A Generator-Produced Gallium-68 Radiopharmaceutical for PET Imaging of Myocardial Perfusion

PubMed Central

Sharma, Vijay; Sivapackiam, Jothilingam; Harpstrite, Scott E.; Prior, Julie L.; Gu, Hannah; Rath, Nigam P.; Piwnica-Worms, David

2014-01-01

Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel 68Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI. PMID:25353349

PET/SPECT: Instrumentation, radiopharmaceuticals, neurology and physiological measurement. Proceedings

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

Not Available

1988-12-31

The following collection of papers was presented at the Department of Energy sponsored symposium ``Frontiers in Nuclear Medicine - PET/SPECT 1987`` held in Washington, D.C. September 27-- 28, 1987. The meeting and these manuscripts concentrate on the techniques of tomography, useful radiopharmaceuticals, and clinical neurologic and cardiac evaluation. The authors of these papers are for the most part those who either developed the techniques or who have extensively applied them to clinical practice. Individual reports are processed separately for the databases.

Design and Optimization of Coin-Shaped Microreactor Chips for PET Radiopharmaceutical Synthesis

PubMed Central

Elizarov, Arkadij M.; van Dam, R. Michael; Shin, Young Shik; Kolb, Hartmuth C.; Padgett, Henry C.; Stout, David; Shu, Jenny; Huang, Jiang; Daridon, Antoine; Heath, James R.

2010-01-01

An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. Methods The unique architecture of the device is centered around a 5-μL coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. Results The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. Conclusion The reactor has the potential to produce multiple human doses of 18F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment. PMID:20124050

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.

Generators and automated generator systems for production and on-line injections of pet radiopharmaceuticals

NASA Astrophysics Data System (ADS)

Shimchuk, G.; Shimchuk, Gr; Pakhomov, G.; Avalishvili, G.; Zavrazhnov, G.; Polonsky-Byslaev, I.; Fedotov, A.; Polozov, P.

2017-01-01

One of the prospective directions of PET development is using generator positron radiating nuclides [1,2]. Introduction of this technology is financially promising, since it does not require expensive special accelerator and radiochemical laboratory in the medical institution, which considerably reduces costs of PET diagnostics and makes it available to more patients. POZITOM-PRO RPC LLC developed and produced an 82Sr-82Rb generator, an automated injection system, designed for automatic and fully-controlled injections of 82RbCl produced by this generator, automated radiopharmaceutical synthesis units based on generated 68Ga produced using a domestically-manufactured 68Ge-68Ga generator for preparing two pharmaceuticals: Ga-68-DOTA-TATE and Vascular Ga-68.

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

Stroma Targeting Nuclear Imaging and Radiopharmaceuticals

PubMed Central

Shetty, Dinesh; Jeong, Jae-Min; Shim, Hyunsuk

2012-01-01

Malignant transformation of tumor accompanies profound changes in the normal neighboring tissue, called tumor stroma. The tumor stroma provides an environment favoring local tumor growth, invasion, and metastatic spreading. Nuclear imaging (PET/SPECT) measures biochemical and physiologic functions in the human body. In oncology, PET/SPECT is particularly useful for differentiating tumors from postsurgical changes or radiation necrosis, distinguishing benign from malignant lesions, identifying the optimal site for biopsy, staging cancers, and monitoring the response to therapy. Indeed, PET/SPECT is a powerful, proven diagnostic imaging modality that displays information unobtainable through other anatomical imaging, such as CT or MRI. When combined with coregistered CT data, [18F]fluorodeoxyglucose ([18F]FDG)-PET is particularly useful. However, [18F]FDG is not a target-specific PET tracer. This paper will review the tumor microenvironment targeting oncologic imaging such as angiogenesis, invasion, hypoxia, growth, and homing, and also therapeutic radiopharmaceuticals to provide a roadmap for additional applications of tumor imaging and therapy. PMID:22685650

PET brain kinetics studies of 11C-ITMM and 11C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate

PubMed Central

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed 11C-labeled PET probes 11C-ITMM and 11C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared 11C-ITMM and 11C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with 11C-ITDM than with 11C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm-3 for 11C-ITMM and 3.6 mL∙cm-3 for 11C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of 11C-ITMM and 11C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that 11C-ITDM may be superior to 11C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with 11C-ITDM were higher than those of 11C-ITMM. Clinical studies of 11C-ITDM in humans will be necessary in the future. PMID:24795840

PET brain kinetics studies of (11)C-ITMM and (11)C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate.

PubMed

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed (11)C-labeled PET probes (11)C-ITMM and (11)C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared (11)C-ITMM and (11)C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with (11)C-ITDM than with (11)C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm(-3) for (11)C-ITMM and 3.6 mL∙cm(-3) for (11)C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of (11)C-ITMM and (11)C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that (11)C-ITDM may be superior to (11)C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with (11)C-ITDM were higher than those of (11)C-ITMM. Clinical studies of (11)C-ITDM in humans will be necessary in the future.

PET Radiopharmaceuticals in Brazil and Belarus: Economic Comparison Using the Case of 18FDG.

PubMed

Brinkevich, Sviatoslav; Pires, Leonardo Paredes; Portilho, Filipe Leal; Santos-Oliveira, Ralph

2018-01-01

The production of radiopharmaceuticals, especially the PET ones, is a complex combination of economic and social factors. Despite the social aspects, that are essential, the economic issue must be considered and play an important parameter for the implementation and maintenance of producer centers around the world, with especial regards for countries which face economic crisis and/or belongs to aegis of under development countries. In order to evaluate this scenario with carried out this study, comparing a well-established producer center in Brazil and a new on in Belarus. The results showed that the producer center in Brazil face serious economic problems and all the production logistic must be re-done. On the other hand the new producer center in Belarus started following a new model of production and although it has not been profitable, the perspectives seem to be better than the Brazilian producer center. The Brazilian model for PET radiopharmaceutical productions should be revised in order to avoid waste and create a new perspective for the research area. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

PubMed Central

Cusnir, Ruslan; Imberti, Cinzia; Hider, Robert C.; Blower, Philip J.; Ma, Michelle T.

