini, Fabio; Bocci, Valerio; Chiodi, Giacomo; Cremonesi, Marta; De Lucia, Erika; Ferrari, Mahila E; Frallicciardi, Paola M; Grana, Chiara M; Marafini, Michela; Mattei, Ilaria; Morganti, Silvio; Patera, Vincenzo; Piersanti, Luca; Recchia, Luigi; Russomando, Andrea; Sarti, Alessio; Sciubba, Adalberto; Senzacqua, Martina; Solfaroli Camillocci, Elena; Voena, Cecilia; Pinci, Davide; Faccini, Riccardo

2015-01-01

A novel radioguided surgery (RGS) technique for cerebral tumors using β(-) radiation is being developed. Checking for a radiotracer that can deliver a β(-) emitter to the tumor is a fundamental step in the deployment of such a technique. This paper reports a study of the uptake of (90)Y-DOTATOC in meningiomas and high-grade gliomas (HGGs) and a feasibility study of the RGS technique in these types of tumor. Estimates were performed assuming the use of a β(-) probe under development with a sensitive area 2.55 mm in radius to detect 0.1-mL residuals. Uptake and background from healthy tissues were estimated on (68)Ga-DOTATOC PET scans of 11 meningioma patients and 12 HGG patients. A dedicated statistical analysis of the DICOM images was developed and validated. The feasibility study was performed using full simulation of emission and detection of the radiation, accounting for the measured uptake and background rate. All meningioma patients but one with an atypical extracranial tumor showed high uptake of DOTATOC. In terms of feasibility of the RGS technique, we estimated that by administering a 3 MBq/kg activity of radiotracer, the time needed to detect a 0.1-mL remnant with 5% false-negative and 1% false-positive rates is less than 1 s. Actually, to achieve a detection time of 1 s the required activities to administer were as low as 0.2-0.5 MBq/kg in many patients. In HGGs, the uptake was lower than in meningiomas, but the tumor-to-nontumor ratio was higher than 4, which implies that the tracer can still be effective for RGS. It was estimated that by administering 3 mBq/kg of radiotracer, the time needed to detect a 0.1-mL remnant is less than 6 s, with the exception of the only oligodendroma in the sample. Uptake of (90)Y-DOTATOC in meningiomas was high in all studied patients. Uptake in HGGs was significantly worse than in meningiomas but was still acceptable for RGS, particularly if further research and development are done to improve the performance of the β(-) probe. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Preclinical evaluation of 99mTc(CO)3-aspartic-N-monoacetic acid, 99mTc(CO)3(ASMA), a new renal radiotracer with pharmacokinetic properties comparable to 131I-OIH

PubMed Central

Lipowska, Malgorzata; Klenc, Jeffrey; Marzilli, Luigi G.; Taylor, Andrew T.

2014-01-01

In an ongoing effort to develop a renal tracer with pharmacokinetic properties comparable to PAH and superior to those of both 99mTc-MAG3 and 131I-OIH, we evaluated a new renal tricarbonyl radiotracer based on the aspartic-N-monoacetic acid ligand, 99mTc(CO)3(ASMA). The ASMA ligand features two carboxyl groups and an amine function for the coordination of the {99mTc(CO)3}+ core as well as a dangling carboxylate to facilitate rapid renal clearance. Methods rac-ASMA and L-ASMA were labeled with a 99mTc-tricarbonyl precursor and radiochemical purity of the labeled products was determined by HPLC. Using 131I-OIH as an internal control, we evaluated biodistribution in normal rats with 99mTc(CO)3(ASMA) isomers and in rats with renal pedicle ligation with 99mTc(CO)3(rac-ASMA). Clearance studies were conducted in 4 additional rats. In vitro radiotracer stability was determined in PBS buffer pH 7.4 and in challenge studies with cysteine and histidine. 99mTc(CO)3(ASMA) metabolites in urine were analyzed by HPLC. Results Both 99mTc(CO)3(ASMA) preparations had > 99% radiochemical purity and were stable in PBS buffer pH 7.4 for 24 h. Challenge studies on both revealed no significant displacement of the ligand. In normal rats, % injected dose in urine at 10 and 60 min for both preparations averaged 103% and 106% that of 131I-OIH, respectively. The renal clearances of 99mTc(CO)3(rac-ASMA) and 131I-OIH were comparable (P = 0.48). The tracer was excreted unchanged in the urine, proving its in vivo stability. In pedicle-ligated rats, 99mTc(CO)3(rac-ASMA) had less excretion into the bowel (P < 0.05) and was better retained in the blood (P < 0.05) than 131I-OIH. Conclusion Both 99mTc(CO)3(ASMA) complexes have pharmacokinetic properties in rats comparable to or superior to those of 131I-OIH, and human studies are warranted for their further evaluation. PMID:22717977

Preliminary PET/CT Imaging with Somatostatin Analogs [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC.

PubMed

Satpati, Drishty; Shinto, Ajit; Kamaleshwaran, K K; Sarma, Haladhar Dev; Dash, Ashutosh

2017-12-01

Somatostatin receptor positron emission tomography/X-ray computed tomography (SSTR-PET/CT) is a well-established technique for staging and detection of neuroendocrine tumors (NETs). Ga-68-labeled DOTA-conjugated octreotide analogs are the privileged radiotracers for diagnosis and therapeutic monitoring of NETs. Hence, we were interested in assessing the influence of promising, newer variant DOTAGA on the hydrophilicity, pharmacokinetics, and lesion pick-up of somatostatin analogs. Herein, the potential of ([ 68 Ga]DOTAGA, Tyr 3 , Thr 8 ) octreotide ([ 68 Ga]DOTAGA-TATE) and ([ 68 Ga]DOTAGA, Tyr 3 ) octreotide ([ 68 Ga]DOTAGA-TOC) as NET imaging agents has been investigated. Amenability of [ 68 Ga]DOTAGA-(TATE/TOC) to kit-type formulation has been demonstrated. Biodistribution studies were carried out in normal rats at 1 h post-injection (p.i.). [ 68 Ga]DOTAGA-(TATE/TOC) PET/CT scans were carried out in patients (70-170 MBq, 1 h p.i.) with histologically confirmed well-differentiated NETs. [ 68 Ga]DOTAGA-TATE exhibited hydrophilicity similar to [ 68 Ga]DOTA-TATE (log P = -3.51 vs -3.69) whereas [ 68 Ga]DOTAGA-TOC was more hydrophilic than [ 68 Ga]DOTA-TOC (log P = -3.27 vs -2.93). [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE showed almost identical blood and kidney uptake in normal rats whereas significantly fast clearance (p < 0.05) of [ 68 Ga]DOTAGA-TATE was observed from other non-specific organs (liver, lungs, spleen, intestine). [ 68 Ga]DOTAGA-TOC also demonstrated rapid clearance from blood and kidneys (p < 0.05) in comparison to [ 68 Ga]DOTA-TOC. The metastatic lesions in NET patients were well identified by [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTAGA-TOC. The phenomenal analogy was observed between [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE as well as between [ 68 Ga]DOTAGA-TOC and [ 68 Ga]DOTA-TOC in biodistribution studies in rats. The good lesion detection ability of the two radiotracers indicates their potential as NET imaging radiotracers.

Comparing 2-[18F]fluoro-2-deoxy-D-glucose and [68Ga]gallium-citrate translocation in Arabidopsis thaliana.

PubMed

Fatangare, Amol; Gebhardt, Peter; Saluz, Hanspeter; Svatoš, Aleš

2014-10-01

2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) is a glucose surrogate commonly used in clinical or animal imaging but rarely in plant imaging to trace glucose metabolism. Recently, (18)FDG has been employed in plant imaging for studying photoassimilate translocation and glycoside biosynthesis. There is growing evidence that (18)FDG could be used as a tracer in plant imaging studies to trace sugar dynamics. However, to confirm this hypothesis, it was necessary to show that the observed (18)FDG distribution in an intact plant is an outcome of the chemical nature of the introduced radiotracer and not of the plant vascular architecture or radiotracer introduction method. In the present work, we fed (18)FDG and [(68)Ga]gallium-citrate ((68)Ga-citrate) solution through mature Arabidopsis thaliana leaf and monitored subsequent radioactivity distribution using positron autoradiography. The possible route of radioactivity translocation was elucidated through stem-girdling experiments. We also employed a bi-functional positron emission tomography/computed tomography (PET/CT) modality to capture (18)FDG radiotracer dynamics in one of the plants in order to assess applicability of PET/CT for 4-D imaging in an intact plant. Autoradiography results showed that [(18)F] radioactivity accumulated mostly in roots and young growing parts such as the shoot apex, which are known to act as sinks for photoassimilate. [(18)F] radioactivity translocation, in this case, occurred mainly via phloem. PET/CT results corroborated with autoradiography. [(68)Ga] radioactivity, on the other hand, was mainly translocated to neighboring leaves and its translocation occurred via both xylem and phloem. The radioactivity distribution pattern and translocation route observed after (18)FDG feeding is markedly different from that of (68)Ga-citrate. [(18)F] radioactivity distribution pattern in an intact plant is found similar to the typical distribution pattern of photoassimilates. Despite its limitations in quantification and resolution, PET/CT could be a useful tool to elucidate in vivo dynamics of [(18)F] radioactivity in intact plants. Copyright © 2014 Elsevier Inc. All rights reserved.

The promise of subtraction ictal SPECT co-registered to MRI for improved seizure localization in pediatric epilepsies: Affecting factors and relationship to the surgical outcome

PubMed Central

Stamoulis, Catherine; Verma, Nishant; Kaulas, Himanshu; Halford, Jonathan J.; Duffy, Frank H.; Pearl, Phillip L.; Treves, S. Ted

2016-01-01

Objective Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery. Methods Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age = 11 years, (25th, 75th) quartiles = (6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at <1, 6 and 12 months. Results Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p<0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p = 0.02) but not MRI findings (p = 0.33), epilepsy etiology (p ≥ 0.27) or seizure duration (p = 0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04). Significance Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to ≤ 25 s, although the origin of seizure onset (specifically temporal versus frontal) also significantly impacts the localization. PMID:27918961

The promise of subtraction ictal SPECT co-registered to MRI for improved seizure localization in pediatric epilepsies: Affecting factors and relationship to the surgical outcome.

PubMed

Stamoulis, Catherine; Verma, Nishant; Kaulas, Himanshu; Halford, Jonathan J; Duffy, Frank H; Pearl, Phillip L; Treves, S Ted

2017-01-01

Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery. Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age=11years, (25th, 75th) quartiles=(6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at <1, 6 and 12 months. Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p<0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p=0.02) but not MRI findings (p=0.33), epilepsy etiology (p≥0.27) or seizure duration (p=0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04). Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to≤25s, although the origin of seizure onset (specifically temporal versus frontal) also significantly impacts the localization. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct Estimation of Kinetic Parametric Images for Dynamic PET

PubMed Central

Wang, Guobao; Qi, Jinyi

2013-01-01

Dynamic positron emission tomography (PET) can monitor spatiotemporal distribution of radiotracer in vivo. The spatiotemporal information can be used to estimate parametric images of radiotracer kinetics that are of physiological and biochemical interests. Direct estimation of parametric images from raw projection data allows accurate noise modeling and has been shown to offer better image quality than conventional indirect methods, which reconstruct a sequence of PET images first and then perform tracer kinetic modeling pixel-by-pixel. Direct reconstruction of parametric images has gained increasing interests with the advances in computing hardware. Many direct reconstruction algorithms have been developed for different kinetic models. In this paper we review the recent progress in the development of direct reconstruction algorithms for parametric image estimation. Algorithms for linear and nonlinear kinetic models are described and their properties are discussed. PMID:24396500

Recent developments of cyclotron produced radionuclides for nuclear cardiology

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Jansen, D. E.; Corbett, J. R.

1987-04-01

For over a decade myocardial perfusion imaging with thallium-201, a cyclotron product, has been routinely used in clinical medicine. Recent advances have allowed the efficient production of very high purity (> 99.8%) iodine-123. New metabolically active 123I labeled radiopharmaceuticals, including alkyl and phenyl fatty acids, and norepinephrine analogs, have been developed and are undergoing clinical trials. Fab' fragments of monoclonal antibodies to cardiac myosin have been labeled with indium-111 ( 111In) and are undergoing clinical evaluation for imaging myocardial infarcts. Monoclonal antibodies to platelets, fibrin, and the thrombolytic agent, tissue plasminogen activator (TPA), have recently been labeled with 111In. Together these developments in radiotracers and instrumentation should have a significant impact on the future of cardiovascular nuclear medicine. This manuscript will discuss developments in single photon emitting radiotracers for myocardial imaging.

Complementarity in radiochemical and infrared spectroscopic characterization of electrode adsorption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wieckowski, A.

1994-03-01

Radioactive labelling and infrared spectroscopy are frequently used as direct, in situ probes into the structure of the electrochemical solid/liquid interface. These techniques are compared, in a polemical fashion, in the context of a recent publication by Parry et al. (Langmuir 1993, 9, 1878) where the research potential of the former technique was not adequately depicted. It is shown that radiotracers can clearly differentiate between the surface and solution species, both neutrals and anions. In addition to the surface specificity, the radiotracers offer a quantitative determination of adsorbate surface concentrations, a feature not yet demonstrated with surface infrared spectroscopy inmore » electrochemistry. Therefore, these two techniques are complementary. Examples of the combined radiochemical and spectroscopic measurements of adsorption with equivalent (smooth) electrode surfaces are quoted. 11 refs., 2 figs.« less

Improving cancer treatment with cyclotron produced radionuclides. Comprehensive progress report, February 1, 1990--January 31, 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M. Finn, R.D.

1992-08-04

This report describes the author`s continuing long term goal of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The program has 3 interactive components: Radiochemistry /Cyclotron; Pharmacology; and Immunology. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Cyclotron section under the DOE grant during the 1989--1992 grant period, will be employed in the Pharmacology and Immunology sections of the DOE grant during the 1992--1995 grant period. The development of novel radionuclides and tracers is of course usefulmore » in and of itself, but their utility is greatly enhanced by the interaction with the immunology and pharmacology components of the program.« less

Convenient Preparation of [(68)Ga]DKFZ-PSMA-11 Using a Robust Single-Vial Kit and Demonstration of Its Clinical Efficacy.

PubMed

Satpati, Drishty; Shinto, Ajit; Kamaleshwaran, K K; Sane, Surekha; Banerjee, Sharmila

2016-06-01

[(68)Ga]DKFZ-PSMA-11 has proved to be an important diagnostic radiotracer for targeting prostate-specific membrane antigen (PSMA) overexpression in both recurrent prostate cancer (PC) and relevant metastatic sites. However, the widespread, routine clinical use of such a potential radiopharmaceutical demands availability of a ready-to-use kit formulation to enable convenient radiopharmaceutical preparation. Herein, we report the development of a freeze-dried kit vial for the formulation of [(68)Ga]DKFZ-PSMA-11 and its clinical use in patients using a "shake-bake-inject" methodology. The freeze-dried kit vial was developed after optimization of ligand content (PSMA-11) and pH conditions. The kit was formulated using (68)Ga from two different commercially available generators. Positron emission tomography/X-ray computed tomography (PET/CT) images of PC patients were obtained using the kit-formulated radiotracer. [(68)Ga]DKFZ-PSMA-11 was prepared in >98 % radiochemical yield and purity using the freeze-dried kit vials. Kits were optimized for the preparation of four patient doses. The clinical utility was evaluated in patients with histologically confirmed prostate cancer, and the images were of good quality as well as conforming to tumor marker and clinical expectations. The development of a simple and ready-to-use freeze-dried DKFZ-PSMA-11 kit for the preparation of Ga-68-based radiotracers constitutes a major step towards the expedition of the widespread and economical screening of PC patients.

The history of cerebral PET scanning

PubMed Central

Portnow, Leah H.; Vaillancourt, David E.; Okun, Michael S.

2013-01-01

Objective: To review the discoveries underpinning the introduction of cerebral PET scanning and highlight its modern applications. Background: Important discoveries in neurophysiology, brain metabolism, and radiotracer development in the post–World War II period provided the necessary infrastructure for the first cerebral PET scan. Methods: A complete review of the literature was undertaken to search for primary and secondary sources on the history of PET imaging. Searches were performed in PubMed, Google Scholar, and select individual journal Web sites. Written autobiographies were obtained through the Society for Neuroscience Web site at www.sfn.org. A reference book on the history of radiology, Naked to the Bone, was reviewed to corroborate facts and to locate references. The references listed in all the articles and books obtained were reviewed. Results: The neurophysiologic sciences required to build cerebral PET imaging date back to 1878. The last 60 years have produced an evolution of technological advancements in brain metabolism and radiotracer development. These advancements facilitated the development of modern cerebral PET imaging. Several key scientists were involved in critical discoveries and among them were Angelo Mosso, Charles Roy, Charles Sherrington, John Fulton, Seymour Kety, Louis Sokoloff, David E. Kuhl, Gordon L. Brownell, Michael Ter-Pogossian, Michael Phelps, and Edward Hoffman. Conclusions: Neurophysiology, metabolism, and radiotracer development in the postwar era synergized the development of the technology necessary for cerebral PET scanning. Continued use of PET in clinical trials and current developments in PET-CT/MRI hybrids has led to advancement in diagnosis, management, and treatment of neurologic disorders. PMID:23460618

Radionuclide thyroid imaging in the newborn with suspected hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoosufani, Z.; Karimeddini, M.K.; Spencer, R.P.

1985-05-01

The authors reviewed their experience with thyroid imaging in newborns with suspected congenital hypothyroidism. The infants were selected through a hypothyroidism screening program. There were 19 infants (14 females, 5 males) from 2 to 8 weeks of age with a blood T4 <6 ..mu..g/dl. Thyroid imaging was performed with either IV or IM injection of 0.5 to 1 mCi of Tc 99m pertechnetate using a gamma camera with a pinhole collimator. Salivary glands and stomach were also imaged for assessing the presence of the transport system. In 6 infants (32%) no thyroid tissue was visualized (thyroid hypoplasia). Four infants (21%)more » showed ectopic thyroid tissue in the lingual or sublingual area. Two infants (10%) had evidence of goiter. The remaining 7 infants (37%) had normal appearing glands in size and position. TSH values were markedly elevated (> 100 ..mu mu../ml) in all 10 patients with hypoplastic or ectopic thyroid. Two patients were subsequently found to have normal thyroid function (one with TBG deficiency and one with transient hypothyroidism). Thyroidal as well as salivary gland trapping of the radiotracer in these two infants was clearly less than that of adults suggesting immaturity of the transport/trapping mechanism. All 4 patients with ectopic thyroid had markedly increased uptake of the radiotracer. All other patients with elevated TSH levels had increased uptake of the radiotracer as compared to the normals. They conclude that thyroid scanning is an important tool in delineating the etiology of congenital hypothyroidism.« less

The history of cerebral PET scanning: from physiology to cutting-edge technology.

PubMed

Portnow, Leah H; Vaillancourt, David E; Okun, Michael S

2013-03-05

To review the discoveries underpinning the introduction of cerebral PET scanning and highlight its modern applications. Important discoveries in neurophysiology, brain metabolism, and radiotracer development in the post-World War II period provided the necessary infrastructure for the first cerebral PET scan. A complete review of the literature was undertaken to search for primary and secondary sources on the history of PET imaging. Searches were performed in PubMed, Google Scholar, and select individual journal Web sites. Written autobiographies were obtained through the Society for Neuroscience Web site at www.sfn.org. A reference book on the history of radiology, Naked to the Bone, was reviewed to corroborate facts and to locate references. The references listed in all the articles and books obtained were reviewed. The neurophysiologic sciences required to build cerebral PET imaging date back to 1878. The last 60 years have produced an evolution of technological advancements in brain metabolism and radiotracer development. These advancements facilitated the development of modern cerebral PET imaging. Several key scientists were involved in critical discoveries and among them were Angelo Mosso, Charles Roy, Charles Sherrington, John Fulton, Seymour Kety, Louis Sokoloff, David E. Kuhl, Gordon L. Brownell, Michael Ter-Pogossian, Michael Phelps, and Edward Hoffman. Neurophysiology, metabolism, and radiotracer development in the postwar era synergized the development of the technology necessary for cerebral PET scanning. Continued use of PET in clinical trials and current developments in PET-CT/MRI hybrids has led to advancement in diagnosis, management, and treatment of neurologic disorders.

Concordance between peri-areolar blue dye and peri-incisional radiotracer injections for sentinel node mapping in patients with a history of primary breast cancer excisonal biopsy.

PubMed

Mehrabibahar, M; Azizi, S; Jangjoo, A; Saremi, E; Kakhki, V R Dabbagh; Sadeghi, R; Chicken, D W; Keshtgar, M

2014-01-01

We evaluated the concordance between peri-areolar blue dye and peri-incisional radiotracer injections for axillary sentinel node mapping of patients with the history of previous breast lesion excisional biopsy. 80 patients with the history of previous excisional biopsy of the breast lesions were included. All patients received two injections of 99mTc-antimony sulfide colloid in both ends of incision line in an intradermal fashion. 2 mL patient blue V dye was injection to all patients in the peri-areolar area of the index quadrant after induction of anesthesia. All blue or hot nodes were harvested as sentinel lymph nodes. At least one sentinel node could be detected during surgery in 79 patients. In total 94 sentinel nodes were detected. All detected sentinel nodes were hot. In three patients sentinel nodes were detected by gamma probe but not blue dye. The tumor location in all of these patients was in the upper lateral quadrant and the incision line was extended into the axillary tail of the breast in all of them. 91 out of 94 sentinel nodes were stained blue, which amounts to 95.8% concordance between blue dye and radiotracer on a per node analysis. Single peri-areolar injection in the index quadrant would suffice for sentinel node mapping of patients with history of excisional biopsy. Care should be taken in patients with large excisional biopsy in the extreme proximity to axilla.

Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.

PubMed

Spreckelmeyer, Katja N; Paulzen, Michael; Raptis, Mardjan; Baltus, Thomas; Schaffrath, Sabrina; Van Waesberghe, Julia; Zalewski, Magdalena M; Rösch, Frank; Vernaleken, Ingo; Schäfer, Wolfgang M; Gründer, Gerhard

2011-10-15

Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system. Availability of D(2/3) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride. Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding (Δ%BP(ND)). The [(18)F]fallypride binding potentials (BP(ND)s) were significantly reduced in the ventral striatum, dorsal putamen, and amygdala after remifentanil application in both patients and control subjects. In the patient group, ventral striatum Δ%BP(ND) was correlated with the Alcohol Use Disorders Identification Test score. The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system, supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway. No difference in dopamine release was found between patients and control subjects, but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence was found. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Diffusion of autoinducer is involved in regulation of the Vibrio fischeri luminescence system.

PubMed Central

Kaplan, H B; Greenberg, E P

1985-01-01

The enzymes for luminescence in Vibrio fischeri are induced by the accumulation of a species-specific metabolite (autoinducer) in the culture medium. Tritium-labeled autoinducer was used to study the mechanism of autoinduction. When 3H-autoinducer was added to suspensions of V. fischeri or Escherichia coli, cellular concentrations equaled external concentrations. For V. fischeri, equilibration of 3H-autoinducer was rapid (within 20 s), and greater than 90% of the cellular tritium remained in unmodified autoinducer. When V. fischeri or E. coli cells containing 3H-autoinducer were transferred to autoinducer-free buffer, 85 to 99.5% of the radiotracer escaped from the cells, depending on the strain. Concentrations of autoinducer as low as 10 nM, which is equivalent to 1 or 2 molecules per cell, were sufficient for induction, and the maximal response to autoinducer occurred at about 200 nM. If external autoinducer concentrations were decreased to below 10 nM after induction had commenced, the induction response did not continue. Based on this study, a model for autoinduction is described wherein autoinducer association with cells is by simple diffusion and binding of autoinducer to its active site is reversible. PMID:3897188

Ion beam induced 18F-radiofluorination: straightforward synthesis of gaseous radiotracers for the assessment of regional lung ventilation using positron emission tomography.

PubMed

Gómez-Vallejo, V; Lekuona, A; Baz, Z; Szczupak, B; Cossío, U; Llop, J

2016-09-29

A simple, straightforward and efficient method for the synthesis of [ 18 F]CF 4 and [ 18 F]SF 6 based on an ion beam-induced isotopic exchange reaction is presented. Positron emission tomography ventilation studies in rodents using [ 18 F]CF 4 showed a uniform distribution of the radiofluorinated gas within the lungs and rapid elimination after discontinuation of the administration.

Synthesis and evaluation of novel 18 F-labeled quinazoline derivatives with low lipophilicity for tumor PET imaging.

PubMed

Chong, Yan; Chang, Jin; Zhao, Wenwen; He, Yong; Li, Yuqiao; Zhang, Huabei; Qi, Chuanmin

2018-02-01

Four novel 18 F-labeled quinazoline derivatives with low lipophilicity, [ 18 F]4-(2-fluoroethoxy)-6,7-dimethoxyquinazoline ([ 18 F]I), [ 18 F]4-(3-((4-(2-fluoroethoxy)-7-methoxyquinazolin-6-yl)oxy)propyl)morpholine ([ 18 F]II), [ 18 F]4-(2-fluoroethoxy)-7-methoxy-6-(2-methoxyethoxy)quinazoline ([ 18 F]III), and [ 18 F]4-(2-fluoroethoxy)-6,7-bis(2-methoxyethoxy)quinazoline ([ 18 F]IV), were synthesized via a 2-step radiosynthesis procedure with an overall radiochemical yield of 10% to 38% (without decay correction) and radiochemical purities of >98%. The lipophilicity and stability of labeled compounds were tested in vitro. The log P values of the 4 radiotracers ranged from 0.52 to 1.07. We then performed ELISA to measure their affinities to EGFR-TK; ELISA assay results indicated that each inhibitor was specifically bounded to EGFR-TK in a dose-dependent manner. The EGFR-TK autophosphorylation IC 50 values of [ 18 F]I, [ 18 F]II, [ 18 F]III, and [ 18 F]IV were 7.732, 0.4698, 0.1174, and 0.1176 μM, respectively. All labeled compounds were evaluated via cellular uptake and blocking studies in HepG2 cell lines in vitro. Cellular uptake and blocking experiment results indicated that [ 18 F]I and [ 18 F]III had excellent cellular uptake at 120-minute postinjection in HepG2 carcinoma cells (51.80 ± 3.42%ID/mg protein and 27.31 ± 1.94%ID/mg protein, respectively). Additionally, biodistribution experiments in S180 tumor-bearing mice in vivo indicated that [ 18 F]I had a very fast clearance in blood and a relatively high uptake ratio of tumor to blood (4.76) and tumor to muscle (1.82) at 60-minute postinjection. [ 18 F]III had a quick clearance in plasma, and its highest uptake ratio of tumor to muscle was 2.55 at 15-minute postinjection. These experimental results and experiences were valuable for the further exploration of novel radiotracers of quinazoline derivatives. Copyright © 2017 John Wiley & Sons, Ltd.

Noninvasive bi-graphical analysis for the quantification of slowly reversible radioligand binding

NASA Astrophysics Data System (ADS)

Seo, Seongho; Kim, Su Jin; Yoo, Hye Bin; Lee, Jee-Young; Kyeong Kim, Yu; Lee, Dong Soo; Zhou, Yun; Lee, Jae Sung

2016-09-01

In this paper, we presented a novel reference-region-based (noninvasive) bi-graphical analysis for the quantification of a reversible radiotracer binding that may be too slow to reach relative equilibrium (RE) state during positron emission tomography (PET) scans. The proposed method indirectly implements the noninvasive Logan plot, through arithmetic combination of the parameters of two other noninvasive methods and the apparent tissue-to-plasma efflux rate constant for the reference region (k2\\prime ). We investigated its validity and statistical properties, by performing a simulation study with various noise levels and k2\\prime values, and also evaluated its feasibility for [18F]FP-CIT PET in human brain. The results revealed that the proposed approach provides distribution volume ratio estimation comparable to the Logan plot at low noise levels while improving underestimation caused by non-RE state differently depending on k2\\prime . Furthermore, the proposed method was able to avoid noise-induced bias of the Logan plot, and the variability of its results was less dependent on k2\\prime than the Logan plot. Therefore, this approach, without issues related to arterial blood sampling given a pre-estimate of k2\\prime (e.g. population-based), could be useful in parametric image generation for slow kinetic tracers staying in a non-RE state within a PET scan.

Discovery of a fluorinated 4-oxo-quinoline derivative as a potential positron emission tomography radiotracer for imaging cannabinoid receptor type 2.

PubMed

Slavik, Roger; Müller Herde, Adrienne; Haider, Ahmed; Krämer, Stefanie D; Weber, Markus; Schibli, Roger; Ametamey, Simon M; Mu, Linjing

2016-09-01

The cannabinoid receptor type 2 (CB2) is part of the endocannabinoid system and has gained growing attention in recent years because of its important role in neuroinflammatory/neurodegenerative diseases. Recently, we reported on a carbon-11 labeled 4-oxo-quinoline derivative, designated RS-016, as a promising radiotracer for imaging CB2 using PET. In this study, three novel fluorinated analogs of RS-016 were designed, synthesized, and pharmacologically evaluated. The results of our efforts led to the identification of N-(1-adamantyl)-1-(2-(2-fluoroethoxy)ethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide (RS-126) as the most potent candidate for evaluation as a CB2 PET ligand. [(18) F]RS-126 was obtained in ≥ 99% radiochemical purity with an average specific radioactivity of 98 GBq/μmol at the end of the radiosynthesis. [(18) F]RS-126 showed a logD7.4 value of 1.99 and is stable in vitro in rat and human plasma over 120 min, whereas 55% intact parent compound was found in vivo in rat blood plasma at 10 min post injection. In vitro autoradiographic studies with CB2-positive rat spleen tissue revealed high and blockable binding which was confirmed in in vivo displacement experiments with rats by dynamic PET imaging. Ex vivo biodistribution studies confirmed accumulation of [(18) F]RS-126 in rat spleen with a specificity of 79% under blocking conditions. The moderate elevated CB2 levels in LPS-treated mice brain did not permit the detection of CB2 by [(18) F]RS-126 using PET imaging. In summary, [(18) F]RS-126 demonstrated high specificity toward CB2 receptor in vitro and in vivo and is a promising radioligand for imaging CB2 receptor expression. Cannabinoid receptor type 2 (CB2) is an interesting target for PET imaging. Specific binding of [(18) F]RS-126 in CB2-positive spleen tissue (white arrow head) was confirmed in in vivo displacement experiments with rats. Time activity curve of [(18) F]RS-126 in the spleen after the addition of GW405833 (CB2 specific ligand, green) demonstrates faster radiotracer elimination (blue) compared to the tracer only (red). © 2016 International Society for Neurochemistry.

Targeting Phosphatidylserine with a 64Cu-Labeled Peptide for Molecular Imaging of Apoptosis.

PubMed

Perreault, Amanda; Richter, Susan; Bergman, Cody; Wuest, Melinda; Wuest, Frank

2016-10-03

Molecular imaging of programmed cell death (apoptosis) in vivo is an innovative strategy for early assessment of treatment response and treatment efficacy in cancer patients. Externalization of phosphatidylserine (PS) to the cell membrane surface of dying cells makes this phospholipid an attractive molecular target for the development of apoptosis imaging probes. In this study, we have radiolabeled PS-binding 14-mer peptide FNFRLKAGAKIRFG (PSBP-6) with positron-emitter copper-64 ( 64 Cu) for PET imaging of apoptosis. Peptide PSBP-6 was conjugated with radiometal chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through an aminovaleric acid (Ava) linker for subsequent radiolabeling with 64 Cu to prepare radiotracer 64 Cu-NOTA-Ava-PSBP-6. PS-binding potencies of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-Ava-PSBP-6 were determined in a competitive radiometric PS-binding assay. Radiotracer 64 Cu-NOTA-Ava-PSBP-6 was studied in camptothecin-induced apoptotic EL4 mouse lymphoma cells and in a murine EL4 tumor model of apoptosis using dynamic PET imaging. Peptide PSBP-6 was also conjugated via an Ava linker with fluorescein isothiocyanate (FITC). FITC-Ava-PSBP-6 was evaluated in flow cytometry and fluorescence confocal microscopy experiments. Radiopeptide 64 Cu-NOTA-Ava-PSBP-6 was synthesized in high radiochemical yields of >95%. The IC 50 values for PS-binding potency of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-PSBP-6 were 600 μM, 30 μM, and 23 μM, respectively. A competitive radiometric cell binding assay confirmed binding of 64 Cu-NOTA-Ava-PSBP-6 to camptothecin-induced apoptotic EL4 cells in a Ca 2+ -independent manner. PET imaging studies demonstrated significantly higher uptake of 64 Cu-NOTA-Ava-PSBP-6 in apoptotic EL4 tumors (SUV 5min 0.95 ± 0.04) compared to control tumors (SUV 5min 0.74 ± 0.03). Flow cytometry studies showed significantly higher binding of FITC-Ava-PSBP-6 to EL4 cells treated with camptothecin compared to untreated cells. Fluorescence microscopy studies revealed that FITC-Ava-PSBP-6 was binding to cell membranes of early apoptotic cells, but was internalized in late apoptotic and necrotic cells. The present study showed that radiotracer 64 Cu-NOTA-Ava-PSBP-6 holds promise as a first peptide-based PET imaging agent for molecular imaging of apoptosis. However, additional "fine-tuning" of 64 Cu-NOTA-Ava-PSBP-6 is required to enhance PS-binding potency and in vivo stability to improve tumor uptake and retention.

A Review on Segmentation of Positron Emission Tomography Images

PubMed Central

Foster, Brent; Bagci, Ulas; Mansoor, Awais; Xu, Ziyue; Mollura, Daniel J.

2014-01-01

Positron Emission Tomography (PET), a non-invasive functional imaging method at the molecular level, images the distribution of biologically targeted radiotracers with high sensitivity. PET imaging provides detailed quantitative information about many diseases and is often used to evaluate inflammation, infection, and cancer by detecting emitted photons from a radiotracer localized to abnormal cells. In order to differentiate abnormal tissue from surrounding areas in PET images, image segmentation methods play a vital role; therefore, accurate image segmentation is often necessary for proper disease detection, diagnosis, treatment planning, and follow-ups. In this review paper, we present state-of-the-art PET image segmentation methods, as well as the recent advances in image segmentation techniques. In order to make this manuscript self-contained, we also briefly explain the fundamentals of PET imaging, the challenges of diagnostic PET image analysis, and the effects of these challenges on the segmentation results. PMID:24845019

Sodium 18F-Fluoride PET/CT of Bone, Joint and Other Disorders

PubMed Central

Jadvar, Hossein; Desai, Bhushan; Conti, Peter S.

2014-01-01

The use of 18F-sodium fluoride (18F-NaF) with positron emission tomography-computed tomography (PET/CT) is increasing. This resurgence of an old tracer has been fueled by several factors including superior diagnostic performance over standard 99mTc-based bone scintigraphy, growth in the availability of PET/CT imaging systems, increase in the number of regional commercial distribution centers for PET radiotracers, the recent concerns about potential chronic shortages with 99mTc based radiotracers, and the recent decision by the Centers for Medicare and Medicaid Services to reimburse for 18F-NaF PET/CT for evaluation of patients with known or suspected bone metastases through the National Oncologic PET Registry. The major goal of this article is to review the current evidence on the diagnostic utility of 18F-NaF in the imaging assessment of bone and joint in a variety of clinical conditions. PMID:25475379

Morphology supporting function: attenuation correction for SPECT/CT, PET/CT, and PET/MR imaging

PubMed Central

Lee, Tzu C.; Alessio, Adam M.; Miyaoka, Robert M.; Kinahan, Paul E.

2017-01-01

Both SPECT, and in particular PET, are unique in medical imaging for their high sensitivity and direct link to a physical quantity, i.e. radiotracer concentration. This gives PET and SPECT imaging unique capabilities for accurately monitoring disease activity for the purposes of clinical management or therapy development. However, to achieve a direct quantitative connection between the underlying radiotracer concentration and the reconstructed image values several confounding physical effects have to be estimated, notably photon attenuation and scatter. With the advent of dual-modality SPECT/CT, PET/CT, and PET/MR scanners, the complementary CT or MR image data can enable these corrections, although there are unique challenges for each combination. This review covers the basic physics underlying photon attenuation and scatter and summarizes technical considerations for multimodal imaging with regard to PET and SPECT quantification and methods to address the challenges for each multimodal combination. PMID:26576737

Axial dispersion, holdup and slip velocity of dispersed phase in a pulsed sieve plate extraction column by radiotracer residence time distribution analysis.

PubMed

Din, Ghiyas Ud; Chughtai, Imran Rafiq; Inayat, Mansoor Hameed; Khan, Iqbal Hussain

2008-12-01

Axial dispersion, holdup and slip velocity of dispersed phase have been investigated for a range of dispersed and continuous phase superficial velocities in a pulsed sieve plate extraction column using radiotracer residence time distribution (RTD) analysis. Axial dispersion model (ADM) was used to simulate the hydrodynamics of the system. It has been observed that increase in dispersed phase superficial velocity results in a decrease in its axial dispersion and increase in its slip velocity while its holdup increases till a maximum asymptotic value is achieved. An increase in superficial velocity of continuous phase increases the axial dispersion and holdup of dispersed phase until a maximum value is obtained, while slip velocity of dispersed phase is found to decrease in the beginning and then it increases with increase in superficial velocity of continuous phase.

Colloidal complexed silver and silver nanoparticles in extrapallial fluid of Mytilus edulis.

PubMed

Zuykov, Michael; Pelletier, Emilien; Demers, Serge

2011-02-01

Metal transport in mollusk extrapallial fluid (EPF) that acts as a "bridge" between soft tissues and shell has surprisingly received little attention until now. Using ultrafiltration and radiotracer techniques we determined silver concentrations and speciation in the EPF of the blue mussel Mytilus edulis after short-term uptake and depuration laboratory experiments. Radiolabelled silver ((¹¹⁰m)Ag) was used in dissolved or nanoparticulate phases (AgNPs < 40 nm), with a similar low Ag concentration (total radioactive and cold Ag ~0.7 μg/L) in a way that mussels could uptake radiotracers only from seawater. Our results indicated that silver nanoparticles were transported to the EPF of blue mussels at a level similar to the Ag ionic form. Bulk activity of radiolabelled silver in the EPF represented only up to 7% of the bulk activity measured in the whole mussels. The EPF extracted from mussels exposed to both treatments exhibited an Ag colloidal complexed form based on EPF ultrafiltration through a 3 kDa filter. This original study brings new insights to internal circulation of nanoparticles in living organisms and contributes to the international effort in studying the potential impacts of engineered nanomaterials on marine bivalves which play an essential role in coastal ecosystems, and are important contributors to human food supply from the sea. © 2010 Elsevier Ltd. All rights reserved.

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foss, Catherine A., E-mail: cfoss1@jhmi.edu; Bedja, Djahida; Faculty of Medicine and Health Sciences, Macquarie University, Sydney

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mousemore » model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Tianwu; Lee, Choonsik; Bolch, Wesley E.

Purpose: Nuclear cardiology plays an important role in clinical assessment and has enormous impact on the management of a variety of cardiovascular diseases. Pediatric patients at different age groups are exposed to a spectrum of radiation dose levels and associated cancer risks different from those of adults in diagnostic nuclear medicine procedures. Therefore, comprehensive radiation dosimetry evaluations for commonly used myocardial perfusion imaging (MPI) and viability radiotracers in target population (children and adults) at different age groups are highly desired. Methods: Using Monte Carlo calculations and biological effects of ionizing radiation VII model, we calculate the S-values for a numbermore » of radionuclides (Tl-201, Tc-99m, I-123, C-11, N-13, O-15, F-18, and Rb-82) and estimate the absorbed dose and effective dose for 12 MPI radiotracers in computational models including the newborn, 1-, 5-, 10-, 15-yr-old, and adult male and female computational phantoms. Results: For most organs, {sup 201}Tl produces the highest absorbed dose whereas {sup 82}Rb and {sup 15}O-water produce the lowest absorbed dose. For the newborn baby and adult patient, the effective dose of {sup 82}Rb is 48% and 77% lower than that of {sup 99m}Tc-tetrofosmin (rest), respectively. Conclusions: {sup 82}Rb results in lower effective dose in adults compared to {sup 99m}Tc-labeled tracers. However, this advantage is less apparent in children. The produced dosimetric databases for various radiotracers used in cardiovascular imaging, using new generation of computational models, can be used for risk-benefit assessment of a spectrum of patient population in clinical nuclear cardiology practice.« less

An experimental phantom study of the effect of gadolinium-based MR contrast agents on PET attenuation coefficients and PET quantification in PET-MR imaging: application to cardiac studies.

PubMed

O' Doherty, Jim; Schleyer, Paul

2017-12-01

Simultaneous cardiac perfusion studies are an increasing trend in PET-MR imaging. During dynamic PET imaging, the introduction of gadolinium-based MR contrast agents (GBCA) at high concentrations during a dual injection of GBCA and PET radiotracer may cause increased attenuation effects of the PET signal, and thus errors in quantification of PET images. We thus aimed to calculate the change in linear attenuation coefficient (LAC) of a mixture of PET radiotracer and increasing concentrations of GBCA in solution and furthermore, to investigate if this change in LAC produced a measurable effect on the image-based PET activity concentration when attenuation corrected by three different AC strategies. We performed simultaneous PET-MR imaging of a phantom in a static scenario using a fixed activity of 40 MBq [18 F]-NaF, water, and an increasing GBCA concentration from 0 to 66 mM (based on an assumed maximum possible concentration of GBCA in the left ventricle in a clinical study). This simulated a range of clinical concentrations of GBCA. We investigated two methods to calculate the LAC of the solution mixture at 511 keV: (1) a mathematical mixture rule and (2) CT imaging of each concentration step and subsequent conversion to LAC at 511 keV. This comparison showed that the ranges of LAC produced by both methods are equivalent with an increase in LAC of the mixed solution of approximately 2% over the range of 0-66 mM. We then employed three different attenuation correction methods to the PET data: (1) each PET scan at a specific millimolar concentration of GBCA corrected by its corresponding CT scan, (2) each PET scan corrected by a CT scan with no GBCA present (i.e., at 0 mM GBCA), and (3) a manually generated attenuation map, whereby all CT voxels in the phantom at 0 mM were replaced by LAC = 0.1 cm -1 . All attenuation correction methods (1-3) were accurate to the true measured activity concentration within 5%, and there were no trends in image-based activity concentrations upon increasing the GBCA concentration of the solution. The presence of high GBCA concentration (representing a worst-case scenario in dynamic cardiac studies) in solution with PET radiotracer produces a minimal effect on attenuation-corrected PET quantification.

Development of dopamine receptor radiopharmaceuticals for the study of neurological and psychiatric disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dr. Jogeshwar Mukherjee

Our goals in this grant application are directed towards the development of radiotracers that may allow the study of the high-affinity state (functional state) of the dopamine receptors. There have been numerous reports on the presence of two inter-convertible states of these (G-protein coupled) receptors in vitro. However, there is no report that establishes the presence of these separate affinity states in vivo. We have made efforts in this direction in order to provide such direct in vivo evidence about the presence of the high affinity state. This understanding of the functional state of the receptors is of critical significancemore » in our overall diagnosis and treatment of diseases that implicate the G-protein coupled receptors. Four specific aims have been listed in the grant application: (1). Design and syntheses of agonists (2). Radiosyntheses of agonists (3). In vitro pharmacology of agonists (4). In vivo distribution and pharmacology of labeled derivatives. We have accomplished the syntheses and radiosyntheses of three agonist radiotracers labeled with carbon-11. In vitro and in vivo pharmacological experiments have been accomplished in rats and preliminary PET studies in non-human primates have been carried out. Various accomplishments during the funded years, briefly outlined in this document, have been disseminated by several publications in various journals and presentations in national and international meetings (Society of Nuclear Medicine, Society for Neuroscience and International Symposium on Radiopharmaceutical Chemistry).« less

Limitations of Poisson statistics in describing radioactive decay.

PubMed

Sitek, Arkadiusz; Celler, Anna M

2015-12-01

The assumption that nuclear decays are governed by Poisson statistics is an approximation. This approximation becomes unjustified when data acquisition times longer than or even comparable with the half-lives of the radioisotope in the sample are considered. In this work, the limits of the Poisson-statistics approximation are investigated. The formalism for the statistics of radioactive decay based on binomial distribution is derived. The theoretical factor describing the deviation of variance of the number of decays predicated by the Poisson distribution from the true variance is defined and investigated for several commonly used radiotracers such as (18)F, (15)O, (82)Rb, (13)N, (99m)Tc, (123)I, and (201)Tl. The variance of the number of decays estimated using the Poisson distribution is significantly different than the true variance for a 5-minute observation time of (11)C, (15)O, (13)N, and (82)Rb. Durations of nuclear medicine studies often are relatively long; they may be even a few times longer than the half-lives of some short-lived radiotracers. Our study shows that in such situations the Poisson statistics is unsuitable and should not be applied to describe the statistics of the number of decays in radioactive samples. However, the above statement does not directly apply to counting statistics at the level of event detection. Low sensitivities of detectors which are used in imaging studies make the Poisson approximation near perfect. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

453rd Brookhaven Lecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richard Ferrieri

2009-10-28

In this lecture titled "Striving Towards Energy Sustainability: How Will Plants Play a Role in Our Future?" Richard Ferrieri discusses how radiotracers and positron emission tomography (PET imaging) are providing a new look into plant processes that could lead to more renewable biofuels.

453rd Brookhaven Lecture

ScienceCinema

Richard Ferrieri

2017-12-09

In this lecture titled "Striving Towards Energy Sustainability: How Will Plants Play a Role in Our Future?" Richard Ferrieri discusses how radiotracers and positron emission tomography (PET imaging) are providing a new look into plant processes that could lead to more renewable biofuels.

Cyclotron Production of High-Specific Activity 55Co and In Vivo Evaluation of the Stability of 55Co Metal-Chelate-Peptide Complexes.

PubMed

Mastren, Tara; Marquez, Bernadette V; Sultan, Deborah E; Bollinger, Elizabeth; Eisenbeis, Paul; Voller, Tom; Lapi, Suzanne E

2015-01-01

This work describes the production of high-specific activity 55Co and the evaluation of the stability of 55Co-metal-chelate-peptide complexes in vivo. 55Co was produced via the 58Ni(p,α)55Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/μmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/μg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET) and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers' uptake in the liver by sixfold at 24 hours with ~ 1% ID/g and at 48 hours with ~ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ~ 0.7% ID/g and sevenfold at 48 hours with ~ 0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for PET imaging of cancer and other diseases.

Complexes of DOTA-bisphosphonate conjugates: probes for determination of adsorption capacity and affinity constants of hydroxyapatite.

PubMed

Vitha, Tomas; Kubícek, Vojtech; Hermann, Petr; Kolar, Zvonimir I; Wolterbeek, Hubert Th; Peters, Joop A; Lukes, Ivan

2008-03-04

The adsorption on hydroxyapatite of three conjugates of a bisphosphonate and a macrocycle having C1, C2, and C3 spacers and their terbium complexes was studied by the radiotracer method using 160Tb as the label. The radiotracer-containing complex of the conjugate with the C3 spacer was used as a probe for the determination of the adsorption parameters of other bisphosphonates that lack a DOTA unit. A physicochemical model describing the competitive adsorption was successfully applied in the fitting of the obtained data. The maximum adsorption capacity of bisphosphonates containing bulky substituents is determined mainly by their size. For bisphosphonates having no DOTA moiety, the maximum adsorption capacity is determined by the electrostatic repulsion between negatively charged bisphosphonate groups. Compounds with a hydroxy or amino group attached to the alpha-carbon atom show higher affinities. Macrocyclic compounds containing a short spacer between the different bisphosphonic acid groups and the macrocyclic unit exhibit high affinities, indicating a synergic effect of the bisphosphonic and the macrocyclic groups during adsorption. The competition method described uses a well-characterized complex and allows a simple evaluation of the adsorption behavior of bisphosphonates. The application of the macrocycle-bisphosphonate conjugates allows easy radiolabeling via complexation of a suitable metal isotope.

Suitability of [18F]altanserin and PET to determine 5-HT2A receptor availability in the rat brain: in vivo and in vitro validation of invasive and non-invasive kinetic models.

PubMed

Kroll, Tina; Elmenhorst, David; Matusch, Andreas; Wedekind, Franziska; Weisshaupt, Angela; Beer, Simone; Bauer, Andreas

2013-08-01

While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats. Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals. Overall brain uptake of [18F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals. [18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.

Numerical study on simultaneous emission and transmission tomography in the MRI framework

NASA Astrophysics Data System (ADS)

Gjesteby, Lars; Cong, Wenxiang; Wang, Ge

2017-09-01

Multi-modality imaging methods are instrumental for advanced diagnosis and therapy. Specifically, a hybrid system that combines computed tomography (CT), nuclear imaging, and magnetic resonance imaging (MRI) will be a Holy Grail of medical imaging, delivering complementary structural/morphological, functional, and molecular information for precision medicine. A novel imaging method was recently demonstrated that takes advantage of radiotracer polarization to combine MRI principles with nuclear imaging. This approach allows the concentration of a polarized Υ-ray emitting radioisotope to be imaged with MRI resolution potentially outperforming the standard nuclear imaging mode at a sensitivity significantly higher than that of MRI. In our work, we propose to acquire MRI-modulated nuclear data for simultaneous image reconstruction of both emission and transmission parameters, suggesting the potential for simultaneous CT-SPECT-MRI. The synchronized diverse datasets allow excellent spatiotemporal registration and unique insight into physiological and pathological features. Here we describe the methodology involving the system design with emphasis on the formulation for tomographic images, even when significant radiotracer signals are limited to a region of interest (ROI). Initial numerical results demonstrate the feasibility of our approach for reconstructing concentration and attenuation images through a head phantom with various radio-labeled ROIs. Additional considerations regarding the radioisotope characteristics are also discussed.

Evaluation of the radiolabeled boronic acid-based FAP inhibitor MIP-1232 for atherosclerotic plaque imaging.

PubMed

Meletta, Romana; Müller Herde, Adrienne; Chiotellis, Aristeidis; Isa, Malsor; Rancic, Zoran; Borel, Nicole; Ametamey, Simon M; Krämer, Stefanie D; Schibli, Roger

2015-01-27

Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging.

Parametric PET/MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies

DTIC Science & Technology

2014-10-01

Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The study investigates whether fusion PET/MRI imaging with 18F- choline PET/CT and...imaging with 18F- choline PET/CT and diffusion-weighted MRI can be successfully applied to target prostate cancer using image-guided prostate...Completed task. The 18F- choline synthesis was implemented and optimized for routine radiotracer production. RDRC committee approval as part of the IRB

Occult Breast Cancer: Scintimammography with High-Resolution Breast-specific Gamma Camera in Women at High Risk for Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rachel F. Brem; Jocelyn A. Rapelyea; , Gilat Zisman

2005-08-01

To prospectively evaluate a high-resolution breast-specific gamma camera for depicting occult breast cancer in women at high risk for breast cancer but with normal mammographic and physical examination findings. MATERIALS AND METHODS: Institutional Review Board approval and informed consent were obtained. The study was HIPAA compliant. Ninety-four high-risk women (age range, 36-78 years; mean, 55 years) with normal mammographic (Breast Imaging Reporting and Data System [BI-RADS] 1 or 2) and physical examination findings were evaluated with scintimammography. After injection with 25-30 mCi (925-1110 MBq) of technetium 99m sestamibi, patients were imaged with a high-resolution small-field-of-view breast-specific gamma camera in craniocaudalmore » and mediolateral oblique projections. Scintimammograms were prospectively classified according to focal radiotracer uptake as normal (score of 1), with no focal or diffuse uptake; benign (score of 2), with minimal patchy uptake; probably benign (score of 3), with scattered patchy uptake; probably abnormal (score of 4), with mild focal radiotracer uptake; and abnormal (score of 5), with marked focal radiotracer uptake. Mammographic breast density was categorized according to BI-RADS criteria. Patients with normal scintimammograms (scores of 1, 2, or 3) were followed up for 1 year with an annual mammogram, physical examination, and repeat scintimammography. Patients with abnormal scintimammograms (scores of 4 or 5) underwent ultrasonography (US), and those with focal hypoechoic lesions underwent biopsy. If no lesion was found during US, patients were followed up with scintimammography. Specific pathologic findings were compared with scintimammographic findings. RESULTS: Of 94 women, 78 (83%) had normal scintimammograms (score of 1, 2, or 3) at initial examination and 16 (17%) had abnormal scintimammograms (score of 4 or 5). Fourteen (88%) of the 16 patients had either benign findings at biopsy or no focal abnormality at US; in two (12%) patients, invasive carcinoma was diagnosed at US-guided biopsy (9 mm each at pathologic examination). CONCLUSION: High-resolution breast-specific scintimammography can depict small (<1-cm), mammographically occult, nonpalpable lesions in women at increased risk for breast cancer not otherwise identified at mammography or physical examination.« less

Synthesis, biological evaluation, and molecular dynamics (MD) simulation studies of three novel F-18 labeled and focal adhesion kinase (FAK) targeted 5-bromo pyrimidines as radiotracers for tumor.

PubMed

Fang, Yu; Wang, Dawei; Xu, Xingyu; Liu, Jianping; Wu, Aiqin; Li, Xiang; Xue, Qianqian; Wang, Huan; Wang, Hang; Zhang, Huabei

2017-02-15

Focal adhesion kinase (FAK) is considered as an attractive target for oncology. A series of F-18 labeled 5-bromo-N 2 -(4-(2-fluoro-pegylated (FPEG))-3,5-dimethoxyphenyl)-N 4 -(4-methoxyphenyl)pyrimidine-2,4-diamine derivatives were prepared and evaluated as the FAK targeted radiotracers for the early diagnoses of tumor. For the study of the FAK targeted drug molecules, this was the first attempt to develop the tumor diagnostic imaging agents on the radiopharmaceutical level. They inhibited the activity of FAK with IC 50 in the range of 91.4-425.7 nM, and among which the result of the [ 19 F]2 was relatively good and had a modest IC 50 of 91.4 nM. The [ 19 F]2 was also profiled in vitro against some other kinds of cancer-related kinases (including two kinds of non-receptor tyrosine kinase: PYK2 and JAK2, and three kinds of receptor tyrosine kinase: IGF-1R, EGFR and PDGFRβ). It displayed 25.2 folds selectivity against PYK2, 35.1 folds selectivity against EGFR, and more than 100 folds selectivity against IGF-1R, JAK2 and PDGFRβ. For the biodistribution in S180 bearing mice, the corresponding [ 18 F]2 were also relatively good, with modest tumor uptake of 5.47 ± 0.19 and 5.80 ± 0.06 %ID/g at 15 and 30 min post-injection, respectively. Furthermore, its tumor/muscle, tumor/bone and tumor/blood ratio at 15 min post-injection were 3.16, 2.53 and 4.52, respectively. And its tumor/muscle, tumor/bone and tumor/blood ratio at 30 min post-injection were 3.14, 2.76 and 4.43, respectively. In addition, coronal micro-PET/CT images of a mouse bearing S180 tumor clearly confirmed that [ 18 F]2 could be accumulated in tumor, especially at 30 min post-injection. Besides, for the [ 18 F]2, both the biodistribution data and the micro-PET/CT imaging study showed significantly reduced uptake of the radiotracer in the tumor tissue at 30 min post-injection in mice that received PF-562,271 (one of the reported best selective FAK inhibitor which was developed by Pfitzer Inc. and inhibited the activity of FAK with IC 50 value of 1.5 nM) at 1 h before the injection of radiotracer. In combination with the above kinase profiling assay, it could be indicated that the uptake of [ 18 F]2 in tumor of the mouse model was due to FAK expression, and that [ 18 F]2 might be a kind of selectively FAK targeted tumor imaging agents. What's more, the results of the MD (molecular dynamics) simulations were in agreement with the changing trends of the interaction between the different F-19 standards and the FAK (expressed as the in vitro inhibitory abilities of enzymatic activities of FAK in this article), which was also in agreement with and had great effect on the changing trends of the uptake of the corresponding F-18 labeled tracers in tumor and some of theirs target/non-target ratios. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparative analysis of 99mTc-depreotide and 99mTc-EDDA/HYNIC-TOC thorax scintigrams acquired for the purpose of differential diagnosis of solitary pulmonary nodules.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Kozak, Józef; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2006-01-01

Aiming at comparison of diagnostic efficacy of 2 radiopharmaceuticals: 99mTc-depreotide (Neospect, Amersham) and 99mTc-EDDA/HYNIC-Tyr3-octreotide (Tektrotyd, Polatom), in differentiation between malignant and benign etiology of solitary pulmonary nodules (SPNs), radionuclide studies with 2 radiotracers were performed in 18 patients. For both radiopharmaceuticals the same acquisition and processing protocols were applied. Studies were acquired with SPECT technique, after administration of 740 MBq of activity. Scintigrams were assessed visually, as: positive (+), equivocal (+/-) and negative (-). Additionally, uptake intensity of both radiotracers in nodules was assessed semiquantitatively, using a tumour-to-background ratio. Verification of scintigraphic results was based in 14 cases upon a pathological examination of tumour samples (histopathology) and in the remaining 4 - on clinical observation and bacteriological studies. Normal scintigrams obtained with both radiopharmaceuticals differed significantly. 99mTc-depreotide was markedly accumulated in spine, sternum, ribs and lungs (mean lung/heart ratio = 2.2). This accumulation was not observed on 99mTc- -EDDA/HYNIC-TOC scintigrams (mean lung/heart ratio = 0.7). In 6 patients a malignant etiology--lung cancer--was revealed (5--adenocarcinoma, 1--squamous cell) and the other 12 cases turned out to be benign (4 hamartomas, 3 tuberculomas, a tuberculous infiltrate, an alien body with inflammatory reaction, a hyperplasia of lymphatic tissue and 2 cases of unknown etiology, from which one had a stable size and the other resolved during a 6 month observation period). In all 6 cases of lung cancer positive results were obtained with both tracers. Moreover, in 2 patients metastases in mediastinum could be observed on scintigrams obtained with both radiopharmaceuticals. From among 12 cases of benign etiology 6 99mTc-depreotide scintigrams were true negative, 1--equivocal and 5--false positive, whereas 6 99mTc-EDDA/HYNIC-TOC scintigrams were true negative, 4--equivocal and 2 false positive. Moreover, 99mTc-depreotide additionally revealed mediastinal and hilar lesions in 9 patients with benign lesions and 99mTc-EDDA/HYNIC-TOC - in 8. A visual comparison of scintigrams revealed a higher quality of 99mTc-Depreotide images in comparison with 99mTc-EDDA/HYNIC-TOC ones. 99mTc-Depreotide showed a higher than 99mTc-EDDA/HYNIC-TOC accumulation in lung tumours compared with blood pool (heart) - 4.5 (s.d. 1.05) and 1.8 (s.d. 0.29), respectively (p < 0.05). However, mean values of tumour-to-lung-background ratio were equal for both radiotracers (2.2 in malignant and 1.4 in benign lesions, respectively). A statistically significantly higher non-uniformity of counts inside lung background regions was found on 99mTc-EDDA/HYNIC-TOC scintigrams than on 99mTc-depreotide ones (16.4% vs. 11.4%; p < 0.01). Although both radiopharmaceuticals show similar diagnostic efficacy in differentiation of SPNs, a tendency toward a higher number of false positive results on 99mTc-depreotide scintigrams probably leads to a lower specificity. Better statistical quality of 99mTc-depreotide scintigrams facilitates their interpretation and a distinct outline of lungs simplify localization of lesions. A substantial number of false positive lesions in mediastinal and hilar regions in patients without a neoplastic process hamper the usefulness of both radiotracers for effective detection of lung cancer metastases to lymph nodes.

Poster — Thur Eve — 03: Application of the non-negative matrix factorization technique to [{sup 11}C]-DTBZ dynamic PET data for the early detection of Parkinson's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Dong-Chang; Jans, Hans; McEwan, Sandy

2014-08-15

In this work, a class of non-negative matrix factorization (NMF) technique known as alternating non-negative least squares, combined with the projected gradient method, is used to analyze twenty-five [{sup 11}C]-DTBZ dynamic PET/CT brain data. For each subject, a two-factor model is assumed and two factors representing the striatum (factor 1) and the non-striatum (factor 2) tissues are extracted using the proposed NMF technique and commercially available factor analysis software “Pixies”. The extracted factor 1 and 2 curves represent the binding site of the radiotracer and describe the uptake and clearance of the radiotracer by soft tissues in the brain, respectively.more » The proposed NMF technique uses prior information about the dynamic data to obtain sample time-activity curves representing the striatum and the non-striatum tissues. These curves are then used for “warm” starting the optimization. Factor solutions from the two methods are compared graphically and quantitatively. In healthy subjects, radiotracer uptake by factors 1 and 2 are approximately 35–40% and 60–65%, respectively. The solutions are also used to develop a factor-based metric for the detection of early, untreated Parkinson's disease. The metric stratifies healthy subjects from suspected Parkinson's patients (based on the graphical method). The analysis shows that both techniques produce comparable results with similar computational time. The “semi-automatic” approach used by the NMF technique allows clinicians to manually set a starting condition for “warm” starting the optimization in order to facilitate control and efficient interaction with the data.« less

Modelling and simulation of [18F]fluoromisonidazole dynamics based on histology-derived microvessel maps

NASA Astrophysics Data System (ADS)

Mönnich, David; Troost, Esther G. C.; Kaanders, Johannes H. A. M.; Oyen, Wim J. G.; Alber, Markus; Thorwarth, Daniela

2011-04-01

Hypoxia can be assessed non-invasively by positron emission tomography (PET) using radiotracers such as [18F]fluoromisonidazole (Fmiso) accumulating in poorly oxygenated cells. Typical features of dynamic Fmiso PET data are high signal variability in the first hour after tracer administration and slow formation of a consistent contrast. The purpose of this study is to investigate whether these characteristics can be explained by the current conception of the underlying microscopic processes and to identify fundamental effects. This is achieved by modelling and simulating tissue oxygenation and tracer dynamics on the microscopic scale. In simulations, vessel structures on histology-derived maps act as sources and sinks for oxygen as well as tracer molecules. Molecular distributions in the extravascular space are determined by reaction-diffusion equations, which are solved numerically using a two-dimensional finite element method. Simulated Fmiso time activity curves (TACs), though not directly comparable to PET TACs, reproduce major characteristics of clinical curves, indicating that the microscopic model and the parameter values are adequate. Evidence for dependence of the early PET signal on the vascular fraction is found. Further, possible effects leading to late contrast formation and potential implications on the quantification of Fmiso PET data are discussed.

Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models.

PubMed

Sharma, Sai Kiran; Chow, Andrew; Monette, Sebastien; Vivier, Delphine; Pourat, Jacob; Edwards, Kimberly J; Dilling, Thomas R; Abdel-Atti, Dalya; Zeglis, Brian M; Poirier, John T; Lewis, Jason S

2018-04-01

A critical benchmark in the development of antibody-based therapeutics is demonstration of efficacy in preclinical mouse models of human disease, many of which rely on immunodeficient mice. However, relatively little is known about how the biology of various immunodeficient strains impacts the in vivo fate of these drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric, and murine mAbs against four therapeutic oncologic targets to interrogate their biodistribution in four different strains of immunodeficient mice bearing lung, prostate, and ovarian cancer xenografts. The immunodeficiency status of the mouse host as well as both the biological origin and glycosylation of the antibody contributed significantly to the anomalous biodistribution of therapeutic monoclonal antibodies in an Fc receptor-dependent manner. These findings may have important implications for the preclinical evaluation of Fc-containing therapeutics and highlight a clear need for biodistribution studies in the early stages of antibody drug development. Significance: Fc/FcγR-mediated immunobiology of the experimental host is a key determinant to preclinical in vivo tumor targeting and efficacy of therapeutic antibodies. Cancer Res; 78(7); 1820-32. ©2018 AACR . ©2018 American Association for Cancer Research.

Fate of 14C-acrylamide in roasted and ground coffee during storage.

PubMed

Baum, Matthias; Böhm, Nadine; Görlitz, Jessica; Lantz, Ingo; Merz, Karl Heinz; Ternité, Rüdiger; Eisenbrand, Gerhard

2008-05-01

Acrylamide (AA) is formed during heating of carbohydrate rich foods in the course of the Maillard reaction. AA has been classified as probably carcinogenic to humans. Storage experiments with roasted coffee have shown that AA levels decrease depending on storage time and temperature. In the present study the fate of AA lost during storage of roasted and ground (R&G) coffee was studied, using 14C-labeled AA as radiotracer. Radiolabel was measured in coffee brew, filter residue, and volatiles. In the brew, total (14)C-label decreased during storage of R&G coffee, while activity in the filter residue built up concomitantly. [2,3-14C]-AA (14C-AA) was the only 14C-related water extractable low molecular compound in the brew detected by radio-HPLC. No formation of volatile 14C-AA-related compounds was detected during storage and coffee brewing. Close to 90% of the radiolabel in the filter residue (spent R&G coffee, spent grounds) remained firmly bound to the matrix, largely resisting extraction by aqueous ammonia, ethyl acetate, chloroform, hexane, and sequential polyenzymatic digest. Furanthiols, which are abundant as aroma components in roasted coffee, have not been found to be involved in the formation of covalent AA adducts and thus do not contribute substantially to the decrease of AA during storage.

Integrin αvβ3 as a Promising Target to Image Neoangiogenesis Using In-House Generator-Produced Positron Emitter (68)Ga-Labeled DOTA-Arginine-Glycine-Aspartic Acid (RGD) Ligand.

PubMed

Vatsa, Rakhee; Bhusari, Priya; Kumar, Sunil; Chakraborty, Sudipta; Dash, Ashutosh; Singh, Gurpreet; Dhawan, Devinder Kumar; Shukla, Jaya; Mittal, Bhagwant Rai

2015-06-01

For the growth and spread of a tumor beyond 2 mm, angiogenesis plays a crucial role, and association of various integrins with angiogenesis is evidential. The aim of the study was radiolabeling of DOTA-chelated RGD (arginine-glycine-aspartic acid) peptide with (68)Ga for PET imaging in locally advanced breast carcinoma. DOTA-RGD was incubated with (68)GaCl3, eluted in 0.05 m HCl. Elution volume, peptide amount, and reaction pH were studied. Radio-ITLC, gas chromatography, endotoxin, and sterility testing were performed. Serial (n=3) and whole-body (n=2) PET/CT imaging was done on patients post i.v. injection of 111-185 MBq of (68)Ga-DOTA-RGD. Maximum radiolabeling yield was achieved with 3 mL elution volume of 15-20 μg peptide at pH 3.5-4.0 with 10 minutes of incubation at 95°C. Product samples were sterile having 99.5% radiochemical purity with residual ethanol content and endotoxins in injectable limits. Intense radiotracer uptake was noticed in the tumor with SUVmax 15.3 at 45 minutes in serial images. Physiological radiotracer uptake was seen in the liver, spleen, ventricles, and thyroid with excretion through the kidneys. The authors concluded that (68)Ga-DOTA-RGD has the potential for imaging α,vβ3 integrin-expressing tumors.

Overview of SIMS-Based Experimental Studies of Tracer Diffusion in Solids and Application to Mg Self-Diffusion

DOE PAGES

Kulkarni, Nagraj S.; Bruce Warmack, Robert J.; Radhakrishnan, Bala; ...

2014-09-23

Tracer diffusivities provide the most fundamental information on diffusion in materials and are the foundation of robust diffusion databases. Compared to traditional radiotracer techniques that utilize radioactive isotopes, the secondary ion mass spectrometry (SIMS) based thin-film technique for tracer diffusion is based on the use of enriched stable isotopes that can be accurately profiled using SIMS. Experimental procedures & techniques that are utilized for the measurement of tracer diffusion coefficients are presented for pure magnesium, which presents some unique challenges due to the ease of oxidation. The development of a modified Shewmon-Rhines diffusion capsule for annealing Mg and an ultra-highmore » vacuum (UHV) system for sputter deposition of Mg isotopes are discussed. Optimized conditions for accurate SIMS depth profiling in polycrystalline Mg are provided. An automated procedure for the correction of heat-up and cool-down times during tracer diffusion annealing is discussed. The non-linear fitting of a SIMS depth profile data using the thin film Gaussian solution to obtain the tracer diffusivity along with the background tracer concentration and tracer film thickness is discussed. An Arrhenius fit of the Mg self-diffusion data obtained using the low-temperature SIMS measurements from this study and the high-temperature radiotracer measurements of Shewmon and Rhines (1954) was found to be a good representation of both types of diffusion data that cover a broad range of temperatures between 250 - 627° C (523 900 K).« less

PET Imaging of Estrogen Metabolism in Breast Cancer

DTIC Science & Technology

2001-06-01

consistently produces a product free from bacteria and fever producing compounds. No allergic reactions caused by contamination of the radiotracer have been... Patologica , Mexico City 1977-1978 Research Assistant, Miles Lab. Exp. Therap., Mexico City, Mexico 1979-1980 Intern, Centre des Maladies et de

Preparation of a novel radiotracer targeting the EphB4 receptor via radiofluorination using spiro azetidinium salts as precursor.

PubMed

Wiemer, Jens; Steinbach, Jörg; Pietzsch, Jens; Mamat, Constantin

2017-08-01

The visualization of Eph receptors, which are overexpressed in various tumor entities, using selective small molecule Eph inhibitors by means of positron emission tomography is a promising approach for tumor imaging. N-(Pyrimidinyl)indazolamines represent a class of compounds, which are known to have high affinity especially for the EphB4 receptor. Radiofluorination of these compounds could provide a highly specific imaging agent and was investigated using a classical nucleophilic introduction of [ 18 F]fluoride as well as a less common nucleophilic ring-opening reaction of azetidinium salts. In the past, radiofluorinations using azetidinium precursors were demonstrated to result in high radiochemical yields in short periods. For this purpose, an azetidinium precursor based on the N-(pyrimidinyl)indazolamine lead compound was developed, and radiofluorination was successfully accomplished. The respective [ 18 F]radiotracer was quickly prepared with high radiochemical purity >97% and in a radiochemical yield of 34%. Copyright © 2017 John Wiley & Sons, Ltd.

The contribution of physics to Nuclear Medicine: physicians' perspective on future directions.

PubMed

Mankoff, David A; Pryma, Daniel A

2014-12-01

Advances in Nuclear Medicine physics enabled the specialty of Nuclear Medicine and directed research in other aspects of radiotracer imaging, ultimately leading to Nuclear Medicine's emergence as an important component of current medical practice. Nuclear Medicine's unique ability to characterize in vivo biology without perturbing it will assure its ongoing role in a practice of medicine increasingly driven by molecular biology. However, in the future, it is likely that advances in molecular biology and radiopharmaceutical chemistry will increasingly direct future developments in Nuclear Medicine physics, rather than relying on physics as the primary driver of advances in Nuclear Medicine. Working hand-in-hand with clinicians, chemists, and biologists, Nuclear Medicine physicists can greatly enhance the specialty by creating more sensitive and robust imaging devices, by enabling more facile and sophisticated image analysis to yield quantitative measures of regional in vivo biology, and by combining the strengths of radiotracer imaging with other imaging modalities in hybrid devices, with the overall goal to enhance Nuclear Medicine's ability to characterize regional in vivo biology.

Design and evaluation of radiotracers for determination of regional cerebral blood flow with PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lambrecht, R.M.; Duncan, C.C.; Shiue, C.Y.

The tracer kinetics of 4-Fluoro(/sup 18/F)-, 4-Bromo(/sup 82/Br)- and 4-Iodo(/sup 125/I)-antipyrine and /sup 15/O-water were compared in a cat or baboon animal model. First-pass cerebral extraction and clearance with alterations in PaCO/sub 2/ were measured for whole brain. The Renkin/Crone model was used to evaluate brain capillary permeability-surface area product for 4-/sup 18/FAP in cats. Positron-emission-tomographic measurements required development of an instrument and technique for control of the arterial concentration of the radiotracer as a ramp function, so that tracer concentration changes due to radioactive decay or altered physiological processes could be accurately described with PET. Pharmacokinetic and tissue-distribution studiesmore » in cats were used to determine dosimetry for 4-/sup 18/FAP. 4-Bromoantipyrine labeled with /sup 78/Br (t = 6.5 m) is suggested as a tracer for determination of rCBF with PET.« less

Over-the-counter drugs block heart accumulation of MIBG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sherman, P.S.; Fisher, S.J.; Wieland, D.M.

1985-05-01

Previous work in the authors' laboratory using chemically sympathectomized animals showed that > 50% of meta-iodobenzyl-guanidine (MIBG) in the heart is localized in adrenergic nerves. In the present study, commonly used drugs known to alter the uptake and/or release of norepinephrine by adrenergic neurons have been evaluated for their effect on the biodistribution of MIBG. Pseudoephedrine (Sudafed), phenylpropanolamine (Dexatrim) and phenylephrine (Neosynephrine) were administered (5 mg/kg, i.p.) to rats; amphetamine was also evaluated (0.8mg/kg, i.p.). Thirty minutes later I-125-MIBG (0.2-0.4 Ci/mm) was injected i.v.; animals (N=3) were sacrificed 2 h following radiotracer. Compared to controls (N = 3), drug pretreatmentsmore » resulted in large decreases in radiotracer concentration in adrenergic-rich tissues such as left atrium, left ventricle, spleen and parotid glands. Pseudoephedrine caused decreases (%) of 78, 57, 48 and 35 in the four tissues, respectively. Each of the four drugs caused a greater decrease in I-125-MIBG concentration in the left atrium than in the left ventricle. Comparative studies using H-3-norepinephrine are in progress. Entex, a nasal decongestant containing both phenylephrine and phenylpropanolamine, markedly diminished the heart and salivary gland accumulation of I-123-MIBG in a normal male volunteer. These preliminary studies suggest that commonly used sympathomimetic agents, including some over-the-counter preparations, decrease the accumulation of MIBG in adrenergic neurons. These results also suggest that patients should be carefully screened for drug usage prior to MIBG scintigraphy of the heart.« less

Adefovir-Induced Hypophosphatemic Osteomalacia Mimicking Bone Metastases From Primary Hepatocarcinoma.

PubMed

Wei, Wei-Jun; Sun, Zhen-Kui; Shen, Chen-Tian; Qiu, Zhong-Ling; Luo, Quan-Yong

2017-09-01

Adefovir-induced hypophosphatemic osteomalacia in the context of hepatocarcinoma is rare and needs to be differentiated from metastatic hepatocarcinoma. We here report a case of severe osteomalacia whose focal uptakes of radiotracer on the Tc-MDP SPECT/CT images mimicked that of metastatic hepatocarcinoma.

Mercury methylation and reduction potentials in marine water: An improved methodology using 197Hg radiotracer.

PubMed

Koron, Neža; Bratkič, Arne; Ribeiro Guevara, Sergio; Vahčič, Mitja; Horvat, Milena

2012-01-01

A highly sensitive laboratory methodology for simultaneous determination of methylation and reduction of spiked inorganic mercury (Hg(2+)) in marine water labelled with high specific activity radiotracer ((197)Hg prepared from enriched (196)Hg stable isotope) was developed. A conventional extraction protocol for methylmercury (CH(3)Hg(+)) was modified in order to significantly reduce the partitioning of interfering labelled Hg(2+) into the final extract, thus allowing the detection of as little as 0.1% of the Hg(2+) spike transformed to labelled CH(3)Hg(+). The efficiency of the modified CH(3)Hg(+) extraction procedure was assessed by radiolabelled CH(3)Hg(+) spikes corresponding to concentrations of methylmercury between 0.05 and 4ngL(-1). The recoveries were 73.0±6.0% and 77.5±3.9% for marine and MilliQ water, respectively. The reduction potential was assessed by purging and trapping the radiolabelled elemental Hg in a permanganate solution. The method allows detection of the reduction of as little as 0.001% of labelled Hg(2+) spiked to natural waters. To our knowledge, the optimised methodology is among the most sensitive available to study the Hg methylation and reduction potential, therefore allowing experiments to be done at spikes close to natural levels (1-10ngL(-1)). Copyright © 2011 Elsevier Ltd. All rights reserved.

Simultaneous in vivo positron emission tomography and magnetic resonance imaging.

PubMed

Catana, Ciprian; Procissi, Daniel; Wu, Yibao; Judenhofer, Martin S; Qi, Jinyi; Pichler, Bernd J; Jacobs, Russell E; Cherry, Simon R

2008-03-11

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner.

Development of Water Target for Radioisotope Production

NASA Astrophysics Data System (ADS)

Tripp, Nathan

2011-10-01

Ongoing studies of plant physiology at TUNL require a supply of nitrogen-13 for use as a radiotracer. Production of nitrogen-13 using a water target and a proton beam follows the nuclear reaction 16-O(p,a)13-N. Unfortunately the irradiation of trace amounts of oxygen-18 within a natural water target produces fluorine-18 by the reaction 18-O(p, n)18-F. The presence of this second radioisotope reduces the efficacy of nitrogen-13 as a radiotracer. Designing a natural water target for nitrogen-13 production at TUNL required the design of several new systems to address the problems inherent in nitrogen-13 production. A heat exchanger cools the target water after irradiation within the target cell. The resulting improved thermal regulation of the target water prevents the system from overheating and minimizes the effect of the cavitations occurring within the target. Alumina pellets within a scrubbing unit remove the fluorine-18 contamination from the irradiated water. The modular design of the water target apparatus makes the system highly adaptable, allowing for easy reuse and adaptation of the different components into future projects. The newly designed and constructed water target should meet the current and future needs of TUNL researchers in the production of nitrogen-13. This TUNL REU project was funded in part by a grant from the National Science Foundation (NSF) NSF-PHY-08-51813.

PIXSIC: A Pixellated Beta-Microprobe for Kinetic Measurements of Radiotracers on Awake and Freely Moving Small Animals

NASA Astrophysics Data System (ADS)

Godart, J.; Weiss, P.; Chantepie, B.; Clemens, J. C.; Delpierre, P.; Dinkespiler, B.; Janvier, B.; Jevaud, M.; Karkar, S.; Lefebvre, F.; Mastrippolito, R.; Menouni, M.; Pain, F.; Pangaud, P.; Pinot, L.; Morel, C.; Laniece, P.

2010-06-01

We present a design study of PIXSIC, a new β+ radiosensitive microprobe implantable in rodent brain dedicated to in vivo and autonomous measurements of local time activity curves of beta radiotracers in a small (a few mm3) volume of brain tissue. This project follows the initial β microprobe previously developed at IMNC, which has been validated in several neurobiological experiments. This first prototype has been extensively used on anesthetized animals, but presents some critical limits for utilization on awake and freely moving animals. Consequently, we propose to develop a wireless setup that can be worn by an animal without constraints upon its movements. To that aim, we have chosen a Silicon-based detector, highly β sensitive, which allows for the development of a compact pixellated probe (typically 600 × 200 × 1000 μm3), read out with miniaturized wireless electronics. Using Monte-Carlo simulations, we show that high resistive Silicon pixels are appropriate for this purpose, assuming that the pixel dimensions are adapted to our specific signals. More precisely, a tradeoff has to be found between the sensitivity to β+ particles and to the 511 keV j background resulting from annihilations of β+ with electrons. We demonstrate that pixels with maximized surface and minimized thickness can lead to an optimization of their β+ sensitivity with a relative transparency to the annihilation background.

Exploring the relationship between social attachment and dopamine D2/3 receptor availability in the brains of healthy humans using [11C]-(+)-PHNO

PubMed Central

Caravaggio, Fernando; Chung, Jun Ku; Gerretsen, Philip; Fervaha, Gagan; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

2017-01-01

Differences in striatal dopamine (DA) function may be related to differences in the degree of social attachment to others. Using positron emission tomography (PET), socially detached persons demonstrate reduced DA D2/3 receptor (D2/3R) availability in the striatum. However, previous PET studies have only used antagonist radiotracers for D2/3R and have not specifically examined regions of interest (ROIs) such as the ventral striatum (VS). In 32 healthy persons, we investigated the relationship between self-reported attachment and DA D2/3R availability in striatal and extrastriatal ROIs as measured using the agonist radiotracer [11C]-(+)-PHNO. Surprisingly, more social attachment—as measured by the attachment subscale of the temperament and character inventory—was related to less [11C]-(+)-PHNO binding in the VS (r(30) =−.43, p = .01). This relationship held in a subsample who also completed the detachment subscale of the Karolinska Scales of Personality (r(10) = .62, p = .03). However, no relationships were observed with BPND in the dorsal striatum or D3R-specific ROIs. One potential explanation for these findings is that persons who are more socially detached have less endogenous DA occupying D2/3R in the VS. This interpretation warrants investigation by future research. These findings may help us better understand the neurochemical basis of attachment. PMID:26873034

Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure† †Electronic supplementary information (ESI) available: 1H NMR and 13C NMR data for characterised compounds, automation setup, HPLC traces from radiosynthesis, Log D7.4 and radiotracer stability procedures, raw data and HPLC traces from all in vitro and in vivo studies. See DOI: 10.1039/c8ob00432c

PubMed Central

King, Alice; Doepner, Andreas; Turton, David; Ciobota, Daniela M.; Da Pieve, Chiara; Wong Te Fong, Anne-Christine; Kramer-Marek, Gabriela; Chung, Yuen-Li

2018-01-01

Trifluoromethyl groups are widespread in medicinal chemistry, yet there are limited 18F-radiochemistry techniques available for the production of the complementary PET agents. Herein, we report the first radiosynthesis of the anticancer nucleoside analogue trifluridine, using a fully automated, clinically-applicable 18F-trifluoromethylation procedure. [18F]Trifluridine was obtained after two synthetic steps in <2 hours. The isolated radiochemical yield was 3% ± 0.44 (n = 5), with a radiochemical purity >99%, and a molar activity of 0.4 GBq μmol–1 ± 0.05. Biodistribution and PET-imaging data using HCT116 tumour-bearing mice showed a 2.5 %ID g–1 tumour uptake of [18F]trifluridine at 60 minutes post-injection, with bone uptake becoming a prominent feature thereafter. In vivo metabolite analysis of selected tissues revealed the presence of the original radiolabelled nucleoside analogue, together with deglycosylated and phosphorylated [18F]trifluridine as the main metabolites. Our findings suggest a potential role for [18F]trifluridine as a PET radiotracer for elucidation of drug mechanism of action. PMID:29629716

VOXEL-LEVEL MAPPING OF TRACER KINETICS IN PET STUDIES: A STATISTICAL APPROACH EMPHASIZING TISSUE LIFE TABLES.

PubMed

O'Sullivan, Finbarr; Muzi, Mark; Mankoff, David A; Eary, Janet F; Spence, Alexander M; Krohn, Kenneth A

2014-06-01

Most radiotracers used in dynamic positron emission tomography (PET) scanning act in a linear time-invariant fashion so that the measured time-course data are a convolution between the time course of the tracer in the arterial supply and the local tissue impulse response, known as the tissue residue function. In statistical terms the residue is a life table for the transit time of injected radiotracer atoms. The residue provides a description of the tracer kinetic information measurable by a dynamic PET scan. Decomposition of the residue function allows separation of rapid vascular kinetics from slower blood-tissue exchanges and tissue retention. For voxel-level analysis, we propose that residues be modeled by mixtures of nonparametrically derived basis residues obtained by segmentation of the full data volume. Spatial and temporal aspects of diagnostics associated with voxel-level model fitting are emphasized. Illustrative examples, some involving cancer imaging studies, are presented. Data from cerebral PET scanning with 18 F fluoro-deoxyglucose (FDG) and 15 O water (H2O) in normal subjects is used to evaluate the approach. Cross-validation is used to make regional comparisons between residues estimated using adaptive mixture models with more conventional compartmental modeling techniques. Simulations studies are used to theoretically examine mean square error performance and to explore the benefit of voxel-level analysis when the primary interest is a statistical summary of regional kinetics. The work highlights the contribution that multivariate analysis tools and life-table concepts can make in the recovery of local metabolic information from dynamic PET studies, particularly ones in which the assumptions of compartmental-like models, with residues that are sums of exponentials, might not be certain.

Development of kit formulations for (99m) TcN-MPO: a cationic radiotracer for myocardial perfusion imaging.

PubMed

Zheng, Yumin; Ji, Shundong; Tomaselli, Elena; Liu, Shuang

2014-07-01

The objective of this study was to develop a kit formulation for [(99m) TcN(mpo)(PNP5)](+) (MPO = 2-mercaptopyridine oxide), ((99m) TcN-MPO) to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two-vial formulation and single-vial formulations with/without SnCl2 ) to explore the factors influencing radiochemical purity (RCP) of (99m) TcN-MPO. We found that the most important factor affecting the RCP of (99m) TcN-MPO was the purity of PNP5. (99m) TcN-MPO was prepared >98% RCP (n = 20) using the two-vial formulation. For single-vial formulations with/without SnCl2 , β-cyclodextrin (β-CD) is particularly useful as a stabilizer for PNP5. The RCP of (99m) TcN-MPO was 95-98% using β-CD, but its RCP was only 90-93% with γ-cyclodextrin (γ-CD). It seems that PNP5 fits better into the inner cavity of β-CD, which forms more stable inclusion complex than γ-CD in the single-vial formulations. The results from biodistribution and imaging studies in Sprague-Dawley rats clearly demonstrated biological equivalence of three different formulations. Single photon-emission computed tomography data suggested that high quality images could be obtained at 0-30-min post-injection without significant interference from the liver radioactivity. Considering the ease for (99m) Tc-labeling and high RCP of (99m) TcN-MPO, the non-SnCl2 single-vial formulation is an attractive choice for future clinical studies. Copyright © 2014 John Wiley & Sons, Ltd.

Iron levels change in larval Heliothis virescens tissues following baculovirus infection

USDA-ARS?s Scientific Manuscript database

Inductively-coupled plasma mass spectrometry (ICP-MS) and 59Fe radiotracers were used to investigate changes in levels of iron (Fe) in the tissues of Heliothis virescens following baculovirus infection. Fe concentrations were determined by ICP-MS in hemolymph collected from 4th instar larvae infect...

Simultaneous acquisition of (99m)Tc- and (123)I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors.

PubMed

Kobayashi, Masato; Matsunari, Ichiro; Nishi, Kodai; Mizutani, Asuka; Miyazaki, Yoshiharu; Ogai, Kazuhiro; Sugama, Jyunko; Shiba, Kazuhiro; Kawai, Keiichi; Kinuya, Seigo

2016-05-01

Simultaneous acquisition of (99m)Tc and (123)I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors. 10-ml cylindrical syringes contained about 37 MBq (99m)Tc-tetrofosmin ((99m)Tc-TF) or 37 MBq (123)I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid ((123)I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP to assess the influence of (99m)Tc upscatter and (123)I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. Two 1-ml syringes contained 105 MBq (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) and 35 MBq (123)I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ((123)I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq (99m)Tc-HMPAO and 35 MBq (123)I-FP-CIT. The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of (123)I-BMIPP exhibited fewer radioactive counts for 300 MBq (99m)Tc-TF without scatter correction (SC) in 125-150 keV. There was no upscatter contamination of (99m)Tc-TF in 150-175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq (99m)Tc-TF without SC in 125-150 keV. In the rats, myocardial images and radioactive counts of (99m)Tc-TF with the dual tracer were identical to those of the (99m)Tc-TF single injection. Downscatter contamination of (123)I-FP-CIT was 4.2 % without SC in 125-150 keV. In the first injection of (99m)Tc-HMPAO and second injection of (123)I-FP-CIT, brain images and radioactive counts of (99m)Tc-HMPAO with the dual tracer in normal mice also were the similar to those of the (99m)Tc-HMPAO single injection. In the first injection of (123)I-FP-CIT and second injection of (99m)Tc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the (123)I-FP-CIT single injection. Dual-tracer imaging of (99m)Tc- and (123)I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of (99m)Tc-labeled radiotracers relative to (123)I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of (99m)Tc- and (123)I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

Fluorescent sensors reporting the activity of ammonium transceptors in live cells

DOE PAGES

De Michele, Roberto; Ast, Cindy; Loqué, Dominique; ...

2013-07-02

Ammonium serves as key nitrogen source and metabolic intermediate, yet excess causes toxicity. Ammonium uptake is mediated by ammonium transporters, whose regulation is poorly understood. While transport can easily be characterized in heterologous systems, measuring transporter activity in vivo remains challenging. Here we developed a simple assay for monitoring activity in vivo by inserting circularly-permutated GFP into conformation-sensitive positions of two plant and one yeast ammonium transceptors (‘AmTrac’ and ‘MepTrac’). Addition of ammonium to yeast cells expressing the sensors triggered concentration-dependent fluorescence intensity (FI) changes that strictly correlated with the activity of the transporter. Fluorescence-based activity sensors present a novelmore » technology for monitoring the interaction of the transporters with their substrates, the activity of transporters and their regulation in vivo, which is particularly valuable in the context of analytes for which no radiotracers exist, as well as for cell-specific and subcellular transport processes that are otherwise difficult to track.« less

Mapping brain function in freely moving subjects

PubMed Central

Holschneider, Daniel P.; Maarek, Jean-Michel I.

2014-01-01

Expression of many fundamental mammalian behaviors such as, for example, aggression, mating, foraging or social behaviors, depend on locomotor activity. A central dilemma in the functional neuroimaging of these behaviors has been the fact that conventional neuroimaging techniques generally rely on immobilization of the subject, which extinguishes all but the simplest activity. Ideally, imaging could occur in freely moving subjects, while presenting minimal interference with the subject’s natural behavior. Here we provide an overview of several approaches that have been undertaken in the past to achieve this aim in both tethered and freely moving animals, as well as in nonrestrained human subjects. Applications of specific radiotracers to single photon emission computed tomography and positron emission tomography are discussed in which brain activation is imaged after completion of the behavioral task and capture of the tracer. Potential applications to clinical neuropsychiatry are discussed, as well as challenges inherent to constraint-free functional neuroimaging. Future applications of these methods promise to increase our understanding of the neural circuits underlying mammalian behavior in health and disease. PMID:15465134

Viability and proliferation potential of adipose-derived stem cells following labeling with a positron-emitting radiotracer.

PubMed

Elhami, Esmat; Goertzen, Andrew L; Xiang, Bo; Deng, Jixian; Stillwell, Chris; Mzengeza, Shadreck; Arora, Rakesh C; Freed, Darren; Tian, Ganghong

2011-07-01

Adipose-derived stem cells (ASCs) have promising potential in regenerative medicine and cell therapy. Our objective is to examine the biological function of the labeled stem cells following labeling with a readily available positron emission tomography (PET) tracer, (18)F-fluoro-2-deoxy-D: -glucose (FDG). In this work we characterize labeling efficiency through assessment of FDG uptake and retention by the ASCs and the effect of FDG on cell viability, proliferation, transdifferentiation, and cell function in vitro using rat ASCs. Samples of 10(5) ASCs (from visceral fat tissue) were labeled with concentrations of FDG (1-55 Bq/cell) in 0.75 ml culture medium. Label uptake and retention, as a function of labeling time, FDG concentration, and efflux period were measured to determine optimum cell labeling conditions. Cell viability, proliferation, DNA structure damage, cell differentiation, and other cell functions were examined. Non-labeled ASC samples were used as a control for all experimental groups. Labeled ASCs were injected via tail vein in several healthy rats and initial cell biodistribution was assessed. Our results showed that FDG uptake and retention by the stem cells did not depend on FDG concentration but on labeling and efflux periods and glucose content of the labeling and efflux media. Cell viability, transdifferentiation, and cell function were not greatly affected. DNA damage due to FDG radioactivity was acute, but reversible; cells managed to repair the damage and continue with cell cycles. Over all, FDG (up to 25 Bq/cell) did not impose severe cytotoxicity in rat ASCs. Initial biodistribution of the FDG-labeled ASCs was 80% + retention in the lungs. In the delayed whole-body images (2-3 h postinjection) there was some activity distribution resembling typical FDG uptake patterns. For in vivo cell tracking studies with PET tracers, the parameter of interest is the amount of radiotracer that is present in the cells being labeled and consequent biological effects. From our study we developed a labeling protocol for labeling ASCs with a readily available PET tracer, FDG. Our results indicate that ASCs can be safely labeled with FDG concentration up to 25 Bq/cell, without compromising their biological function. A labeling period of 90 min in glucose-free medium and efflux of 60 min in complete media resulted in optimum label retention, i.e., 60% + by the stem cells. The initial biodistribution of the implanted FDG-labeled stem cells can be monitored using microPET imaging.

TH-C-17A-02: New Radioluminescence Strategies Based On CRET (Cerenkov Radiation Energy Transfer) for Imaging and Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volotskova, O; Sun, C; Pratx, G

2014-06-15

Purpose: Cerenkov photons are produced when charged particles, emitted from radionuclides, travel through a media with a speed greater than that of the light in the media. Cerenkov radiation is mostly in the UV/Blue region and, thus, readily absorbed by biological tissue. Cerenkov Radiation Energy Transfer (CRET) is a wavelength-shifting phenomenon from blue Cerenkov light to more penetrating red wavelengths. We demonstrate the feasibility of in-depth imaging of CRET light originating from radionuclides realized by down conversion of gold nanoclusters (AuNCs, a novel particle composed of few atoms of gold coated with serum proteins) in vivo. Methods: Bovine Serum Albumin,more » Human Serum Albumin and Transferrin conjugated gold nanoclusters were synthesized, characterized and examined for CRET. Three different clinically used radiotracers: 18F-FDG, 90Y and 99mTc were used. Optical spectrum (440–750 nm) was recorded by sensitive bioluminescence imaging system at physiological temperature. Dose dependence (activity range from 0.5 up to 800uCi) and concentration dependence (0.01 to 1uM) studies were carried out. The compound was also imaged in a xenograft mouse model. Results: Only β+ and β--emitting radionuclides (18F-FDG, 90Y) are capable of CRET; no signal was found in 99mTc (γ-emitter). The emission peak of CRET by AuNCs was found to be ∼700 nm and was ∼3 fold times of background. In vitro studies showed a linear dependency between luminescence intensity and dose and concentration. CRET by gold nanoclusters was observed in xenografted mice injected with 100uCi of 18F-FDG. Conclusion: The unique optical, transport and chemical properties of AuNCs (gold nanoclusters) make them ideal candidates for in-vivo imaging applications. Development of new molecular imaging probes will allow us to achieve substantially improved spatiotemporal resolution, sensitivity and specificity for tumor imaging and detection.« less

Positron Emission Tomography Molecular Imaging in Late-Life Depression

PubMed Central

Hirao, Kentaro; Smith, Gwenn S.

2017-01-01

Molecular imaging represents a bridge between basic and clinical neuroscience observations and provides many opportunities for translation and identifying mechanisms that may inform prevention and intervention strategies in late-life depression (LLD). Substantial advances in instrumentation and radiotracer chemistry have resulted in improved sensitivity and spatial resolution and the ability to study in vivo an increasing number of neurotransmitters, neuromodulators, and, importantly, neuropathological processes. Molecular brain imaging studies in LLD will be reviewed, with a primary focus on positron emission tomography. Future directions for the field of molecular imaging in LLD will be discussed, including integrating molecular imaging with genetic, neuropsychiatric, and cognitive outcomes and multimodality neuroimaging. PMID:24394152

(R)-N-Methyl-3-(3′-[18F]fluoropropyl)phenoxy)-3-phenylpropanamine (18F-MFP3) as a potential PET imaging agent for norepinephrine transporter

PubMed Central

Nguyen, Vivien L.; Pichika, Rama; Bhakta, Paayal H.; Kant, Ritu; Mukherjee, Jogeshwar

2010-01-01

A decline of norepinephrine transporter (NET) level is associated with several psychiatric and neurological disorders. Therefore positron emission tomography (PET) imaging agents are greatly desired to study the NET pathway. We have developed a C-fluoropropyl analog of nisoxetine: (R)-N-methyl-3-(3′-[18F]fluoropropyl)phenoxy)-3-phenylpropanamine (18F-MFP3) as a new potential PET radiotracer for NET with the advantage of the longer half-life of fluorine-18 (110 min compared with carbon-11 (20 min). Synthesis of (R)-N-methyl-3-(3′-fluoropropyl)phenoxy)-3-phenylpropanamine (MFP3) was achieved in five steps starting from (S)-N-methyl-3-ol-3-phenylpropanamine in approx. 3–5% overall yields. In vitro binding affinity of nisoxetine and MFP3 in rat brain homogenates labeled with 3H-nisoxetine gave Ki values of 8.02 nM and 23 nM, respectively. For radiosynthesis of 18F-MFP3, fluorine-18 was incorporated into a tosylate precursor, followed by the deprotection of the N-BOC-protected amine group with a 15% decay corrected yield in 2.5 h. Reverse-phase chromatographic purification provided 18F-MFP3 in specific activities of >2000 Ci/mmol. Fluorine-18 labeled 18F-MFP3 has been produced in modest radiochemical yields and in high specific activities. Evaluation of 18F-MFP3 in animal imaging studies is in progress in order to validate this new fluorine-18 radiotracer for PET imaging of NET. PMID:20495670

Assessing activation of hepatic stellate cells by (99m)Tc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study.

PubMed

Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

2015-03-01

Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose. We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94). (99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for assessing activation of HSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study.

PubMed

Brody, Arthur L; Hubert, Robert; Enoki, Ryutaro; Garcia, Lizette Y; Mamoun, Michael S; Okita, Kyoji; London, Edythe D; Nurmi, Erika L; Seaman, Lauren C; Mandelkern, Mark A

2017-07-01

In the brain, microglia continuously scan the surrounding extracellular space in order to respond to damage or infection by becoming activated and participating in neuroinflammation. When activated, microglia increase the expression of translocator protein (TSPO) 18 kDa, thereby making the TSPO expression a marker for neuroinflammation. We used the radiotracer [ 11 C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation. Forty-five participants (30 smokers and 15 non-smokers) completed the study and had usable data. Participants underwent a dynamic PET scanning session with bolus injection of [ 11 C]DAA1106 (with smokers in the satiated state) and blood draws during PET scanning to determine TSPO affinity genotype and plasma nicotine levels. Whole-brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (smoker vs non-smoker) and genotype as factors, thereby controlling for genotype. Smokers and non-smokers differed in whole-brain SUVs (P=0.006) owing to smokers having 16.8% lower values than non-smokers. The groups did not differ in injected radiotracer dose or body weight, which were used to calculate SUV. An inverse association was found between whole-brain SUV and reported cigarettes per day (P<0.05), but no significant relationship was found for plasma nicotine. Thus, smokers have less [ 11 C]DAA1106 binding globally than non-smokers, indicating less microglial activation. Study findings are consistent with much prior research demonstrating that smokers have impaired inflammatory functioning compared with non-smokers and that constituents of tobacco smoke other than nicotine affect inflammatory processes.

Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment.

PubMed

Shokouhi, Sepideh; Mckay, John W; Baker, Suzanne L; Kang, Hakmook; Brill, Aaron B; Gwirtsman, Harry E; Riddle, William R; Claassen, Daniel O; Rogers, Baxter P

2016-01-15

Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-β (Aβ) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test-retest (18)F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions. We calculated the correlation between (18)F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ1-42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique-the weighted two-point correlation function (wS2)-to capture potentially more subtle changes in Aβ-PET data. Compared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF Aβ1-42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS2 values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aβ1-42 levels across all time points and reference regions, including the cerebellar gray matter. The selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical (18)F-florbetapir uptake in longitudinal studies.

Sex steroid hormones and brain function: PET imaging as a tool for research.

PubMed

Moraga-Amaro, R; van Waarde, A; Doorduin, J; de Vries, E F J

2018-02-01

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non-invasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. © 2017 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

Multimodal molecular imaging reveals high target uptake and specificity of 111In and 68Ga labeled fibrin-binding probes for thrombus detection in rats

PubMed Central

Oliveira, Bruno L.; Blasi, Francesco; Rietz, Tyson A.; Rotile, Nicholas J.; Day, Helen; Caravan, Peter

2016-01-01

We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F positron emission tomography (PET) probes for non-invasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and single-photon emission computed tomography (SPECT). In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in two animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Methods Radiotracers were synthesized using a known fibrin-binding peptide conjugated to NODAGA, DOTA-MA, or a diethylenetriamine ligand (DETA-PA), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA) or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a non-binding control probe using SPECT/PET/CT imaging. Results All three radiotracers showed similar affinity to soluble fibrin fragment DD(E) (Ki = 0.53–0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0 ± 0.2% ID/g) with low off-target accumulation. Both radiotracers underwent fast systemic elimination (t1/2 = 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation and/or degradation. Triple isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target specificity. Conclusion 68Ga-FBP14 and 111In-FBP15 have high fibrin affinity and thrombus specificity, and represent useful PET and SPECT probes for thrombus detection. PMID:26251420

Engineering refinements to overcome default nuclide regulatory constraints

NASA Astrophysics Data System (ADS)

Finn, R.; Capitelli, P.; Sheh, Y.; Lom, C.; Graham, M.; Germain, J. St.

2005-12-01

The "classical" positron emitting radionuclides include oxygen-15, nitrogen-13 and carbon-11 which possess unique properties for medical imaging. They are radionuclides of the fundamental elements of biological matter. They each possess short half-lives which allow their use in designed radiotracers for clinical investigations with minimal risk and they are readily able to be produced in sufficient activities by low energy nuclear reactions. At present several accelerator manufacturers offer production packages for these radionuclides emphasizing targetry with consideration of the cyclotron extracted energies for nuclide production and on-line chemistry systems for the continuous production of specific precursors or radiotracers. Following the installation and acceptance of the MSKCC TR 19/9 Cyclotron, our experience with the procured chemistry module for the preparation of oxygen-15 labeled water has forced us to examine the design and the operation of the synthetic unit with a view toward the state of New York's regulations addressing the environmental pollution from radioactive materials. The chemistry module was refined with subtle modifications to the chemistry procedure/unit and our experience with the unit is presented as an example of our approach to insure regulatory compliance.

Investigation of flow dynamics of liquid phase in a pilot-scale trickle bed reactor using radiotracer technique.

PubMed

Pant, H J; Sharma, V K

2016-10-01

A radiotracer investigation was carried out to measure residence time distribution (RTD) of liquid phase in a trickle bed reactor (TBR). The main objectives of the investigation were to investigate radial and axial mixing of the liquid phase, and evaluate performance of the liquid distributor/redistributor at different operating conditions. Mean residence times (MRTs), holdups (H) and fraction of flow flowing along different quadrants were estimated. The analysis of the measured RTD curves indicated radial non-uniform distribution of liquid phase across the beds. The overall RTD of the liquid phase, measured at the exit of the reactor was simulated using a multi-parameter axial dispersion with exchange model (ADEM), and model parameters were obtained. The results of model simulations indicated that the TBR behaved as a plug flow reactor at most of the operating conditions used in the investigation. The results of the investigation helped to improve the existing design as well as to design a full-scale industrial TBR for petroleum refining applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigation of holdup and axial dispersion of liquid phase in a catalytic exchange column using radiotracer technique.

PubMed

Kumar, Rajesh; Pant, H J; Goswami, Sunil; Sharma, V K; Dash, A; Mishra, S; Bhanja, K; Mohan, Sadhana; Mahajani, S M

2017-03-01

Holdup and axial dispersion of liquid phase in a catalytic exchange column were investigated by measuring residence time distributions (RTD) using a radiotracer technique. RTD experiments were independently carried out with two different types of packings i.e. hydrophobic water-repellent supported platinum catalyst and a mixture (50% (v/v)) of hydrophobic catalyst and a hydrophillic wettable packing were used in the column. Mean residence times and hold-ups of the liquid phase were estimated at different operating conditions. Axial dispersion model (ADM) and axial dispersion with exchange model (ADEM) were used to simulate the measured RTD data. Both the models were found equally suitable to describe the measured data. The degree of axial mixing was estimated in terms of Peclet number (Pe) and Bodenstein number (Bo). Based on the obtained parameters of the ADM, correlations for total liquid hold-up (H T ) and axial mixing in terms of Bo were proposed for design and scale up of the full-scale catalytic exchange column. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neurobiology of addiction: insight from neurochemical imaging.

PubMed

Urban, Nina B L; Martinez, Diana

2012-06-01

Neuroimaging studies have been crucial in understanding changes in the various neurotransmitter systems implicated in addiction in the living human brain. Predominantly reduced striatal dopamine transmission appears to play an important role in psychostimulant, alcohol and heroin addiction, while addiction to cannabis may be mediated primarily by the endocannabinoid system. However, the study of other neurotransmitter systems likely involved in addiction, for example glutamate, has been limited by the number and quality of available radiotracers, and data on changes in these systems in the most common addictions are emerging only now. Further studies are needed to understand fully how the interplay of various neurotransmitter systems contributes to addiction and to ultimately help to develop more effective treatment approaches.

Temperature dependence of the Haven ratio in silver beta-alumina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, K. K.; Chandrashekhar, G. V.; Chen, W. K.

Measurements of Ag diffusivity (D) and ionic conductivity (sigma) have been made on the same single crystals of silver beta-alumina with composition 1.23 Ag/sub 2/0.11 Al/sub 2/O/sub 3/. The D values were obtained from the cation exchange rate of radiotracer /sup 110/Ag in molten AgNO/sub 3/ over 210/sup 0/ C approx. 400/sup 0/C. The sigma measurements were made using an impedance bridge with sputtered silver electrodes at a frequency of 3 x 10/sup 5/ Hz over R.T approx. 450/sup 0/C. Both D and sigma can be expressed in a simple Arrhenius form as: D = 1.47 x 10/sup -4/(cm/sup 2//sec)more » exp (-4.05(Kcal/mol)/RT); sigmaT = 1.58 x 10/sup 3/(ohm/sup -1/cm/sup -1/K) exp (-3.77(Kcal/mol)/RT). The Haven ratio varies from 0.51 at 200/sup 0/C to 0.56 at 400/sup 0/C. The magnitude of these values is very close to the theoretical value of 0.6 for interstitialcy mechanism. The temperature dependence is strikingly similar to the case of sodium beta-alumina.« less

Nuclear Medicine in Prostate Cancer: A New Era for Radiotracers.

PubMed

Cuccurullo, Vincenzo; Di Stasio, Giuseppe Danilo; Mansi, Luigi

2018-01-01

Natural history of prostate cancer (PCa) is extremely variable, as it ranges from indolent and slow growing tumors to highly aggressive histotypes. Genetic background and environmental factors co-operate to the genesis and clinical manifestation of the tumor and include among the others race, family, specific gene variants (i.e., BRCA1 and BRCA2 mutations), acute and chronic inflammation, infections, diet and drugs. In this scenario, remaining actual the clinical interest of bone scan (BS) in detecting skeletal metastases, an important role in diagnostic imaging may be also carried out by, positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI), which combine morphological information provided by CT and MRI with functional and metabolic data provided by PET acquisitions. With respect to PET radiotracers, being ancillary the usefulness of F-18 fluoro-deoxyglucose and not yet demonstrated the cost-effectiveness of F-18 Fluoride respect to BS, the main role is now played by choline derivatives, in particular by 11C-choline and 18F-fluorocholine. More recently, a greater interest for both diagnostic and therapeutic purposes has been associated with radiotracers directed to prostate-specific membrane antigen (PSMA), a transmembrane protein expressed on the cell surface, which showed high selective expression in PCa, metastatic lymph nodes and bone metastases. Several PSMA-targeted PET tracers have been developed many of which showing promising results for accurate diagnosis and staging of primary PCa and re-staging after biochemical recurrence, even in case of low prostate specific antigen values. In particular, the most widely used PSMA ligand for PET imaging is a 68 Ga-labelled PSMA inhibitor, 68 Ga-PSMA-HBED-CC ( 68 Ga-PSMA-11). 99m Tc-HYNIC-Glu-Urea-A for single photon emission computed tomography, and 177 Lu-PSMA-617 for radioligand therapy has also been applied in humans, with interesting preliminary results related to a possible theranostic approach. A potential role of PSMA radioligands in radio-guided surgery has also been proposed.

Nuclear Medicine in Prostate Cancer: A New Era for Radiotracers

PubMed Central

Cuccurullo, Vincenzo; Di Stasio, Giuseppe Danilo; Mansi, Luigi

2018-01-01

Natural history of prostate cancer (PCa) is extremely variable, as it ranges from indolent and slow growing tumors to highly aggressive histotypes. Genetic background and environmental factors co-operate to the genesis and clinical manifestation of the tumor and include among the others race, family, specific gene variants (i.e., BRCA1 and BRCA2 mutations), acute and chronic inflammation, infections, diet and drugs. In this scenario, remaining actual the clinical interest of bone scan (BS) in detecting skeletal metastases, an important role in diagnostic imaging may be also carried out by, positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI), which combine morphological information provided by CT and MRI with functional and metabolic data provided by PET acquisitions. With respect to PET radiotracers, being ancillary the usefulness of F-18 fluoro-deoxyglucose and not yet demonstrated the cost-effectiveness of F-18 Fluoride respect to BS, the main role is now played by choline derivatives, in particular by 11C-choline and 18F-fluorocholine. More recently, a greater interest for both diagnostic and therapeutic purposes has been associated with radiotracers directed to prostate-specific membrane antigen (PSMA), a transmembrane protein expressed on the cell surface, which showed high selective expression in PCa, metastatic lymph nodes and bone metastases. Several PSMA-targeted PET tracers have been developed many of which showing promising results for accurate diagnosis and staging of primary PCa and re-staging after biochemical recurrence, even in case of low prostate specific antigen values. In particular, the most widely used PSMA ligand for PET imaging is a 68Ga-labelled PSMA inhibitor, 68Ga-PSMA-HBED-CC (68Ga-PSMA-11). 99mTc-HYNIC-Glu-Urea-A for single photon emission computed tomography, and 177Lu-PSMA-617 for radioligand therapy has also been applied in humans, with interesting preliminary results related to a possible theranostic approach. A potential role of PSMA radioligands in radio-guided surgery has also been proposed. PMID:29719480

Development of computational pregnant female and fetus models and assessment of radiation dose from positron-emitting tracers.

PubMed

Xie, Tianwu; Zaidi, Habib

2016-12-01

Molecular imaging using PET and hybrid (PET/CT and PET/MR) modalities nowadays plays a pivotal role in the clinical setting for diagnosis and staging, treatment response monitoring, and radiation therapy treatment planning of a wide range of oncologic malignancies. The developing embryo/fetus presents a high sensitivity to ionizing radiation. Therefore, estimation of the radiation dose delivered to the embryo/fetus and pregnant patients from PET examinations to assess potential radiation risks is highly praised. We constructed eight embryo/fetus models at various gestation periods with 25 identified tissues according to reference data recommended by the ICRP publication 89 representing the anatomy of the developing embryo/fetus. The developed embryo/fetus models were integrated into realistic anthropomorphic computational phantoms of the pregnant female and used for estimating, using Monte Carlo calculations, S-values of common positron-emitting radionuclides, organ absorbed dose, and effective dose of a number of positron-emitting labeled radiotracers. The absorbed dose is nonuniformly distributed in the fetus. The absorbed dose of the kidney and liver of the 8-week-old fetus are about 47.45 % and 44.76 % higher than the average absorbed dose of the fetal total body for all investigated radiotracers. For 18 F-FDG, the fetal effective doses are 2.90E-02, 3.09E-02, 1.79E-02, 1.59E-02, 1.47E-02, 1.40E-02, 1.37E-02, and 1.27E-02 mSv/MBq at the 8th, 10th, 15th, 20th, 25th, 30th, 35th, and 38th weeks of gestation, respectively. The developed pregnant female/fetus models matching the ICRP reference data can be exploited by dedicated software packages for internal and external dose calculations. The generated S-values will be useful to produce new standardized dose estimates to pregnant patients and embryo/fetus from a variety of positron-emitting labeled radiotracers.

In‐loop flow [11C]CO2 fixation and radiosynthesis of N,N′‐[11C]dibenzylurea

PubMed Central

Downey, Joseph; Bongarzone, Salvatore; Hader, Stefan

2017-01-01

Cyclotron‐produced carbon‐11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon‐11 carbon dioxide ([11C]CO2), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [11C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop‐based system used in 11C‐methylation and 11C‐carboxylation reactions inspired us to apply the [11C]CO2 fixation “in‐loop.” In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop‐based [11C]CO2 fixation method, enabling the fast and efficient, direct‐from‐cyclotron, in‐loop trapping of [11C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof‐of‐concept in‐loop flow radiosynthesis of N,N′‐[11C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio‐HPLC), giving an overall nonisolated radiochemical yield of 72% (decay‐corrected) within just 3 minutes from end of bombardment. This proof‐of‐concept reaction has demonstrated that efficient [11C]CO2 fixation can be achieved in a low‐volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in‐loop flow radiosynthesis of carbon‐11–labelled products. This new in‐loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers. PMID:28977686

In-loop flow [11 C]CO2 fixation and radiosynthesis of N,N'-[11 C]dibenzylurea.

PubMed

Downey, Joseph; Bongarzone, Salvatore; Hader, Stefan; Gee, Antony D

2018-03-01

Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([ 11 C]CO 2 ), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [ 11 C]CO 2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [ 11 C]CO 2 , and the advantages afforded by the use of a loop-based system used in 11 C-methylation and 11 C-carboxylation reactions inspired us to apply the [ 11 C]CO 2 fixation "in-loop." In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [ 11 C]CO 2 fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [ 11 C]CO 2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N'-[ 11 C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3 minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [ 11 C]CO 2 fixation can be achieved in a low-volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11-labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [ 11 C]CO 2 trapping/fixation reactions for the production of PET radiotracers. © 2017 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals Published by John Wiley & Sons, Ltd.

Predicting Future Morphological Changes of Lesions from Radiotracer Uptake in 18F-FDG-PET Images

PubMed Central

Bagci, Ulas; Yao, Jianhua; Miller-Jaster, Kirsten; Chen, Xinjian; Mollura, Daniel J.

2013-01-01

We introduce a novel computational framework to enable automated identification of texture and shape features of lesions on 18F-FDG-PET images through a graph-based image segmentation method. The proposed framework predicts future morphological changes of lesions with high accuracy. The presented methodology has several benefits over conventional qualitative and semi-quantitative methods, due to its fully quantitative nature and high accuracy in each step of (i) detection, (ii) segmentation, and (iii) feature extraction. To evaluate our proposed computational framework, thirty patients received 2 18F-FDG-PET scans (60 scans total), at two different time points. Metastatic papillary renal cell carcinoma, cerebellar hemongioblastoma, non-small cell lung cancer, neurofibroma, lymphomatoid granulomatosis, lung neoplasm, neuroendocrine tumor, soft tissue thoracic mass, nonnecrotizing granulomatous inflammation, renal cell carcinoma with papillary and cystic features, diffuse large B-cell lymphoma, metastatic alveolar soft part sarcoma, and small cell lung cancer were included in this analysis. The radiotracer accumulation in patients' scans was automatically detected and segmented by the proposed segmentation algorithm. Delineated regions were used to extract shape and textural features, with the proposed adaptive feature extraction framework, as well as standardized uptake values (SUV) of uptake regions, to conduct a broad quantitative analysis. Evaluation of segmentation results indicates that our proposed segmentation algorithm has a mean dice similarity coefficient of 85.75±1.75%. We found that 28 of 68 extracted imaging features were correlated well with SUVmax (p<0.05), and some of the textural features (such as entropy and maximum probability) were superior in predicting morphological changes of radiotracer uptake regions longitudinally, compared to single intensity feature such as SUVmax. We also found that integrating textural features with SUV measurements significantly improves the prediction accuracy of morphological changes (Spearman correlation coefficient = 0.8715, p<2e-16). PMID:23431398

Synthesis, Bioconjugation and Stability Studies of [18 F] Ethenesulfonyl Fluoride.

PubMed

Zhang, Bo; Pascali, Giancarlo; Wyatt, Naomi; Matesic, Lidia; Klenner, Mitchell A; Sia, Tiffany R; Guastella, Adam J; Massi, Massimiliano; Robinson, Andrea J; Fraser, Benjamin H

2018-06-20

Fluorine-18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [ 18 F] ethenesulfonylfluoride ([ 18 F] ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [ 18 F] ESF was optimised using a microfluidic reactor under both carrier-added (c.a.) and no-carrier-added (n.c.a.) conditions, affording, in a straightforward procedure, 30-50% radiochemical yield (RCY) for c.a. [ 18 F] ESF and 60-70% RCY for n.c.a. [ 18 F] ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [ 18 F] ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging. This article is protected by copyright. All rights reserved.

Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain.

PubMed

Nabulsi, Nabeel B; Mercier, Joël; Holden, Daniel; Carré, Stephane; Najafzadeh, Soheila; Vandergeten, Marie-Christine; Lin, Shu-Fei; Deo, Anand; Price, Nathalie; Wood, Martyn; Lara-Jaime, Teresa; Montel, Florian; Laruelle, Marc; Carson, Richard E; Hannestad, Jonas; Huang, Yiyun

2016-05-01

The synaptic vesicle glycoprotein 2A (SV2A) is found in secretory vesicles in neurons and endocrine cells. PET with a selective SV2A radiotracer will allow characterization of drugs that modulate SV2A (e.g., antiepileptic drugs) and potentially could be a biomarker of synaptic density (e.g., in neurodegenerative disorders). Here we describe the synthesis and characterization of the SV2A PET radiotracer (11)C-UCB-J ((R)-1-((3-((11)C-methyl-(11)C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) in nonhuman primates, including whole-body biodistribution. (11)C-UCB-J was prepared by C-(11)C-methylation of the 3-pyridyl trifluoroborate precursor with (11)C-methyl iodide via the Suzuki-Miyaura cross-coupling method. Rhesus macaques underwent multiple scans including coinjection with unlabeled UCB-J (17, 50, and 150 μg/kg) or preblocking with the antiepileptic drug levetiracetam at 10 and 30 mg/kg. Scans were acquired for 2 h with arterial sampling and metabolite analysis to measure the input function. Regional volume of distribution (VT) was estimated using the 1-tissue-compartment model. Target occupancy was assessed using the occupancy plot; the dissociation constant (Kd) was determined by fitting self-blocking occupancies to a 1-site model, and the maximum number of receptor binding sites (Bmax) values were derived from baseline VT and from the estimated Kd and the nondisplaceable distribution volume (VND). (11)C-UCB-J was synthesized with greater than 98% purity. (11)C-UCB-J exhibited high free fraction (0.46 ± 0.02) and metabolized at a moderate rate (39% ± 5% and 24% ± 3% parent remaining at 30 and 90 min) in plasma. In the monkey brain, (11)C-UCB-J displayed high uptake and fast kinetics. VT was high (∼25-55 mL/cm(3)) in all gray matter regions, consistent with the ubiquitous expression of SV2A. Preblocking with 10 and 30 mg/kg of levetiracetam resulted in approximately 60% and 90% occupancy, respectively. Analysis of the self-blocking scans yielded a Kd estimate of 3.4 nM and Bmax of 125-350 nM, in good agreement with the in vitro inhibition constant (Ki) of 6.3 nM and regional Bmax in humans. Whole-body biodistribution revealed that the liver and the brain are the dose-limiting organs for males and females, respectively. (11)C-UCB-J exhibited excellent characteristics as an SV2A PET radiotracer in nonhuman primates. The radiotracer is currently undergoing first-in-human evaluation. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Impaired spine formation and learning in GPCR kinase 2 interacting protein-1 (GIT1) knockout mice.

PubMed

Menon, Prashanthi; Deane, Rashid; Sagare, Abhay; Lane, Steven M; Zarcone, Troy J; O'Dell, Michael R; Yan, Chen; Zlokovic, Berislav V; Berk, Bradford C

2010-03-04

The G-protein coupled receptor (GPCR)-kinase interacting proteins 1 and 2 (GIT1 and GIT2) are scaffold proteins with ADP-ribosylating factor GTPase activity. GIT1 and GIT2 control numerous cellular functions and are highly expressed in neurons, endothelial cells and vascular smooth muscle cells. GIT1 promotes dendritic spine formation, growth and motility in cultured neurons, but its role in brain in vivo is unknown. By using global GIT1 knockout mice (GIT1 KO), we show that compared to WT controls, deletion of GIT1 results in markedly reduced dendritic length and spine density in the hippocampus by 36.7% (p<0.0106) and 35.1% (p<0.0028), respectively. This correlated with their poor adaptation to new environments as shown by impaired performance on tasks dependent on learning. We also studied the effect of GIT1 gene deletion on brain microcirculation. In contrast to findings in systemic circulation, GIT1 KO mice had an intact blood-brain barrier and normal regional cerebral blood flow as determined with radiotracers. Thus, our data suggest that GIT1 plays an important role in brain in vivo by regulating spine density involved in synaptic plasticity that is required for processes involved in learning. 2009 Elsevier B.V. All rights reserved.

Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [11C]CURB.

PubMed

Boileau, Isabelle; Mansouri, Esmaeil; Williams, Belinda; Le Foll, Bernard; Rusjan, Pablo; Mizrahi, Romina; Tyndale, Rachel F; Huestis, Marilyn A; Payer, Doris E; Wilson, Alan A; Houle, Sylvain; Kish, Stephen J; Tong, Junchao

2016-11-01

One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence. However, the status of brain FAAH in cannabis use disorder is unknown. Brain FAAH binding was measured with positron emission tomography and [ 11 C]CURB in 22 healthy control subjects and ten chronic cannabis users during early abstinence. The FAAH genetic polymorphism (rs324420) and blood, urine, and hair levels of cannabinoids and metabolites were determined. In cannabis users, FAAH binding was significantly lower by 14%-20% across the brain regions examined than in matched control subjects (overall Cohen's d = 0.96). Lower binding was negatively correlated with cannabinoid concentrations in blood and urine and was associated with higher trait impulsiveness. Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids. Further studies are needed to examine possible changes in FAAH binding during prolonged cannabis abstinence and whether lower FAAH binding predates drug use. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging with the Novel Radiotracer [11C]CURB

PubMed Central

Boileau, Isabelle; Mansouri, Esmaeil; Williams, Belinda; Le Foll, Bernard; Rusjan, Pablo; Mizrahi, Romina; Tyndale, Rachel F.; Huestis, Marilyn A.; Payer, Doris E.; Wilson, Alan A.; Houle, Sylvain; Kish, Stephen J.; Tong, Junchao

2016-01-01

Background One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH) and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence. However, the status of brain FAAH in cannabis use disorder is unknown. Methods Brain FAAH binding was measured with positron emission tomography and [11C]CURB in 22 healthy control subjects and ten chronic, frequent cannabis users during early abstinence. The FAAH genetic polymorphism (rs324420) and blood, urine and hair levels of cannabinoids and metabolites were determined. Results In cannabis users FAAH binding was significantly lower by 14–20% across the brain regions examined as compared to matched control subjects (overall Cohen’s d=0.96). Lower binding was negatively correlated with cannabinoid concentrations in blood and urine and was associated with higher trait impulsiveness. Conclusions Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids. Further studies are needed to examine possible changes in FAAH binding during prolonged cannabis abstinence and whether lower FAAH binding predates drug use. PMID:27345297

Scintigraphic imaging of Staphylococcus aureus infection using 99mTc radiolabeled aptamers.

PubMed

Santos, Sara Roberta Dos; de Sousa Lacerda, Camila Maria; Ferreira, Iêda Mendes; de Barros, André Luís Branco; Fernandes, Simone Odília; Cardoso, Valbert Nascimento; de Andrade, Antero Silva Ribeiro

2017-10-01

Staphylococcus aureus is a specie of great medical importance associated with many infections as bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device related infections. Early identification of infectious foci is crucial for successful treatment. Scintigraphy could contribute to this purpose since specific radiotracers were available. Aptamers due to their high specificity have great potential for radiopharmaceuticals development. In the present study scintigraphic images of S. aureus infectious foci were obtained using specific S. aureus aptamers radiolabeled with 99m Tc. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Update on the use of PET radiopharmaceuticals in inflammatory disease].

PubMed

Martínez-Rodríguez, I; Carril, J M

2013-01-01

The use of molecular imaging with PET/CT technology using different radiotracers, especially the (18)F-FDG is currently spreading beyond the area of oncology, the most interest being placed on inflammatory and infectious diseases. This article presents a review of its contribution in different inflammatory conditions in the context of structural and conventional nuclear medicine imaging. Special emphasis is placed on the more significant diseases such as large-vessel vasculitis, sarcoidosis, rheumatoid arthritis and inflammatory bowel disease and the study of the atheroma plaque. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

A Profilometry-Based Dentifrice Abrasion Method for V8 Brushing Machines Part III: Multi-Laboratory Validation Testing of RDA-PE.

PubMed

Schneiderman, Eva; Colón, Ellen L; White, Donald J; Schemehorn, Bruce; Ganovsky, Tara; Haider, Amir; Garcia-Godoy, Franklin; Morrow, Brian R; Srimaneepong, Viritpon; Chumprasert, Sujin

2017-09-01

We have previously reported on progress toward the refinement of profilometry-based abrasivity testing of dentifrices using a V8 brushing machine and tactile or optical measurement of dentin wear. The general application of this technique may be advanced by demonstration of successful inter-laboratory confirmation of the method. The objective of this study was to explore the capability of different laboratories in the assessment of dentifrice abrasivity using a profilometry-based evaluation technique developed in our Mason laboratories. In addition, we wanted to assess the interchangeability of human and bovine specimens. Participating laboratories were instructed in methods associated with Radioactive Dentin Abrasivity-Profilometry Equivalent (RDA-PE) evaluation, including site visits to discuss critical elements of specimen preparation, masking, profilometry scanning, and procedures. Laboratories were likewise instructed on the requirement for demonstration of proportional linearity as a key condition for validation of the technique. Laboratories were provided with four test dentifrices, blinded for testing, with a broad range of abrasivity. In each laboratory, a calibration curve was developed for varying V8 brushing strokes (0, 4,000, and 10,000 strokes) with the ISO abrasive standard. Proportional linearity was determined as the ratio of standard abrasion mean depths created with 4,000 and 10,000 strokes (2.5 fold differences). Criteria for successful calibration within the method (established in our Mason laboratory) was set at proportional linearity = 2.5 ± 0.3. RDA-PE was compared to Radiotracer RDA for the four test dentifrices, with the latter obtained by averages from three independent Radiotracer RDA sites. Individual laboratories and their results were compared by 1) proportional linearity and 2) acquired RDA-PE values for test pastes. Five sites participated in the study. One site did not pass proportional linearity objectives. Data for this site are not reported at the request of the researchers. Three of the remaining four sites reported herein tested human dentin and all three met proportional linearity objectives for human dentin. Three of four sites participated in testing bovine dentin and all three met the proportional linearity objectives for bovine dentin. RDA-PE values for test dentifrices were similar between sites. All four sites that met proportional linearity requirement successfully identified the dentifrice formulated above the industry standard 250 RDA (as RDA-PE). The profilometry method showed at least as good reproducibility and differentiation as Radiotracer assessments. It was demonstrated that human and bovine specimens could be used interchangeably. The standardized RDA-PE method was reproduced in multiple laboratories in this inter-laboratory study. Evidence supports that this method is a suitable technique for ISO method 11609 Annex B.

Functional Imaging for Prostate Cancer: Therapeutic Implications

PubMed Central

Aparici, Carina Mari; Seo, Youngho

2012-01-01

Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

Exploring the relationship between social attachment and dopamine D2/3 receptor availability in the brains of healthy humans using [11C]-(+)-PHNO.

PubMed

Caravaggio, Fernando; Chung, Jun Ku; Gerretsen, Philip; Fervaha, Gagan; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

2017-04-01

Differences in striatal dopamine (DA) function may be related to differences in the degree of social attachment to others. Using positron emission tomography (PET), socially detached persons demonstrate reduced DA D 2/3 receptor (D 2/3 R) availability in the striatum. However, previous PET studies have only used antagonist radiotracers for D 2/3 R and have not specifically examined regions of interest (ROIs) such as the ventral striatum (VS). In 32 healthy persons, we investigated the relationship between self-reported attachment and DA D 2/3 R availability in striatal and extrastriatal ROIs as measured using the agonist radiotracer [ 11 C]-(+)-PHNO. Surprisingly, more social attachment-as measured by the attachment subscale of the temperament and character inventory-was related to less [ 11 C]-(+)-PHNO binding in the VS (r(30) = -.43, p = .01). This relationship held in a subsample who also completed the detachment subscale of the Karolinska Scales of Personality (r(10) = .62, p = .03). However, no relationships were observed with BP ND in the dorsal striatum or D 3 R-specific ROIs. One potential explanation for these findings is that persons who are more socially detached have less endogenous DA occupying D 2/3 R in the VS. This interpretation warrants investigation by future research. These findings may help us better understand the neurochemical basis of attachment.

Chalcone Based Homodimeric PET Agent, 11C-(Chal)2DEA-Me, for Beta Amyloid Imaging: Synthesis and Bioevaluation.

PubMed

Chauhan, Kanchan; Tiwari, Anjani K; Chadha, Nidhi; Kaul, Ankur; Singh, Ajai Kumar; Datta, Anupama

2018-04-02

Homodimeric chalcone based 11 C-PET radiotracer, 11 C-(Chal) 2 DEA-Me, was synthesized, and binding affinity toward beta amyloid (Aβ) was evaluated. The computational studies revealed multiple binding of the tracer at the recognition sites of Aβ fibrils. The bivalent ligand 11 C-(Chal) 2 DEA-Me displayed higher binding affinity compared to the corresponding monomer, 11 C-Chal-Me, and classical Aβ agents. The radiolabeling yield with carbon-11 was 40-55% (decay corrected) with specific activity of 65-90 GBq/μmol. A significant ( p < 0.0001) improvement in the binding affinity of 11 C-(Chal) 2 DEA-Me with synthetic Aβ42 aggregates over the monomer, 11 C-Chal-Me, demonstrates the utility of the bivalent approach. The PET imaging and biodistribution data displayed suitable brain pharmacokinetics of both ligands with higher brain uptake in the case of the bivalent ligand. Metabolite analysis of healthy ddY mouse brain homogenates exhibited high stability of the radiotracers in the brain with >93% intact tracer at 30 min post injection. Both chalcone derivatives were fluorescent in nature and demonstrated significant changes in the emission properties after binding with Aβ42. The preliminary analysis indicates high potential of 11 C-(Chal) 2 DEA-Me as in vivo Aβ42 imaging tracer and highlights the significance of the bivalent approach to achieve a higher biological response for detection of early stages of amyloidosis.

Bioaccumulation of (63)Ni in the scleractinian coral Stylophora pistillata and isolated Symbiodinium using radiotracer techniques.

PubMed

Hédouin, Laetitia; Metian, Marc; Teyssié, Jean-Louis; Oberhänsli, François; Ferrier-Pagès, Christine; Warnau, Michel

2016-08-01

Development of nickel mining activities along the New Caledonia coasts threatens the biodiversity of coral reefs. Although the validation of tropical marine organisms as bioindicators of metal mining contamination has received much attention in the literature over the last decade, few studies have examined the potential of corals, the fundamental organisms of coral reefs, to monitor nickel (Ni) contamination in tropical marine ecosystems. In an effort to bridge this gap, the present work investigated the bioaccumulation of (63)Ni in the scleractinian coral Stylophora pistillata and in its isolated zooxanthellae Symbiodinium, using radiotracer techniques. Results highlight the high capacities of coral tissues (zooxanthellae and host tissues) to efficiently bioconcentrate (63)Ni compared to skeleton (Concentration Factors CF at 14 days of exposure are 3 orders of magnitude higher in tissues than in skeleton). When non-contaminated conditions were restored, (63)Ni was more efficiently retained in skeleton than in coral tissues, with biological half-lives (Tb½) of 44.3 and 6.5 days, respectively. In addition, our work showed that Symbiodinium bioconcentrated (63)Ni exponentially, with a vol/vol concentration factor at steady state (VCFSS) reaching 14,056. However, compilation of our results highlighted that despite efficient bioconcentration of (63)Ni in Symbiodinium, their contribution to the whole (63)Ni accumulation in coral nubbins represents less than 7%, suggesting that other biologically controlled processes occur in coral host allowing such efficient bioconcentration in coral tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging

PubMed Central

Adler, Stephen; Mena, Esther; Kurdziel, Karen; Maltzman, Julia; Wallin, Bruce; Hoffman, Kimberly; Pastan, Ira; Paik, Chang Hum; Choyke, Peter; Hassan, Raffit

2015-01-01

Amatuximab is a chimeric high-affinity monoclonal IgG1/k antibody targeting mesothelin that is being developed for treatment of mesothelin-expressing cancers. Considering the ongoing clinical development of amatuximab in these cancers, our objective was to characterize the biodistribution, and dosimetry of 111Indium (111In) radiolabelled amatuximab in mesothelin-expressing cancers. Between October 2011 and February 2013, six patients including four with malignant mesothelioma and two with pancreatic adenocarcinoma underwent Single Photon Emission Computed Tomography-Computed Tomography (SPECT/CT) imaging following administration of 111In amatuximab. SPECT/CT images were obtained at 2–4 hours, 24–48 hours and 96–168 hours after radiotracer injection. In all patients, tumor to background ratios (TBR) consistently met or exceeded an uptake of 1.2 (range 1.2–62.0) which is considered the minimum TBR that can be visualized. TBRs were higher in tumors of patients with mesothelioma than pancreatic adenocarcinoma. 111In-amatuximab uptake was noted in both primary tumors and metastatic sites. The radiotracer dose was generally well-tolerated and demonstrated physiologic uptake in the heart, liver, kidneys and spleen. This is the first study to show tumor localization of an anti-mesothelin antibody in humans. Our results show that 111In-amatuximab was well tolerated with a favorable dosimetry profile. It localizes to mesothelin expressing cancers with a higher uptake in mesothelioma than pancreatic cancer. PMID:25756664

AN OVERVIEW ON PET RADIOCHEMISTRY: PART 2 - RADIOMETALS.

PubMed

Brandt, Marie; Cardinale, Jens; Aulsebrook, Margaret; Gasser, Gilles; Mindt, Thomas

2018-05-10

This continuing educational review provides an overview on radiometals used for PET. General aspects of radiometal-based radiotracers are covered and the most frequently applied metallic PET radionuclides 68 Ga, 89 Zr, and 64 Cu are highlighted with a discussion of their strengths and limitations. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Preclinical assessment of dopaminergic system in rats by MicroPET using three positron-emitting radiopharmaceuticals

NASA Astrophysics Data System (ADS)

Lara-Camacho, V. M.; Ávila-García, M. C.; Ávila-Rodríguez, M. A.

2014-11-01

Different diseases associated with dysfunction of dopaminergic system such as Parkinson, Alzheimer, and Schizophrenia are being widely studied with positron emission tomography (PET) which is a noninvasive method useful to assess the stage of these illnesses. In our facility we have recently implemented the production of [11C ]-DTBZ, [11C ]-RAC, and [18F ]-FDOPA, which are among the most common PET radiopharmaceuticals used in neurology applications to get information about the dopamine pathways. In this study two healthy rats were imaged with each of those radiotracers in order to confirm selective striatum uptake as a proof of principle before to release them for human use.

Novel methodology for the study of mercury methylation and reduction in sediments and water using 197Hg radiotracer.

PubMed

Ribeiro Guevara, Sergio; Zizek, Suzana; Repinc, Urska; Pérez Catán, Soledad; Jaćimović, Radojko; Horvat, Milena

2007-03-01

Mercury tracers are powerful tools that can be used to study mercury transformations in environmental systems, particularly mercury methylation, demethylation and reduction in sediments and water. However, mercury transformation studies using tracers can be subject to error, especially when used to assess methylation potential. The organic mercury extracted can be as low as 0.01% of the endogenous labeled mercury, and artefacts and contamination present during methylmercury (MeHg) extraction processes can cause interference. Solvent extraction methods based on the use of either KBr/H2SO4 or HCl were evaluated in freshwater sediments using 197Hg radiotracer. Values obtained for the 197Hg tracer in the organic phase were up to 25-fold higher when HCl was used, which is due to the coextraction of 197Hg2+ into the organic phase during MeHg extraction. Evaluations of the production of MeHg gave similar results with both MeHg extraction procedures, but due to the higher Hg2+ contamination of the controls, the uncertainty in the determination was higher when HCl was used. The Hg2+ contamination of controls in the HCl extraction method showed a nonlinear correlation with the humic acid content of sediment pore water. Therefore, use of the KBr/H2SO4 method is recommended, since it is free from these interferences. 197Hg radiotracer (T1/2=2.673 d) has a production rate that is about 50 times higher than that of 203Hg (T1/2=46.595 d), the most frequently used mercury radiotracer. Hence it is possible to obtain a similar level of performance to 203Hg when it is used it in short-term experiments and produced by the irradiation of 196Hg with thermal neutrons, using mercury targets with the natural isotopic composition. However, if the 0.15% natural abundance of the 196Hg isotope is increased, the specific activity of the 197Hg tracer can be significantly improved. In the present work, 197Hg tracer was produced from mercury 51.58% enriched in the 196Hg isotope, and a 340-fold increase in specific activity with respect to natural mercury targets was obtained. When this high specific activity tracer is employed, mercury methylation and reduction experiments with minimum mercury additions are feasible. Tracer recovery in methylation experiments (associated with Me197Hg production from 197Hg2+ spike, but also with Hg2+ contamination and Me197Hg artefacts) with marine sediments was about 0.005% g-1 WS (WS: wet sediment) after 20 h incubation with mercury additions of 0.05 ng g-1 WS, which is far below natural mercury levels. In this case, the amount of Hg2+ reduced to Hg0 (expressed as the percent 197Hg0 recovered with respect to the 197Hg2+ added) varied from 0.13 to 1.6% g-1 WS. Me197Hg production from 197Hg2+ spike after 20 h of incubation of freshwater sediment ranged from 0.02 to 0.13% g-1 WS with mercury additions of 2.5 ng g-1 WS, which is also far below natural levels. 197Hg0 recoveries were low, 0.0058+/-0.0013% g-1 WS, but showed good reproducibility in five replicates. Me197Hg production from 197Hg2+ spiked in freshwater samples ranged from 0.1 to 0.3% over a period of three days with mercury additions of 10 ng L-1. A detection limit of 0.05% for Me197Hg production from 197Hg2+ spike was obtained in seawater in a 25 h incubation experiment with mercury additions of 12 ng L-1.

Studies of the brain cannabinoid system using positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gatley, S.J.; Volkow, N.D.

Studies using radiolabeled psychoactive drugs in conjunction with positron emission tomography (PET) have permitted the imaging of binding sites in the human brain. Similar studies of marijuana have been hampered by the unsuitability of radiolabeled THC for PET studies, and the current unavailability of other in vivo imaging agents for cannabinoid receptors. Recent developments in medicinal chemistry suggest that a PET radiotracer for cannabinoid receptors will soon become available. This chapter briefly reviews these developments, together with the results of PET studies of the effects of marijuana and other abused drugs on brain metabolism. It also reviews PET studies ofmore » cocaine binding sites, to demonstrate the kind of investigations that will be possible when a cannabinoid receptor PET radioligand becomes available.« less

Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT

DOE PAGES

Huber, Jennifer S.; Hernandez, Andrew M.; Janabi, Mustafa; ...

2017-09-06

Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid ( 18F-FTHA) and glucose analog 18F-fluorodeoxyglucose ( 18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol ( 18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimatemore » the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant (P = .1) and distribution volume (P = .1), significantly higher 18F-FDG myocardial influx rate constant (P = 4×10 –8), and significantly lower 18F-FTHA myocardial influx rate constant (P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant (P = 5×10 –6) and distribution volume (P = 3×10 –8), significantly higher 18F-FDG myocardial influx rate constant (P = 3×10 –8), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011–2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.« less

Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huber, Jennifer S.; Hernandez, Andrew M.; Janabi, Mustafa

Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid ( 18F-FTHA) and glucose analog 18F-fluorodeoxyglucose ( 18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol ( 18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimatemore » the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant (P = .1) and distribution volume (P = .1), significantly higher 18F-FDG myocardial influx rate constant (P = 4×10 –8), and significantly lower 18F-FTHA myocardial influx rate constant (P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant (P = 5×10 –6) and distribution volume (P = 3×10 –8), significantly higher 18F-FDG myocardial influx rate constant (P = 3×10 –8), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011–2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.« less

First experience with early dynamic (18)F-NaF-PET/CT in patients with chronic osteomyelitis.

PubMed

Freesmeyer, Martin; Stecker, Franz F; Schierz, Jan-Henning; Hofmann, Gunther O; Winkens, Thomas

2014-05-01

This study investigates whether early dynamic positron emission tomography/computed tomography (edPET/CT) using (18)F-sodium fluoride-((18)F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed(18)F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late (18)F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUVmax, edSUVmean, respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late (18)F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed(18)F-NaF -PET offers additional information about early radiotracer distribution to standard (18)F-NaF -PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed(18)F-NaF-PET to a three-phase bone scan.

Diagnostic value of 99mTc-bombesin scintigraphy for differentiation of malignant from benign breast lesions.

PubMed

Shariati, Farzaneh; Aryana, Kamran; Fattahi, Asiehsadat; Forghani, Mohammad N; Azarian, Azita; Zakavi, Seyed R; Sadeghi, Ramin; Ayati, Narjes; Sadri, Keyvan

2014-06-01

In this study, we evaluated the diagnostic accuracy of (99m)Tc-bombesin scintigraphy for differentiation of benign from malignant palpable breast lesions. (99m)Tc-Bombesin is a tracer with high affinity for gastrin-releasing peptide receptor, which is overexpressed on a variety of human tumors including breast carcinoma. We examined 33 consecutive women who were referred to our center with suspicious palpable breast lesions but had no definitive diagnosis in other imaging procedures. A volume of 370-444 MBq of (99m)Tc-bombesin was injected and dynamic 1-min images were taken for 20 min immediately after injection in anterior view. Thereafter, two static images in anterior and prone-lateral views were taken for 5 min. Finally, single-photon emission computed tomography images were taken for each patient. Definitive diagnosis was based on biopsy and histopathological evaluation. The scan findings were positive in 19 patients and negative in 11 on visual assessment of the planar and single-photon emission computed tomography images. Pathologic examination confirmed breast carcinoma in 12 patients with positive scans and benign pathology for 18 patients. The overall sensitivity, specificity, negative and positive predictive values, and accuracy of this radiotracer for diagnosis of breast cancer were 100, 66.1, 100, 63, and 76%, respectively. Semiquantitative analysis improved the specificity of the visual assessment from 66 to 84%. Our study showed that (99m)Tc-bombesin scintigraphy has a high sensitivity and negative predictive value for detecting malignant breast lesions, but the specificity and positive predictive value of this radiotracer for differentiation of malignant breast abnormalities from benign ones are relatively low.

Synthesis and evaluation of 68Ga-labeled DOTA-2-deoxy-D-glucosamine as a potential radiotracer in μPET imaging

PubMed Central

Yang, Zhi; Xiong, Chiyi; Zhang, Rui; Zhu, Hua; Li, Chun

2012-01-01

The purposes of this study were to develop an efficient method of labeling D-glucosamine hydrochloride with gallium 68 (68Ga) and investigate the imaging properties of the resulting radiotracer in a human tumor xenograft model using micro-positron emission tomography (μPET). The precursor compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-2-deoxy-D-glucosamine (DOTA-DG) was synthesized from D-glucosamine hydrochloride and 2-(4-isothiocyanatobenzyl)-DOTA. Radiolabeling of DOTA-DG with 68Ga was achieved in 10 minutes using microwave heating. The labeling efficiency a nd radiochemical purity after purification of 68Ga-DOTA-DG were ~85% and greater than 98%, respectively. In A431 cells, the percentages of 68Ga-DOTA-DG and 18F-FDG uptakes after 60 min incubation were 15.7% and 16.2%, respectively. In vivo, the mean ± standard deviation of 68Ga-DOTADG uptake values in A431 tumors were 2.38±0.30, 0.75±0.13, and 0.39±0.04 percent of the injected dose per gram of tissue at 10, 30, and 60 minutes after intravenous injection, respectively. μPET imaging of A431-bearing mice clearly delineated tumors at 60 minutes after injection of 68Ga-DOTA-DG at a dose of 3.7 MBq. 68Ga-DOTA-DG displayed significantly higher tumor-to-heart, tumor-to-brain, and tumor-to-muscle ratios than 18F-FDG did. Further studies are needed to identify the mechanism of tumor uptake of this new glucosamine-based PET imaging tracer. PMID:23145365

Synthesis and evaluation of (68)Ga-labeled DOTA-2-deoxy-D-glucosamine as a potential radiotracer in μPET imaging.

PubMed

Yang, Zhi; Xiong, Chiyi; Zhang, Rui; Zhu, Hua; Li, Chun

2012-01-01

The purposes of this study were to develop an efficient method of labeling D-glucosamine hydrochloride with gallium 68 ((68)Ga) and investigate the imaging properties of the resulting radiotracer in a human tumor xenograft model using micro-positron emission tomography (μPET). The precursor compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-2-deoxy-D-glucosamine (DOTA-DG) was synthesized from D-glucosamine hydrochloride and 2-(4-isothiocyanatobenzyl)-DOTA. Radiolabeling of DOTA-DG with (68)Ga was achieved in 10 minutes using microwave heating. The labeling efficiency a nd radiochemical purity after purification of (68)Ga-DOTA-DG were ~85% and greater than 98%, respectively. In A431 cells, the percentages of (68)Ga-DOTA-DG and (18)F-FDG uptakes after 60 min incubation were 15.7% and 16.2%, respectively. In vivo, the mean ± standard deviation of (68)Ga-DOTADG uptake values in A431 tumors were 2.38±0.30, 0.75±0.13, and 0.39±0.04 percent of the injected dose per gram of tissue at 10, 30, and 60 minutes after intravenous injection, respectively. μPET imaging of A431-bearing mice clearly delineated tumors at 60 minutes after injection of (68)Ga-DOTA-DG at a dose of 3.7 MBq. (68)Ga-DOTA-DG displayed significantly higher tumor-to-heart, tumor-to-brain, and tumor-to-muscle ratios than (18)F-FDG did. Further studies are needed to identify the mechanism of tumor uptake of this new glucosamine-based PET imaging tracer.

In vitro kinetic studies on the mechanism of oxygen-dependent cellular uptake of copper radiopharmaceuticals.

PubMed

Holland, Jason P; Giansiracusa, Jeffrey H; Bell, Stephen G; Wong, Luet-Lok; Dilworth, Jonathan R

2009-04-07

The development of hypoxia-selective radiopharmaceuticals for use as therapeutic and/or imaging agents is of vital importance for both early identification and treatment of cancer and in the design of new drugs. Radiotracers based on copper for use in positron emission tomography have received great attention due to the successful application of copper(II) bis(thiosemicarbazonato) complexes, such as [(60/62/64)Cu(II)ATSM] and [(60/62/64)Cu(II)PTSM], as markers for tumour hypoxia and blood perfusion, respectively. Recent work has led to the proposal of a revised mechanism of hypoxia-selective cellular uptake and retention of [Cu(II)ATSM]. The work presented here describes non-steady-state kinetic simulations in which the reported pO(2)-dependent in vitro cellular uptake and retention of [(64)Cu(II)ATSM] in EMT6 murine carcinoma cells has been modelled by using the revised mechanistic scheme. Non-steady-state (NSS) kinetic analysis reveals that the model is in very good agreement with the reported experimental data with a root-mean-squared error of less than 6% between the simulated and experimental cellular uptake profiles. Estimated rate constants are derived for the cellular uptake and washout (k(1) = 9.8 +/- 0.59 x 10(-4) s(-1) and k(2) = 2.9 +/- 0.17 x 10(-3) s(-1)), intracellular reduction (k(3) = 5.2 +/- 0.31 x 10(-2) s(-1)), reoxidation (k(4) = 2.2 +/- 0.13 mol(-1) dm(3) s(-1)) and proton-mediated ligand dissociation (k(5) = 9.0 +/- 0.54 x 10(-5) s(-1)). Previous mechanisms focused on the reduction and reoxidation steps. However, the data suggest that the origins of hypoxia-selective retention may reside with the stability of the copper(I) anion with respect to protonation and ligand dissociation. In vitro kinetic studies using the nicotimamide adenine dinucleotide (NADH)-dependent ferredoxin reductase enzyme PuR isolated from the bacterium Rhodopseudomonas palustris have also been conducted. NADH turnover frequencies are found to be dependent on the structure of the ligand and the results confirm that the proposed reduction step in the mechanism of hypoxia selectivity is likely to be mediated by NADH-dependent enzymes. Further understanding of the mechanism of hypoxia selectivity may facilitate the development of new imaging and radiotherapeutic agents with increased specificity for tumour hypoxia.

In vitro kinetic studies on the mechanism of oxygen-dependent cellular uptake of copper radiopharmaceuticals

NASA Astrophysics Data System (ADS)

Holland, Jason P.; Giansiracusa, Jeffrey H.; Bell, Stephen G.; Wong, Luet-Lok; Dilworth, Jonathan R.

2009-04-01

The development of hypoxia-selective radiopharmaceuticals for use as therapeutic and/or imaging agents is of vital importance for both early identification and treatment of cancer and in the design of new drugs. Radiotracers based on copper for use in positron emission tomography have received great attention due to the successful application of copper(II) bis(thiosemicarbazonato) complexes, such as [60/62/64Cu(II)ATSM] and [60/62/64Cu(II)PTSM], as markers for tumour hypoxia and blood perfusion, respectively. Recent work has led to the proposal of a revised mechanism of hypoxia-selective cellular uptake and retention of [Cu(II)ATSM]. The work presented here describes non-steady-state kinetic simulations in which the reported pO2-dependent in vitro cellular uptake and retention of [64Cu(II)ATSM] in EMT6 murine carcinoma cells has been modelled by using the revised mechanistic scheme. Non-steady-state (NSS) kinetic analysis reveals that the model is in very good agreement with the reported experimental data with a root-mean-squared error of less than 6% between the simulated and experimental cellular uptake profiles. Estimated rate constants are derived for the cellular uptake and washout (k1 = 9.8 ± 0.59 × 10-4 s-1 and k2 = 2.9 ± 0.17 × 10-3 s-1), intracellular reduction (k3 = 5.2 ± 0.31 × 10-2 s-1), reoxidation (k4 = 2.2 ± 0.13 mol-1 dm3 s-1) and proton-mediated ligand dissociation (k5 = 9.0 ± 0.54 × 10-5 s-1). Previous mechanisms focused on the reduction and reoxidation steps. However, the data suggest that the origins of hypoxia-selective retention may reside with the stability of the copper(I) anion with respect to protonation and ligand dissociation. In vitro kinetic studies using the nicotimamide adenine dinucleotide (NADH)-dependent ferredoxin reductase enzyme PuR isolated from the bacterium Rhodopseudomonas palustris have also been conducted. NADH turnover frequencies are found to be dependent on the structure of the ligand and the results confirm that the proposed reduction step in the mechanism of hypoxia selectivity is likely to be mediated by NADH-dependent enzymes. Further understanding of the mechanism of hypoxia selectivity may facilitate the development of new imaging and radiotherapeutic agents with increased specificity for tumour hypoxia.

Reaeration capacity of the Rock River between Lake Koshkonong, Wisconsin and Rockton, Illinois

USGS Publications Warehouse

Grant, R. Stephen

1978-01-01

The reaeration capacity of the Rock River from Lake Koshkonong, Wisconsin, to Rockton, Illinois, was determined using the energy-dissipation model. The model was calibrated using data from radioactive-tracer measurements in the study reach. Reaeration coefficients (K2) were computed for the annual minimum 7-day mean discharge that occurs on the average of once in 10 years (Q7,10). A time-of-travel model was developed using river discharge, slope, and velocity data from three dye studies. The model was used to estimate traveltime for the Q7,10 for use in the energy-dissipation model. During one radiotracer study, 17 mile per hour winds apparently increased the reaeration coefficient about 40 times. (Woodard-USGS)

Nuclear medicine and imaging research: Quantitative studies in radiopharmaceutical science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Copper, M.; Beck, R.N.

1991-06-01

During the past three years the program has undergone a substantial revitalization. There has been no significant change in the scientific direction of this grant, in which emphasis continues to be placed on developing new or improved methods of obtaining quantitative data from radiotracer imaging studies. However, considerable scientific progress has been made in the three areas of interest: Radiochemistry, Quantitative Methodologies, and Experimental Methods and Feasibility Studies, resulting in a sharper focus of perspective and improved integration of the overall scientific effort. Changes in Faculty and staff, including development of new collaborations, have contributed to this, as has acquisitionmore » of additional and new equipment and renovations and expansion of the core facilities. 121 refs., 30 figs., 2 tabs.« less

99mTc-DMSA Uptake in a Sister Mary Joseph's Nodule From Ovarian Cancer.

PubMed

Naddaf, Sleiman; Azzumeea, Fahad; Fahad Alzayed, Mohammed

2016-12-01

A 50-year-old woman with ovarian cancer underwent Tc-DMSA scan to evaluate the functional status of the right hydronephrotic kidney. The images incidentally revealed a well-defined focus of mild radiotracer uptake at the midanterior abdominal wall, which correlated with a metastatic Sister Mary Joseph's nodule seen on CT performed a week earlier.

Ga-67 positivity in sarcoidosis of the skin with coincident thyroid uptake of uncertain etiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreno, A.J.; Brown, J.M.; Salinas, J.A.

1984-03-01

Gallium-67 citrate scintigraphy of a 26-year-old woman with systemic sarcoidosis demonstrated abnormal radiotracer uptake within multiple biopsy-proven sarcoidal cutaneous lesions and within both lobes of the thyroid gland. The etiology of the thyroidal uptake of the Ga-67 was uncertain but it may represent sarcoidal involvement of the gland.

Automated solid-phase radiofluorination using polymer-supported phosphazenes.

PubMed

Mathiessen, Bente; Zhuravlev, Fedor

2013-08-30

The polymer supported phosphazene bases PS-P₂(tBu) and the novel PS-P₂(PEG) allowed for efficient extraction of [¹⁸F]F⁻ from proton irradiated [¹⁸O]H₂O and subsequent radiofluorination of a broad range of substrates directly on the resin. The highest radiochemical yields were obtained with aliphatic sulfonates (69%) and bromides (42%); the total radiosynthesis time was 35-45 min. The multivariate analysis showed that the radiochemical yields and purities were controlled by the resin load, reaction temperature, and column packing effects. The resins could be reused several times with the same or different substrates. The fully automated on-column radiofluorination methodology was applied to the radiosynthesis of the important PET radiotracers [¹⁸F]FLT and [¹⁸F]FDG. The latter was produced with 40% yield on a 120 GBq scale and passed GMP-regulated quality control required for commercial production of [1¹⁸F]FDG. The combination of compact form factor, simplicity of [¹⁸F]F⁻ recovery and processing, and column reusability can make solid phase radiofluorination an attractive radiochemistry platform for the emerging dose-on-demand instruments for bedside production of PET radiotracers.

Positron emission tomography in renal cell carcinoma: an imaging biomarker in development.

PubMed

Khandani, Amir H; Rathmell, W Kimryn

2012-07-01

Positron emission tomography (PET) has revolutionized cancer imaging. The current workhorse of molecular imaging, fluorodeoxyglucose (FDG) PET is used in the majority of malignant tumors with a few exceptions. Renal cell carcinoma (RCC) is one of those exceptions because of its variable uptake of FDG, although this variable uptake may actually be an asset in predicting response to some targeted agents, as will be discussed later. Beyond FDG, there is only scattered information in the literature on the use of PET in RCC. The purpose of this review is to summarize the current status of PET usage in RCC and point out its potentials and future directions. We will start with a brief overview of the demographics, molecular pathogenesis, and evolving treatment strategies in RCC because this information is essential for better understanding of uptake of various PET radiotracers in this cancer and their indications. This will be followed by discussing the role of PET in characterization of indeterminate renal masses, in staging and restaging of RCC, and, finally, in predicting and monitoring therapy response. Each of these 3 areas of PET usage will include the relevant radiotracers currently in use or in development. Copyright © 2012 Elsevier Inc. All rights reserved.

[Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use].

PubMed

Arbizu, J; Luquin, M R; Abella, J; de la Fuente-Fernández, R; Fernandez-Torrón, R; García-Solís, D; Garrastachu, P; Jiménez-Hoyuela, J M; Llaneza, M; Lomeña, F; Lorenzo-Bosquet, C; Martí, M J; Martinez-Castrillo, J C; Mir, P; Mitjavila, M; Ruiz-Martínez, J; Vela, L

2014-01-01

Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson's disease progression. Copyright © 2014 Elsevier España, S.L. and SEMNIM. All rights reserved.

(99m)Tc-EDDA/HYNIC-octreotate - a new radiotracer for detection and staging of NET: a case of metastatic duodenal carcinoid.

PubMed

Hubalewska-Dydejczyk, Alicja; Szybiński, Piotr; Fröss-Baron, Katarzyna; Mikolajczak, Renata; Huszno, Bohdan; Sowa-Staszczak, Anna

2005-01-01

Somatostatin receptor scintigraphy (SRS) has become a routine imaging method for the diagnostics of neuroendocrine tumours (NET). (99m)Tc-EDDA/HYNIC-octreotate (Polatom, Poland) is a new radiotracer with high affinity for SSTR2 and similar physiological biodistribution to (111)In-Octreoscan. We present a case of a 47-year-old man with disseminated duodenal carcinoid. The patient had been operated due to the tumour mass detected in pancreatic head area. Histopathology revealed carcinoid of the duodenal wall with local lymph node and liver metastases. The patient was qualified for chemotherapy stopped due to severe leucopenia. (99m)Tc EDDA/HYNIC-octreotate scintigraphy was performed for staging and to determine SSTR status of the tumour before planned 90Y-DOTATATE therapy. The multiple metastatic lesions were detected all over the body. The high quality images with high target/non target ratio were obtained. (99m)Tc-MDP scintigraphy confirmed multiple bone metastases. On the basis of SRS result the patient was qualified for 90Y-DOTA-TATE therapy. In conclusion, (99m)Tc EDDA/HYNIC-octreotate can be regarded as a promising tracer for staging and to determine SSTR status of NET.

Study of ⁷Be and ²¹⁰Pb as radiotracers of African intrusions in Malaga (Spain).

PubMed

Gordo, E; Liger, E; Dueñas, C; Fernández, M C; Cañete, S; Pérez, M

2015-10-01

The relationship between the particulate matter in the atmosphere of Malaga and the origin of air masses with special attention to African intrusions was analyzed. The concentrations of PM10 and the activities of some radionuclides ((7)Be and (210)Pb) as tracers of these intrusions are discussed. The origin of these radiotracers is completely different. (210)Pb is a good tracer of air masses traveling close to the ground and come from inland areas. On the other hand, the production of (7)Be is very low in the vicinity of the Earth's surface, and increases with altitude, making it a great tracer of stratospheric air masses in the troposphere. Studies of radionuclide activities in aerosol particles provide a means for evaluating the integrated effects of transport and meteorology on the atmospheric loadings of substances with different sources. Measurements of aerosol mass concentration and specific activities of (7)Be and (210)Pb in aerosols at Malaga (36° 43' 40″ N; 4° 28' 8″ W) for the period 2009-2011 were used to obtain the relationships between radionuclide activities and airflow patterns by comparing the data grouped by air mass trajectory. The average concentration values of (7)Be and (210)Pb over the 3-year period have been found to be 5.05 and 0.55 mBq m(-3), respectively, with mean aerosol mass concentration of 53.6 μg m(-3). Taking into account the outbreaks of the daily values limits of PM10 in the study period (2009-2011), the origin of air masses is studied to explain three different situations of both radionuclides (7)Be and (210)Pb: 1) high concentrations of (7)Be and low concentrations of (210)Pb; 2) high concentrations of (210)Pb and low concentrations of (7)Be and 3) high concentrations of (7)Be and (210)Pb. Copyright © 2015 Elsevier Ltd. All rights reserved.

Noninvasive monitoring of cancer therapy induced activated T cells using [18F]FB-IL-2 PET imaging.

PubMed

Hartimath, S V; Draghiciu, O; van de Wall, S; Manuelli, V; Dierckx, R A J O; Nijman, H W; Daemen, T; de Vries, E F J

2017-01-01

Cancer immunotherapy urgently calls for methods to monitor immune responses at the site of the cancer. Since activated T lymphocytes may serve as a hallmark for anticancer responses, we targeted these cells using the radiotracer N-(4-[ 18 F]fluorobenzoyl)-interleukin-2 ([ 18 F]FB-IL-2) for positron emission tomography (PET) imaging. Thus, we noninvasively monitored the effects of local tumor irradiation and/or immunization on tumor-infiltrating and systemic activated lymphocytes in tumor-bearing mice. A 10- and 27-fold higher [ 18 F]FB-IL-2 uptake was observed in tumors of mice receiving tumor irradiation alone or in combination with immunization, respectively. This increased uptake was extended to several non-target tissues. Administration of the CXCR4 antagonist AMD3100 reduced tracer uptake by 2.8-fold, indicating a CXCR4-dependent infiltration of activated T lymphocytes upon cancer treatment. In conclusion, [ 18 F]FB-IL-2 PET can serve as a clinical biomarker to monitor treatment-induced infiltration of activated T lymphocytes and, on that basis, may guide cancer immunotherapies.

[Treatment of hyperthyroidism with radioiodine during hemodialysis: Report of one case].

PubMed

Hurtado, Claudia; Báez, María Soledad; Bate, Anabel; Opazo, Claudio; Troncoso, Mauricio

2017-05-01

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

Release of Taurine and Glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium.

PubMed

Netti, Vanina; Pizzoni, Alejandro; Peréz-Domínguez, Martha; Ford, Paula; Pasantes-Morales, Herminia; Ramos-Mandujano, Gerardo; Capurro, Claudia

2018-05-23

Neuronal activity in the retina generates osmotic gradients that lead to Müller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Müller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca 2+ release from intracellular stores. Here we investigate the contribution of Taurine (Tau) and Glutamate (Glu), the most relevant amino acids in Müller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca 2+ -dependency in MIO-M1 cells. Swelling-induced [ 3 -H]-Tau/[ 3 H]-Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [ 3 H]-Tau and [ 3 H]-Glu (Tau > Glu) blunted by the VRAC inhibitors DCPIB and CBX, reducing RVD. Only [ 3 H]-Tau efflux was dependent on Ca 2+ release from intracellular stores. RVD was unaffected in a Ca 2+ -free medium, probably due to Ca 2+ -independent Tau and Glu release, but was reduced by chelating intracellular Ca 2+ . The inhibition of phosphatidylinositol-3-kinase reduced [ 3 H]-Glu efflux but also the Ca 2+ -insensitive [ 3 H]-Tau fraction and decreased RVD, evidencing the relevance of this Ca 2+ -independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Müller cells. The observed disparities in Ca 2+ influence on amino acid release support the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology.

Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine.

PubMed

Fischer, Steffen; Wiese, Christian; Maestrup, Eva Grosse; Hiller, Achim; Deuther-Conrad, Winnie; Scheunemann, Matthias; Schepmann, Dirk; Steinbach, Jörg; Wünsch, Bernhard; Brust, Peter

2011-03-01

Neuroimaging of σ(1) receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable (18)F-labelled PET radioligands for that purpose. The selective σ(1) receptor ligand [(18)F]fluspidine (1'-benzyl-3-(2-[(18)F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]) was synthesized by nucleophilic (18)F(-) substitution of the tosyl precursor. In vitro receptor binding affinity and selectivity were assessed by radioligand competition in tissue homogenate and autoradiographic approaches. In female CD-1 mice, in vivo properties of [(18)F]fluspidine were evaluated by ex vivo brain section imaging and organ distribution of intravenously administered radiotracer. Target specificity was validated by organ distribution of [(18)F]fluspidine after treatment with 1 mg/kg i.p. of the σ receptor antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen. In vitro metabolic stability and in vivo metabolism were investigated by LC-MS(n) and radio-HPLC analysis. [(18)F]Fluspidine was obtained with a radiochemical yield of 35-45%, a radiochemical purity of ≥ 99.6% and a specific activity of 150-350 GBq/μmol (n = 6) within a total synthesis time of 90-120 min. In vitro, fluspidine bound specifically and with high affinity to σ(1) receptors (K (i) = 0.59 nM). In mice, [(18)F]fluspidine rapidly accumulated in brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and 13 at 5 and 30 min after intravenous application of the radiotracer, respectively. By ex vivo autoradiography of brain slices, resemblance between binding site occupancy of [(18)F]fluspidine and the expression of σ(1) receptors was shown. The radiotracer uptake in the brain as well as in peripheral σ(1) receptor expressing organs was significantly inhibited by haloperidol but not by tamoxifen. Incubation with rat liver microsomes led to a fast biotransformation of fluspidine. After an incubation period of 30 min only 13% of the parent compound was left. Seven metabolites were identified by HPLC-UV and LC-MS(n) techniques. However, [(18)F]fluspidine showed a higher metabolic stability in vivo. In plasma samples ∼ 94% of parent compound remained at 30 min and ∼ 67% at 60 min post-injection. Only one major radiometabolite was detected. None of the radiometabolites crossed the blood-brain barrier. [(18)F]Fluspidine demonstrated favourable target affinity and specificity as well as metabolic stability both in vitro and in animal experiments. The in vivo properties of [(18)F]fluspidine offer a high potential of this radiotracer for neuroimaging and quantitation of σ(1) receptors in vivo.

Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

PubMed

Bailey, J J; Dewaraja, Y; Hubers, D; Srinivasa, R N; Frey, K A

2017-10-01

To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer.

PubMed

Gao, Mingzhang; Wang, Min; Miller, Kathy D; Zheng, Qi-Huang

2011-09-01

The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [(11)C]4a-c and [(11)C]8a-d, were prepared by O-[(11)C] methylation of their corresponding precursors using [(11)C]CH(3)OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 52 ± 2% (n = 5) and 57 ± 3% (n = 5) radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). The IC(50) values to block COX-2 for known compounds celecoxib (4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a-d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

A new method measuring the interaction of radiotracers with the human P-glycoprotein (P-gp) transporter.

PubMed

Vraka, Chrysoula; Dumanic, Monika; Racz, Teresa; Pichler, Florian; Philippe, Cecile; Balber, Theresa; Klebermass, Eva-Maria; Wagner, Karl-Heinz; Hacker, Marcus; Wadsak, Wolfgang; Mitterhauser, Markus

2018-05-01

In drug development, biomarkers for cerebral applications have a lower success rate compared to cardiovascular drugs or tumor therapeutics. One reason is the missing blood brain barrier penetration, caused by the tracer's interaction with efflux transporters such as the P-gp (MDR1 or ABCB1). Aim of this study was the development of a reliable model to measure the interaction of radiotracers with the human efflux transporter P-gp in parallel to the radiolabeling process. LigandTracer® Technology was used with the wildtype cell line MDCKII and the equivalent cell line overexpressing human P-gp (MDCKII-hMDR1). The method was evaluated based on established PET tracers with known interaction with the human P-gp transporter and in nanomolar concentration (15 nM). [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP were used as P-gp substrates by comparing the real-time model with an uptake assay and μPET images. [ 11 C]DASB [ 11 C]Harmine, [ 18 F]FMeNER,[ 18 F]FE@SUPPY and [ 11 C]Me@HAPTHI were used as tracers without interactions with P-gp in vitro. However, [ 11 C]Me@HAPTHI shows a significant increase in SUV levels after blocking with Tariquidar. The developed real-time kinetic model uses directly PET tracers in a compound concentration, which is reflecting the in vivo situation. This method may be used at an early stage of radiopharmaceutical development to measure interactions to P-gp before conducting animal experiments. Copyright © 2018 Elsevier Inc. All rights reserved.

Tyrosine-Kinase Inhibitors Therapies with Mainly Anti-Angiogenic Activity in Advanced Renal Cell Carcinoma: Value of PET/CT in Response Evaluation

PubMed Central

Ranieri, Girolamo; Marech, Ilaria; Niccoli Asabella, Artor; Di Palo, Alessandra; Porcelli, Mariangela; Lavelli, Valentina; Rubini, Giuseppe; Ferrari, Cristina; Gadaleta, Cosmo Damiano

2017-01-01

Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib. As anti-angiogenic agents, TKIs interfere the loop, being able to inhibit tumor proliferation. TKIs are now available treatments for advanced RCC, which demonstrated to improve overall survival and/or progression free survival. Their effects can be detectable early on Positron Emission Tomography/Computed Tomography (PET/CT) by change in 18F-fluoro-2-deoxy-2-d-glucose (18F-FDG) uptake, the main radiotracer used to date, as a strong indicator of biological response. 18F-FDG PET/CT demonstrated an ability to predict and monitor disease progression, allowing an early and reliable identification of responders, and could be used for image-guided optimization and “personalization” of anti-angiogenic regimens. New radiotracers for biometabolic imaging are currently under investigation, which exploit the other pathways involved in the cancer process, including cellular proliferation, aerobic metabolism, cell membrane synthesis, hypoxia and amino acid transport, as well as the angiogenic process, but they require further studies. PMID:28891933

Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of 111In- and 68Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats.

PubMed

Oliveira, Bruno L; Blasi, Francesco; Rietz, Tyson A; Rotile, Nicholas J; Day, Helen; Caravan, Peter

2015-10-01

We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F PET probes for noninvasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and SPECT. In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in 2 animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Radiotracers were synthesized using a known fibrin-binding peptide conjugated to 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DOTA-MA), or a diethylenetriamine ligand (DETA-propanoic acid [PA]), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA), or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics, and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a nonbinding control probe using SPECT/PET/CT imaging. All 3 radiotracers showed affinity similar to soluble fibrin fragment DD(E) (inhibition constant=0.53-0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0±0.2 percentage injected dose per gram), with low off-target accumulation. Both radiotracers underwent fast systemic elimination (half-life, 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation or degradation. Triple-isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target specificity. 68Ga-FBP14 and 111In-FBP15 have high fibrin affinity and thrombus specificity and represent useful PET and SPECT probes for thrombus detection. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Diagnosis of abnormal biliary copper excretion by positron emission tomography with targeting of 64Copper-asialofetuin complex in LEC rat model of Wilson’s disease

PubMed Central

Bahde, Ralf; Kapoor, Sorabh; Bhargava, Kuldeep K; Palestro, Christopher J; Gupta, Sanjeev

2014-01-01

Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson’s disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson’s disease. After complexing 64Cu to asialofetuin we studied handling of this complex compared with 64Cu in healthy LEA rats and diseased homozygous LEC rats lacking ATP7B and exhibiting hepatic copper toxicosis. We analyzed radiotracer clearance from blood, organ uptake, and biliary excretion, including sixty minute dynamic positron emission tomography recordings. In LEA rats, 64Cu-asialofetuin was better cleared from blood followed by liver uptake and greater biliary excretion than 64Cu. In LEC rats, 64Cu-asialofetuin activity cleared even more rapidly from blood followed by greater uptake in liver, but neither 64Cu-asialofetuin nor 64Cu appeared in bile. Image analysis demonstrated rapid visualization of liver after 64Cu-asialofetuin administration followed by decreased liver activity in LEA rats while liver activity progressively increased in LEC rats. Image analysis resolved this difference in hepatic activity within one hour. We concluded that 64Cu-asialofetuin complex was successfully targeted to the liver and radiocopper was then excreted into bile in an ATP7B-dependent manner. Therefore, hepatic targeting of radiocopper will be appropriate for improving molecular diagnosis and for developing drug/cell/gene therapies in Wilson’s disease. PMID:25250203

Unique Distribution of Aromatase in the Human Brain: In Vivo Studies With PET and [N-Methyl-11C]Vorozole

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biegon, A.; Biegon, A.; Kim, S.W.

Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-{sup 11}C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-minmore » period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V{sub T}) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region-dependent, ranging from {approx}70% blocking in thalamus andpreoptic area to {approx}10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.« less

Preclinical assessment of dopaminergic system in rats by MicroPET using three positron-emitting radiopharmaceuticals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lara-Camacho, V. M., E-mail: victormlc13@hotmail.com; Ávila-García, M. C., E-mail: victormlc13@hotmail.com; Ávila-Rodríguez, M. A., E-mail: victormlc13@hotmail.com

Different diseases associated with dysfunction of dopaminergic system such as Parkinson, Alzheimer, and Schizophrenia are being widely studied with positron emission tomography (PET) which is a noninvasive method useful to assess the stage of these illnesses. In our facility we have recently implemented the production of [{sup 11}C]-DTBZ, [{sup 11}C]-RAC, and [{sup 18}F]-FDOPA, which are among the most common PET radiopharmaceuticals used in neurology applications to get information about the dopamine pathways. In this study two healthy rats were imaged with each of those radiotracers in order to confirm selective striatum uptake as a proof of principle before to releasemore » them for human use.« less

Novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.

PubMed

Liu, Min; Zheng, Yumin; Avcibasi, Ugur; Liu, Shuang

2016-11-01

In this study, novel 99m Tc(III)-azide complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] ( 99m Tc-ISboroxime-N 3 : R=IS; 99m Tc-MPboroxime-N 3 : R=MP; 99m Tc-PAboroxime-N 3 : R=PA; 99m Tc-PYboroxime-N 3 : R=PY; and 99m Tc-Uboroxime-N 3 : R=5U) were evaluated as heart imaging agents. Complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN 3 and [ 99m TcCl(CDO)(CDOH) 2 B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention. 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were prepared with high RCP (93-98%) while the RCP of 99m Tc-MPboroxime-N 3 and 99m Tc-PAboroxime-N 3 was 80-85%. The myocardial retention curves of 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for 99m Tc-ISboroxime-N 3 , 0.7±0.1min for 99m Tc-PYboroxime-N 3 and 0.9±0.4min for 99m Tc-Uboroxime-N 3 . The 2-min heart uptake from biodistribution studies followed the ranking order of 99m Tc-ISboroxime-N 3 (3.60±0.68%ID/g)> 99m Tc-PYboroxime-N 3 (2.35±0.37%ID/g)≫ 99m Tc-Uboroxime-N 3 (1.29±0.06%ID/g). 99m Tc-ISboroxime-N 3 had the highest 2-min heart uptake among 99m Tc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for 99m Tc-ISboroxime-N 3 . Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R]. Among the radiotracers evaluated in SD rats, 99m Tc-ISboroxime-N 3 has the highest initial heart uptake with the heart retention comparable to that of 99m Tc-Teboroxime. 99m Tc-ISboroxime-N 3 is a promising alternative to 99m Tc-Teboroxime for SPECT MPI. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

DTIC Science & Technology

2016-10-01

small-molecule peptidomimetic imaging agents labeled with positron emitting fluorine- 18 . These data will enable the filing of an exploratory IND...outcome. 15. SUBJECT TERMS Prostate Cancer, Prostate Specific Membrane Antigen (PSMA), Fluorine- 18 , Molecular Imaging, Radiotracer, Automated...Synthesis, Phosphoramidate, Inhibitor, Peptide Mimic, Peptidomimetic 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a

A one-pot radioiodination of aryl amines via stable diazonium salts: preparation of 125I-imaging agents.

PubMed

Sloan, Nikki L; Luthra, Sajinder K; McRobbie, Graeme; Pimlott, Sally L; Sutherland, Andrew

2017-10-05

An operationally simple, one-pot, two-step tandem procedure that allows the incorporation of radioactive iodine into aryl amines via stable diazonium salts is described. The mild conditions are tolerant of various functional groups and substitution patterns, allowing late-stage, rapid access to a wide range of 125 I-labelled aryl compounds and SPECT radiotracers.

Monitoring Tc dynamics in a bioreduced sediment: an investigation with gamma camera imaging of (99m)Tc-pertechnetate and (99m)Tc-DTPA.

PubMed

Vandehey, Nicholas T; O'Neil, James P; Slowey, Aaron J; Boutchko, Rostyslav; Druhan, Jennifer L; Moses, William W; Nico, Peter S

2012-11-20

We demonstrate the utility of nuclear medical imaging technologies and a readily available radiotracer, [(99m)Tc]TcO(4)(-), for the noninvasive monitoring of Fe(II) production in acetate-stimulated sediments from Old Rifle, CO, USA. Microcosms consisting of sediment in artificial groundwater media amended with acetate were probed by repeated injection of radiotracer over three weeks. Gamma camera imaging was used to noninvasively quantify the rate and extent of [(99m)Tc]TcO(4)(-) partitioning from solution to sediment. Aqueous Fe(II) and sediment-associated Fe(II) were also measured and correlated with the observed tracer behavior. For each injection of tracer, curves of (99m)Tc concentration in solution vs time were fitted to an analytic function that accounts for both the observed rate of sedimentation as well as the rate of (99m)Tc association with the sediment. The rate and extent of (99m)Tc association with the biostimulated sediment correlated well with the production of Fe(II), and a mechanism of [(99m)Tc]TcO(4)(-) reduction via reaction with surface-bound Fe(II) to form an immobile Tc(IV) species was inferred. After three weeks of bioreduction, a subset of microcosms was aerated in order to reoxidize the Fe(II) to Fe(III), which also destroyed the affinity of the [(99m)Tc]TcO(4)(-) for the sediments. However, within 3 days postoxidation, the rate of Tc(VII) reduction was faster than immediately before oxidation implying a rapid return to more extensive bioreduction. Furthermore, aeration soon after a tracer injection showed that sediment-bound Tc(IV) is rapidly resolubilized to Tc(VII). In contrast to the [(99m)Tc]TcO(4)(-), a second commercially available tracer, (99m)Tc-DTPA (diethylenetriaminepentaacetic acid), had minimal association with sediment in both controls and biostimulated sediments. These experiments show the promise of [(99m)Tc]TcO(4)(-) and (99m)Tc-DTPA as noninvasive imaging probes for a redox-sensitive radiotracer and a conservative flow tracer, respectively.

Semi-automated lab-on-a-chip for dispensing GA-68 radiotracers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weinberg, Irving

We solved a technical problem that is hindering American progress in molecular medicine, and restricting US citizens from receiving optimal diagnostic care. Specifically, the project deals with a mother/daughter generator of positron-emitting radiotracers (Ge-68/Ga-68). These generator systems are approved in Europe but cannot be used in the USA, because of safety issues related to possible breakthrough of long-lived Ge-68 (mother) atoms. Europeans have demonstrated abilities of Ga-68-labeled radiotracers to image cancer foci with high sensitivity and specificity, and to use such methods to effectively plan therapy.The USA Food and Drug Administration (FDA) and Nuclear Regulatory Commission (NRC) have taken themore » position that every patient administration of Ga-68 should be preceded by an assay demonstrated that Ge-68 breakthrough is within acceptable limits. Breakthrough of parent elements is a sensitive subject at the FDA, as evidenced by the recent recall of Rb-82 generators due to inadvertent administrations of Sr-82. Commercially, there is no acceptable rapid method for assaying breakthrough of Ge-68 prior to each human administration. The gamma emissions of daughter Ga-68 have higher energies than the parent Ge-68, so that the shielding assays typically employed for Mo-99/Tc-99m generators cannot be applied to Ga-68 generators. The half-life of Ga-68 is 68 minutes, so that the standard 10-half-life delay (used to assess breakthrough in Sr-82/Rb-82 generators) cannot be applied to Ga-68 generators. As a result of the aforementioned regulatory requirements, Ga-68 generators are sold in the USA for animal use only.The American clinical community’s inability to utilize Ga-68 generators impairs abilities to treat patients domestically, and puts the USA at a disadvantage in developing exportable products. The proposed DOE project aimed to take advantage of recent technological advances developed for lab-on-a-chip (LOC) applications. Based on our experiences constructing such devices, the proposed microfluidics-based approach could provide cost-effective validation of breakthrough compliance in minutes.« less

Optimizing Imaging Instruments for Emission Mammography

NASA Astrophysics Data System (ADS)

Weinberg, Irving N.

1996-05-01

Clinical studies have demonstrated that radiotracer methods can noninvasively detect breast cancers in vivo(L.P. Adler, J.P.Crowe, N.K. Al-Kaisis, et al, Radiology 187,743-750 (1993)) (I. Khalkhali, I. Mena, E. Jouanne, et al, J. Am. Coll. Surg. 178, 491-497 (1994)). Due to spatial resolution and count efficiency considerations, users of conventional nuclear medicine instruments have had difficulty in detecting subcentimeter cancers. This limitation is unfortunate, since cancer therapy is generally most efficacious when tumor diameter at detection is less than a centimeter. A more subtle limitation of conventional nuclear medicine imaging instruments is that they are poorly suited to guiding interventions. With the assistance of C.J. Thompson from McGill University, and the CEBAF Detector Physics Group, we have explored the possibility of configuring detectors for nuclear medicine imaging devices into geometries that resemble conventional x-ray mammography cameras(I.N. Weinberg, U.S.Patent 5,252,830 (1993)). Phantom and pilot clinical studies suggest that applying breast compression within such geometries may offer several advantages(C.J. Thompson, K. Murthy, I.N. Weinberg, et al, Med. Physics 21, 259-538 (1994)): For coincident detection of positron emitters, efficiency and spatial resolution are improved by bringing the detectors very close to the source (the breast tumor). For single-photon detection, attenuation due to overlying tissue is reduced. Since, for a high-efficiency collimator, spatial resolution worsens with increasing source to collimator distance, adoption of compression allows more efficient collimators to be employed. Economics are favorable in that detectors can be deployed in the region of interest, rather than around the entire body, and that such detectors can be mounted in conventional mammographic gantries. The application of conventional mammographic geometry promises to assist physicians in conducting radiotracer-guided biopsies, and in correlating biochemical with x-ray data. The primary challenge of conducting studies with dedicated emission mammography devices has been dealing with high count rates due to cardiac activity.

Using radioactive drugs could lead to better imaging of prostate cancer | Center for Cancer Research

Cancer.gov

Medical imaging (x-ray, ultrasound, MRI, CT, PET scan) is a noninvasive way to view the internal structures of the body. However, these tools are not ideal for detecting cancer that has spread, or metastasized, because the precise location of these cancer cells is unknown. Researchers are now testing an experimental radiotracer called 18F-DCFPyL to help find sites of cancer in

In Vivo PET Imaging of Myelin Damage and Repair in the Spinal Cord

DTIC Science & Technology

2012-10-01

oligodendrocyte precursor cells ( OPCs ) that are subsequently activated and distributed to the damaged axons. However, the remyelination process is often...We hypothesize that myelin repair can be achieved by therapeutic agents that stimulate the endogenous promotion of remyelination by host OPCs ...specific uptake signal; 5) Rapid clearance of radiotracer from other organs (e.g, lung, heart, liver , etc) to ensure optimal dosimetry; 6) Minimal probe

Development of F-18 Labeled Radiotracers for PET Imaging of Brain Alpha-1 Noradrenergic Receptors: Potential PTSD Vulnerability and Diagnostic Biomarkers

DTIC Science & Technology

2012-09-01

Amitriptyline D1 [3H]SCH233930 SKF38393 D2 [3H]N-methylspiperone Haloperidol D3 [3H]N-methylspiperone Chlorpromazine D4 [3H]N...Salvinorin A OPIOIDS Mu Opioid [3H]DAMGO DAMGO Sigma 1 [3H]Pentazocine Haloperidol UNCLEAR Sigma 2 [3H]DTG Haloperidol GABA GABAA [3H]Muscimol GABA

Synthesis of [ 18F]arenes via the copper-mediated [ 18F]fluorination of boronic acids

DOE PAGES

Mossine, Andrew V.; Brooks, Allen F.; Makaravage, Katarina J.; ...

2015-11-14

Here, a copper-mediated radiofluorination of aryl- and vinylboronic acids with K 18F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [ 18F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors.

Synthesis of [ 18F]arenes via the copper-mediated [ 18F]fluorination of boronic acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mossine, Andrew V.; Brooks, Allen F.; Makaravage, Katarina J.

Here, a copper-mediated radiofluorination of aryl- and vinylboronic acids with K 18F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [ 18F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors.

Comparison of short-lived medical isotopes activation by laser thin target induced protons and conventional cyclotron proton beams

NASA Astrophysics Data System (ADS)

Murray, Joseph; Dudnikova, Galina; Liu, Tung-Chang; Papadopoulos, Dennis; Sagdeev, Roald; Su, J. J.; UMD MicroPET Team

2014-10-01

Production diagnostic or therapeutic nuclear medicines are either by nuclear reactors or by ion accelerators. In general, diagnostic nuclear radioisotopes have a very short half-life varying from tens of minutes for PET tracers and few hours for SPECT tracers. Thus supplies of PET and SPECT radiotracers are limited by regional production facilities. For example 18F-fluorodeoxyglucose (FDG) is the most desired tracer for positron emission tomography because its 110 minutes half-life is sufficient long for transport from production facilities to nearby users. From nuclear activation to completing image taking must be done within 4 hours. Decentralized production of diagnostic radioisotopes will be idea to make high specific activity radiotracers available to researches and clinicians. 11 C, 13 N, 15 O and 18 F can be produced in the energy range from 10-20 MeV by protons. Protons of energies up to tens of MeV generated by intense laser interacting with hydrogen containing targets have been demonstrated by many groups in the past decade. We use 2D PIC code for proton acceleration, Geant4 Monte Carlo code for nuclei activation to compare the yields and specific activities of short-lived isotopes produced by cyclotron proton beams and laser driven protons.

Methodological considerations regarding the use of inorganic 197Hg(II) radiotracer to assess mercury methylation potential rates in lake sediment

USGS Publications Warehouse

Perez, Catan S.; Guevara, S.R.; Marvin-DiPasquale, M.; Magnavacca, C.; Cohen, I.M.; Arribere, M.

2007-01-01

Methodological considerations on the determination of benthic methyl-mercury (CH3Hg) production potentials were investigated on lake sediment, using 197Hg radiotracer. Three methods to arrest bacterial activity were compared: flash freezing, thermal sterilization, and ??-irradiation. Flash freezing showed similar CH3Hg recoveries as thermal sterilization, which was both 50% higher than the recoveries obtained with ??-ray irradiation. No additional radiolabel was recovered in kill-control samples after an additional 24 or 65 h of incubation, suggesting that all treatments were effective at arresting Hg(II)-methylating bacterial activity, and that the initial recoveries are likely due to non-methylated 197Hg(II) carry-over in the organic extraction and/or [197Hg]CH3Hg produced via abiotic reactions. Two CH3Hg extraction methods from sediment were compared: (a) direct extraction into toluene after sediment leaching with CuSO4 and HCl and (b) the same extraction with an additional back-extraction step to thiosulphate. Similar information was obtained with both methods, but the low efficiency observed and the extra work associated with the back-extraction procedure represent significant disadvantages, even tough the direct extraction involves higher Hg(II) carry over. ?? 2007 Elsevier Ltd. All rights reserved.

OpenPET: A Flexible Electronics System for Radiotracer Imaging

NASA Astrophysics Data System (ADS)

Moses, W. W.; Buckley, S.; Vu, C.; Peng, Q.; Pavlov, N.; Choong, W.-S.; Wu, J.; Jackson, C.

2010-10-01

We present the design for OpenPET, an electronics readout system designed for prototype radiotracer imaging instruments. The critical requirements are that it has sufficient performance, channel count, channel density, and power consumption to service a complete camera, and yet be simple, flexible, and customizable enough to be used with almost any detector or camera design. An important feature of this system is that each analog input is processed independently. Each input can be configured to accept signals of either polarity as well as either differential or ground referenced signals. Each signal is digitized by a continuously sampled ADC, which is processed by an FPGA to extract pulse height information. A leading edge discriminator creates a timing edge that is “time stamped” by a TDC implemented inside the FPGA. This digital information from each channel is sent to an FPGA that services 16 analog channels, and information from multiple channels is processed by this FPGA to perform logic for crystal lookup, DOI calculation, calibration, etc. As all of this processing is controlled by firmware and software, it can be modified/customized easily. The system is open source, meaning that all technical data (specifications, schematics and board layout files, source code, and instructions) will be publicly available.

64Cu-Labeled triphenylphosphonium and triphenylarsonium cations as highly tumor-selective imaging agents.

PubMed

Wang, Jianjun; Yang, Chang-Tong; Kim, Young-Seung; Sreerama, Subramanya G; Cao, Qizhen; Li, Zi-Bo; He, Zhengjie; Chen, Xiaoyuan; Liu, Shuang

2007-10-18

This report presents synthesis and evaluation of the 64Cu-labeled triphenylphosphonium (TPP) cations as new radiotracers for imaging tumors by positron emission tomography. Biodistribution properties of 64Cu-L1, 64Cu-L2, 64Cu-L3, and 99mTc-Sestamibi were evaluated in athymic nude mice bearing U87MG human glioma xenografts. The most striking difference is that 64Cu-L1, 64Cu-L2, and 64Cu-L3 have much lower heart uptake (<0.6% ID/g) than 99mTc-Sestamibi ( approximately 18% ID/g) at >30 min p.i. Their tumor/heart ratios increase steadily from approximately 1 at 5 min p.i. to approximately 5 at 120 min p.i. The tumor/heart ratio of 64Cu-L3 is approximately 40 times better than that of 99mTc-Sestamibi at 120 min postinjection. Results from in vitro assays show that 64Cu-L1 is able to localize in tumor mitochondria. The tumor is clearly visualized in the tumor-bearing mice administered with 64Cu-L1 as 30 min postinjection. The 64Cu-labeled TPP/TPA cations are very selective radiotracers that are able to provide the information of mitochondrial bioenergetic function in tumors by monitoring mitochondrial potential in a noninvasive fashion.

Isolation and N-terminal sequencing of a novel cadmium-binding protein from Boletus edulis

NASA Astrophysics Data System (ADS)

Collin-Hansen, C.; Andersen, R. A.; Steinnes, E.

2003-05-01

A Cd-binding protein was isolated from the popular edible mushroom Boletus edulis, which is a hyperaccumulator of both Cd and Hg. Wild-growing samples of B. edulis were collected from soils rich in Cd. Cd radiotracer was added to the crude protein preparation obtained from ethanol precipitation of heat-treated cytosol. Proteins were then further separated in two consecutive steps; gel filtration and anion exchange chromatography. In both steps the Cd radiotracer profile showed only one distinct peak, which corresponded well with the profiles of endogenous Cd obtained by atomic absorption spectrophotometry (AAS). Concentrations of the essential elements Cu and Zn were low in the protein fractions high in Cd. N-terminal sequencing performed on the Cd-binding protein fractions revealed a protein with a novel amino acid sequence, which contained aromatic amino acids as well as proline. Both the N-terminal sequencing and spectrofluorimetric analysis with EDTA and ABD-F (4-aminosulfonyl-7-fluoro-2, 1, 3-benzoxadiazole) failed to detect cysteine in the Cd-binding fractions. These findings conclude that the novel protein does not belong to the metallothionein family. The results suggest a role for the protein in Cd transport and storage, and they are of importance in view of toxicology and food chemistry, but also for environmental protection.

New SPECT and PET Radiopharmaceuticals for Imaging Cardiovascular Disease

PubMed Central

Sogbein, Oyebola O.; Pelletier-Galarneau, Matthieu; Schindler, Thomas H.; Wei, Lihui; Wells, R. Glenn; Ruddy, Terrence D.

2014-01-01

Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET) and magnetic resonance imaging (MRI) continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed. PMID:24901002

Characterization of the novel positive allosteric modulator, LY2119620, at the muscarinic M(2) and M(4) receptors.

PubMed

Croy, Carrie H; Schober, Douglas A; Xiao, Hongling; Quets, Anne; Christopoulos, Arthur; Felder, Christian C

2014-07-01

The M(4) receptor is a compelling therapeutic target, as this receptor modulates neural circuits dysregulated in schizophrenia, and there is clinical evidence that muscarinic agonists possess both antipsychotic and procognitive efficacy. Recent efforts have shifted toward allosteric ligands to maximize receptor selectivity and manipulate endogenous cholinergic and dopaminergic signaling. In this study, we present the pharmacological characterization of LY2119620 (3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy] thieno[2,3-b]pyridine-2-carboxamide), a M(2)/M(4) receptor-selective positive allosteric modulator (PAM), chemically evolved from hits identified through a M4 allosteric functional screen. Although unsuitable as a therapeutic due to M(2) receptor cross-reactivity and, thus, potential cardiovascular liability, LY2119620 surpassed previous congeners in potency and PAM activity and broadens research capabilities through its development into a radiotracer. Characterization of LY2119620 revealed evidence of probe dependence in both binding and functional assays. Guanosine 5'-[γ-(35)S]-triphosphate assays displayed differential potentiation depending on the orthosteric-allosteric pairing, with the largest cooperativity observed for oxotremorine M (Oxo-M) LY2119620. Further [(3)H]Oxo-M saturation binding, including studies with guanosine-5'-[(β,γ)-imido]triphosphate, suggests that both the orthosteric and allosteric ligands can alter the population of receptors in the active G protein-coupled state. Additionally, this work expands the characterization of the orthosteric agonist, iperoxo, at the M(4) receptor, and demonstrates that an allosteric ligand can positively modulate the binding and functional efficacy of this high efficacy ligand. Ultimately, it was the M(2) receptor pharmacology and PAM activity with iperoxo that made LY2119620 the most suitable allosteric partner for the M(2) active-state structure recently solved (Kruse et al., 2013), a structure that provides crucial insights into the mechanisms of orthosteric activation and allosteric modulation of muscarinic receptors. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Single-photon emitting radiotracers produced by cyclotrons for myocardial imaging

NASA Astrophysics Data System (ADS)

Kulkarni, Padmakar V.

1989-04-01

Radionuclides produced by cyclotron have played an important role in clinical nuclear medicine. Among these, 210T1, 123I, 111In and 67Ga in various chemical forms have important applications in the diagnosis of cancer and heart disease using scintigraphic imaging techniques. Cardiac imaging using nuclear scintigraphy and echocardiography has been among the fastest growing diagnostic technologies in medicine during the past 15 years. Development of new tracers in conjunction with new equipment with better resolution has contributed to the better quantification and analysis of test results. The development of new biomolecules, monoclonal antibodies to myosin, platelets, fibrin and other receptor binding agents has added a new dimension to nuclear imaging studies.

Investigating the binding properties of porous drug delivery systems using nuclear sensors (radiotracers) and positron annihilation lifetime spectroscopy--predicting conditions for optimum performance.

PubMed

Mume, Eskender; Lynch, Daniel E; Uedono, Akira; Smith, Suzanne V

2011-06-21

Understanding how the size, charge and number of available pores in porous material influences the uptake and release properties is important for optimising their design and ultimately their application. Unfortunately there are no standard methods for screening porous materials in solution and therefore formulations must be developed for each encapsulated agent. This study investigates the potential of a library of radiotracers (nuclear sensors) for assessing the binding properties of hollow silica shell materials. Uptake and release of Cu(2+) and Co(2+) and their respective complexes with polyazacarboxylate macrocycles (dota and teta) and a series of hexa aza cages (diamsar, sarar and bis-(p-aminobenzyl)-diamsar) from the hollow silica shells was monitored using their radioisotopic analogues. Coordination chemistry of the metal (M) species, subtle alterations in the molecular architecture of ligands (Ligand) and their resultant complexes (M-Ligand) were found to significantly influence their uptake over pH 3 to 9 at room temperature. Positively charged species were selectively and rapidly (within 10 min) absorbed at pH 7 to 9. Negatively charged species were preferentially absorbed at low pH (3 to 5). Rates of release varied for each nuclear sensor, and time to establish equilibrium varied from minutes to days. The subtle changes in design of the nuclear sensors proved to be a valuable tool for determining the binding properties of porous materials. The data support the development of a library of nuclear sensors for screening porous materials for use in optimising the design of porous materials and the potential of nuclear sensors for high through-put screening of materials.

Long-circulating, pH-sensitive liposomes versus long-circulating, non-pH-sensitive liposomes as a delivery system for tumor identification.

PubMed

de Barros, André Luís Branco; Mota, Luciene das Graças; Soares, Daniel Crístian Ferreira; de Souza, Cristina Maria; Cassali, Geovanni Dantas; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2013-09-01

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. Several forms of cancer, including lung, prostate, breast, and colon over-express receptors for bombesin-like peptides. Therefore, radiolabeled bombesin analogs might be useful for tumor identification. Nevertheless, it is well known that higher tumor uptake can yield images in higher quality. Hence, drug delivery systems, such as liposomes, can be used to achieve a higher concentration of radiotracer in tumor site, and also improve the radiotracer stability, since peptides can suffer easily degradation in vivo by natural plasma and tissue peptides. In this paper, we prepared long-circulating, pH-sensitive liposomes and long-circulation, non-pH sensitive liposomes. Both formulations were able to encapsulate the radiolabeled bombesin derivative (99mTc-BBN(7_14)), and also showing high in vitro stability. Biodistribution studies were performed in Ehrlich tumor bearing-mice to compare the ability of pH-sensitive and non-pH sensitive liposomes to deliver 99mTc-BBN(7_14) to tumor site. Results showed higher tumor uptake (2-fold) when pH-sensitive liposomes were used, suggesting that these vesicles can facilitate the access to the tumor by releasing the diagnostic agent into the ideal area. As a result, tumor-to-muscle ratio achieved with pH-sensitive liposomes was higher than that obtained with non-pH-sensitive formulation. In addition, scintigraphic images for pH-sensitive liposomes showed evident tumor uptake, corroborating with biodistribution data. Therefore, the results presented in this paper suggest that pH-sensitive liposomes are able to deliver more efficiently the radiolabeled bombesin analog. This finding poses a new possibility to improve images quality, since the tumor-to-muscle ratio was strongly enhanced.

Dual-isotope PET using positron-gamma emitters.

PubMed

Andreyev, A; Celler, A

2011-07-21

Positron emission tomography (PET) is widely recognized as a highly effective functional imaging modality. Unfortunately, standard PET cannot be used for dual-isotope imaging (which would allow for simultaneous investigation of two different biological processes), because positron-electron annihilation products from different tracers are indistinguishable in terms of energy. Methods that have been proposed for dual-isotope PET rely on differences in half-lives of the participating isotopes; these approaches, however, require making assumptions concerning kinetic behavior of the tracers and may not lead to optimal results. In this paper we propose a novel approach for dual-isotope PET and investigate its performance using GATE simulations. Our method requires one of the two radioactive isotopes to be a pure positron emitter and the second isotope to emit an additional high-energy gamma in a cascade simultaneously with positron emission. Detection of this auxiliary prompt gamma in coincidence with the annihilation event allows us to identify the corresponding 511 keV photon pair as originating from the same isotope. Two list-mode datasets are created: a primary dataset that contains all detected 511 keV photon pairs from both isotopes, and a second, tagged (much smaller) dataset that contains only those PET events for which a coincident prompt gamma has also been detected. An image reconstructed from the tagged dataset reflects the distribution of the second positron-gamma radiotracer and serves as a prior for the reconstruction of the primary dataset. Our preliminary simulation study with partially overlapping (18)F/(22)Na and (18)F/(60)Cu radiotracer distributions showed that in these two cases the dual-isotope PET method allowed for separation of the two activity distributions and recovered total activities with relative errors of about 5%.

Comparison of phosphodiesterase 10A, dopamine receptors D1 and D2 and dopamine transporter ligand binding in the striatum of the R6/2 and BACHD mouse models of Huntington's disease.

PubMed

Miller, Silke; Hill Della Puppa, Geraldine; Reidling, Jack; Marcora, Edoardo; Thompson, Leslie M; Treanor, James

2014-01-01

Phosphodiesterase 10A (PDE10A) is expressed at high levels in the striatum and has been proposed both as a biomarker for Huntington's disease pathology and as a target for intervention. PDE10A radiotracers have been successfully used to measure changes in binding density in Huntington's disease patients, but little is known about PDE10A binding in mouse models that are used extensively to model pathology and test therapeutic interventions. Our study investigated changes in PDE10A binding using the selective tracer 3H-7980 at specific ages of two Huntington's disease transgenic mouse models: R6/2, a short-lived model carrying exon-1 of mutant HTT and BACHD, a longer-lived model carrying full-length mutant HTT. PDE10A binding was compared to binding of known markers of striatal atrophy in Huntington's disease, e.g. dopamine transporter (DAT) and dopamine receptors D1 and D2. We found that in the R6/2 model at 6 weeks of age, mice showed high variability of binding, however binding of all ligands was significantly decreased at 8 and 12 weeks of age. In contrast, no changes were detectable in the BACHD model at 8, 10 or 12 month of age. These findings suggest that radiotracer binding of PDE10A, DAT, D1 and D2 receptor in the R6/2 model may be a good indicator of striatal pathological changes that are observed in Huntington's disease patients, and that the first 12 months in the BACHD model may be more reflective of early stages of the disease.

Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

PubMed

Papantoniou, Vassilios; Valsamaki, Pipitsa; Sotiropoulou, Evangelia; Tsaroucha, Angeliki; Tsiouris, Spyridon; Sotiropoulou, Maria; Marinopoulos, Spyridon; Kounadi, Evangelia; Karianos, Theodore; Fothiadaki, Athina; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Ptohis, Nikolaos; Makris, Nikolaos; Limouris, Georgios; Antsaklis, Aris

2011-10-01

The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

Preparation and preclinical evaluation of a 68Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me.

PubMed

Läppchen, Tilman; Holland, Jason P; Kiefer, Yvonne; Bartholomä, Mark D

2018-01-01

We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three, five-membered azaheterocyclic arms for the development of 68 Ga- and 64 Cu-based radiopharmaceuticals. Here, a 68 Ga-labelled conjugate comprising the bifunctional chelator NODIA-Me in combination with the α v ß 3 -targeting peptide c(RGDfK) has been synthesized and characterized. The primary aim was to evaluate further the potential of our NODIA-Me chelating system for the development of 68 Ga-labelled radiotracers. The BFC NODIA-Me was conjugated to c(RGDfK) by standard peptide chemistry to obtain the final bioconjugate NODIA-Me-c(RGDfK) 3 in 72% yield. Labelling with [ 68 Ga]GaCl 3 was accomplished in a fully automated, cGMP compliant process to give [ 68 Ga]3 in high radiochemical yield (98%) and moderate specific activity (~ 8 MBq nmol- 1 ). Incorporation of the Ga-NODIA-Me chelate to c(RGDfK) 2 had only minimal influence on the affinity to integrin α v ß 3 (IC 50 values [ nat Ga]3 = 205.1 ± 1.4 nM, c(RGDfK) 2 = 159.5 ± 1.3 nM) as determined in competitive cell binding experiments in U-87 MG cell line. In small-animal PET imaging and ex vivo biodistribution studies, the radiotracer [ 68 Ga]3 showed low uptake in non-target organs and specific tumor uptake in U-87 MG tumors. The results suggest that the bifunctional chelator NODIA-Me is an interesting alternative to existing ligands for the development of 68 Ga-labelled radiopharmaceuticals.

Fluorine-18 labeled tracers for PET studies in the neurosciences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Yu-Shin; Fowler, J.S.

This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18more » labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments.« less

PET/CT With 68Ga-DOTA-TATE for Diagnosis of Neuroendocrine: Differentiation in Patients With Castrate-Resistant Prostate Cancer.

PubMed

Gofrit, Ofer Nathan; Frank, Stephen; Meirovitz, Amichay; Nechushtan, Hovav; Orevi, Marina

2017-01-01

Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrine differentiation (NED). To evaluate the extent of NED in patients with CRPC, we used PET/CT with Ga-[DOTA-Tyr]-octreotate (Ga-DOTA-TATE), a somatostatin analog that binds somatostatin receptor 2 with high affinity. This radiotracer is used in imaging of neuroendocrine tumors. Twelve patients (mean age, 65 [SD, 12] years) with CRPC were studied. Their mean prostate-specific antigen level at scanning was 85.6 (SD, 144.6) ng/mL. PET/CT images were obtained after the injection of 120 to 200 MBq of Ga-DOTA-TATE. All participants had at least 1 blastic metastasis demonstrating uptake of Ga-DOTA-TATE (mean SUVmax of 5.3 [SD, 2.3]). In 6 patients, moderately high to high uptakes (SUVmax, >5) were seen. Patients with multiple bone metastases had a significantly higher SUVmax compared with patients with few metastases (mean of 5.8 vs 3.8, P = 0.05). In 4 patients, lytic bone lesions or lymph node metastases also showed uptake of the tracer (mean SUVmax of 7.2 [SD, 3.2]). Uptake of the radiotracer was also observed in bones showing normal architecture in CT, suggesting that NED cells appear early during metastases development. Uptake of Ga-DOTA-TATE is a common finding in metastases of CRPC patients, suggesting that NED is frequent in these patients. In half of the patients, widespread uptake of Ga-DOTA-TATE was observed. This suggests that the possibility of treating selected CRCP patients with anti-neuroendocrine tumor therapies should be explored and that Ga-DOTA-TATE scanning could have a role in predicting the efficacy of these treatments.

Radionuclides and mercury in the salt lakes of the Crimea

NASA Astrophysics Data System (ADS)

Mirzoyeva, Natalya; Gulina, Larisa; Gulin, Sergey; Plotitsina, Olga; Stetsuk, Alexandra; Arkhipova, Svetlana; Korkishko, Nina; Eremin, Oleg

2015-11-01

90Sr concentrations, resulting from the Chernobyl NPP accident, were determined in the salt lakes of the Crimea (Lakes Kiyatskoe, Kirleutskoe, Kizil-Yar, Bakalskoe and Donuzlav), together with the redistribution between the components of the ecosystems. The content of mercury in the waters of the studied reservoirs was also established. Vertical distributions of natural radionuclide activities (238U, 232Th, 226Ra, 210Pb, 40K) and anthropogenic 137Cs concentrations (as radiotracers) were determined in the bottom sediments of the Koyashskoe salt lake (located in the south-eastern Crimea) to evaluate the longterm dynamics and biogeochemical processes. Radiochemical and chemical analysis was undertaken and radiotracer and statistical methods were applied to the analytical data. The highest concentrations of 90Sr in the water of Lake Kiyatskoe (350.5 and 98.0 Bq/m3) and Lake Kirleutskoe (121.3 Bq/m3) were due to the discharge of the Dnieper water from the North-Crimean Canal. The high content of mercury in Lake Kiyatskoe (363.2 ng/L) and in seawater near Lake Kizil-Yar (364 ng/L) exceeded the maximum permissible concentration (3.5 times the maximum). Natural radionuclides provide the main contribution to the total radioactivity (artificial and natural combined) in the bottom sediments of Lake Koyashskoe. The significant concentration of 210Pb in the upper layer of bottom sediments of the lake indicates an active inflow of its parent radionuclide—gaseous 222Rn from the lower layers of the bottom sediment. The average sedimentation rates in Lake Koyashskoe, determined using 210Pb and 137Cs data, were 0.117 and 0.109 cm per year, respectively.

Viable myocardium scintigraphy with intravenous nitroglycerine by computed tomography with Tc-99m (MIBI).

PubMed

Ramos Filho, José; Nascimento, Marcos Welber; Silva, Rafael Mariano Gislon da; Camargo, Thiago Negrini de; Almeida, Roberto Simões de; Lima, Eloá Jacinto

2008-09-01

The selection of patients with chronic coronary disease for recanalization is based on the detection of the affected myocardium that is potentially viable. To evaluate the potentially viable ischemic myocardium through single photon emission computed tomography (SPECT) with MIBI after a maximum tolerated dose of I.V. nitroglycerin. We prospectively investigated by SPECT with Tc-99m (MIBI), from April 2004 to November 2005, 40 patients (mean age: 62 +/- 8.9 yrs, 30 men) with coronary obstruction demonstrated angiographically; the myocardium scintigraphy was carried out at rest and after intravenous (I.V.) nitroglycerin, which was started at a dose of 1 microg/kg/min and increased every minute until the systolic blood pressure decreased by 20 mmHg. The decrease in the perfusion of the segments was classified as moderate or severe and compared after the nitroglycerin. The angiographic, hemodynamic and myocardial perfusion variables were analyzed. We analyzed 680 myocardial segments at rest: 538 with a homogenous distribution and 142 with hypoperfusion (54 with moderate and 88 with severe decrease). After the nitroglycerin, there was an increase in the perfusion in 19 (47.5%) of 40 patients and 55 of 142 segments became viable: 33 (61.1%) with moderate and 22 (25%) with severe decrease; both presented a significant increase in the radiotracer distribution (p < 0.001, Chi-square). One of the components with Tc-99m is Tc-99m 2-methoxy-isobutyl-isonitrile (MIBI), which, when used with an optimized dose of I.V. nitroglycerin, can increase the radiotracer uptake in areas with moderate and severe hypoperfusion. The results of the present study suggest the increase in the Tc-99m (MIBI) sensitivity by nitroglycerin for the detection of viable myocardium.

Radiotracer Imaging Allows for Noninvasive Detection and Quantification of Abnormalities in Angiosome Foot Perfusion in Diabetic Patients With Critical Limb Ischemia and Nonhealing Wounds

PubMed Central

Alvelo, Jessica L.; Papademetris, Xenophon; Mena-Hurtado, Carlos; Jeon, Sangchoon; Sumpio, Bauer E.; Sinusas, Albert J.

2018-01-01

Background: Single photon emission computed tomography (SPECT)/computed tomography (CT) imaging allows for assessment of skeletal muscle microvascular perfusion but has not been quantitatively assessed in angiosomes, or 3-dimensional vascular territories, of the foot. This study assessed and compared resting angiosome foot perfusion between healthy subjects and diabetic patients with critical limb ischemia (CLI). Additionally, the relationship between SPECT/CT imaging and the ankle–brachial index—a standard tool for evaluating peripheral artery disease—was assessed. Methods and Results: Healthy subjects (n=9) and diabetic patients with CLI and nonhealing ulcers (n=42) underwent SPECT/CT perfusion imaging of the feet. CT images were segmented into angiosomes for quantification of relative radiotracer uptake, expressed as standardized uptake values. Standardized uptake values were assessed in ulcerated angiosomes of patients with CLI and compared with whole-foot standardized uptake values in healthy subjects. Serial SPECT/CT imaging was performed to assess uptake kinetics of technetium-99m-tetrofosmin. The relationship between angiosome perfusion and ankle–brachial index was assessed via correlational analysis. Resting perfusion was significantly lower in CLI versus healthy subjects (P=0.0007). Intraclass correlation coefficients of 0.95 (healthy) and 0.93 (CLI) demonstrated excellent agreement between serial perfusion measurements. Correlational analysis, including healthy and CLI subjects, demonstrated a significant relationship between ankle–brachial index and SPECT/CT (P=0.01); however, this relationship was not significant for diabetic CLI patients only (P=0.2). Conclusions: SPECT/CT imaging assesses regional foot perfusion and detects abnormalities in microvascular perfusion that may be undetectable by conventional ankle–brachial index in patients with diabetes mellitus. SPECT/CT may provide a novel approach for evaluating responses to targeted therapies. PMID:29748311

Cardiac PET perfusion tracers: current status and future directions.

PubMed

Maddahi, Jamshid; Packard, René R S

2014-09-01

PET myocardial perfusion imaging (MPI) is increasingly being used for noninvasive detection and evaluation of coronary artery disease. However, the widespread use of PET MPI has been limited by the shortcomings of the current PET perfusion tracers. The availability of these tracers is limited by the need for an onsite ((15)O water and (13)N ammonia) or nearby ((13)N ammonia) cyclotron or commitment to costly generators ((82)Rb). Owing to the short half-lives, such as 76 seconds for (82)Rb, 2.06 minutes for (15)O water, and 9.96 minutes for (13)N ammonia, their use in conjunction with treadmill exercise stress testing is either not possible ((82)Rb and (15)O water) or not practical ((13)N ammonia). Furthermore, the long positron range of (82)Rb makes image resolution suboptimal and its low myocardial extraction limits its defect resolution. In recent years, development of an (18)F-labeled PET perfusion tracer has gathered considerable interest. The longer half-life of (18)F (109 minutes) would make the tracer available as a unit dose from regional cyclotrons and allow use in conjunction with treadmill exercise testing. Furthermore, the short positron range of (18)F would result in better image resolution. Flurpiridaz F 18 is by far the most thoroughly studied in animal models and is the only (18)F-based PET MPI radiotracer currently undergoing clinical evaluation. Preclinical and clinical experience with Flurpiridaz F 18 demonstrated a high myocardial extraction fraction, high image and defect resolution, high myocardial uptake, slow myocardial clearance, and high myocardial-to-background contrast that was stable over time-important properties of an ideal PET MPI radiotracer. Preclinical data from other (18)F-labeled myocardial perfusion tracers are encouraging. Copyright © 2014. Published by Elsevier Inc.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

PubMed

Fu, Yilong; Ong, Lai-Chun; Ranganath, Sudhir H; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K H; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

PubMed Central

Ranganath, Sudhir H.; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K. H.; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

In vivo assessment and dosimetry of 2 novel PDE10A PET radiotracers in humans: 18F-MNI-659 and 18F-MNI-654.

PubMed

Barret, Olivier; Thomae, David; Tavares, Adriana; Alagille, David; Papin, Caroline; Waterhouse, Rikki; McCarthy, Timothy; Jennings, Danna; Marek, Ken; Russell, David; Seibyl, John; Tamagnan, Gilles

2014-08-01

Phosphodiesterase (PDE) 10A is an enzyme involved in the regulation of cyclic adenosine monophosphate and cyclic guanosine monophosphate and is highly expressed in medium-sized spiny neurons of the striatum, making it an attractive target for novel therapies for a variety of neurologic and psychiatric disorders that involve striatal function. Potential ligands for PET imaging of PDE10A have been reported. Here, we report the first-in-human characterization of 2 new PDE10A radioligands, 2-(2-(3-(1-(2-fluoroethyl)-1H-indazol-6-yl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI-654) and 2-(2-(3-(4-(2-fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI-659), with the goal of selecting the best one for use in future studies interrogating pathophysiologic changes in neuropsychiatric disorders and aiding pharmaceutical development targeting PDE10A. Eleven healthy volunteers participated in this study ((18)F-MNI-654 test-retest, 2 men; (18)F-MNI-659 test-retest, 4 men and 1 woman; (18)F-MNI-659 dosimetry, 2 men and 2 women). Brain PET images were acquired over 5.5 h for (18)F-MNI-654 and over 3.5 h for (18)F-MNI-659, and pharmacokinetic modeling with plasma- and reference-region (cerebellar cortex)-based methods was performed. Whole-body PET images were acquired over 6 h for (18)F-MNI-659 and radiation dosimetry estimated with OLINDA. Both radiotracers were similarly metabolized, with about 20% of intact parent remaining at 120 min after injection. PET time-activity data demonstrated that (18)F-MNI-654 kinetics were much slower than (18)F-MNI-659 kinetics. For (18)F-MNI-659, there was good agreement between the Logan and simplified reference tissue models for nondisplaceable binding potential (BPND), supporting noninvasive quantification, with test-retest variability less than 10% and intraclass correlation greater than 0.9. The (18)F-MNI-659 effective dose was estimated at 0.024 mSv/MBq. PET imaging in the human brain with 2 novel PDE10A (18)F tracers is being reported. Noninvasive quantification of (18)F-MNI-659 with the simplified reference tissue model using the cerebellum as a reference is possible. In addition, (18)F-MNI-659 kinetics are fast enough for a good estimate of BPND with 90 min of data, with values around 3.0 in the basal ganglia. Finally, (18)F-MNI-659 dosimetry is favorable and consistent with values reported for other PET radiotracers currently used in humans. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PET Radiotracers for Imaging the Proliferation Status of Breast Tumors

DTIC Science & Technology

2004-12-01

390 627 ±244 12,900±111 8.2± 1.415 58.8± 13.7 2.1 ±0.4 809±66 75.0±4.1 75-85% yield. Reduction with either lithium aluminum 16 107.0± 19.0 10.2±5.3 751... hexafluorophosphate (BOP) or 1,3- dicyclohexylcarbodiimide (DCC) and 2.5 equivalents of triethylamine were added, and the solution was allowed to warm

Multicystic dysplastic kidneys suggesting hydronephrosis during Tc-DTPA imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siddiqui, A.R.; Cohen, M.; Mitchell, M.E.

1982-10-01

Tc-99m DTPA renal scans on two infants with flank masses were interpreted as consistent with hydronephrosis and obstruction of the uretopelvic junction because of delayed accumulation of the radiotracer in the initially photon-deficient regions. However, both these patients were found to have multicystic dysplastic kidney. It appears that for proper diagnosis more attention should be paid to the location of the functioning cortex rather than to the delayed images.

Gallium-67 imaging in muscular sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edan, G.; Bourguet, P.; Delaval, P.

1984-07-01

A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

Comparison of the pharmacokinetics of different analogs of 11C-labeled TZTP for imaging muscarinic M2 receptors with PET.

PubMed

Reid, Alicia E; Ding, Yu-Shin; Eckelman, William C; Logan, Jean; Alexoff, David; Shea, Colleen; Xu, Youwen; Fowler, Joanna S

2008-04-01

The only radiotracer available for the selective imaging of muscarinic M2 receptors in vivo is 3-(3-(3-[18F]fluoropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine) ([18F]FP-TZTP). We have prepared and labeled 3-(3-(3-fluoropropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridne (FP-TZTP, 3) and two other TZTP derivatives with 11C at the methylpyridine moiety to explore the potential of using 11C-labeled FP-TZTP for positron emission tomography imaging of M2 receptors and to compare the effect of small structural changes on tracer pharmacokinetics (PK) in brain and peripheral organs. 11C-radiolabeled FP-TZTP, 3-(3-propylthio)-TZTP (6) and 3,3,3-(3-(3-trifluoropropyl)-TZTP (10) were prepared, and log D, plasma protein binding (PPB), affinity constants, time-activity curves (TACs), area under the curve (AUC) for arterial plasma, distribution volumes (DV) and pharmacological blockade in baboons were compared. Values for log D, PPB and affinity constants were similar for 3, 6 and 10. The fraction of parent radiotracer in the plasma was higher and the AUC lower for 10 than for 3 and 6. TACs for brain regions were similar for 3 and 6, which showed PK similar to the 18F tracer, while 10 showed slower uptake and little clearance over 90 min. DVs for 3 and 6 were similar to the 18F tracer but higher for 10. Uptake of the three tracers was significantly reduced by coinjection of unlabeled 3 and 6. Small structural variations on the TZTP structure greatly altered the PK in brain and behavior in blood with little change in the log D, PPB or affinity. The study suggests that 11C-radiolabeled 3 will be a suitable alternative to [18F]FP-TZTP for translational studies in humans.

Proof of Concept: Design and Initial Evaluation of a Device to Measure Gastrointestinal Transit Time.

PubMed

Wagner, Robert H; Savir-Baruch, Bital; Halama, James R; Venu, Mukund; Gabriel, Medhat S; Bova, Davide

2017-09-01

Chronic constipation and gastrointestinal motility disorders constitute a large part of a gastroenterology practice and have a significant impact on a patient's quality of life and lifestyle. In most cases, medications are prescribed to alleviate symptoms without there being an objective measurement of response. Commonly used investigations of gastrointestinal transit times are currently limited to radiopaque markers or electronic capsules. Repeated use of these techniques is limited because of the radiation exposure and the significant cost of the devices. We present the proof of concept for a new device to measure gastrointestinal transit time using commonly available and inexpensive materials with only a small amount of radiotracer. Methods: We assembled gelatin capsules containing a 67 Ga-citrate-radiolabeled grain of rice embedded in paraffin for use as a point-source transit device. It was tested for stability in vitro and subsequently was given orally to 4 healthy volunteers and 10 patients with constipation or diarrhea. Imaging was performed at regular intervals until the device was excreted. Results: The device remained intact and visible as a point source in all subjects until excretion. When used along with a diary of bowel movement times and dates, the device could determine the total transit time. The device could be visualized either alone or in combination with a barium small-bowel follow-through study or a gastric emptying study. Conclusion: The use of a point-source transit device for the determination of gastrointestinal transit time is a feasible alternative to other methods. The device is inexpensive and easy to assemble, requires only a small amount of radiotracer, and remains inert throughout the gastrointestinal tract, allowing for accurate determination of gastrointestinal transit time. Further investigation of the device is required to establish optimum imaging parameters and reference values. Measurements of gastrointestinal transit time may be useful in managing patients with dysmotility and in selecting the appropriate pharmaceutical treatment. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Optimal reproducibility of gated sestamibi and thallium myocardial perfusion study left ventricular ejection fractions obtained on a solid-state CZT cardiac camera requires operator input.

PubMed

Cherk, Martin H; Ky, Jason; Yap, Kenneth S K; Campbell, Patrina; McGrath, Catherine; Bailey, Michael; Kalff, Victor

2012-08-01

To evaluate the reproducibility of serial re-acquisitions of gated Tl-201 and Tc-99m sestamibi left ventricular ejection fraction (LVEF) measurements obtained on a new generation solid-state cardiac camera system during myocardial perfusion imaging and the importance of manual operator optimization of left ventricular wall tracking. Resting blinded automated (auto) and manual operator optimized (opt) LVEF measurements were measured using ECT toolbox (ECT) and Cedars-Sinai QGS software in two separate cohorts of 55 Tc-99m sestamibi (MIBI) and 50 thallium (Tl-201) myocardial perfusion studies (MPS) acquired in both supine and prone positions on a cadmium zinc telluride (CZT) solid-state camera system. Resting supine and prone automated LVEF measurements were similarly obtained in a further separate cohort of 52 gated cardiac blood pool scans (GCBPS) for validation of methodology and comparison. Appropriate use of Bland-Altman, chi-squared and Levene's equality of variance tests was used to analyse the resultant data comparisons. For all radiotracer and software combinations, manual checking and optimization of valve planes (+/- centre radius with ECT software) resulted in significant improvement in MPS LVEF reproducibility that approached that of planar GCBPS. No difference was demonstrated between optimized MIBI/Tl-201 QGS and planar GCBPS LVEF reproducibility (P = .17 and P = .48, respectively). ECT required significantly more manual optimization compared to QGS software in both supine and prone positions independent of radiotracer used (P < .02). Reproducibility of gated sestamibi and Tl-201 LVEF measurements obtained during myocardial perfusion imaging with ECT toolbox or QGS software packages using a new generation solid-state cardiac camera with improved image quality approaches that of planar GCBPS however requires visual quality control and operator optimization of left ventricular wall tracking for best results. Using this superior cardiac technology, Tl-201 reproducibility also appears at least equivalent to sestamibi for measuring LVEF.

Advances in radioguided surgery in oncology.

PubMed

Valdés Olmos, Renato A; Vidal-Sicart, Sergi; Manca, Gianpiero; Mariani, Giuliano; León-Ramírez, Luisa F; Rubello, Domenico; Giammarile, Francesco

2017-09-01

The sentinel lymph node (SLN) biopsy is probably the most well-known radioguided technique in surgical oncology. Today SLN biopsy reduces the morbidity associated with lymphadenectomy and increases the identification rate of occult lymphatic metastases by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. These advantages may result in a change in clinical management both in melanoma and breast cancer patients. The SLN evaluation by pathology currently implies tumor burden stratification for further prognostic information. The concept of SLN biopsy includes pre-surgical lymphoscintigraphy as a "roadmap" to guide the surgeon toward the SLNs and to localize unpredictable lymphatic drainage patterns. In addition to planar images, SPECT/CT improves SLN detection, especially in sites closer to the injection site, providing anatomic landmarks which are helpful in localizing SLNs in difficult to interpret studies. The use of intraoperative imaging devices allows a better surgical approach and SLN localization. Several studies report the value of such devices for excision of additional sentinel nodes and for monitoring the whole procedure. The combination of preoperative imaging and radioguided localization constitutes the basis for a whole spectrum of basic and advanced nuclear medicine procedures, which recently have been encompassed under the term "guided intraoperative scintigraphic tumor targeting" (GOSTT). Excepting SLN biopsy, GOSTT includes procedures based on the detection of target lesions with visible uptake of tumor-seeking radiotracers on SPECT/CT or PET/CT enabling their subsequent radioguided excisional biopsy for diagnostic of therapeutic purposes. The incorporation of new PET-tracers into nuclear medicine has reinforced this field delineating new strategies for radioguided excision. In cases with insufficient lesion uptake after systemic radiotracer administration, intralesional injection of a tracer without migration may enable subsequent excision of the targeted tissue. This approach has been helpful in non-palpable breast cancer and in solitary pulmonary nodules. The introduction of allied technologies like fluorescence constitutes a recent advance aimed to refine the search for SLNs and tracer-avid lesions in the operation theatre in combination with radioguidance.

The potential of multiparametric MRI of the breast

PubMed Central

Pinker, Katja; Helbich, Thomas H

2017-01-01

MRI is an essential tool in breast imaging, with multiple established indications. Dynamic contrast-enhanced MRI (DCE-MRI) is the backbone of any breast MRI protocol and has an excellent sensitivity and good specificity for breast cancer diagnosis. DCE-MRI provides high-resolution morphological information, as well as some functional information about neoangiogenesis as a tumour-specific feature. To overcome limitations in specificity, several other functional MRI parameters have been investigated and the application of these combined parameters is defined as multiparametric MRI (mpMRI) of the breast. MpMRI of the breast can be performed at different field strengths (1.5–7 T) and includes both established (diffusion-weighted imaging, MR spectroscopic imaging) and novel MRI parameters (sodium imaging, chemical exchange saturation transfer imaging, blood oxygen level-dependent MRI), as well as hybrid imaging with positron emission tomography (PET)/MRI and different radiotracers. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the underlying oncogenic processes of cancer development and progression and can provide additional specificity. This article will review the current and emerging functional parameters for mpMRI of the breast for improved diagnostic accuracy in breast cancer. PMID:27805423

Accumulation of radioactive corrosion products on steel surfaces of VVER type nuclear reactors. I. 110mAg

NASA Astrophysics Data System (ADS)

Hirschberg, Gábor; Baradlai, Pál; Varga, Kálmán; Myburg, Gerrit; Schunk, János; Tilky, Péter; Stoddart, Paul

Formation, presence and deposition of corrosion product radionuclides (such as 60Co, 51Cr, 54Mn, 59Fe and/or 110mAg) in the primary circuits of water-cooled nuclear reactors (PWRs) throw many obstacles in the way of normal operation. During the course of the work presented in this series, accumulations of such radionuclides have been studied at austenitic stainless steel type 08X18H10T (GOST 5632-61) surfaces (this austenitic stainless steel corresponds to AISI 321). Comparative experiments have been performed on magnetite-covered carbon steel (both materials are frequently used in some Soviet VVER type PWRs). For these laboratory-scale investigations a combination of the in situ radiotracer `thin gap' method and voltammetry is considered to be a powerful tool due to its high sensitivity towards the detection of the submonolayer coverages of corrosion product radionuclides. An independent technique (XPS) is also used to characterize the depth distribution and chemical state of various contaminants in the passive layer formed on austenitic stainless steel. In the first part of the series the accumulation of 110mAg has been investigated. Potential dependent sorption of Ag + ions (cementation) is found to be the predominant process on austenitic steel, while in the case of magnetite-covered carbon steel the silver species are mainly depleted in the form of Ag 2O. The XPS depth profile of Ag gives an evidence about the embedding of metallic silver into the entire passive layer of the austenitic stainless steel studied.

Impact of clinically tested NEP/ACE inhibitors on tumor uptake of [(111)In-DOTA]MG11-first estimates for clinical translation.

PubMed

Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Valkema, Roelf; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

2016-12-01

We have recently shown that treatment of mice with the neutral endopeptidase (NEP) inhibitor phosphoramidon (PA) improves the bioavailability and tumor uptake of biodegradable radiopeptides. For the truncated gastrin radiotracer [(111)In-DOTA]MG11 ([(DOTA)DGlu(10)]gastrin(10-17)), this method led to impressively high tumor-to-kidney ratios. Translation of this concept in the clinic requires the use of certified NEP inhibitors, such as thiorphan (TO) and its orally administered prodrug racecadotril (Race). Besides NEP, angiotensin-converting enzyme (ACE) has also been implicated in the catabolism of gastrin analogs. In the present study, we first compared the effects induced by NEP inhibition (using PA, TO, or Race) and/or by ACE inhibition (using lisinopril, Lis) on the biodistribution profile of [(111)In-DOTA]MG11 in mice. In addition, we compared the efficacy of PA and TO at different administered doses to enhance tumor uptake. [(111)In-DOTA]MG11 was coinjected with (a) vehicle, (b) PA (300 μg), (c) TO (150 μg), (d) Lis (100 μg), (e) PA (300 μg) plus Lis (100 μg), or (f) 30-40 min after intraperitoneal (ip) injection of Race (3 mg) in SCID mice bearing AR42J xenografts. In addition, [(111)In-DOTA]MG11 was coinjected with vehicle, or with progressively increasing amounts of PA (3, 30, or 300 μg) or TO (1.5, 15, and 150 μg) in SCID mice bearing twin A431-CCK2R(+/-) tumors. In all above cases, biodistribution was conducted at 4 h postinjection (pi). During NEP inhibition, the uptake of [(111)In-DOTA]MG11 in the AR42J tumors impressively increased from 1.8 ± 1.0 % ID/g (controls) to 15.3 ± 4.7 % ID/g (PA) and 12.3 ± 3.6 % ID/g (TO), while with Race tumor values reached 6.8 ± 2.8 % ID/g. Conversely, Lis had no effect on tumor uptake and no additive effect when coinjected with PA. During the dose dependence study in mice, PA turned out to be more efficacious in enhancing tumor uptake of [(111)In-DOTA]MG11 in the CCK2R-positive tumors compared to equimolar amounts of TO. In all cases, renal accumulation remained low, resulting in notable increases of tumor-to-kidney ratios. This study has confirmed NEP as the predominant degrading enzyme of [(111)In-DOTA]MG11 and ruled out the involvement of ACE in the in vivo catabolism of the radiotracer. NEP inhibition with the clinically tested NEP inhibitors TO and Race resulted in significant enhancement of tumor-to-kidney ratios vs. However, compared with PA, TO and its prodrug Race induced less potent increases of tumor uptake, highlighting the significance of inhibitor type, administration route, and dose for implementing a first proof-of-principle study in human.

Magnetic iron oxide and manganese-doped iron oxide nanoparticles for the collection of alpha-emitting radionuclides from aqueous solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Hara, Matthew J.; Carter, Jennifer C.; Warner, Cynthia L.

Magnetic nanoparticles are well known to possess chemically active surfaces and large surface areas that can be employed to extract a range of ions from aqueous solutions. In addition, their superparamagnetic properties provide a convenient means for bulk collection of the material from solution after the targeted ions have been adsorbed. We evaluated two nanoscale amphoteric metal oxides, each possessing useful magnetic attributes for their ability to collect trace levels of a chemically diverse range of alpha emitting radioactive isotopes (polonium (Po), radium (Ra), uranium (U), and americium (Am)) from a wide range of aqueous solutions. The nanomaterials include commerciallymore » available magnetite (Fe3O4) and magnetite modified to incorporate manganese (Mn) into the crystal structure. The chemical stability of these nanomaterials was evaluated in Hanford Site, WA ground water between the natural pH (~8) and pH 1. Whereas the magnetite was observed to have good stability over the pH range, the Mn-doped material was observed to leach Mn at low pH. The materials were evaluated in parallel to characterize their uptake performance of the alpha-emitting radionuclide spikes from ground water across a range of pH (from ~8 down to 2). In addition, radiotracer uptake experiments were performed on Columbia River water, seawater, and human urine at their natural pH and at pH 2. Despite the observed leaching of Mn from the Mn-doped nanomaterial in the lower pH range, it exhibited generally superior analyte extraction performance compared to the magnetite, and analyte uptake was observed across a broader pH range. We show that the uptake behavior of the various radiotracers on these two materials at different pH levels can generally be explained by the amphoteric nature of the nanoparticle surfaces. Finally, the rate of sorption of the radiotracers on the two materials in unacidified ground water was evaluated. The uptake curves generally indicate that equilibrium is obtained within a few minutes, which is attributed to the high surface areas of the nanomaterials and the high level of dispersion in the liquids. In sum, our results indicate that these nanomaterials may have the potential to be employed for a range of applications to extract radionuclides from aqueous solutions.« less

Magnetic iron oxide and manganese-doped iron oxide nanoparticles for the collection of alpha-emitting radionuclides from aqueous solutions

DOE PAGES

O'Hara, Matthew J.; Carter, Jennifer C.; Warner, Cynthia L.; ...

2016-10-31

Magnetic nanoparticles are well known to possess chemically active surfaces and large surface areas that can be employed to extract a range of ions from aqueous solutions. In addition, their superparamagnetic properties provide a convenient means for bulk collection of the material from solution after the targeted ions have been adsorbed. We evaluated two nanoscale amphoteric metal oxides, each possessing useful magnetic attributes for their ability to collect trace levels of a chemically diverse range of alpha emitting radioactive isotopes (polonium (Po), radium (Ra), uranium (U), and americium (Am)) from a wide range of aqueous solutions. The nanomaterials include commerciallymore » available magnetite (Fe3O4) and magnetite modified to incorporate manganese (Mn) into the crystal structure. The chemical stability of these nanomaterials was evaluated in Hanford Site, WA ground water between the natural pH (~8) and pH 1. Whereas the magnetite was observed to have good stability over the pH range, the Mn-doped material was observed to leach Mn at low pH. The materials were evaluated in parallel to characterize their uptake performance of the alpha-emitting radionuclide spikes from ground water across a range of pH (from ~8 down to 2). In addition, radiotracer uptake experiments were performed on Columbia River water, seawater, and human urine at their natural pH and at pH 2. Despite the observed leaching of Mn from the Mn-doped nanomaterial in the lower pH range, it exhibited generally superior analyte extraction performance compared to the magnetite, and analyte uptake was observed across a broader pH range. We show that the uptake behavior of the various radiotracers on these two materials at different pH levels can generally be explained by the amphoteric nature of the nanoparticle surfaces. Finally, the rate of sorption of the radiotracers on the two materials in unacidified ground water was evaluated. The uptake curves generally indicate that equilibrium is obtained within a few minutes, which is attributed to the high surface areas of the nanomaterials and the high level of dispersion in the liquids. In sum, our results indicate that these nanomaterials may have the potential to be employed for a range of applications to extract radionuclides from aqueous solutions.« less

Influence of diesel contamination on the benthic microbial/meiofaunal food web of a Louisiana salt marsh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carman, K.R.; Fleeger, J.W.; Pomarico, S.

The authors studied the influence of diesel-contaminated sediments on the benthic microbial/meiofaunal food web from a Louisiana salt marsh. Diesel-contaminated sediment was added to microcosms (intact cores of marsh mud) in a range of doses, and a suite of microbial and meiofaunal responses were measured over a 28-day period. The authors measured bacterial and microalgal (Chl a) abundance, bacterial and microalgal activity using radiotracers ({sup 14}C-acetate and {sup 14}CO{sub 2}, respectively), meiofaunal grazing on microalgae, meiofaunal community structure, and meiofaunal physiological condition. Preliminary results indicate that diesel-contaminated sediments influence microalgal biomass and activity, as well as the life histories ofmore » benthic copepod species.« less

Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT

PubMed Central

Rempel, Brian P.; Price, Eric W.

2017-01-01

Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents. PMID:28927325

Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.

PubMed

Rempel, Brian P; Price, Eric W; Phenix, Christopher P

2017-01-01

Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents.

Marine anthropogenic radiotracers in the Southern Hemisphere: New sampling and analytical strategies

NASA Astrophysics Data System (ADS)

Levy, I.; Povinec, P. P.; Aoyama, M.; Hirose, K.; Sanchez-Cabeza, J. A.; Comanducci, J.-F.; Gastaud, J.; Eriksson, M.; Hamajima, Y.; Kim, C. S.; Komura, K.; Osvath, I.; Roos, P.; Yim, S. A.

2011-04-01

The Japan Agency for Marine Earth Science and Technology conducted in 2003-2004 the Blue Earth Global Expedition (BEAGLE2003) around the Southern Hemisphere Oceans, which was a rare opportunity to collect many seawater samples for anthropogenic radionuclide studies. We describe here sampling and analytical methodologies based on radiochemical separations of Cs and Pu from seawater, as well as radiometric and mass spectrometry measurements. Several laboratories took part in radionuclide analyses using different techniques. The intercomparison exercises and analyses of certified reference materials showed a reasonable agreement between the participating laboratories. The obtained data on the distribution of 137Cs and plutonium isotopes in seawater represent the most comprehensive results available for the Southern Hemisphere Oceans.

Secondary Ion Mass Spectrometry for Mg Tracer Diffusion: Issues and Solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuggle, Jay; Giordani, Andrew; Kulkarni, Nagraj S

2014-01-01

A Secondary Ion Mass Spectrometry (SIMS) method has been developed to measure stable Mg isotope tracer diffusion. This SIMS method was then used to calculate Mg self- diffusivities and the data was verified against historical data measured using radio tracers. The SIMS method has been validated as a reliable alternative to the radio-tracer technique for the measurement of Mg self-diffusion coefficients and can be used as a routine method for determining diffusion coefficients.

Gate simulation of Compton Ar-Xe gamma-camera for radionuclide imaging in nuclear medicine

NASA Astrophysics Data System (ADS)

Dubov, L. Yu; Belyaev, V. N.; Berdnikova, A. K.; Bolozdynia, A. I.; Akmalova, Yu A.; Shtotsky, Yu V.

2017-01-01

Computer simulations of cylindrical Compton Ar-Xe gamma camera are described in the current report. Detection efficiency of cylindrical Ar-Xe Compton camera with internal diameter of 40 cm is estimated as1-3%that is 10-100 times higher than collimated Anger’s camera. It is shown that cylindrical Compton camera can image Tc-99m radiotracer distribution with uniform spatial resolution of 20 mm through the whole field of view.

Accomplishing Equilibrium in ALSEP: Demonstrations of Modified Process Chemistry on 3-D Printed Enhanced Annular Centrifugal Contactors

DOE PAGES

Brown, M. Alex; Wardle, Kent E.; Lumetta, Gregg; ...

2016-12-01

Here, the major components of the modified ALSEP process have been demonstrated on a modified 2-cm annular centrifugal contactor with an enhanced mixing zone using stable fission products and radiotracers. The results show that by decreasing the pH of the minor actinide stripping solution, using HEDTA instead of DTPA, and increasing contact time, the process is very effective in separating americium from the lanthanides and the fission products.

Using radioactive drugs could lead to better imaging of prostate cancer | Center for Cancer Research

Cancer.gov

Medical imaging (x-ray, ultrasound, MRI, CT, PET scan) is a noninvasive way to view the internal structures of the body. However, these tools are not ideal for detecting cancer that has spread, or metastasized, because the precise location of these cancer cells is unknown. Researchers are now testing an experimental radiotracer called 18F-DCFPyL to help find sites of cancer in the body.  Learn more...

64Cu-PSMA-617: A novel PSMA-targeted radio-tracer for PET imaging in gastric adenocarcinoma xenografted mice model.

PubMed

Han, Xue-Di; Liu, Chen; Liu, Fei; Xie, Qing-Hua; Liu, Te-Li; Guo, Xiao-Yi; Xu, Xiao-Xia; Yang, Xing; Zhu, Hua; Yang, Zhi

2017-09-26

Here, we report that it's feasible for imaging gastric adenocarcinoma mice model with prostate-specific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric adenocarcinoma. DKFZ-PSMA-617, a PSMA targeting ligand reported recently, was chosen to be radio-labeled with nuclide 64 Cu. 64 Cu-PSMA-617 was radio-synthesized in high radio-chemical yield and specific activity up to 19.3 GBq/µmol. It showed good stability in vitro . The specificity of 64 Cu-PSMA-617 was confirmed by cell uptake experiments in PSMA (+) LNCaP cell and PSMA (-) PC-3 and gastric adenocarcinoma BGC-823 cells. Micro-PET imaging in BGC-823 and PC-3 xenografts nude mice was evaluated ( n = 4). And the tumors were visualized and better tumor-to-background achieved till 24 h. Co-administration of N- [[[(1S)-1-Carboxy-3-methylbutyl]amino]-carbonyl]-L-glutamic acid (ZJ-43) can substantially block the uptake in those tumors. Dissected tumor tissues were analyzed by auto-radiography and immunohistochemistry, and these results confirmed the PSMA expression in neo-vasculature which explained the target molecular imaging of 64 Cu-PSMA-617. All those results suggested 64 Cu-PSMA-617 may serve as a novel radio-tracer for tumor imaging more than prostate cancer.

An Analysis of the Utility of Handheld PET Probes for the Intraoperative Localization of Malignant Tissue

PubMed Central

González, Segundo Jaime; González, Lorena; Wong, Joyce; Brader, Peter; Zakowski, Maureen; Gönen, Mithat; Daghighian, Farhad; Fong, Yuman

2012-01-01

Introduction The intraoperative localization of suspicious lesions detected by positron emission tomography (PET) scan remains a challenge. To solve this, two novel probes have been created to accurately detect the 18F-FDG radiotracer intraoperatively. Methods Nude rats were inoculated with mesothelioma. When PET scans detected 10-mm tumors, animals were dissected and the PET probes analyzed the intraoperative radiotracer uptake of these lesions as tumor to background ratio (TBR). Results The 17 suspicious lesions seen on PET scan were localized intraoperatively (by their high TBR) using the PET probes and found malignant on pathology. Interestingly, smaller tumors not visualized on PET scan were detected intraoperatively by their high TBR and found malignant on pathology. Furthermore, using a TBR threshold as low as 2.0, both gamma (sensitivity, 100%; specificity, 80%; positive predictive value (PPV), 96%; and negative predictive value (NPV), 100%) and beta (sensitivity, 100%; specificity, 60%; PPV, 93%; and NPV, 100%) probes reliably detected suspicious lesions on PET scan imaging. They also showed an excellent area under the curve of 0.9 and 0.97 (95% CI of 0.81–0.99 and 0.93–1.0) for gamma and beta probes, respectively, in the receiver operating characteristic analysis for detecting malignancy. Conclusion This novel tool could be used synergistically with a PET scan imaging to maximize tissue selection intraoperatively. PMID:21108016

Towards the PET radiotracer for p75 neurotrophin receptor: [(11)C]LM11A-24 shows biological activity in vitro, but unfavorable ex vivo and in vivo profile.

PubMed

Gibon, Julien; Kang, Min Su; Aliaga, Arturo; Sharif, Behrang; Rosa-Neto, Pedro; Séguéla, Philippe; Barker, Philip A; Kostikov, Alexey

2016-10-01

Mature neurotrophins as well as their pro forms are critically involved in the regulation of neuronal functions. They are signaling through three distinct types of receptors: tropomyosin receptor kinase family (TrkA/B/C), p75 neurotrophin receptor (p75(NTR)) and sortilin. Aberrant expression of p75(NTR) in the CNS is implicated in a variety of neurodegenerative diseases, including Alzheimer's disease. The goal of this work was to evaluate one of the very few reported p75(NTR) small molecule ligands as a lead compound for development of novel PET radiotracers for in vivo p75(NTR) imaging. Here we report that previously described ligand LM11A-24 shows significant inhibition of carbachol-induced persistent firing (PF) of entorhinal cortex (EC) pyramidal neurons in wild-type mice via selective interaction with p75(NTR). Based on this electrophysiological assay, the compound has very high potency with an EC50<10nM. We optimized the radiosynthesis of [(11)C]LM11A-24 as the first attempt to develop PET radioligand for in vivo imaging of p75(NTR). Despite some weak interaction with CNS tissues, the radiolabeled compound showed unfavorable in vivo profile presumably due to high hydrophilicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

64Cu-PSMA-617: A novel PSMA-targeted radio-tracer for PET imaging in gastric adenocarcinoma xenografted mice model

PubMed Central

Han, Xue-Di; Liu, Chen; Liu, Fei; Xie, Qing-Hua; Liu, Te-Li; Guo, Xiao-Yi; Xu, Xiao-Xia; Yang, Xing; Zhu, Hua; Yang, Zhi

2017-01-01

Here, we report that it’s feasible for imaging gastric adenocarcinoma mice model with prostate-specific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric adenocarcinoma. DKFZ-PSMA-617, a PSMA targeting ligand reported recently, was chosen to be radio-labeled with nuclide 64Cu. 64Cu-PSMA-617 was radio-synthesized in high radio-chemical yield and specific activity up to 19.3 GBq/µmol. It showed good stability in vitro. The specificity of 64Cu-PSMA-617 was confirmed by cell uptake experiments in PSMA (+) LNCaP cell and PSMA (-) PC-3 and gastric adenocarcinoma BGC-823 cells. Micro-PET imaging in BGC-823 and PC-3 xenografts nude mice was evaluated (n = 4). And the tumors were visualized and better tumor-to-background achieved till 24 h. Co-administration of N- [[[(1S)-1-Carboxy-3-methylbutyl]amino]-carbonyl]-L-glutamic acid (ZJ-43) can substantially block the uptake in those tumors. Dissected tumor tissues were analyzed by auto-radiography and immunohistochemistry, and these results confirmed the PSMA expression in neo-vasculature which explained the target molecular imaging of 64Cu-PSMA-617. All those results suggested 64Cu-PSMA-617 may serve as a novel radio-tracer for tumor imaging more than prostate cancer. PMID:29088775

Expanding the menu for carnivorous plants: uptake of potassium, iron and manganese by carnivorous pitcher plants.

PubMed

Adlassnig, Wolfram; Steinhauser, Georg; Peroutka, Marianne; Musilek, Andreas; Sterba, Johannes H; Lichtscheidl, Irene K; Bichler, Max

2009-12-01

Carnivorous plants use animals as fertiliser substitutes which allow them to survive on nutrient deficient soils. Most research concentrated on the uptake of the prey's nitrogen and phosphorus; only little is known on the utilisation of other elements. We studied the uptake of three essential nutrients, potassium, iron and manganese, in three species of carnivorous pitcher plants (Cephalotus follicularis LaBilladiere, Sarracenia purpureaL., Heliamphora nutans Bentham). Using relatively short-lived and gamma-emitting radiotracers, we significantly improved the sensitivity compared to conventional protocols and gained the following results. We demonstrated the uptake of trace elements like iron and manganese. In addition, we found direct evidence for the uptake of potassium into the pitcher tissue. Potassium and manganese were absorbed to virtually 100% if offered in physiological concentrations or below in Cephalotus. Analysis of pitcher fluid collected in the natural habitat showed that uptake was performed here as efficiently as in the laboratory. The absorption of nutrients is an active process depending on living glandular cells in the pitcher epidermis and can be inhibited by azide. Unphysiologically high amounts of nutrients were taken up for a short time, but after a few hours the absorbing cells were damaged, and uptake stopped. Absorption rates of pitcher leaves from plants under controlled conditions varied highly, indicating that each trap is functionally independent. The comparison of minerals in typical prey with the plants' tissues showed that a complete coverage of the plants' needs by prey capture is improbable.

A historical perspective on radioisotopic tracers in metabolism and biochemistry.

PubMed

Lappin, Graham

2015-01-01

Radioisotopes are used routinely in the modern laboratory to trace and quantify a myriad of biochemical processes. The technique has a captivating history peppered with groundbreaking science and with more than its share of Nobel Prizes. The discovery of radioactivity at the end of the 19th century paved the way to understanding atomic structure and quickly led to the use of radioisotopes to trace the fate of molecules as they flowed through complex organic life. The 1940s saw the first radiotracer studies using homemade instrumentation and analytical techniques such as paper chromatography. This article follows the history of radioisotopic tracers from meager beginnings, through to the most recent applications. The author hopes that those researchers involved in radioisotopic tracer studies today will pause to remember the origins of the technique and those who pioneered this fascinating science.

Robust fitting for neuroreceptor mapping.

PubMed

Chang, Chung; Ogden, R Todd

2009-03-15

Among many other uses, positron emission tomography (PET) can be used in studies to estimate the density of a neuroreceptor at each location throughout the brain by measuring the concentration of a radiotracer over time and modeling its kinetics. There are a variety of kinetic models in common usage and these typically rely on nonlinear least-squares (LS) algorithms for parameter estimation. However, PET data often contain artifacts (such as uncorrected head motion) and so the assumptions on which the LS methods are based may be violated. Quantile regression (QR) provides a robust alternative to LS methods and has been used successfully in many applications. We consider fitting various kinetic models to PET data using QR and study the relative performance of the methods via simulation. A data adaptive method for choosing between LS and QR is proposed and the performance of this method is also studied.

The recoil implantation technique developed at the U-120 cyclotron in Bucharest

NASA Astrophysics Data System (ADS)

Muntele, C. I.; Simil, L. Popa; Racolta, P. M.; Voiculescu, D.

1999-06-01

At the U-120 cyclotron in Bucharest was developed 15 years ago the thin layer activation (TLA) technique for radioactive labeling of metallic components on depths ranging between 100 μm and 300 μm, for wear/corrosion studies. Aiming to extend these kinds of studies on non-metallic components and at sub-micrometric level we were led to the development of the recoil implantation technique for ultra thin layer activation (UTLA) applications. Due to the low energy of the recoils obtained in a sacrificial target from a nuclear reaction, the surface layer of material to be labeled must be as thick as a few hundred nanometers. Also, since the radiotracer is externally created, there are no restrictions for the kind of material to be labeled, except to be a solid. In this paper we present some results of our studies concerning the actual status of this application at our accelerator.

FDG uptake heterogeneity in FIGO IIb cervical carcinoma does not predict pelvic lymph node involvement.

PubMed

Brooks, Frank J; Grigsby, Perry W

2013-12-23

Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology. We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas. We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (ζ) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally, we observed that S is strongly dependent upon tumor volume and that ζ moderately correlates with mean FDG uptake. FDG uptake heterogeneity did not indicate patients with differing prognoses. Apparent heterogeneity differences between clinical groups may be an artifact arising from either the dependence of some image metrics upon other factors such as tumor volume or upon the underlying variations in the patient populations compared.

Bombesin Encapsulated in Long-Circulating pH-Sensitive Liposomes as a Radiotracer for Breast Tumor Identification.

PubMed

De Barros, André Luís Branco; Mota, Luciene Das Graças; Coelho, Marina Melo Antunes; Corrêa, Natássia Caroline Resende; De Góes, Alfredo Miranda; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2015-02-01

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. These receptors are over-expressed in several forms of cancer; radiolabeled BBN could therefore be used to detect such cancers. However, the degradation of peptides is a critical issue in the development of tumor tracers. Liposomes can be used to overcome this problem and improve the uptake of tracers by tumors. Therefore, the purpose of this study was to prepare and characterize long-circulating and pH-sensitive liposomes (SpHL) containing 99mTc-HYNIC-βAla-Bombesin(7-14) (99mTc-BBN(7-14). In addition, the ability of this system to identify human breast cancer tissue was evaluated using biodistribution studies and scintigraphic images. Long-circulating and pH-sensitive liposomes (SpHL) were prepared and freeze-dried in the presence of cryoprotectants (glucose, mannitol, and trehalose). They were subsequently reconstituted with a solution of 99mTc-HYNIC-βAla-Bombesin(7-14) (99mTc-BBN(7-14)). The liposomes were evaluated for size, encapsulation percentage, radiotracer leakage, and storage stability. In addition, in vivo studies were performed in breast tumor-bearing nude mice. Liposomes in the presence of glucose (SpHLG), exhibited a mean diameter of 164.5 ± 6.5 nm and exhibited a 99mTc-BBN(7-14) encapsulation percentage of 30%. In addition, they remained highly stable for up to 120 days of storage. SpHLG- 99mTc-BBN(7-14) showed longer blood circulation than free 99mTc-BBN(7-14), did. The tumor-to-muscle and tumor-to-blood ratios for SpHLG-99mTc-BBN(7-14 were high at 4 h post-injection (9.31%ID/g and 7.93%ID/g, respectively). Furthermore, scintigraphic images revealed a strong signal in the tumor area, indicating tumor specificity of SpHLG-99mTc-BBN(7-14). In summary, SpHLG-99mTc-BBN(7-14) presented characteristics suitable for a diagnostic agent, and is a potential tool for tumor identification.

Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

PubMed Central

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

2011-01-01

Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in brain and peripheral organs. PMID:19217534

Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

PubMed

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

2009-02-01

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in the brain and peripheral organs.

PET Imaging of Fatty Acid Amide Hydrolase with [ 18F]DOPP in Nonhuman Primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rotstein, Benjamin H.; Wey, Hsiao -Ying; Shoup, Timothy M.

Here, the fatty acid amide hydrolase (FAAH) regulates endocannabinoid signaling. [ 11C]CURB, an irreversibly binding FAAH inhibitor, has been developed for clinical research imaging with PET. However, no fluorine-18 labeled radiotracer for FAAH has yet advanced to human studies. [ 18F]DOPP ([ 18F]3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate) has been identified as a promising 18F-labeled analogue based on rodent studies. The goal of this work is to evaluate [ 18F]DOPP in nonhuman primates to support its clinical translation. High specific activity [ 18F]DOPP (5–6 Ci·μmol –1) was administered intravenously (iv) to three baboons (2M/1F, 3–4 years old). The distribution and pharmacokinetics were quantified followingmore » a 2 h dynamic imaging session using a simultaneous PET/MR scanner. Pretreatment with the FAAH-selective inhibitor, URB597, was carried out at 200 or 300 μg/kg iv, 10 min prior to [ 18F]DOPP administration. Rapid arterial blood sampling for the first 3 min was followed by interval sampling with metabolite analysis to provide a parent radiotracer plasma input function that indicated ~95% baseline metabolism at 60 min and a reduced rate of metabolism after pretreatment with URB597. Regional distribution data were analyzed with 1-, 2-, and 3-tissue compartment models (TCMs), with and without irreversible trapping since [ 18F]DOPP covalently links to the active site of FAAH. Consistent with previous findings for [ 11C]CURB, the 2TCM with irreversible binding was found to provide the best fit for modeling the data in all regions. The composite parameter λk 3 was therefore used to evaluate whole brain (WB) and regional binding of [ 18F]DOPP. Pretreatment studies showed inhibition of λk 3 across all brain regions (WB baseline: 0.112 mL/cm3/min; 300 μg/kg URB597: 0.058 mL/cm 3/min), suggesting that [ 18F]DOPP binding is specific for FAAH, consistent with previous rodent data.« less

PET Imaging of Fatty Acid Amide Hydrolase with [ 18F]DOPP in Nonhuman Primates

DOE PAGES

Rotstein, Benjamin H.; Wey, Hsiao -Ying; Shoup, Timothy M.; ...

2014-07-08

Here, the fatty acid amide hydrolase (FAAH) regulates endocannabinoid signaling. [ 11C]CURB, an irreversibly binding FAAH inhibitor, has been developed for clinical research imaging with PET. However, no fluorine-18 labeled radiotracer for FAAH has yet advanced to human studies. [ 18F]DOPP ([ 18F]3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate) has been identified as a promising 18F-labeled analogue based on rodent studies. The goal of this work is to evaluate [ 18F]DOPP in nonhuman primates to support its clinical translation. High specific activity [ 18F]DOPP (5–6 Ci·μmol –1) was administered intravenously (iv) to three baboons (2M/1F, 3–4 years old). The distribution and pharmacokinetics were quantified followingmore » a 2 h dynamic imaging session using a simultaneous PET/MR scanner. Pretreatment with the FAAH-selective inhibitor, URB597, was carried out at 200 or 300 μg/kg iv, 10 min prior to [ 18F]DOPP administration. Rapid arterial blood sampling for the first 3 min was followed by interval sampling with metabolite analysis to provide a parent radiotracer plasma input function that indicated ~95% baseline metabolism at 60 min and a reduced rate of metabolism after pretreatment with URB597. Regional distribution data were analyzed with 1-, 2-, and 3-tissue compartment models (TCMs), with and without irreversible trapping since [ 18F]DOPP covalently links to the active site of FAAH. Consistent with previous findings for [ 11C]CURB, the 2TCM with irreversible binding was found to provide the best fit for modeling the data in all regions. The composite parameter λk 3 was therefore used to evaluate whole brain (WB) and regional binding of [ 18F]DOPP. Pretreatment studies showed inhibition of λk 3 across all brain regions (WB baseline: 0.112 mL/cm3/min; 300 μg/kg URB597: 0.058 mL/cm 3/min), suggesting that [ 18F]DOPP binding is specific for FAAH, consistent with previous rodent data.« less

PET Imaging of D2/3 agonist binding in healthy human subjects with the radiotracer [11C]-N-propyl-nor-apomorphine (NPA): preliminary evaluation and reproducibility studies

PubMed Central

Narendran, Rajesh; Frankle, W. Gordon; Mason, N. Scott; Laymon, Charles M.; Lopresti, Brian J; Price, Julie C.; Kendro, Steve; Vora, Shivangi; Litschge, Maralee; Mountz, James M.; Mathis, Chester A.

2009-01-01

Objective (-)-N-[11C]-Propyl-norapomorphine (NPA) is a full dopamine D2/3 receptor agonist radiotracer suitable for imaging D2/3 receptors configured in a state of high affinity for agonists using Positron Emission Tomography (PET). The aim of the present study was to define the optimal analytic method to derive accurate and reliable D2/3 receptor parameters with [11C]NPA. Methods Six healthy subjects (4 females/2 males) underwent two [11C]NPA scans in the same day. D2/3 receptor binding parameters were estimated using kinetic analysis (using 1- and 2- tissue compartment models) as well as simplified reference tissue method in the three functional subdivisions of the striatum (associative striatum, AST; limbic striatum LST and sensorimotor striatum SMST). The test-retest variability and intraclass correlation coefficient were assessed for distribution volume (VT), binding potential relative to plasma concentration (BPP), and binding potential relative to nondisplaceable uptake (BPND) Results A two-tissue compartment kinetic model adequately described the functional subdivisions of the striatum as well as cerebellum time-activity data. The reproducibility of VT was excellent (≤ 10%) in all regions, for this approach. The reproducibility of both BPP (≤ 12%) and BPND (≤ 10%) was also excellent. The intraclass correlation coefficient of BPP and BPND were acceptable as well (> 0.75) in the three functional subdivisions of the striatum. Although SRTM led to an underestimation of BPND values relative to that estimated by kinetic analysis by 8 to 13%, the values derived using both the methods were reasonably well correlated (r2 = 0.89, n = 84). Both methods were similarly effective at detecting the differences in [11C]NPA BPND between subjects. Conclusion The results of this study indicate that [11C]NPA can be used to measure D2/3 receptors configured in a state of high affinity for the agonists with high reliability and reproducibility in the functional subdivisions of the human striatum. PMID:19301416

Development and Optimization of a Dedicated, Hybrid Dual-Modality SPECT-CmT System for Improved Breast Lesion Diagnosis

DTIC Science & Technology

2009-01-01

breast are radiotracer uptake by heart and liver. Glandular Tissue Implant Biopsy Clip Streak Artifact Adipose Tissue FIGURE 10: CmT reconstructed... adipose tissue and implants. The cylindrical artifact is due to the offset geometry (further explanation in Task 2(a)). The second patient was...and Image Reconstruction Our emission tomography system is composed of a compact 16x20cm2 field of view cadmium zinc telluride (CZT) LumaGEM

Method for image reconstruction of moving radionuclide source distribution

DOEpatents

Stolin, Alexander V.; McKisson, John E.; Lee, Seung Joon; Smith, Mark Frederick

2012-12-18

A method for image reconstruction of moving radionuclide distributions. Its particular embodiment is for single photon emission computed tomography (SPECT) imaging of awake animals, though its techniques are general enough to be applied to other moving radionuclide distributions as well. The invention eliminates motion and blurring artifacts for image reconstructions of moving source distributions. This opens new avenues in the area of small animal brain imaging with radiotracers, which can now be performed without the perturbing influences of anesthesia or physical restraint on the biological system.

Subcellular compartmentalization of Cd and Zn in two bivalves. II. Significance of trophically available metal (TAM)

USGS Publications Warehouse

Wallace, W.G.; Luoma, S.N.

2003-01-01

This paper examines how the subcellular partitioning of Cd and Zn in the bivalves Macoma balthica and Potamocorbula amurensis may affect the trophic transfer of metal to predators. Results show that the partitioning of metals to organelles, 'enzymes' and metallothioneins (MT) comprise a subcellular compartment containing trophically available metal (TAM; i.e. metal trophically available to predators), and that because this partitioning varies with species, animal size and metal, TAM is similarly influenced. Clams from San Francisco Bay, California, were exposed for 14 d to 3.5 ??g 1-1 Cd and 20.5 ??g 1-1 Zn, including 109Cd and 65Zn as radiotracers, and were used in feeding experiments with grass shrimp Palaemon macrodatylus, or used to investigate the subcellular partitioning of metal. Grass shrimp fed Cd-contaminated P. amurensis absorbed ???60% of ingested Cd, which was in accordance with the partitioning of Cd to the bivalve's TAM compartment (i.e. Cd associated with organelles, 'enzymes' and MT); a similar relationship was found in previous studies with grass shrimp fed Cd-contaminated oligochaetes. Thus, TAM may be used as a tool to predict the trophic transfer of at least Cd. Subcellular fractionation revealed that ???34% of both the Cd and Zn accumulated by M. balthica was associated with TAM, while partitioning to TAM in P. amurensis was metal-dependent (???60% for TAM-Cd%, ???73% for TAM-Zn%). The greater TAM-Cd% of P. amurensis than M. balthica is due to preferential binding of Cd to MT and 'enzymes', while enhanced TAM-Zn% of P. amurensis results from a greater binding of Zn to organelles. TAM for most species-metal combinations was size-dependent, decreasing with increased clam size. Based on field data, it is estimated that of the 2 bivalves, P. amurensis poses the greater threat of Cd exposure to predators because of higher tissue concentrations and greater partitioning as TAM; exposure of Zn to predators would be similar between these species.

Disease quantification on PET/CT images without object delineation

NASA Astrophysics Data System (ADS)

Tong, Yubing; Udupa, Jayaram K.; Odhner, Dewey; Wu, Caiyun; Fitzpatrick, Danielle; Winchell, Nicole; Schuster, Stephen J.; Torigian, Drew A.

2017-03-01

The derivation of quantitative information from images to make quantitative radiology (QR) clinically practical continues to face a major image analysis hurdle because of image segmentation challenges. This paper presents a novel approach to disease quantification (DQ) via positron emission tomography/computed tomography (PET/CT) images that explores how to decouple DQ methods from explicit dependence on object segmentation through the use of only object recognition results to quantify disease burden. The concept of an object-dependent disease map is introduced to express disease severity without performing explicit delineation and partial volume correction of either objects or lesions. The parameters of the disease map are estimated from a set of training image data sets. The idea is illustrated on 20 lung lesions and 20 liver lesions derived from 18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scans of patients with various types of cancers and also on 20 NEMA PET/CT phantom data sets. Our preliminary results show that, on phantom data sets, "disease burden" can be estimated to within 2% of known absolute true activity. Notwithstanding the difficulty in establishing true quantification on patient PET images, our results achieve 8% deviation from "true" estimates, with slightly larger deviations for small and diffuse lesions where establishing ground truth becomes really questionable, and smaller deviations for larger lesions where ground truth set up becomes more reliable. We are currently exploring extensions of the approach to include fully automated body-wide DQ, extensions to just CT or magnetic resonance imaging (MRI) alone, to PET/CT performed with radiotracers other than FDG, and other functional forms of disease maps.

High rates of sulfate reduction in a low-sulfate hot spring microbial mat are driven by a low level of diversity of sulfate-respiring microorganisms.

PubMed

Dillon, Jesse G; Fishbain, Susan; Miller, Scott R; Bebout, Brad M; Habicht, Kirsten S; Webb, Samuel M; Stahl, David A

2007-08-01

The importance of sulfate respiration in the microbial mat found in the low-sulfate thermal outflow of Mushroom Spring in Yellowstone National Park was evaluated using a combination of molecular, microelectrode, and radiotracer studies. Despite very low sulfate concentrations, this mat community was shown to sustain a highly active sulfur cycle. The highest rates of sulfate respiration were measured close to the surface of the mat late in the day when photosynthetic oxygen production ceased and were associated with a Thermodesulfovibrio-like population. Reduced activity at greater depths was correlated with novel populations of sulfate-reducing microorganisms, unrelated to characterized species, and most likely due to both sulfate and carbon limitation.

High Rates of Sulfate Reduction in a Low-Sulfate Hot Spring Microbial Mat Are Driven by a Low Level of Diversity of Sulfate-Respiring Microorganisms▿

PubMed Central

Dillon, Jesse G.; Fishbain, Susan; Miller, Scott R.; Bebout, Brad M.; Habicht, Kirsten S.; Webb, Samuel M.; Stahl, David A.

2007-01-01

The importance of sulfate respiration in the microbial mat found in the low-sulfate thermal outflow of Mushroom Spring in Yellowstone National Park was evaluated using a combination of molecular, microelectrode, and radiotracer studies. Despite very low sulfate concentrations, this mat community was shown to sustain a highly active sulfur cycle. The highest rates of sulfate respiration were measured close to the surface of the mat late in the day when photosynthetic oxygen production ceased and were associated with a Thermodesulfovibrio-like population. Reduced activity at greater depths was correlated with novel populations of sulfate-reducing microorganisms, unrelated to characterized species, and most likely due to both sulfate and carbon limitation. PMID:17575000

Midi-maxi computer interaction in the interpretation of nuclear medicine procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlapper, G.A.

1977-01-01

A study of renal function with an Anger Gamma Camera coupled with a Digital Equipment Corporation Gamma-11 System and an IBM System 370 demonstrates the potential of quantitative determinations of physiological function through the application of midi-maxi computer interaction in the interpretation of nuclear medicine procedures. It is shown that radiotracers can provide an opportunity to assess physiological processes of renal function by noninvasively following the path of a tracer as a function of time. Time-activity relationships obtained over seven anatomically defined regions are related to parameters of a seven compartment model employed to describe the renal clearance process. Themore » values obtained for clinically significant parameters agree with known renal pathophysiology. Differentiation of failure of acute, chronic, and obstructive forms is indicated.« less

Simple, rapid method for the preparation of isotopically labeled formaldehyde

DOEpatents

Hooker, Jacob Matthew [Port Jefferson, NY; Schonberger, Matthias [Mains, DE; Schieferstein, Hanno [Aabergen, DE; Fowler, Joanna S [Bellport, NY

2011-10-04

Isotopically labeled formaldehyde (*C.sup..sctn.H.sub.2O) is prepared from labeled methyl iodide (*C.sup..sctn.H.sub.3I) by reaction with an oxygen nucleophile having a pendant leaving group. The mild and efficient reaction conditions result in good yields of *C.sup..sctn.H.sub.2O with little or no *C isotopic dilution. The simple, efficient production of .sup.11CH.sub.2O is described. The use of the .sup.11CH.sub.2O for the formation of positron emission tomography tracer compounds is described. The reaction can be incorporated into automated equipment available to radiochemistry laboratories. The isotopically labeled formaldehyde can be used in a variety of reactions to provide radiotracer compounds for imaging studies as well as for scintillation counting and autoradiography.

Toward a Droplet-Based Single-Cell Radiometric Assay.

PubMed

Gallina, Maria Elena; Kim, Tae Jin; Shelor, Mark; Vasquez, Jaime; Mongersun, Amy; Kim, Minkyu; Tang, Sindy K Y; Abbyad, Paul; Pratx, Guillem

2017-06-20

Radiotracers are widely used to track molecular processes, both in vitro and in vivo, with high sensitivity and specificity. However, most radionuclide detection methods have spatial resolution inadequate for single-cell analysis. A few existing methods can extract single-cell information from radioactive decays, but the stochastic nature of the process precludes high-throughput measurement (and sorting) of single cells. In this work, we introduce a new concept for translating radioactive decays occurring stochastically within radiolabeled single-cells into an integrated, long-lasting fluorescence signal. Single cells are encapsulated in radiofluorogenic droplets containing molecular probes sensitive to byproducts of ionizing radiation (primarily reactive oxygen species, or ROS). Different probes were examined in bulk solutions, and dihydrorhodamine 123 (DHRh 123) was selected as the lead candidate due to its sensitivity and reproducibility. Fluorescence intensity of DHRh 123 in bulk increased at a rate of 54% per Gy of X-ray radiation and 15% per MBq/ml of 2-deoxy-2-[ 18 F]-fluoro-d-glucose ([ 18 F]FDG). Fluorescence imaging of microfluidic droplets showed the same linear response, but droplets were less sensitive overall than the bulk ROS sensor (detection limit of 3 Gy per droplet). Finally, droplets encapsulating radiolabeled cancer cells allowed, for the first time, the detection of [ 18 F]FDG radiotracer uptake in single cells through fluorescence activation. With further improvements, we expect this technology to enable quantitative measurement and selective sorting of single cells based on the uptake of radiolabeled small molecules.

Assimilation of trace elements ingested by the mussel Mytilus edulis: effects of algal food abundance

USGS Publications Warehouse

Wang, W.-X.; Fisher, N.S.; Luoma, S.N.

1995-01-01

Pulse-chase feeding and multi-labeled radiotracer techniques were employed to measure the assimilation of 6 trace elements (110mAg, 241Am, 109Cd, 57Co, 75Se and 65Zn) from ingested diatoms in the mussel Mytilus edulis feeding at different rates (0.1, 0.49 and 1.5 mg dry wt h-1). Uniformly radiolabeled diatoms Thalassiosira pseudonana were fed to mussels for 0.5 h, and the behavior of the radiotracers in individual mussels was followed for 96 h in a depuration seawater system. Assimilation efficiency (AE) of each element declined with increasing ingestion rate and increased with gut passage time. The importance of extracellular digestion relative to intracellular digestion increased with ingestion activity, which, when coupled with a decline in AE, suggested that extracellular digestion is less efficient in metal absorption. Zn assimilation was most affected by ingestion rate, suggesting that AE may play a role in the physiological regulation of this metal in M. edulis. In an experiment to simulate the effects of an acidic gut, lowered pH (5.5) enhanced the release of elements from intact diatom cells, especially at low particle concentration. These results indicate that both feeding components of the mussel (i.e. gut passage time, digestive partitioning) and metal chemistry (i.e. metal release at lowered pH within the bivalve gut) are responsible for the difference in the assimilation of trace metals at different food quantities observed in mussels.

Method for selective recovery of PET-usable quantities of [.sup.18 F] fluoride and [.sup.13 N] nitrate/nitrite from a single irradiation of low-enriched [.sup.18 O] water

DOEpatents

Ferrieri, Richard A.; Schlyer, David J.; Shea, Colleen

1995-06-13

A process for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- for radiotracer synthesis is disclosed. The process includes producing [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- simultaneously by exposing a low-enriched (20%-30%) [.sup.18 O]H.sub.2 O target to proton irradiation, sequentially isolating the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- from the [.sup.18 O]H.sub.2 O target, and reducing the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- to [.sup.13 N]NH.sub.3. The [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- products are then conveyed to a laboratory for radiotracer applications. The process employs an anion exchange resin for isolation of the isotopes from the [.sup.18 O]H.sub.2 O, and sequential elution of [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [ .sup.18 F]F.sup.- fractions. Also the apparatus is disclosed for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- from a single irradiation of a single low-enriched [.sup.18 O]H.sub.2 O target.

Imaging Amyloidopathy in Parkinson Disease and Parkinsonian Dementia Syndromes.

PubMed

Frey, Kirk A; Petrou, Myria

2015-02-01

Dementia arising in patients with Parkinson disease or parkinsonian neurodegeneration comprises a heterogeneous neuropathology. Clinical labeling of patients with both dementia and Parkinson disease is dichotomous, depending on the temporal development of cognitive impairment and motor parkinsonism. Patients with dementia arising first (or within the first year of PD) are classified as dementia with Lewy bodies; patients with PD for more than one year before cognitive decline are classified as Parkinson disease with dementia. Despite this differential clinical classification, autopsy studies demonstrate variable admixtures of cortical synuicleinopathy, Aβ-amyloidopathy and tau neurofibrillary tangle deposition. There are no routine clinical diagnostic measures that accurately distinguish the underlying neuropathologies in individual patients. In the present paper, we review the published literature describing characteristics of fibrillary Aβ-amyloid deposition on the basis of PET radiotracer imaging in patients with Parkinson disease and in parkinsonian dementia syndromes. Although individual reports often include only small-to-modest subject numbers, there is overall suggestion that PD patients have a lower incidence of Aβ-amyloid deposition than seen amongst elderly normal subjects, and that Parkinson disease with dementia patients have a lower incidence of Aβ-amyloid deposition than do patients with dementia with Lewy bodies. These apparent features contrast the findings of Aβ-amyloid-PET imaging in normal aging and the development of Alzheimer disease, where Aβ-amyloid deposition arises asymptomatically and apparently many years before development of signs or symptoms of dementia. It is proposed that focused, prospective studies are needed to further address and understand the complex role(s) of Aβ-amyloid pathology in Parkinson disease, and that this understanding will be critical to the development of targeted disease-modifying therapy for dementia in PD.

Functional assessment of sodium chloride cotransporter NCC mutants in polarized mammalian epithelial cells.

PubMed

Rosenbaek, Lena L; Rizzo, Federica; MacAulay, Nanna; Staub, Olivier; Fenton, Robert A

2017-08-01

The thiazide-sensitive sodium chloride cotransporter NCC is important for maintaining serum sodium (Na + ) and, indirectly, serum potassium (K + ) levels. Functional studies on NCC have used cell lines with native NCC expression, transiently transfected nonpolarized cell lines, or Xenopus laevis oocytes. Here, we developed the use of polarized Madin-Darby canine kidney type I (MDCKI) mammalian epithelial cell lines with tetracycline-inducible human NCC expression to study NCC activity and membrane abundance in the same system. In radiotracer assays, induced cells grown on filters had robust thiazide-sensitive and chloride dependent sodium-22 ( 22 Na) uptake from the apical side. To minimize cost and maximize throughput, assays were modified to use cells grown on plastic. On plastic, cells had similar thiazide-sensitive 22 Na uptakes that increased following preincubation of cells in chloride-free solutions. NCC was detected in the plasma membrane, and both membrane abundance and phosphorylation of NCC were increased by incubation in chloride-free solutions. Furthermore, in cells exposed for 15 min to low or high extracellular K + , the levels of phosphorylated NCC increased and decreased, respectively. To demonstrate that the system allows rapid and systematic assessment of mutated NCC, three phosphorylation sites in NCC were mutated, and NCC activity was examined. 22 Na fluxes in phosphorylation-deficient mutants were reduced to baseline levels, whereas phosphorylation-mimicking mutants were constitutively active, even without chloride-free stimulation. In conclusion, this system allows the activity, cellular localization, and abundance of wild-type or mutant NCC to be examined in the same polarized mammalian expression system in a rapid, easy, and low-cost fashion. Copyright © 2017 the American Physiological Society.

Accumulation of radioactive corrosion products on steel surfaces of VVER-type nuclear reactors. II. 60Co

NASA Astrophysics Data System (ADS)

Varga, Kálmán; Hirschberg, Gábor; Németh, Zoltán; Myburg, Gerrit; Schunk, János; Tilky, Péter

2001-10-01

In the case of intact fuel claddings, the predominant source of radioactivity in the primary circuits of water-cooled nuclear reactors is the activation of corrosion products in the core. The most important corrosion product radionuclides in the primary coolant of pressurized water reactors (PWRs) are 60Co, 58Co, 51Cr, 54Mn, 59Fe (as well as 110mAg in some Soviet-made VVER-type reactor). The second part of this series is focused on the complex studies of the formation and build-up of 60Co-containing species on an austenitic stainless steel type 08X18H10T (GOST 5632-61) and magnetite-covered carbon steel often to be used in Soviet-planned VVERs. The kinetics and mechanism of the cobalt accumulation were studied by a combination (coupling) of an in situ radiotracer method and voltammetry in a model solution of the primary circuit coolant. In addition, independent techniques such as X-ray photoelectron spectroscopic (XPS) and ICP-OES are also used to analyze the chemical state of Co species in the passive layer formed on stainless steel as well as the chemical composition of model solution. The experimental results have revealed that: (i) The passive behavior of the austenitic stainless steel at open-circuit conditions, the slightly alkaline pH and the reducing water chemistry can be considered to be optimal to minimize the 60Co contamination. (ii) The highly potential dependent deposition of various Co-oxides at E>1.10 V (vs. RHE) offers a unique possibility to elaborate a novel electrochemical method for the decrease or removal of cobalt traces from borate-containing coolants contaminated with 60Co and/or 58Co radionuclides.

The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11 C]-raclopride and [11 C]-(+)-PHNO PET.

PubMed

Caravaggio, Fernando; Ku Chung, Jun; Plitman, Eric; Boileau, Isabelle; Gerretsen, Philip; Kim, Julia; Iwata, Yusuke; Patel, Raihaan; Chakravarty, M Mallar; Remington, Gary; Graff-Guerrero, Ariel

2017-11-01

Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D 2/3 receptors (D 2/3 R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D 2/3 R availability measured with an antagonist radiotracer ([ 11 C]-raclopride) versus an agonist radiotracer ([ 11 C]-(+)-PHNO) were examined. Data from 62 subjects scanned with [ 11 C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [ 11 C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume. For [ 11 C]-(+)-PHNO, ventral caudate volumes were positively correlated with BP ND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BP ND in the VS. With [ 11 C]-raclopride, BP ND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BP ND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus. Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D 2/3 R and brain morphology are observed. Hum Brain Mapp 38:5519-5534, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The influence of nepheloid layers on global model simulations of 231Pa and 230Th.

NASA Astrophysics Data System (ADS)

Basak, C.; Plancherel, Y.; Khatiwala, S.; Anderson, R. F.

2016-12-01

231Pa and 230Th in the ocean are produced at a constant ratio by Uranium decay but adsorption onto particles removes these tracers differentially. This fractionation process makes it possible to use the elemental 231Pa/230Th ratio as a paleoceanography proxy, frequently used for deriving the strength of Atlantic Meridional Overturning Circulation. The removal process, however, is further complicated by the abundance and composition of the available particle types. Understanding how dissolved tracers interact with the particle field in the ocean is key to better understand the biogeochemical cycling of these particle-reactive elements and their use as a flux tracer in present and past oceans. We here present simulations of the 231Pa/230Th ratio using the Transport Matrix Method (TMM, Khatiwala, 2007), focusing especially on the role of the nepheloid layer in controlling the distribution of these radiotracers. The model simulates each tracer separately, with advective-diffusive transport based on the ECCO ocean state estimate (Stammer et al., 2004). Sources include production by Uranium decay and dust dissolution. Radioactive decay and importantly, reversible scavenging and sedimentation are the main sinks that control the removal of the radiotracers. Similar to previous studies, we consider particle fields consisting of calcium carbonate, opal, particle organic matter, and dust. A novelty is that we explicitly consider the influence of an additional bottom particle layer (nepheloid). Simulations that include a nepheloid layer produce vertical profiles that better fit the observed distribution of 230Th and 231Pa. Specifically, observational data in the South Atlantic and eastern South Pacific indicate a mid-depth inflection (for both Pa and Th), a feature that can only be obtained if a nepheloid layer is included in the simulation. Our simulations reinforce the idea that nepheloid layers play an important role in Pa and Th cycling in the ocean (Deng et al., 2014; Hayes et al., 2015).

99mTc-labeling of HYNIC-conjugated cyclic RGDfK dimer and tetramer using EDDA as coligand.

PubMed

Wang, Jianjun; Kim, Young-Seung; Liu, Shuang

2008-03-01

In this study, EDDA (ethylenediamine- N, N'-diacetic acid) was used as the coligand for 99mTc-labeling of cyclic RGDfK conjugates: HYNIC-dimer (HYNIC = 6-hydrazinonicotinamide; dimer = E[c(RGDfK)]2) and HYNIC-tetramer (tetramer = E{E[c(RGDfK)]2}2). First, HYNIC-dimer was allowed to react with 99mTcO4 (-) in the presence of excess tricine and stannous chloride to form the intermediate complex [99mTc(HYNIC-dimer)(tricine)2], which was then allowed to react with EDDA to afford [99mTc(HYNIC-dimer)(EDDA)] with high yield (>90%) and high specific activity ( approximately 8.0 Ci/micromol). Under the same radiolabeling conditions, the yield for [99mTc(HYNIC-tetramer)(EDDA)] was always <65%. The results from a mixed-ligand experiment show that there is only one EDDA bonding to the 99mTc-HYNIC core in [99mTc(HYNIC-dimer)(EDDA)]. The athymic nude mice bearing subcutaneous U87MG human glioma xenografts were used to evaluate the impact of EDDA coligand on the biodistribution characteristics and excretion kinetics of the 99mTc-labeled HYNIC-dimer and HYNIC-tetramer. Surprisingly, [99mTc(HYNIC-dimer)(EDDA)] and [99mTc(HYNIC-tetramer)(EDDA)] had almost identical tumor uptake over the 2 h period. The use of EDDA as coligand to replace tricine/TPPTS (TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) did not significantly change the uptake of the 99mTc-labeled HYNIC-dimer in noncancerous organs, such as the liver, kidneys, and lungs; but it did result in a significantly lower kidney uptake for the 99mTc-labeled HYNIC-tetramer due to faster renal excretion. It was also found that the radiotracer tumor uptake decreases in a linear fashion as the tumor size increases. The smaller the tumors are, the higher the tumor uptake is regardless of the identity of radiotracer.

The short-term effects of increasing plasma colloid osmotic pressure in patients with noncardiac pulmonary edema

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sibbald, W.J.; Driedger, A.A.; Wells, G.A.

1983-05-01

We infused hyperoncotic albumin (25 or 50 gm of a 50% solution) into patients with noncardiac pulmonary edema (adult respiratory distress syndrome (ARDS)) to evaluate its effect on the transmicrovascular flux from blood to pulmonary edema fluid of two radiotracers--/sup 111/In-DTPA (mol wt 504) and /sup 125/I-human serum albumin (HSA) (mol wt 69,000). Two groups of patients were studied--one with a modest increase in permeability of the pulmonary alveolocapillary membrane to /sup 125/I-HSA (group 1) and another with a large increase in permeability to /sup 125/I-HSA (group 2). We used furosemide, when necessary, to minimize the effect of albumin infusionmore » to increase the pulmonary microvascular hydrostatic pressure (Pmv), measured clinically as the pulmonary capillary wedge pressure (PCWP). Therapy significantly increased the mean colloid osmotic pressure (COP) in both groups, but not the mean PCWP or calculated Pmv. Albumin had no significant effect on the mean pulmonary transmicrovascular flux of the radiotracers in either group, despite the increase in COP. In individual patients, a change in the Pmv in response to albumin infusion was directly correlated with the change in flux of /sup 111/In-DTPA (group 1: delta In-DTPA (%) . 8.66 + 1.4 delta Pmv (%) r . 0.51, P less than 0.02; group 2: delta In-DTPA (%) . -3.43 + 1.6 delta Pmv (%) r . 0.67, P less than 0.01). A change in the transmicrovascular flux of I-HSA also correlated with a change in the intravascular Starling forces in both groups. We conclude that albumin infusion in patients with ARDS will not augment the pulmonary transmicrovascular flux of low or high molecular-weight solutes when the effect of albumin to increase the Pmv is minimized; nor, however, does an increase in plasma COP significantly reduce the flux of such solutes.« less

Magnetic iron oxide and manganese-doped iron oxide nanoparticles for the collection of alpha-emitting radionuclides from aqueous solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Hara, Matthew J.; Carter, Jennifer C.; Warner, Cynthia L.

Magnetic nanoparticles are well known to possess chemically active surfaces and high surface areas that can be employed to extract a range of ions from aqueous solutions. Additionally, their paramagnetic property provides a convenient means for bulk collection of the material from solution after the targeted ions have been adsorbed. Herein, two nanoscale amphoteric metal oxides, each possessing useful magnetic attributes, were evaluated for their ability to collect both naturally occurring radioactive isotopes (polonium (Po), radium (Ra), and uranium (U)) as well as the transuranic element americium (Am) from a suite of naturally occurring aqueous matrices. The nanomaterials include commerciallymore » available paramagnetic magnetite (Fe3O4) and magnetite that was modified to incorporate manganese (Mn) into the crystal structure. The chemical stability of these nanomaterials was evaluated in Hanford Site, WA ground water between the natural pH (~8) and pH 1 (acidified with HCl). Whereas the magnetite was observed to have good stability over the pH range, the Mn-doped material was observed to leach Mn at low pH. The materials were evaluated in parallel to characterize their uptake performance of the aforementioned alpha-emitting radionuclide spikes from Hanford Site ground water across a range of pH (from ~8 down to 2). In addition, radiotracer uptake experiments were performed on Columbia River water, seawater, and human urine at their natural pH and at pH 2. Despite the observed leaching of Mn from the Mn-doped nanomaterial in the lower pH range, it exhibited generally superior analyte extraction performance compared to the magnetite, and analyte uptake was observed across a broader pH range. The uptake behavior of the various radiotracers on these two materials at different pH levels can generally be explained by the amphoteric nature of the nanoparticle surfaces. Finally, the rate of sorption of the radiotracers on the two materials in unacidified groundwater was evaluated. The uptake curves generally indicate that equilibrium is obtained within a few minutes, which is attributed to the high surface areas of the nanomaterials and the high level of dispersion in the liquids. Overall, the results indicate that these nanomaterials may have the potential to be employed for a range of applications to extract radionuclides from aqueous solutions. These applications may include analytical chemistry, waste water treatment and remediation, mining, and in vitro radiobioassay.« less

The Utility of [18F]DASA-23 for Molecular Imaging of Prostate Cancer with Positron Emission Tomography.

PubMed

Beinat, Corinne; Haywood, Tom; Chen, Yun-Sheng; Patel, Chirag B; Alam, Israt S; Murty, Surya; Gambhir, Sanjiv Sam

2018-05-07

There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8-10 tumors compared to Gleason 6-7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer. We have recently reported the development of a PKM2-specific radiopharmaceutical [ 18 F]DASA-23 and herein describe its evaluation in cell culture and preclinical models of prostate cancer. The cellular uptake of [ 18 F]DASA-23 was evaluated in a panel of prostate cancer cell lines and compared to that of [ 18 F]FDG. The specificity of [ 18 F]DASA-23 to measure PKM2 levels in cell culture was additionally confirmed through the use of PKM2-specific siRNA. PET imaging studies were then completed utilizing subcutaneous prostate cancer xenografts using either PC3 or DU145 cells in mice. [ 18 F]DASA-23 uptake values over 60-min incubation period in PC3, LnCAP, and DU145 respectively were 23.4 ± 4.5, 18.0 ± 2.1, and 53.1 ± 4.6 % tracer/mg protein. Transient reduction in PKM2 protein expression with siRNA resulted in a 50.1 % reduction in radiotracer uptake in DU145 cells. Small animal PET imaging revealed 0.86 ± 0.13 and 1.6 ± 0.2 % ID/g at 30 min post injection of radioactivity in DU145 and PC3 subcutaneous tumor bearing mice respectively. Herein, we evaluated a F-18-labeled PKM2-specific radiotracer, [ 18 F]DASA-23, for the molecular imaging of prostate cancer with PET. [ 18 F]DASA-23 revealed rapid and extensive uptake levels in cellular uptake studies of prostate cancer cells; however, there was only modest tumor uptake when evaluated in mouse subcutaneous tumor models.

DOE Office of Scientific and Technical Information (OSTI.GOV)

kil K. E.; Biegon A.; Kil, K.-E.

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara{reg_sign}) is a high affinity aromatase inhibitor (K{sub i}=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [{sup 11}C]cyanide with the bromo-precursor (3). PET studies inmore » the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [{sup 11}C-cyano]letrozole fraction in the arterial plasma were also measured. [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16 {+-} 2.21 Ci/{micro}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in brain and peripheral organs.« less

MC225, a Novel Probe for P-glycoprotein PET Imaging at the Blood-brain Barrier: In Vitro Cardiovascular Safety Evaluation.

PubMed

Fusi, Fabio; Durante, Miriam; Gorelli, Beatrice; Perrone, Maria Grazia; Colabufo, Nicola Antonio; Saponara, Simona

2017-12-01

The P-glycoprotein (P-gp) substrate MC225, at concentrations ≤10 nM, is a valuable radiotracer for positron emission tomography imaging of P-gp function in rats and mice. The aim of this study was to evaluate its potential toxic hazard toward the cardiovascular system through an in-depth analysis of its effects on rat aorta rings, on CaV1.2 channel current (ICa1.2) of A7r5 cells and on Langendorff-perfused rat heart. In aortic rings, MC225 relaxed phenylephrine-induced contraction in a concentration-dependent and endothelium-independent manner, with an IC50 value of about 1 μM. At concentrations ≥3 μM, it antagonized the response to cumulative concentrations of K. MC225, 1 and 10 μM, inhibited ICa1.2 by 15% and 31%, respectively, without affecting either current activation or inactivation kinetics. In Langendorff-perfused rat hearts, only 10 μM MC225 significantly decreased left ventricular pressure and increased coronary perfusion pressure while reducing heart rate and prolonging the cardiac cycle length as well as the atrioventricular conduction time (PQ interval) on the electrocardiogram. Lower concentrations of the drug were ineffective. These findings demonstrate that MC225-induced cardiovascular effects took place at concentrations that are at least 2 orders of magnitude higher than those allowing in vivo measurement of P-gp function. Therefore, MC225 represents a promising positron emission tomography tool for in vivo straightforward P-gp quantification.

Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone-secreting adrenal phaeochromocytoma: review of the literature and report of a case

PubMed Central

Ruggeri, R.M.; Ferraù, F.; Campennì, A.; Simone, A.; Barresi, V.; Giuffrè, G.; Tuccari, G.; Baldari, S.; Trimarchi, F.

2009-01-01

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochromocytoma, causing ectopic Cushing’s syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous, 9-cm mass in the right adrenal gland, and [111In-DTPA0] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region, corresponding to the adrenal mass. The patient underwent laparoscopic surgery and formalin-fixed and paraffin-embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed. Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma, which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR1, SSTR2A, SSTR2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing’s disease was dependent on CRH overproduction by the pheochromocytoma, in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas, and provide further evidence for functional SSTR subtype SSTR2a in a subgroup of pheochromocytomas, suggesting that these tumours may represent potential target for octreotide treatment.

Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone- secreting adrenal phaeochromocytoma: review of the literature and report of a case.

PubMed

Ruggeri, Rosaria M; Ferraù, F; Campennì, A; Simone, A; Barresi, V; Giuffrè, G; Tuccari, G; Baldari, S; Trimarchi, F

2009-01-01

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochro-mocytoma,causing ectopic Cushing's syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous,9-cm mass in the right adrenal gland,and [111In-DTPA0] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region,corresponding to the adrenal mass.The patient underwent laparoscopic surgery and formalin-fixed and paraffin embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed.Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma,which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR1, SSTR2A, SSTR2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing's disease was dependent on CRH overproduction by the pheochromocytoma,in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas,and provide further evidence for functional SSTR subtype SSTR2a in a subgroup of pheochromocytomas,suggesting that these tumours may represent potential target for octreotide treatment.

Differential diagnosis of regional cerebral hyperfixation of TC-99m HMPAO on SPECT imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirazi, P.; Konopka, L.; Crayton, J.W.

1994-05-01

Accurate diagnostic evaluation of patients with neurologic and neuropsychiatric disease is important because early treatment may halt disease progression and prevent impairment or disability. Cerebral hyperfixation of HMPAO has been ascribed to luxury perfusion following ischemic infarction. The present study sought to identify other conditions that also display radiotracer hyperfixation in order to develop a differential diagnosis of this finding on SPECT imaging. Two hundred fifty (n=250) successive cerebral SPECT images were reviewed for evidence of HMPAO hyperfixation. Hyperfixation was defined as enhanced focal perfusion surrounded by a zone of diminished or normal cerebral perfusion. All patients were scanned aftermore » intravenous injection of 25 mCi Tc-99m HMPAO. Volume-rendered and oblique images were obtained with a Trionix triple-head SPECT system using ultra high resolution fan beam collimators. Thirteen (13/250; 5%) of the patients exhibited regions of HMPAO hyperfixation. CT or MRI abnormalities were detected in 6/13 cases. Clinical diagnoses in these patients included intractable psychosis, post-traumatic stress disorder, alcohol and narcotic dependence, major depression, acute closed-head trauma, hypothyroidism, as well as subacute ischemic infarction. A wide variety of conditions may be associated with cerebral hyperfixation of HMPAO. These conditions include neurologic and psychiatric diagnoses, and extend the consideration of hyperfixation beyond ischemic infarction. Consequently, a differential diagnosis of HMPAO hyperfixation may be broader than originally considered, and this may suggest a fundamental role for local cerebral hyperperfusion. Elucidation of the fundamental mechanism(s) for cerebral hyperperfusion requires further investigation.« less

Impairment of paravascular clearance pathways in the aging brain

PubMed Central

Kress, Benjamin T.; Iliff, Jeffrey J.; Xia, Maosheng; Wang, Minghuan; Wei, Helen; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason; Plog, Benjamin A.; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-01-01

Objective In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal and interstitial fluids. Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular cerebrospinal fluid (CSF) pathways. The Objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. Methods CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy while interstitial solute clearance was evaluated by radio-tracer clearance assays in young (2–3 month), middle age (10–12 month) and old (18–20 month) wild type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function were evaluated by immunofluorescence. Results Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparechamally injected amyloid β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. Interpretation We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of mis-folded protein aggregates. PMID:25204284

Impairment of paravascular clearance pathways in the aging brain.

PubMed

Kress, Benjamin T; Iliff, Jeffrey J; Xia, Maosheng; Wang, Minghuan; Wei, Helen S; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason A; Plog, Benjamin A; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-12-01

In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. © 2014 American Neurological Association.

Incidental Detection of Head and Neck Squamous Cell Carcinoma on 68Ga-PSMA-11 PET/CT.

PubMed

Lawhn-Heath, Courtney; Flavell, Robert R; Glastonbury, Christine; Hope, Thomas A; Behr, Spencer C

2017-04-01

We present a case of an incidentally detected squamous cell carcinoma of the oropharynx on Ga-PSMA-11 PET. A 71-year-old man's condition was diagnosed as prostate carcinoma after a year of rising serum prostate-specific antigen. The staging Ga-PSMA PET/CT demonstrated focal radiotracer uptake in the prostate corresponding to his known primary prostate cancer. However, a PSMA-avid 3.4-cm mass was incidentally found in the right tongue base that was biopsied, confirming squamous cell carcinoma.

Imaging Prostate Cancer with Positron Emission Tomography

DTIC Science & Technology

2016-07-01

pool. Radioactivity was retained in kidney tissue and suggests that this is the primary route of excretion. Tumor targeting was inefficient.    15...radioactivity in hepatic tissue. Elevated levels of radioactivity were observed in kidney tissue suggesting that these radiotracers are excreted...20, 21], and its Blood 0 10 20 30 0.00 0.05 0.10 0.15 0.20 Time (h) % ID /g Liver 0 10 20 30 0.0 0.5 1.0 1.5 2.0 Time (h) % ID /g Kidney 0 10 20 30

Gallium-67 imaging in muscular sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edan, G.; Bourguet, P.; Delaval, P.

1984-07-01

A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid muscle disease but is consistent with the rarity of clinical evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

Limitations in the application of the Gibbs equation to anionic surfactants at the air/water surface: sodium dodecylsulfate and sodium dodecylmonooxyethylenesulfate above and below the CMC.

PubMed

Xu, Hui; Li, Pei Xun; Ma, Kun; Thomas, Robert K; Penfold, Jeffrey; Lu, Jian Ren

2013-07-30

This is a second paper responding to recent papers by Menger et al. and the ensuing discussion about the application of the Gibbs equation to surface tension (ST) data. Using new neutron reflection (NR) measurements on sodium dodecylsulfate (SDS) and sodium dodecylmonooxyethylene sulfate (SLES) above and below their CMCs and with and without added NaCl, in conjunction with the previous ST measurements on SDS by Elworthy and Mysels (EM), we conclude that (i) ST measurements are often seriously compromised by traces of divalent ions, (ii) adsorption does not generally reach saturation at the CMC, making it difficult to obtain the limiting Gibbs slope, and (iii) the significant width of micellization may make it impossible to apply the Gibbs equation in a significant range of concentration below the CMC. Menger et al. proposed ii as a reason for the difficulty of applying the Gibbs equation to ST data. Conclusions i and iii now further emphasize the failings of the ST-Gibbs analysis for determining the limiting coverage at the CMC, especially for SDS. For SDS, adsorption increases above the CMC to a value of 10 × CMC, which is about 25% greater than at the CMC and about the same as at the CMC in the presence of 0.1 M NaCl. In contrast, the adsorption of SLES reaches a limit at the CMC with no further increase up to 10 × CMC, but the addition of 0.1 M NaCl increases the surface excess by 20-25%. The results for SDS are combined with earlier NR results to generate an adsorption isotherm from 2 to 100 mM. The NR results for SDS are compared to the definitive surface tension (ST) measurements of EM, and the surface excesses agree over the range where they can safely be compared, from 2 to 6 mM. This confirms that the anomalous decrease in the slope of EM's σ - ln c curve between 6 mM and the CMC at 8.2 mM results from changes in activity associated with a significant width of micellization. This anomaly shows that it is impossible to apply the Gibbs equation usefully from 6 to 8.2 mM (i.e., the lack of knowledge of the activity in this range is the same as above the CMC (8.2 mM)). It was found that a mislabeling of the original data in EM may have prevented the use of this excellent ST data as a standard by other authors. Although NR and ST results for SDS in the absence of added electrolyte show that the discrepancies can be rationalized, ST is generally shown to be less accurate and more vulnerable to impurities, especially divalent ions, than NR. The radiotracer technique is shown to be less accurate than ST-Gibbs in that the four radiotracer measurements of the surface excess are consistent neither with each other nor with ST and NR. It is also shown that radiotracer results on aerosol-OT are likely to be incorrect. Application of the mass action (MA) model of micellization to the ST curves of SDS and SLES through and above the CMC shows that they can be explained by this model and that they depend on the degree of dissociation of the micelle, which leads to a larger change in the mean activity, and hence the adsorption, for the more highly dissociated SDS micelles than for SLES. Previous measurements of the activity of SDS above the CMC were found to be semiquantitatively consistent with the change in mean activity predicted by the MA model but inconsistent with the combined ST, NR, and Gibbs equation results.

Subcellular compartmentalization of Cd and Zn in two bivalves. I. Significance of metal-sensitive fractions (MSF) and biologically detoxified metal (BDM)

USGS Publications Warehouse

Wallace, W.G.; Lee, B.-G.; Luoma, S.N.

2003-01-01

Many aspects of metal accumulation in aquatic invertebrates (i.e. toxicity, tolerance and trophic transfer) can be understood by examining the subcellular partitioning of accumulated metal. In this paper, we use a compartmentalization approach to interpret the significance of metal, species and size dependence in the subcellular partitioning of Cd and Zn in the bivalves Macoma balthica and Potamocorbula amurensis. Of special interest is the compartmentalization of metal as metal-sensitive fractions (MSF) (i.e. organelles and heat-sensitive proteins, termed 'enzymes' hereafter) and biologically detoxified metal (BDM) (i.e. metallothioneins [MT] and metal-rich granules [MRG]). Clams from San Francisco Bay, CA, were exposed for 14 d to seawater (20??? salinity) containing 3.5 ??g l-1 Cd and 20.5 ??g l-1 Zn, including 109Cd and 65Zn as radiotracers. Uptake was followed by 21 d of depuration. The subcellular partitioning of metal within clams was examined following exposure and loss. P. amurensis accumulated ???22x more Cd and ???2x more Zn than M. balthica. MT played an important role in the storage of Cd in P. amurensis, while organelles were the major site of Zn accumulation. In M. balthica, Cd and Zn partitioned similarly, although the pathway of detoxification was metal-specific (MRG for Cd; MRG and MT for Zn). Upon loss, M. balthica depurated ???40% of Cd with Zn being retained; P. amurensis retained Cd and depurated Zn (???40%). During efflux, Cd and Zn concentrations in the MSF compartment of both clams declined with metal either being lost from the animal or being transferred to the BDM compartment. Subcellular compartmentalization was also size-dependent, with the importance of BDM increasing with clam size; MSF decreased accordingly. We hypothesized that progressive retention of metal as BDM (i.e. MRG) with age may lead to size dependency of metal concentrations often observed in some populations of M. balthica.

The recoil implantation technique developed at the U-120 cyclotron in Bucharest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muntele, C. I.; Simil, L. Popa; Racolta, P. M.

1999-06-10

At the U-120 cyclotron in Bucharest was developed 15 years ago the thin layer activation (TLA) technique for radioactive labeling of metallic components on depths ranging between 100 {mu}m and 300 {mu}m, for wear/corrosion studies. Aiming to extend these kinds of studies on non-metallic components and at sub-micrometric level we were led to the development of the recoil implantation technique for ultra thin layer activation (UTLA) applications. Due to the low energy of the recoils obtained in a sacrificial target from a nuclear reaction, the surface layer of material to be labeled must be as thick as a few hundredmore » nanometers. Also, since the radiotracer is externally created, there are no restrictions for the kind of material to be labeled, except to be a solid. In this paper we present some results of our studies concerning the actual status of this application at our accelerator.« less

Carbon-11 labelling of 8[[3-[4-(2-[(11)C]methoxyphenyl)piperazin-1-yl]-2-hydroxypropyl]oxy]thiochroman, a presynaptic 5-HT(1A) receptor agonist, and its in vivo evaluation in anaesthetised rat and in awake cat.

PubMed

Zimmer, Luc; Fournet, Guy; Benoît, Joseph; Guillaumet, Gérald; Le Bars, Didier

2003-07-01

A new compound, 8[[3-[4-(2-[(11)C]methoxyphenyl)piperazin-1-yl]-2-hydroxypropyl]oxy]thiochroman was labeled via O-methylation with [(11)C]methyl iodide in good yield and specific activity. Original biological evaluations included (i) the study in anesthetized rat with a beta-sensitive intracerebral probe (beta-Microprobe), allowing to measure locally the kinetic of the new PET ligand, and (ii) a PET-scan on a conditioned cat maintained awake during the acquisition. In both in vivo techniques, the new ligand did not reveal any specific binding in hippocampus indicating that this radiotracer is not suitable for mapping 5HT(1A) receptors using positron emission tomography.

Advances in Aβ plaque detection and the value of knowing: overcoming challenges to improving patient outcomes in Alzheimer's disease.

PubMed

Jovalekic, Aleksandar; Bullich, Santiago; Catafau, Ana; de Santi, Susan

2016-12-01

Clinical diagnosis of Alzheimer's disease (AD) can be challenging as numerous diseases mimic the characteristics of AD. In this light, recent guidelines developed by different associations and working groups point out the need for biomarkers to support AD diagnosis. This paper discusses 18F-labeled radiotracers (which are indicated for PET imaging of the brain) and ongoing clinical studies that aim to generate new evidence for the usage of amyloid imaging. In addition to their relatively long half-life, these agents are known for their high sensitivity and high negative predictive values for detection of neuritic Aβ plaques. Comparisons with other biomarkers are provided and implications of diagnostic disclosures discussed. Finally, recent data from clinical trials underscore the importance of amyloid PET for detecting, quantifying and monitoring Aβ plaque deposits.

Carbon-14 radiolabelling and tissue distribution evaluation of a potential anti-TB compound.

PubMed

Sonopo, Molahlehi S; Venter, Kobus; Winks, Susan; Marjanovic-Painter, Biljana; Morgans, Garreth L; Zeevaart, Jan R

2016-06-15

This paper describes a five-step synthesis of a carbon-14-labelled pyrazole compound (11). A total of 2.96 MBq of 11 was obtained with the specific activity of 2242.4 MBq/mmol. The radiochemical purity was >99%, and the overall radiochemical yield was 60% based on the [(14) C6 ] 4-bromoaniline starting material. Biodistribution results showed that the radiotracer (administrated orally) has a high accumulation in the small intestine, large intestine and liver of both non-infected and tuberculosis (TB)-infected mice. Therefore, this suggests that compound 11 undergoes hepatobiliary clearance. The compound under investigation has been found to be slowly released from the liver between 2 and 8 h. The study revealed that 11 has no affinity for TB cells. Copyright © 2016 John Wiley & Sons, Ltd.

Extension of activation cross section data of long lived products in deuteron induced nuclear reactions on platinum up to 50 MeV

NASA Astrophysics Data System (ADS)

Ditrói, F.; Tárkányi, F.; Takács, S.; Hermanne, A.

2017-06-01

In the frame of a systematical study of light ion induced nuclear reactions on platinum, activation cross sections for deuteron induced reactions were investigated. Excitation functions were measured in the 20.8-49.2 MeV energy range for the natPt(d,xn)191,192,193,194,195,196m2,196g,198g,199Au, natPt(d,x)188,189,191,195m,197m,197gPt and natPt(d,x)189,190,192,194m2Ir reactions by using the stacked foil irradiation technique. The experimental results are compared with previous results from the literature and with the theoretical predictions in the TENDL-2014 and TENDL-2015 libraries. The applicability of the produced radio-tracers for wear measurements has been presented.

Sensitivity improvement of Cerenkov luminescence endoscope with terbium doped Gd{sub 2}O{sub 2}S nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, Xin; Chen, Xueli, E-mail: xlchen@xidian.edu.cn, E-mail: jimleung@mail.xidian.edu.cn; Cao, Xu

2015-05-25

Our previous study showed a great attenuation for the Cerenkov luminescence endoscope (CLE), resulting in relatively low detection sensitivity of radiotracers. Here, a kind of radioluminescence nanoparticles (RLNPs), terbium doped Gd{sub 2}O{sub 2}S was mixed with the radionuclide {sup 68}Ga to enhance the intensity of emitted luminescence, which finally improved the detection sensitivity of the CLE by using the radioluminescence imaging technique. With the in vitro and in vivo pseudotumor experiments, we showed that the use of RLNPs mixed with the radionuclide {sup 68}Ga enabled superior sensitivity compared with the radionuclide {sup 68}Ga only, with 50-fold improvement on detection sensitivity,more » which guaranteed meeting the demands of the clinical diagnosis of gastrointestinal tract tumors.« less

Assimilation of trace elements ingested by the mussel Mytilus edulis: effects of algal food abundance

USGS Publications Warehouse

Wang, W.-X.; Fisher, N.S.; Luoma, S. N.

1995-01-01

Pulse-chase feeding and multi-labeled radiotracer techniques were employed to measure the assimilation of 6 trace elements (110mAg, 241Am, 109Cd, 57Co, 75Se and 65Zn) from ingested diatoms in the mussel Mytilus edulis feeding at different rates (0.1, 0.49 and 1.5 mg dry wt h-1). Uniformly radiolabeled diatoms Thalassiosira pseudonana were fed to mussels for 0.5 h, and the behavior of the radiotracers in individual mussels was followed for 96 h in a depuration seawater system. Assimilation efficiency (AE) of each element declined with increasing ingestion rate and increased with gut passage time. The importance of extracellular digestion relative to intracellular digestion increased with ingestion activity, which, when coupled with a decline in AE, suggested that extracellular digestion is less efficient in metal absorption. Zn assimilation was most affected by ingestion rate, suggesting that AE may play a role in the physiological regulation of this metal in M. edulis. In an experiment to simulate the effects of an acidic gut, lowered pH (5.5) enhanced the release of elements from intact diatom cells, especially at low particle concentration. These results indicate that both feeding components of the mussel (i.e. gut passage time, digestive partitioning) and metal chemistry (i.e. metal release at lowered pH within the bivalve gut) are responsible for the difference in the assimilation of trace metals at different food quantities observed in mussels.

[Disposal of radioactive contaminated waste from Ga-68-PET - calculation of a clearance level for Ge-68].

PubMed

Solle, Alexander; Wanke, Carsten; Geworski, Lilli

2017-03-01

Ga-68-labeled radiotracers, particularly used for the detection of neuroendocrine tumors by means of Ga-68-DOTA-TATE or -DOTA-TOC or for the diagnosis of prostate cancer by means of Ga-68-labeled antigens (Ga 68-PSMA), become increasingly important. In addition to the high sensitivity and specificity of these radiopharmaceuticals, the short-lived radionuclide Ga-68 offers almost ideal nuclear characteristics for use in PET. Ga-68 is obtained from a germanium-gallium-generator system, so that the availability of Ga-68-labeled radiotracers is independent of an on-site-cyclotron regardless of the short half-life of Ga-68 of about 68minutes. Regarding the disposal of the radioactively contaminated waste from the preparation of the radiopharmaceutical, the eluted Ga-68 has to be considered to be additionally contaminated with its parent nuclide Ge-68. Due to this production-related impurity in combination with the short half-life of Ga-68, the radioactive waste has to be considered to be contaminated with Ge-68 and Ga-68 in radioactive equilibrium (hereafter referred to as Ge-68+). As there are no clearance levels for Ge-68+ given in the German Radiation Protection Ordinance, this work presents a method to calculate the missing value basing on a recommendation of the German Radiation Protection Commission in combination with simple geometric models of practical radiation protection. Regarding the relevant exposure scenarios, a limit value for the unrestricted clearance of Ge-68+ of 0.4 Bq/g was determined. Copyright © 2016. Published by Elsevier GmbH.

Synthesis and preclinical evaluation of [(11)C]PAQ as a PET imaging tracer for VEGFR-2.

PubMed

Samén, Erik; Thorell, Jan-Olov; Lu, Li; Tegnebratt, Tetyana; Holmgren, Lars; Stone-Elander, Sharon

2009-08-01

(R,S)-N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-3-piperidinyl)methoxy)-4-quinazolinamine (PAQ) is a tyrosine kinase inhibitor with high affinity for the vascular endothelial growth factor receptor 2 (VEGFR-2), which plays an important role in tumour angiogenesis. The aim of this work was to develop and evaluate in mice the (11)C-labelled analogue as an in vivo tracer for VEGFR-2 expression in solid tumours. [(11)C]PAQ was synthesized by an N-methylation of desmethyl-PAQ using [(11)C]methyl iodide. The tracer's pharmacokinetic properties and its distribution in both subcutaneous and intraperitoneal tumour models were evaluated with positron emission tomography (PET). [(18)F]FDG was used as a reference tracer for tumour growth. PET results were corroborated by ex vivo and in vitro phosphor imaging and immunohistochemical analyses. In vitro assays and PET in healthy animals revealed low tracer metabolism, limited excretion over 60 min and a saturable and irreversible binding. Radiotracer uptake in subcutaneous tumour masses was low, while focal areas of high uptake (up to 8% ID/g) were observed in regions connecting the tumour to the host. Uptake was similarly high but more distributed in tumours growing within the peritoneum. The pattern of radiotracer uptake was generally different from that of the metabolic tracer [(18)F]FDG and correlated well with variations in VEGFR-2 expression determined ex vivo by immunohistochemical analysis. These results suggest that [(11)C]PAQ has potential as a noninvasive PET tracer for in vivo imaging of VEGFR-2 expression in angiogenic "hot spots".

Method for selective recovery of PET-usable quantities of [{sup 18}F] fluoride and [{sup 13}N] nitrate/nitrite from a single irradiation of low-enriched [{sup 18}O] water

DOEpatents

Ferrieri, R.A.; Schlyer, D.J.; Shea, C.

1995-06-13

A process for simultaneously producing PET-usable quantities of [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} for radiotracer synthesis is disclosed. The process includes producing [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}}and [{sup 18}F]F{sup {minus}} simultaneously by exposing a low-enriched (20%-30%) [{sup 18}O]H{sub 2}O target to proton irradiation, sequentially isolating the [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} and [{sup 18}F]F{sup {minus}} from the [{sup 18}O]H{sub 2}O target, and reducing the [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} to [{sup 13}N]NH{sub 3}. The [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} products are then conveyed to a laboratory for radiotracer applications. The process employs an anion exchange resin for isolation of the isotopes from the [{sup 18}O]H{sub 2}O, and sequential elution of [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} and [{sup 18}F]F{sup {minus}} fractions. Also the apparatus is disclosed for simultaneously producing PET-usable quantities of [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} from a single irradiation of a single low-enriched [{sup 18}O]H{sub 2}O target. 2 figs.

Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [(18)F]UCB-H: First-in-Human Study.

PubMed

Bretin, F; Bahri, M A; Bernard, C; Warnock, G; Aerts, J; Mestdagh, N; Buchanan, T; Otoul, C; Koestler, F; Mievis, F; Giacomelli, F; Degueldre, C; Hustinx, R; Luxen, A; Seret, A; Plenevaux, A; Salmon, E

2015-08-01

[(18)F]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [(18)F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1-156.5 MBq) of [(18)F]UCB-H. Major organs were delineated on CT images, and time-activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 × 10(-2) ± 6.84 × 10(-4) millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer's main organ of interest, received an absorbed dose of 1.89 × 10(-2) ± 2.32 × 10(-3) mGy/MBq. This first human dosimetry study of [(18)F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.

Design and utilisation of protocols to characterise dynamic PET uptake of two tracers using basis pursuit.

PubMed

Bell, Christopher; Puttick, Simon; Rose, Stephen; Smith, Jye; Thomas, Paul; Dowson, Nicholas

2017-06-21

Imaging using more than one biological process using PET could be of great utility, but despite previously proposed approaches to dual-tracer imaging, it is seldom performed. The alternative of performing multiple scans is often infeasible for clinical practice or even in research studies. Dual-tracer PET scanning allows for multiple PET radiotracers to be imaged within the same imaging session. In this paper we describe our approach to utilise the basis pursuit method to aid in the design of dual-tracer PET imaging experiments, and later in separation of the signals. The advantage of this approach is that it does not require a compartment model architecture to be specified or even that both signals are distinguishable in all cases. This means the method for separating dual-tracer signals can be used for many feasible and useful combinations of biology or radiotracer, once an appropriate scanning protocol has been decided upon. Following a demonstration in separating the signals from two consecutively injected radionuclides in a controlled experiment, phantom and list-mode mouse experiments demonstrated the ability to test the feasibility of dual-tracer imaging protocols for multiple injection delays. Increases in variances predicted for kinetic macro-parameters V D and K I in brain and tumoral tissue were obtained when separating the synthetically combined data. These experiments confirmed previous work using other approaches that injections delays of 10-20 min ensured increases in variance were kept minimal for the test tracers used. On this basis, an actual dual-tracer experiment using a 20 min delay was performed using these radio tracers, with the kinetic parameters (V D and K I ) extracted for each tracer in agreement with the literature. This study supports previous work that dual-tracer PET imaging can be accomplished provided certain constraints are adhered to. The utilisation of basis pursuit techniques, with its removed need to specify a model architecture, allows the feasibility of a range of imaging protocols to be investigated via simulation in a straight-forward manner for a wide range of possible scenarios. The hope is that the ease of utilising this approach during feasibility studies and in practice removes any perceived technical barrier to performing dual-tracer imaging.

Time Evolution of DOTATOC Uptake in Neuroendocrine Tumors in View of a Possible Application of Radioguided Surgery with β- Decay.

PubMed

Collamati, Francesco; Bellini, Fabio; Bocci, Valerio; De Lucia, Erika; Ferri, Valentina; Fioroni, Federica; Grassi, Elisa; Iori, Mauro; Marafini, Michela; Morganti, Silvio; Paramatti, Riccardo; Patera, Vincenzo; Recchia, Luigi; Russomando, Andrea; Sarti, Alessio; Sciubba, Adalberto; Senzacqua, Martina; Solfaroli Camillocci, Elena; Versari, Annibale; Voena, Cecilia; Faccini, Riccardo

2015-10-01

A novel radioguided surgery (RGS) technique exploiting β- radiation has been proposed. To develop such a technique, a suitable radiotracer able to deliver a β- emitter to the tumor has to be identified. A first candidate is represented by 90Y-labeled DOTATOC, a compound commonly used today for peptide radioreceptor therapy. The application of this β- RGS to neuroendocrine tumors (NET) requires study of the uptake of DOTATOC and its time evolution both in tumors and in healthy organs and evaluation of the corresponding performance of the technique. Uptake by lesions and healthy organs (kidneys, spleen, liver and healthy muscle) was estimated on 177Lu-DOTATOC SPECT/CT scans of 15 patients affected by NET with different localizations, treated at IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. For each patient, SPECT/CT images, acquired at 0.5, 4, 20, 40, and 70 h after injection, were studied. For each lesion, the tumor-to-nontumor ratio (TNR) with respect to all healthy organs and its time evolution were studied. A subset of patients showing hepatic lesions was selected, and the TNR with respect to the nearby healthy tissue was calculated. By means of a Monte Carlo simulation of the probe for β- RGS, the activity that is to be administered for a successful detection was estimated lesion-by-lesion. Uptake of DOTATOC on NETs maximized at about 24 h after injection. The cases of hepatic lesions showed a TNR with respect to the tumor margins compatible with the application of β- RGS. In particular, 0.1-mL residuals are expected to be detectable within 1 s with 5% false-negative and 1% false-positive by administering the patient as little as 1 MBq/kg. The balance between tumor uptake and metabolic washout in healthy tissue causes the TNR to increase with time, reaching its maximum after 24 h, and this characteristic can be exploited when a radiotracer with a long half-life, such as 90Y, is used. In particular, if 90Y-DOTATOC is used with liver NET metastases, the proposed RGS technique is believed to be feasible by injecting an activity that is one third of that commonly used for PET imaging. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Design and utilisation of protocols to characterise dynamic PET uptake of two tracers using basis pursuit

NASA Astrophysics Data System (ADS)

Bell, Christopher; Puttick, Simon; Rose, Stephen; Smith, Jye; Thomas, Paul; Dowson, Nicholas

2017-06-01

Imaging using more than one biological process using PET could be of great utility, but despite previously proposed approaches to dual-tracer imaging, it is seldom performed. The alternative of performing multiple scans is often infeasible for clinical practice or even in research studies. Dual-tracer PET scanning allows for multiple PET radiotracers to be imaged within the same imaging session. In this paper we describe our approach to utilise the basis pursuit method to aid in the design of dual-tracer PET imaging experiments, and later in separation of the signals. The advantage of this approach is that it does not require a compartment model architecture to be specified or even that both signals are distinguishable in all cases. This means the method for separating dual-tracer signals can be used for many feasible and useful combinations of biology or radiotracer, once an appropriate scanning protocol has been decided upon. Following a demonstration in separating the signals from two consecutively injected radionuclides in a controlled experiment, phantom and list-mode mouse experiments demonstrated the ability to test the feasibility of dual-tracer imaging protocols for multiple injection delays. Increases in variances predicted for kinetic macro-parameters V D and K I in brain and tumoral tissue were obtained when separating the synthetically combined data. These experiments confirmed previous work using other approaches that injections delays of 10-20 min ensured increases in variance were kept minimal for the test tracers used. On this basis, an actual dual-tracer experiment using a 20 min delay was performed using these radio tracers, with the kinetic parameters (V D and K I) extracted for each tracer in agreement with the literature. This study supports previous work that dual-tracer PET imaging can be accomplished provided certain constraints are adhered to. The utilisation of basis pursuit techniques, with its removed need to specify a model architecture, allows the feasibility of a range of imaging protocols to be investigated via simulation in a straight-forward manner for a wide range of possible scenarios. The hope is that the ease of utilising this approach during feasibility studies and in practice removes any perceived technical barrier to performing dual-tracer imaging.

Improving PET Quantification of Small Animal [68Ga]DOTA-Labeled PET/CT Studies by Using a CT-Based Positron Range Correction.

PubMed

Cal-Gonzalez, Jacobo; Vaquero, Juan José; Herraiz, Joaquín L; Pérez-Liva, Mailyn; Soto-Montenegro, María Luisa; Peña-Zalbidea, Santiago; Desco, Manuel; Udías, José Manuel

2018-01-19

Image quality of positron emission tomography (PET) tracers that emits high-energy positrons, such as Ga-68, Rb-82, or I-124, is significantly affected by positron range (PR) effects. PR effects are especially important in small animal PET studies, since they can limit spatial resolution and quantitative accuracy of the images. Since generators accessibility has made Ga-68 tracers wide available, the aim of this study is to show how the quantitative results of [ 68 Ga]DOTA-labeled PET/X-ray computed tomography (CT) imaging of neuroendocrine tumors in mice can be improved using positron range correction (PRC). Eighteen scans in 12 mice were evaluated, with three different models of tumors: PC12, AR42J, and meningiomas. In addition, three different [ 68 Ga]DOTA-labeled radiotracers were used to evaluate the PRC with different tracer distributions: [ 68 Ga]DOTANOC, [ 68 Ga]DOTATOC, and [ 68 Ga]DOTATATE. Two PRC methods were evaluated: a tissue-dependent (TD-PRC) and a tissue-dependent spatially-variant correction (TDSV-PRC). Taking a region in the liver as reference, the tissue-to-liver ratio values for tumor tissue (TLR tumor ), lung (TLR lung ), and necrotic areas within the tumors (TLR necrotic ) and their respective relative variations (ΔTLR) were evaluated. All TLR values in the PRC images were significantly different (p < 0.05) than the ones from non-PRC images. The relative differences of the tumor TLR values, respect to the case with no PRC, were ΔTLR tumor 87 ± 41 % (TD-PRC) and 85 ± 46 % (TDSV-PRC). TLR lung decreased when applying PRC, being this effect more remarkable for the TDSV-PRC method, with relative differences respect to no PRC: ΔTLR lung  = - 45 ± 24 (TD-PRC), - 55 ± 18 (TDSV-PRC). TLR necrotic values also decreased when using PRC, with more noticeable differences for TD-PRC: ΔTLR necrotic  = - 52 ± 6 (TD-PRC), - 48 ± 8 (TDSV-PRC). The PRC methods proposed provide a significant quantitative improvement in [ 68 Ga]DOTA-labeled PET/CT imaging of mice with neuroendocrine tumors, hence demonstrating that these techniques could also ameliorate the deleterious effect of the positron range in clinical PET imaging.

Copper-Mediated Radiofluorination of Arylstannanes with [18F]KF

PubMed Central

2016-01-01

A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [18F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [18F]F-phenylalanine and [18F]F-DOPA. In addition, an automated synthesis of [18F]MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol. PMID:27718581

Coexistent Superscan and Lincoln Sign on Bone Scintigraphy.

PubMed

Kulkarni, Mukta; Soni, Atul; Shetkar, Shubhangi; Amer, Momin; Mulavekar, Amruta; Joshi, Prathamesh

2017-08-01

A 70-year-old man underwent Tc-methylene diphosphonate scintigraphy for staging of adenocarcinoma prostate. Scintigraphy revealed diffuse increased tracer uptake in skeletal system along with faint renal visualization, a pattern compatible with metastatic superscan. The scintigraphy also revealed increased radiotracer uptake in the body of the mandible-Lincoln sign or black beard sign. Radiological imaging revealed sclerotic lesions throughout the skeleton including the mandible, confirming widespread skeletal metastases. Lincoln sign is previously described in monostotic Paget disease of the mandible and in contiguous spread of oral malignancy. We describe this pattern in distant metastatic involvement from carcinoma prostate with coexistent superscan pattern.

Metastatic Neuroblastoma in Adult Patient, Presenting as a Super Scan on 68Ga-DOTANOC PET/CT Imaging.

PubMed

Malik, Dharmender; Jois, Abhiram; Singh, Harmandeep; Bora, Girdhar S; Basher, Rajender Kumar; Mittal, Bhagwant Rai

2017-09-01

We report a case of 23-year-old man who presented with complaints of progressive abdominal distension for the past 3 months along with the loss of appetite and weight and had a large solid cystic mass in the left half of the abdominal cavity revealed on ultrasonography and contrast-enhanced CT of the abdomen. Subsequent biopsy and histopathology revealed it to be neuroblastoma. Ga-DOTANOC PET/CT scan performed to rule out distant metastasis showed intense radiotracer uptake distributed throughout the skeleton, mimicking a super scan.

Molecular Imaging and Precision Medicine in Prostate Cancer.

PubMed

Ceci, Francesco; Fiorentino, Michelangelo; Castellucci, Paolo; Fanti, Stefano

2017-01-01

The aim of the present review is to discuss about the role of new probes for molecular imaging in the evaluation of prostate cancer (PCa). This review focuses particularly on the role of new promising radiotracers for the molecular imaging with PET/computed tomography in the detection of PCa recurrence. The role of these new imaging techniques to guide lesion-target therapies and the potential application of these molecular probes as theranostics agents is discussed. Finally, the molecular mechanisms underlying resistance to castration in PCa and the maintenance of active androgen receptor are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Diverse bone scan abnormalitites in "shin splints".

PubMed

Spencer, R P; Levinson, E D; Baldwin, R D; Sziklas, J J; Witek, J T; Rosenberg, R

1979-12-01

Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of the foot.

Asymptomatic solitary cerebral metastasis from papillary carcinoma thyroid: 131I SPECT/CT for accurate staging.

PubMed

Jain, Tarun Kumar; Karunanithi, Sellam; Sharma, Punit; Vijay, Maneesh Kumar; Ballal, Sanjana; Bal, Chandrasekhar

2014-11-01

Isolated asymptomatic brain metastasis in papillary carcinoma thyroid (PCT) is extremely rare. We here present such a case of a 48-year-old woman with PCT. SPECT/CT localized the 131I radiotracer concentration seen on whole-body scan in this patient to the right posterior parietal cortex, suggesting brain metastasis. Contrast-enhanced MRI and 18F-FDG PET/CT confirmed the diagnosis and the patient was taken for gamma-knife radiosurgery. 131I SPECT/CT in this case accurately restaged the patient by detecting asymptomatic isolated brain metastasis and correctly directed the management strategy.

Being Relevant in Tough Times: TRIUMF's Five-Year Plan

ScienceCinema

Tim, Mayer [TRIUMF

2017-12-09

Perhaps better known to the international community than its own neighbors, TRIUMF is Canada's national laboratory for particle and nuclear physics.  Working with the Canadian scientific community, TRIUMF has formulated a new vision to transform the laboratory and deliver a whole new level of performance and impact.  The plan capitalizes on platform technologies (superconducting RF cavities for accelerator physics and radiotracers in nuclear medicine) and exploits Canada's role in ATLAS and the LHC.  I will describe the key elements of the plan and discuss the science-policy landscape in which TRIUMF must make its case.

Copper-Mediated Radiofluorination of Arylstannanes with [ 18F]KF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makaravage, Katarina J.; Brooks, Allen F.; Mossine, Andrew V.

In this article, a copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [ 18F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [ 18F]F-phenylalanine and [ 18F]F-DOPA. In addition, an automated synthesis of [ 18F]MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol.

Copper-Mediated Radiofluorination of Arylstannanes with [ 18F]KF

DOE PAGES

Makaravage, Katarina J.; Brooks, Allen F.; Mossine, Andrew V.; ...

2016-10-10

In this article, a copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [ 18F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [ 18F]F-phenylalanine and [ 18F]F-DOPA. In addition, an automated synthesis of [ 18F]MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol.

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

PubMed Central

Schuster, Sabine; Biri-Kovács, Beáta; Szeder, Bálint; Farkas, Viktor; Buday, László; Szabó, Zsuzsanna; Halmos, Gábor

2018-01-01

Gonadotropin releasing hormone-III (GnRH-III), a native isoform of the human GnRH isolated from sea lamprey, specifically binds to GnRH receptors on cancer cells enabling its application as targeting moieties for anticancer drugs. Recently, we reported on the identification of a novel daunorubicin–GnRH-III conjugate (GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] with efficient in vitro and in vivo antitumor activity. To get a deeper insight into the mechanism of action of our lead compound, the cellular uptake was followed by confocal laser scanning microscopy. Hereby, the drug daunorubicin could be visualized in different subcellular compartments by following the localization of the drug in a time-dependent manner. Colocalization studies were carried out to prove the presence of the drug in lysosomes (early stage) and on its site of action (nuclei after 10 min). Additional flow cytometry studies demonstrated that the cellular uptake of the bioconjugate was inhibited in the presence of the competitive ligand triptorelin indicating a receptor-mediated pathway. For comparative purpose, six novel daunorubicin–GnRH-III bioconjugates have been synthesized and biochemically characterized in which 6Asp was replaced by D-Asp, D-Glu and D-Trp. In addition to the analysis of the in vitro cytostatic effect and cellular uptake, receptor binding studies with 125I-triptorelin as radiotracer and degradation of the GnRH-III conjugates in the presence of rat liver lysosomal homogenate have been performed. All derivatives showed high binding affinities to GnRH receptors and displayed in vitro cytostatic effects on HT-29 and MCF-7 cancer cells with IC50 values in a low micromolar range. Moreover, we found that the release of the active drug metabolite and the cellular uptake of the bioconjugates were strongly affected by the amino acid exchange which in turn had an impact on the antitumor activity of the bioconjugates. PMID:29719573

Bioavailability and toxicity of trace metals to the cladoceran Daphnia magna in relation to cadmium exposure history

NASA Astrophysics Data System (ADS)

Guan, Rui

The cladoceran Daphnia magna is widely used in freshwater bioassessments and ecological risk assessments. This study designed a series of experiments employing radiotracer methodology to quantify the trace metals (mainly Cd and Zn) biokinetics in D. magna under different environmental and biological conditions and to investigate the influences of different Cd exposure histories on the bioavailability and toxicity of trace metals to D. magna. A bioenergetic-based kinetic model was finally applied in predicting the Cd accumulation dynamics in D. magna and the model validity under non-steady state was assessed. Cd assimilation was found in this study to be influenced by the food characteristics (e.g., metal concentration in food particles), the metal exposure history of the animals, and the genetic characteristics. Some of these influences could be interpreted by the capacity and/or competition of those metal binding sites within the digestive tract and/or the detoxifying proteins metallothionein (MT). My study demonstrated a significant induction of MT in response to Cd exposure and it was the dominant fraction in sequestering the internal nonessential trace metals in D. magna. The ratio of Cd body burden to MT might better predict the Cd toxicity on the digestion systems of D. magna than the Cd tissue burden alone within one-generational exposure to Cd. It was found that metal elimination (rate constant and contribution of different release routes) was independent of the food concentration and the dietary metal concentration, implying that the elimination may not be metabolically controlled. The incorporation of the bioenergetic-based kinetic model, especially under non-steady state, is invaluable in helping to understand the fate of trace metals in aquatic systems and potential environmental risks. The dependence of biokinetic parameters on environmental factors rather than on genotypes implies a great potential of using biokinetics in inter-laboratory comparisons.

Effects of Substitutions on the Biodegradation Potential of Benzotriazole Derivatives

NASA Astrophysics Data System (ADS)

Abu-Dalo, M. A.; O'Brien, I.; Hernandez, M. T.

2018-02-01

Fourteen benzotriazole derivatives were subjected to microcosm tests to study the influence of substitutions on their biodegradation potential. Methylated, nitrated, carboxylated, and propionated bezotriazoles, a heterocyclic triazole, as well as methylated benzimidazoles, were introduced to activated sludge and soil enrichment cultures as the only carbon source. Some of the enrichment cultures were derived from airport soils that had been previously contaminated with aircraft deicing fluids and subsequently enriched with the commercially significant corrosion inhibitor methylbenzotriazole. The 5-methylbenzotriazole and only the carboxylated derivatives were degraded by soil or activated sludge biomass regardless of acclimation conditions. Radiotracer studies of [U-14C] 5-methylbenzotriazole, and [U-14C] 5-carboxybenzotriazole confirmed that relatively high concentrations (25mg L-1) of these derivatives can be completely mineralized in relatively short time frames by microbial consortia regardless of prior exposure. Observations suggested that the growth yield on these compounds is likely low. Biodegradation patterns suggested that carboxylated benzotriazole derivatives are more readily biodegradable than their more popular methylated counterparts.

Progress toward automatic classification of human brown adipose tissue using biomedical imaging

NASA Astrophysics Data System (ADS)

Gifford, Aliya; Towse, Theodore F.; Walker, Ronald C.; Avison, Malcom J.; Welch, E. B.

2015-03-01

Brown adipose tissue (BAT) is a small but significant tissue, which may play an important role in obesity and the pathogenesis of metabolic syndrome. Interest in studying BAT in adult humans is increasing, but in order to quantify BAT volume in a single measurement or to detect changes in BAT over the time course of a longitudinal experiment, BAT needs to first be reliably differentiated from surrounding tissue. Although the uptake of the radiotracer 18F-Fluorodeoxyglucose (18F-FDG) in adipose tissue on positron emission tomography (PET) scans following cold exposure is accepted as an indication of BAT, it is not a definitive indicator, and to date there exists no standardized method for segmenting BAT. Consequently, there is a strong need for robust automatic classification of BAT based on properties measured with biomedical imaging. In this study we begin the process of developing an automated segmentation method based on properties obtained from fat-water MRI and PET-CT scans acquired on ten healthy adult subjects.

Nuclear medicine and quantitative imaging research (quantitative studies in radiopharmaceutical science): Comprehensive progress report, April 1, 1986-December 31, 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooper, M.D.; Beck, R.N.

1988-06-01

This document describes several years research to improve PET imaging and diagnostic techniques in man. This program addresses the problems involving the basic science and technology underlying the physical and conceptual tools of radioactive tracer methodology as they relate to the measurement of structural and functional parameters of physiologic importance in health and disease. The principal tool is quantitative radionuclide imaging. The overall objective of this program is to further the development and transfer of radiotracer methodology from basic theory to routine clinical practice in order that individual patients and society as a whole will receive the maximum net benefitmore » from the new knowledge gained. The focus of the research is on the development of new instruments and radiopharmaceuticals, and the evaluation of these through the phase of clinical feasibility. The reports in the study were processed separately for the data bases. (TEM)« less

Synthesis of 99mTc-nimotuzumab with tricarbonyl ion: in vitro and in vivo studies.

PubMed

Garcia, Maria Fernanda; Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Porcal, Williams; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2012-01-01

The Epidermal growth factor receptor (EGFR) family plays an important role in carcinogenesis. CIMAher® (Nimotuzumab), is a humanized monoclonal antibody, which recognizes EGFR with high affinity. The aim of this work was to perform the direct labeling of Nimotuzumab with [99mTc(CO)3(H2O)3]+ as precursor and to evaluate its labeling conditions, in vitro and in vivo stability and biodistrution in normal C57 BL/6J mice. 99mTc(CO3)-Nimotuzumab labeling yields were up to 90%. More than 90% of the complex remained intact after 24 h of incubation with L-Histidine (1/300 molar ratio). Biodistribution studies in normal mice were also performed. Inmunoreactivity was confirmed by cell binding assays with A431cells. These results encourage the evaluation of the potential role of 99mTc(CO)3-Nimotuzumab as a novel tumor-avid radiotracer for targeting in vivo EGFR expression.

Microfluidic 68Ga-labeling: a proof of principle study.

PubMed

Pfaff, Sarah; Philippe, Cecile; Pichler, Verena; Hacker, Marcus; Mitterhauser, Markus; Wadsak, Wolfgang

2018-05-01

Positron emission tomography (PET) as a tool for molecular imaging of cancer has gained huge interest in the last few years. Gallium-68 is a popular PET nuclide due to its favorable characteristics, like advantageous half-life (68 min) and independency of a cyclotron on-site for its production. Accordingly, several 68Ga-complexes for cancer imaging via PET have been made available during the last few years. In this work, 68Ga-labeled compounds were synthesized applying a commercially available microfluidic device for the first time. Therefore, a proof of principle study using three important radiotracers, [68Ga]Ga-PSMA-11, [68Ga]Ga-NODAGA-RGDyk and [68Ga]Ga-DOTA-NOC, was designed. For all three radioligands, various synthesis parameters were evaluated and the feasibility of using a continuous flow reactor was assessed. All of the precursors were successfully radiolabeled with a radiochemical yield higher than 80%, proving the principle that a microfluidic set-up is a suitable approach for the production of 68Ga-labeled tracers.

Infrared thermography, a new method for detection of brown adipose tissue activity after a meal in humans

NASA Astrophysics Data System (ADS)

Habek, Nikola; Kordić, Milan; Jurenec, Franjo; Dugandžić, Aleksandra

2018-03-01

The activation of brown adipose tissue (BAT) after cold exposure leads to heat production. However, the activation of BAT activity after a meal as part of diet induced thermogenesis is still controversial. A possible reason is that measuring BAT activity by positron emission tomography-computed tomography (PET CT) via accumulation of radiotracer fludeoxyglucose (18F-FDG), which competes with an increase in glucose concentration after a meal, fails as the method of choice. In this study, activity of BAT was determined by infrared thermography. Activation of BAT 30 min after a meal increases glucose consumption, decreases plasma glucose concentration, and leads to changes of body temperature (diet-induced thermogenesis). Detecting pathophysiological changes in BAT activity after a meal by infrared thermography, a non-invasive more sensitive method, will be of great importance for people with increased body weight and diabetes mellitus type 2.

Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems.

PubMed

Vaquero, Juan José; Kinahan, Paul

2015-01-01

Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges.

Biodegradation of p-nitrophenol via 1,2,4-benzenetriol by an Arthrobacter sp.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, R.K.; Spain, J.C.; Dreisbach, J.H.

1994-08-01

The degradation of p-nitrophenol (PNP) by Moraxella and Pseudomonas spp. involves an initial monooxygenase-catalyzed removal of the nitro group. The resultant hydroquinone is subject to ring fission catalyzed by a dioxygenase enzyme. A strain of an Arthrobacter sp. JS443, capable of degrading PNP with stoichiometric release of nitrite has been isolated. During induction of the enzymes required for growth on PNP, 1,2,4-benzenetriol was identified as an intermediate by gas chromatography-mass spectroscopy and radiotracer studies. 1,2,4-Benzenetriol was converted to maleylacetic acid, which was further degraded by the beta-ketoadipate pathway. Conversion of PNP to 1,2,4-benzenetriol is catalyzed by a monooxygenase system inmore » strain JS443 through the formation of 4-nitrocatechol, 4-nitroresorcinol, or both. Results clearly indicate the existence of an alternative pathway for the biodegradation of PNP. 15 refs, 2 figs., 2 tabs.« less

Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems

PubMed Central

Vaquero, Juan José; Kinahan, Paul

2017-01-01

Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges. PMID:26643024

Diffusion processes in tumors: A nuclear medicine approach

NASA Astrophysics Data System (ADS)

Amaya, Helman

2016-07-01

The number of counts used in nuclear medicine imaging techniques, only provides physical information about the desintegration of the nucleus present in the the radiotracer molecules that were uptaken in a particular anatomical region, but that information is not a real metabolic information. For this reason a mathematical method was used to find a correlation between number of counts and 18F-FDG mass concentration. This correlation allows a better interpretation of the results obtained in the study of diffusive processes in an agar phantom, and based on it, an image from the PETCETIX DICOM sample image set from OsiriX-viewer software was processed. PET-CT gradient magnitude and Laplacian images could show direct information on diffusive processes for radiopharmaceuticals that enter into the cells by simple diffusion. In the case of the radiopharmaceutical 18F-FDG is necessary to include pharmacokinetic models, to make a correct interpretation of the gradient magnitude and Laplacian of counts images.

Elucidating the biosynthesis of 2-carboxyarabinitol 1-phosphate through reduced expression of chloroplastic fructose 1,6-bisphosphate phosphatase and radiotracer studies with 14CO2

PubMed Central

Andralojc, P. John; Keys, Alfred J.; Kossmann, Jens; Parry, Martin A. J.

2002-01-01

2-Carboxyarabinitol 1-phosphate limits photosynthetic CO2 assimilation at low light because it is a potent, naturally occurring inhibitor of ribulose 1,5-bisphosphate carboxylase/oxygenase. Evidence is presented that this inhibitor is derived from chloroplastic fructose 1,6-bisphosphate. First, transgenic plants containing decreased amounts of chloroplastic fructose 1,6-bisphosphate phosphatase contained increased amounts of fructose 1,6-bisphosphate and 2-carboxyarabinitol 1-phosphate and greatly increased amounts of the putative intermediates hamamelose and 2-carboxyarabinitol, which in some cases were as abundant as sucrose. Second, French bean leaves in the light were shown to incorporate 14C from 14CO2 sequentially into fructose 1,6-bisphosphate, hamamelose bisphosphate, hamamelose monophosphate, hamamelose, and 2-carboxyarabinitol. As shown previously, 14C assimilated by photosynthesis was also incorporated into 2-carboxyarabinitol 1-phosphate during subsequent darkness. PMID:11917127

Image reconstruction for PET/CT scanners: past achievements and future challenges

PubMed Central

Tong, Shan; Alessio, Adam M; Kinahan, Paul E

2011-01-01

PET is a medical imaging modality with proven clinical value for disease diagnosis and treatment monitoring. The integration of PET and CT on modern scanners provides a synergy of the two imaging modalities. Through different mathematical algorithms, PET data can be reconstructed into the spatial distribution of the injected radiotracer. With dynamic imaging, kinetic parameters of specific biological processes can also be determined. Numerous efforts have been devoted to the development of PET image reconstruction methods over the last four decades, encompassing analytic and iterative reconstruction methods. This article provides an overview of the commonly used methods. Current challenges in PET image reconstruction include more accurate quantitation, TOF imaging, system modeling, motion correction and dynamic reconstruction. Advances in these aspects could enhance the use of PET/CT imaging in patient care and in clinical research studies of pathophysiology and therapeutic interventions. PMID:21339831

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisenberger, Andrew G.; Kross, Brian J.; Lee, Seung Joo

The ability to detect the emissions of radioactive isotopes through radioactive decay (e.g. beta particles, x-rays and gamma-rays) has been used for over 80 years as a tracer method for studying natural phenomena. More recently a positron emitting radioisotope of carbon: {sup 11}C has been utilized as a {sup 11}CO{sub 2} tracer for plant ecophysiology research. Because of its ease of incorporation into the plant via photosynthesis, the {sup 11}CO{sub 2} radiotracer is a powerful tool for use in plant biology research. Positron emission tomography (PET) imaging has been used to study carbon transport in live plants using {sup 11}CO{submore » 2}. Presently there are several groups developing and using new PET instrumentation for plant based studies. Thomas Jefferson National Accelerator Facility (Jefferson Lab) in collaboration with the Duke University Phytotron and the Triangle Universities Nuclear Laboratory (TUNL) is involved in PET detector development for plant imaging utilizing technologies developed for nuclear physics research. The latest developments of the use of a LYSO scintillator based PET detector system for {sup 11}CO{sub 2} tracer studies in plants will be briefly outlined.« less

Sorption of thallium(I) onto geological materials: influence of pH and humic matter.

PubMed

Liu, Juan; Lippold, Holger; Wang, Jin; Lippmann-Pipke, Johanna; Chen, Yongheng

2011-02-01

The sorption behaviour of the severely toxic heavy metal thallium (Tl) as a monovalent cation onto three representative materials (goethite, pyrolusite and a natural sediment sampled from a field site) was examined as a function of pH in the absence and presence of two natural humic acids (HAs), using 204Tl(I) as a radiotracer. In order to obtain a basic understanding of trends in the pH dependence of Tl(I) sorption with and without HA, sorption of HAs and humate complexation of Tl(I) as a function of pH were investigated as well. In spite of the low complexation between Tl(I) and HAs, the presence of HAs results in obvious alterations of Tl(I) sorption onto pyrolusite and sediment. An influence on Tl(I) sorption onto goethite was not observed. Predictions of Kd (distribution coefficient) for Tl(I) on goethite in the presence of HAs, based on a linear additive model, agree well with the experimental data, while a notable disagreement occurs for the pyrolusite and sediment systems. Accordingly, it is suggested that HAs and goethite may act as a non-interacting sorbent mixture under the given conditions, but more complex interactions may take place between the HAs and the mineral phases of pyrolusite or sediment. Copyright © 2010 Elsevier Ltd. All rights reserved.

Sulfate transport kinetics and toxicity are modulated by sodium in aquatic insects.

PubMed

Scheibener, Shane; Conley, Justin M; Buchwalter, David

2017-09-01

The salinization of freshwater ecosystems is emerging as a major ecological issue. Several anthropogenic causes of salinization (e.g. surface coal mining, hydro-fracking, road de-icing, irrigation of arid lands, etc.) are associated with biodiversity losses in freshwater ecosystems. Because insects tend to dominate freshwater ecology, it is important that we develop a better understanding of how and why different species respond to salinity matrices dominated by different major ions. This study builds upon previous work demonstrating that major ion toxicity to the mayfly Neocloeon triangulifer was apparently due to the ionic composition of water rather than specific conductance. Synthetic waters with low Ca:Mg ratios and high SO 4 :Na ratios produced toxicity, whereas waters with higher Ca:Mg ratios and lower SO 4 :Na ratios were not toxic to mayflies at comparable conductivities. Here we used a radiotracer approach to show that Mg did not competitively exclude Ca uptake at environmentally realistic ratios in 4 aquatic insect species. We characterized SO 4 uptake kinetics in 5 mayflies and assessed the influence of different ions on SO 4 uptake. Dual label experiments show an inverse relationship between SO 4 and Na transport rates as SO 4 was held constant and Na was increased, suggesting that Na (and not Cl or HCO 3 ) is antagonistic to SO 4 transport. Based on this observation, we tested the hypothesis that increasing Na would protect against SO 4 induced toxicity in a Na-dependent manner. Increasing Na from 0.7 to 10.9mM improved 96-h survivorship associated with 20.8mM SO 4 from 44% to 73% in a concentration dependent manner. However, when Na reached 21.8mM, survivorship decreased to 16%, suggesting that other interactive effects of major ions caused toxicity under those conditions. Thus, the combination of elevated sulfate and low sodium commonly observed in streams affected by mountaintop coal mining has the potential to cause toxicity in sensitive aquatic insects. Overall, it is important that we develop a better understanding of major ion toxicity to effectively mitigate and protect freshwater biodiversity from salinization. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluorine-labeled Dasatinib Nanoformulations as Targeted Molecular Imaging Probes in a PDGFB-driven Murine Glioblastoma Model12

PubMed Central

Benezra, Miriam; Hambardzumyan, Dolores; Penate-Medina, Oula; Veach, Darren R; Pillarsetty, Nagavarakishore; Smith-Jones, Peter; Phillips, Evan; Ozawa, Tatsuya; Zanzonico, Pat B; Longo, Valerie; Holland, Eric C; Larson, Steven M; Bradbury, Michelle S

2012-01-01

Dasatinib, a new-generation Src and platelet-derived growth factor receptor (PDGFR) inhibitor, is currently under evaluation in high-grade glioma clinical trials. To achieve optimum physicochemical and/or biologic properties, alternative drug delivery vehicles may be needed. We used a novel fluorinated dasatinib derivative (F-SKI249380), in combination with nanocarrier vehicles and metabolic imaging tools (microPET) to evaluate drug delivery and uptake in a platelet-derived growth factor B (PDGFB)-driven genetically engineered mouse model (GEMM) of high-grade glioma. We assessed dasatinib survival benefit on the basis of measured tumor volumes. Using brain tumor cells derived from PDGFB-driven gliomas, dose-dependent uptake and time-dependent inhibitory effects of F-SKI249380 on biologic activity were investigated and compared with the parent drug. PDGFR receptor status and tumor-specific targeting were non-invasively evaluated in vivo using 18F-SKI249380 and 18F-SKI249380-containing micellar and liposomal nanoformulations. A statistically significant survival benefit was found using dasatinib (95 mg/kg) versus saline vehicle (P < .001) in tumor volume-matched GEMM pairs. Competitive binding and treatment assays revealed comparable biologic properties for F-SKI249380 and the parent drug. In vivo, Significantly higher tumor uptake was observed for 18F-SKI249380-containing micelle formulations [4.9 percentage of the injected dose per gram tissue (%ID/g); P = .002] compared to control values (1.6%ID/g). Saturation studies using excess cold dasatinib showed marked reduction of tumor uptake values to levels in normal brain (1.5%ID/g), consistent with in vivo binding specificity. Using 18F-SKI249380-containing micelles as radiotracers to estimate therapeutic dosing requirements, we calculated intratumoral drug concentrations (24–60 nM) that were comparable to in vitro 50% inhibitory concentration values. 18F-SKI249380 is a PDGFR-selective tracer, which demonstrates improved delivery to PDGFB-driven high-grade gliomas and facilitates treatment planning when coupled with nanoformulations and quantitative PET imaging approaches. PMID:23308046

Interstitial diffusion and the relationship between compartment modelling and multi-scale spatial-temporal modelling of (18)F-FLT tumour uptake dynamics.

PubMed

Liu, Dan; Chalkidou, Anastasia; Landau, David B; Marsden, Paul K; Fenwick, John D

2014-09-07

Tumour cell proliferation can be imaged via positron emission tomography of the radiotracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT). Conceptually, the number of proliferating cells might be expected to correlate more closely with the kinetics of 18F-FLT uptake than with uptake at a fixed time. Radiotracer uptake kinetics are standardly visualized using parametric maps of compartment model fits to time-activity-curves (TACs) of individual voxels. However the relationship between the underlying spatiotemporal accumulation of FLT and the kinetics described by compartment models has not yet been explored. In this work tumour tracer uptake is simulated using a mechanistic spatial-temporal model based on a convection-diffusion-reaction equation solved via the finite difference method. The model describes a chain of processes: the flow of FLT between the spatially heterogeneous tumour vasculature and interstitium; diffusion and convection of FLT within the interstitium; transport of FLT into cells; and intracellular phosphorylation. Using values of model parameters estimated from the biological literature, simulated FLT TACs are generated with shapes and magnitudes similar to those seen clinically. Results show that the kinetics of the spatial-temporal model can be recovered accurately by fitting a 3-tissue compartment model to FLT TACs simulated for those tumours or tumour sub-volumes that can be viewed as approximately closed, for which tracer diffusion throughout the interstitium makes only a small fractional change to the quantity of FLT they contain. For a single PET voxel of width 2.5-5 mm we show that this condition is roughly equivalent to requiring that the relative difference in tracer uptake between the voxel and its neighbours is much less than one.

Dosimetry Prediction for Clinical Translation of 64Cu-Pembrolizumab ImmunoPET Targeting Human PD-1 Expression.

PubMed

Natarajan, Arutselvan; Patel, Chirag B; Habte, Frezghi; Gambhir, Sanjiv S

2018-01-12

The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64 Cu-pembrolizumab radiotracer and evaluated human dosimetry. The tracer was utilized to image hPD-1 levels in two subcutaneous mouse models: (a) 293 T/hPD-1 cells xenografted into NOD-scid IL-2Rγnull mice (NSG/293 T/hPD-1) and (b) human peripheral blood mononuclear cells engrafted into NSG bearing A375 human melanoma tumors (hNSG/A375). In each mouse model two cohorts were evaluated (hPD-1 blockade with pembrolizumab [blk] and non-blocked [nblk]), for a total of four groups (n = 3-5/group). The xenograft-to-muscle ratio in the NSG/293 T/hPD-1 model at 24 h was significantly increased in the nblk group (7.0 ± 0.5) compared to the blk group (3.4 ± 0.9), p = 0.01. The radiotracer dosimetry evaluation (PET/CT ROI-based and ex vivo) in the hNSG/A375 model revealed the highest radiation burden to the liver. In summary, we validated the 64 Cu-pembrolizumab tracer's specific hPD-1 receptor targeting and predicted human dosimetry.

Myocardial imaging with 99mTc-Tetrofosmin: Influence of post-stress acquisition time, regional radiotracer uptake, and wall motion abnormalities on the clinical result.

PubMed

Giorgetti, Assuero; Kusch, Annette; Casagranda, Mirta; Tagliavia, Irene D'Aragona; Marzullo, Paolo

2010-04-01

We previously demonstrated that early (15', T1) post-stress myocardial imaging with Tetrofosmin could be more accurate than standard acquisitions (45', T2) in identifying coronary artery disease. To clarify this phenomenon, 120 subjects (age 61 +/- 10 years) with both T1 and T2 scans were divided into Group 1 (53/120 pts) with more ischemia at T1 vs T2 imaging (T1-T2SDS > or = 3); Group 2 (67/120 pts) with similar results (T1-T2SDS < or = 2). Myocardial areas were categorized as control nonischemic, ischemic, and scarred on the basis of perfusion/contraction properties and coronary anatomy. In each area, regional myocardial count statistic and semiquantitative wall motion/thickening values were obtained. Analysis of T1 and T2 post-stress myocardial counts demonstrated a significant Tetrofosmin wash-out rate that was higher in Group 1 control nonischemic regions (15 +/- 8% vs 13.6 +/- 9.6%, P < .02), significantly lower in Group 1 ischemic regions (7 +/- 10% vs 12.2 +/- 9.5%, P < .0001), and comparable between scarred areas of the two groups (P = NS). Delta post-stress wall thickening (T1-T2) was lower in Group 1 ischemic regions (-4.5 +/- 9.15% vs -1.90 +/- 7.0%, P < .001) and comparable in both control nonischemic and scarred areas of the two groups (P = NS). The clinical result of Tetrofosmin gated-SPECT can be influenced by the post-stress acquisition time because of ischemic-induced regional wall thickening abnormalities and the existence of a differential radiotracer myocardial wash-out.

Single-Cell Analysis of [18F]Fluorodeoxyglucose Uptake by Droplet Radiofluidics.

PubMed

Türkcan, Silvan; Nguyen, Julia; Vilalta, Marta; Shen, Bin; Chin, Frederick T; Pratx, Guillem; Abbyad, Paul

2015-07-07

Radiolabels can be used to detect small biomolecules with high sensitivity and specificity without interfering with the biochemical activity of the labeled molecule. For instance, the radiolabeled glucose analogue, [18F]fluorodeoxyglucose (FDG), is routinely used in positron emission tomography (PET) scans for cancer diagnosis, staging, and monitoring. However, despite their widespread usage, conventional radionuclide techniques are unable to measure the variability and modulation of FDG uptake in single cells. We present here a novel microfluidic technique, dubbed droplet radiofluidics, that can measure radiotracer uptake for single cells encapsulated into an array of microdroplets. The advantages of this approach are multiple. First, droplets can be quickly and easily positioned in a predetermined pattern for optimal imaging throughput. Second, droplet encapsulation reduces cell efflux as a confounding factor, because any effluxed radionuclide is trapped in the droplet. Last, multiplexed measurements can be performed using fluorescent labels. In this new approach, intracellular radiotracers are imaged on a conventional fluorescence microscope by capturing individual flashes of visible light that are produced as individual positrons, emitted during radioactive decay, traverse a scintillator plate placed below the cells. This method is used to measure the cell-to-cell heterogeneity in the uptake of tracers such as FDG in cell lines and cultured primary cells. The capacity of the platform to perform multiplexed measurements was demonstrated by measuring differential FDG uptake in single cells subjected to different incubation conditions and expressing different types of glucose transporters. This method opens many new avenues of research in basic cell biology and human disease by capturing the full range of stochastic variations in highly heterogeneous cell populations in a repeatable and high-throughput manner.

Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma

PubMed Central

Haralampieva, Deana; Salemi, Souzan; Betzel, Thomas; Dinulovic, Ivana; Krämer, Stefanie D.; Schibli, Roger; Sulser, Tullio; Ametamey, Simon M.

2018-01-01

While many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize the functional regenerative potential of hMPC by genetic modification to overexpress human peroxisome proliferator-activated receptor gamma coactivator 1-alpha (hPGC-1α), key regulator of exercise-mediated adaptation. Moreover, we aimed at establishing a feasible methodology for noninvasive PET visualization of implanted cells and their microenvironment in muscle crush injury model. PGC-1α-bioengineered muscles showed enhanced marker expression for myogenesis (α-actinin, MyHC, and Desmin), vascularization (VEGF), neuronal (ACHE), and mitochondrial (COXIV) activity. Consistently, use of hPGC-1α_hMPCs produced significantly increased contractile force one to three weeks postinjury. PET imaging showed distinct differences in radiotracer signals ([18F]Fallypride and [11C]Raclopride (both targeting dopamine 2 receptors (D2R)) and [64Cu]NODAGA-RGD (targeting neovascularization)) between GFP_hMPCs and hD2R_hPGC-1α_hMPCs. After muscle harvesting, inflammation levels were in parallel to radiotracer uptake amount, with significantly lower uptake in hPGC-1α overexpressing samples. In summary, we facilitated early functional muscle tissue regeneration, introducing a novel approach to improve skeletal muscle regeneration. Besides successful tracking of hMPCs in muscle crush injuries, we showed that in high-inflammation areas, the specificity of radioligands might be significantly reduced, addressing a possible bottleneck of neovascularization PET imaging. PMID:29531537

A High Resolution Monolithic Crystal, DOI, MR Compatible, PET Detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robert S Miyaoka

The principle objective of this proposal is to develop a positron emission tomography (PET) detector with depth-of-interaction (DOI) positioning capability that will achieve state of the art spatial resolution and sensitivity performance for small animal PET imaging. When arranged in a ring or box detector geometry, the proposed detector module will support <1 mm3 image resolution and >15% absolute detection efficiency. The detector will also be compatible with operation in a MR scanner to support simultaneous multi-modality imaging. The detector design will utilize a thick, monolithic crystal scintillator readout by a two-dimensional array of silicon photomultiplier (SiPM) devices using amore » novel sensor on the entrance surface (SES) design. Our hypothesis is that our single-ended readout SES design will provide an effective DOI positioning performance equivalent to more expensive dual-ended readout techniques and at a significantly lower cost. Our monolithic crystal design will also lead to a significantly lower cost system. It is our goal to design a detector with state of the art performance but at a price point that is affordable so the technology can be disseminated to many laboratories. A second hypothesis is that using SiPM arrays, the detector will be able to operate in a MR scanner without any degradation in performance to support simultaneous PET/MR imaging. Having a co-registered MR image will assist in radiotracer localization and may also be used for partial volume corrections to improve radiotracer uptake quantitation. The far reaching goal of this research is to develop technology for medical research that will lead to improvements in human health care.« less

From Conventional Radiotracer Tc-99(m) with Blue Dye to Indocyanine Green Fluorescence: A Comparison of Methods Towards Optimization of Sentinel Lymph Node Mapping in Early Stage Cervical Cancer for a Laparoscopic Approach.

PubMed

Buda, Alessandro; Papadia, Andrea; Zapardiel, Ignacio; Vizza, Enrico; Ghezzi, Fabio; De Ponti, Elena; Lissoni, Andrea Alberto; Imboden, Sara; Diestro, Maria Dolores; Verri, Debora; Gasparri, Maria Luisa; Bussi, Beatrice; Di Martino, Giampaolo; de la Noval, Begoña Diaz; Mueller, Michael; Crivellaro, Cinzia

2016-09-01

The credibility of sentinel lymph node (SLN) mapping is becoming increasingly more established in cervical cancer. We aimed to assess the sensitivity of SLN biopsy in terms of detection rate and bilateral mapping in women with cervical cancer by comparing technetium-99 radiocolloid (Tc-99(m)) and blue dye (BD) versus fluorescence mapping with indocyanine green (ICG). Data of patients with cervical cancer stage 1A2 to 1B1 from 5 European institutions were retrospectively reviewed. All centers used a laparoscopic approach with the same intracervical dye injection. Detection rate and bilateral mapping of ICG were compared, respectively, with results obtained by standard Tc-99(m) with BD. Overall, 76 (53 %) of 144 of women underwent preoperative SLN mapping with radiotracer and intraoperative BD, whereas 68 of (47 %) 144 patients underwent mapping using intraoperative ICG. The detection rate of SLN mapping was 96 % and 100 % for Tc-99(m) with BD and ICG, respectively. Bilateral mapping was achieved in 98.5 % for ICG and 76.3 % for Tc-99(m) with BD; this difference was statistically significant (p < 0.0001). The fluorescence SLN mapping with ICG achieved a significantly higher detection rate and bilateral mapping compared to standard radiocolloid and BD technique in women with early stage cervical cancer. Nodal staging with an intracervical injection of ICG is accurate, safe, and reproducible in patients with cervical cancer. Before replacing lymphadenectomy completely, the additional value of fluorescence SLN mapping on both perioperative morbidity and survival should be explored and confirmed by ongoing controlled trials.

Radionavigated detection of sentinel nodes in breast carcinoma--first experiences of our department.

PubMed

Duchaj, B; Chvalny, P; Vesely, J; Makaiova, I; Durdik, S; Straka, V; Palaj, J; Procka, V; Aksamitova, K; Skraskova, S; Banki, P; Kovacova, S; Galbavy, S

2010-01-01

Biopsy and histological evaluation of sentinel lymphatic node limits the axillary node dissection only in cases of positive histological finding and decreases the occurrence of postoperative complications related to the axillary node dissection. We used radiotracer SentiScint, Medi-Radiopharma Ltd, Hungary and preoperatively administered blue dye--Blue Patenté V, Guebert, Aulnay-Sous-Bios, France. 11 (18%) patients were subdued to deep peritimorous application of radiotracer, 10 (16.4%) to sub/intradermal application over the lesions and n 40 (65.6%) patients the application was sub/intradermal and periareolar. The patients underwent an operation protocol of corresponding quadrantectomy, radionavigated blue-dye sentinel node biopsy and axillary dissection. From May 2006 to June 2008, we examined 61 patients with breast carcinoma. They underwent radionavigated and blue-dye sentinel node biopsy. We detected 57 (93.4%) sentinel nodes with preoperative scintigraphy, of which only 51 (83.6%) were detected peroperatively and underwent histological evaluation. In six (9.8%) cases, the "frozen cut" histology of the primary lesion had shown a benign lesion; hence no sentinel node biopsy or axillary disection was performed. 12 (19.7%) of 51 histologically evaluated sentinel nodes had metastatic invasion. We retrospectively compared the histological fund in sentinel and axillary nodes in patients with metastatic sentinel nodes. In 6 (16.6%) cases, the sentinel node was positive of metastatic invasion but axillary nodes were histologically negative, in 6 (16.6%) cases the sentinel node and axillary nodes were positive for metastatic invasion. We observed falsely negative findings in 3 (8.3%) patients with negative histological fund in the sentinel node, but positive axillary nodes (Tab. 3, Fig. 2, Ref. 11). Full Text (Free, PDF) www.bmj.sk.

Model-based versus specific dosimetry in diagnostic context: Comparison of three dosimetric approaches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marcatili, S., E-mail: sara.marcatili@inserm.fr; Villoing, D.; Mauxion, T.

Purpose: The dosimetric assessment of novel radiotracers represents a legal requirement in most countries. While the techniques for the computation of internal absorbed dose in a therapeutic context have made huge progresses in recent years, in a diagnostic scenario the absorbed dose is usually extracted from model-based lookup tables, most often derived from International Commission on Radiological Protection (ICRP) or Medical Internal Radiation Dose (MIRD) Committee models. The level of approximation introduced by these models may impact the resulting dosimetry. The aim of this work is to establish whether a more refined approach to dosimetry can be implemented in nuclearmore » medicine diagnostics, by analyzing a specific case. Methods: The authors calculated absorbed doses to various organs in six healthy volunteers administered with flutemetamol ({sup 18}F) injection. Each patient underwent from 8 to 10 whole body 3D PET/CT scans. This dataset was analyzed using a Monte Carlo (MC) application developed in-house using the toolkit GATE that is capable to take into account patient-specific anatomy and radiotracer distribution at the voxel level. They compared the absorbed doses obtained with GATE to those calculated with two commercially available software: OLINDA/EXM and STRATOS implementing a dose voxel kernel convolution approach. Results: Absorbed doses calculated with GATE were higher than those calculated with OLINDA. The average ratio between GATE absorbed doses and OLINDA’s was 1.38 ± 0.34 σ (from 0.93 to 2.23). The discrepancy was particularly high for the thyroid, with an average GATE/OLINDA ratio of 1.97 ± 0.83 σ for the six patients. Differences between STRATOS and GATE were found to be higher. The average ratio between GATE and STRATOS absorbed doses was 2.51 ± 1.21 σ (from 1.09 to 6.06). Conclusions: This study demonstrates how the choice of the absorbed dose calculation algorithm may introduce a bias when gamma radiations are of importance, as is the case in nuclear medicine diagnostics.« less

Prediction of Clinical Outcomes in Prenatal Hydronephrosis: Importance of Gravity Assisted Drainage.

PubMed

Sussman, Rachael D; Blum, Emily S; Sprague, Bruce M; Majd, Massoud; Rushton, H Gil; Pohl, Hans G

2017-03-01

In infants with SFU (Society for Fetal Urology) grade 3-4 congenital hydronephrosis, 99m Tc-mercaptoacetyltriglycine diuretic renography assesses differential function and drainage half-time. We routinely also include the percent of radiotracer drained after 30 minutes of diuresis as well as after 15 minutes with the patient in the upright position. We investigated whether any 1 or more of these parameters on initial diuretic renography predicts persistent or worsening drainage parameters. Infants 6 months or younger with grade 3-4 congenital hydronephrosis who presented between January 2009 and December 2014 were identified from billing data and included in analysis if they underwent at least 1 baseline diuretic renography. Those with structural anomalies were excluded from study. Baseline and followup differential function, diuresis half-time, clearance at 30 minutes and clearance with the patient upright were abstracted and comparisons were made between those with initially indeterminate diuresis half-time who underwent pyeloplasty vs those showing spontaneous improvement. A total of 74 patients (82 renal units) with presumed ureteropelvic junction obstruction met inclusion/exclusion criteria. All 10 renal units with initial diuresis half-time less than 5 minutes resolved spontaneously and all 25 renal units with initial diuresis half-time greater than 75 minutes underwent pyeloplasty. Therefore, we defined the indeterminate group as the 47 renal units with initial half-time between 5 and 75 minutes. Of those 47 renal units with indeterminate initial diuresis half-time 23 (47%) underwent pyeloplasty and 25 (53%) resolved spontaneously. Indications for pyeloplasty included worsening in 17 cases, persistent obstruction in 4 and urinary tract infection in 1. Among renal units with indeterminate drainage clearance while upright and clearance at 30 minutes were the only variables that differed significantly between surgical cases and those that resolved spontaneously. Radiotracer clearance with the patient upright and clearance at 30 minutes are more predictive of surgical management than diuresis half-time or differential function for renal units with indeterminate drainage. They should be included in the standard assessment of ureteropelvic junction obstruction. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

In Vivo Quantification of Human Serotonin 1A Receptor Using 11C-CUMI-101, an Agonist PET Radiotracer

PubMed Central

Milak, Matthew S.; DeLorenzo, Christine; Zanderigo, Francesca; Prabhakaran, Jaya; Kumar, J.S. Dileep; Majo, Vattoly J.; Mann, J. John; Parsey, Ramin V.

2013-01-01

The serotonin (5-hydroxytryptamine, or 5-HT) type 1A receptor (5-HT1AR) is implicated in the pathophysiology of numerous neuropsychiatric disorders. We have published the initial evaluation and reproducibility in vivo of [O-methyl-11C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5 (2H,4H)dione (11C-CUMI-101), a novel 5-HT1A agonist radiotracer, in Papio anubis. Here, we report the optimal modeling parameters of 11C-CUMI-101 for human PET studies. Methods PET scans were obtained for 7 adult human volunteers. 11C-CUMI-101 was injected as an intravenous bolus, and emission data were collected for 120 min in 3-dimensional mode. We evaluated 10 different models using metabolite-corrected arterial input functions or reference region approaches and several outcome measures. Results When using binding potential (BPF = Bavail/KD [total available receptor concentration divided by the equilibrium dissociation constant]) as the outcome measure, the likelihood estimation in the graphical analysis (LEGA) model performed slightly better than the other methods evaluated at full scan duration. The average test–retest percentage difference was 9.90% ± 5.60%. When using BPND (BPND = fnd × Bavail/KD; BPND equals the product of BPF and fnd [free fraction in the nondisplaceable compartment]), the simplified reference tissue method (SRTM) achieved the lowest percentage difference and smallest bias when compared with nondisplaceable binding potential obtained from LEGA using the metabolite-corrected plasma input function (r2 = 0.99; slope = 0.92). The time–stability analysis indicates that a 120-min scan is sufficient for the stable estimation of outcome measures. Voxel results were comparable to region-of-interest–based analysis, with higher spatial resolution. Conclusion On the basis of its measurable and stable free fraction, high affinity and selectivity, good blood–brain barrier permeability, and plasma and brain kinetics, 11C-CUMI-101 is suitable for the imaging of high-affinity 5-HT1A binding in humans. PMID:21098796

Response Assessment of 68Ga-DOTA-E-[c(RGDfK)]2 PET/CT in Lung Adenocarcinoma Patients Treated with Nintedanib Plus Docetaxel.

PubMed

Arrieta, Oscar; Garcia-Perez, Francisco O; Michel-Tello, David; Ramírez-Tirado, Laura-Alejandra; Pitalua-Cortes, Quetzali; Cruz-Rico, Graciela; Macedo-Pérez, Eleazar-Omar; Cardona, Andrés F; Garza-Salazar, Jaime de la

2018-03-01

Nintedanib is an oral angiokinase inhibitor used as second-line treatment for non-small cell lung cancer. New radiotracers, such as 68 Ga-DOTA-E-[c(RGDfK)] 2 , that target α v β 3 integrin might have an impact as a noninvasive method for assessing angiogenesis inhibitors. Methods: From July 2011 through October 2015, 38 patients received second-line nintedanib plus docetaxel. All patients underwent PET/CT with 68 Ga-DOTA-E-[c(RGDfK)] 2 radiotracer and blood-sample tests to quantify angiogenesis factors (fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor AB) before and after completing 2 therapy cycles. Results: Of the 38 patients, 31 had available baseline and follow-up PET/CT. Baseline lung tumor volume addressed with 68 Ga-DOTA-E-[c(RGDfK)] 2 PET/CT correlated with serum vascular endothelial growth factor levels, whereas baseline lung/liver SUV max index correlated with platelet-derived growth factor AB. After treatment, the overall response rate and disease control rate were 7.9% and 47.3%, respectively. A greater decrease in lung tumor volume (-37.2% vs. -27.6%) was associated with a better disease control rate in patients ( P = 0.005). Median progression-free survival was 3.7 mo. Nonsmokers and patients with a higher baseline lung tumor volume were more likely to have a higher progression-free survival (6.4 vs. 3.74 [ P = 0.023] and 6.4 vs. 2.1 [ P = 0.003], respectively). Overall survival was not reached. Patients with a greater decrease in lung SUV max (not reached vs. 7.1 mo; P = 0.016) and a greater decrease in the lung/spleen SUV max index (not reached vs. 7.1; P = 0.043) were more likely to have a longer overall survival. Conclusion: 68 Ga-DOTA-E-[c(RGDfK)] 2 PET/CT is a potentially useful tool for assessing responses to angiogenesis inhibitors. Further analysis and novel studies are warranted to identify patients who might benefit from this therapy. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.