2017-01-01

Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68Ga3+, which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68Ga PET radiopharmaceuticals. 68Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images. PMID:28075350

Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68.

PubMed

Cusnir, Ruslan; Imberti, Cinzia; Hider, Robert C; Blower, Philip J; Ma, Michelle T

2017-01-08

Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe 3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe 3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68 Ga 3+ , which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68 Ga 3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68 Ga PET radiopharmaceuticals. 68 Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.

18F-Labelled catecholamine type radiopharmaceuticals in the diagnosis of neurodegenerative diseases and neuroendocrine tumours: approaches to synthesis and development prospects

NASA Astrophysics Data System (ADS)

Vatsadze, S. Z.; Eremina, O. E.; Veselova, I. A.; Kalmykov, S. N.; Nenajdenko, V. G.

2018-04-01

The pathogenesis of many socially significant diseases such as neurodegenerative dementias and neuroendocrine tumours involves imbalance of neurotransmitters. Among the known neuroimaging methods, positron emission tomography (PET) is the most perfect and informative technique for diagnosing these diseases. The potential of PET is largely determined by the inventory of available radiopharmaceuticals, that is, biologically active molecules containing short-lived nuclides with positron decay. This review gives a systematic account of the application of fluorine-18-labelled catecholamine type radiopharmaceuticals in clinical investigations of the sympathetic and central nervous systems. The methods for the synthesis of these agents and existing problems are considered. The material is arranged according to the mechanisms of reactions that underlie the synthetic approaches: electrophilic, nucleophilic and metal-catalyzed reactions. The bibliography includes 198 references.

Positron Emission Tomography (PET)

DOE R&D Accomplishments Database

Welch, M. J.

1990-01-01

Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET.

Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations.

PubMed

Tronel, Claire; Largeau, Bérenger; Santiago Ribeiro, Maria Joao; Guilloteau, Denis; Dupont, Anne-Claire; Arlicot, Nicolas

2017-04-11

Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors (purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β) and enzymes (cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway), with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians' expectations.

Synthesis and Preclinical Evaluation of Three Novel Fluorine-18 Labeled Radiopharmaceuticals for P-Glycoprotein PET Imaging at the Blood-Brain Barrier.

PubMed

Savolainen, Heli; Cantore, Mariangela; Colabufo, Nicola A; Elsinga, Philip H; Windhorst, Albert D; Luurtsema, Gert

2015-07-06

P-Glycoprotein (P-gp), along with other transporter proteins at the blood-brain barrier (BBB), limits the entry of many pharmaceuticals into the brain. Altered P-gp function has been found in several neurological diseases. To study the P-gp function, many positron emission tomography (PET) radiopharmaceuticals have been developed. Most P-gp radiopharmaceuticals are labeled with carbon-11, while labeling with fluorine-18 would increase their applicability due to longer half-life. Here we present the synthesis and in vivo evaluation of three novel fluorine-18 labeled radiopharmaceuticals: 4-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-2-(4-fluorophenyl)oxazole (1a), 2-biphenyl-4-yl-2-fluoroethoxy-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline (2), and 5-(1-(2-fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen (3). Compounds were characterized as P-gp substrates in vitro, and Mdr1a/b((-/-))Bcrp1((-/-)) and wild-type mice were used to assess the substrate potential in vivo. Comparison was made to (R)-[(11)C]verapamil, which is currently the most frequently used P-gp substrate. Compound [(18)F]3 was performing the best out of the new radiopharmaceuticals; it had 2-fold higher brain uptake in the Mdr1a/b((-/-))Bcrp1((-/-)) mice compared to wild-type and was metabolically quite stable. In the plasma, 69% of the parent compound was intact after 45 min and 96% in the brain. Selectivity of [(18)F]3 to P-gp was tested by comparing the uptake in Mdr1a/b((-/-)) mice to uptake in Mdr1a/b((-/-))Bcrp1((-/-)) mice, which was statistically not significantly different. Hence, [(18)F]3 was found to be selective for P-gp and is a promising new radiopharmaceutical for P-gp PET imaging at the BBB.

Clinical applications of PET in oncology.

PubMed

Rohren, Eric M; Turkington, Timothy G; Coleman, R Edward

2004-05-01

Positron emission tomography (PET) provides metabolic information that has been documented to be useful in patient care. The properties of positron decay permit accurate imaging of the distribution of positron-emitting radiopharmaceuticals. The wide array of positron-emitting radiopharmaceuticals has been used to characterize multiple physiologic and pathologic states. PET is used for characterizing brain disorders such as Alzheimer disease and epilepsy and cardiac disorders such as coronary artery disease and myocardial viability. The neurologic and cardiac applications of PET are not covered in this review. The major utilization of PET clinically is in oncology and consists of imaging the distribution of fluorine 18 fluorodeoxyglucose (FDG). FDG, an analogue of glucose, accumulates in most tumors in a greater amount than it does in normal tissue. FDG PET is being used in diagnosis and follow-up of several malignancies, and the list of articles supporting its use continues to grow. In this review, the physics and instrumentation aspects of PET are described. Many of the clinical applications in oncology are mature and readily covered by third-party payers. Other applications are being used clinically but have not been as carefully evaluated in the literature, and these applications may not be covered by third-party payers. The developing applications of PET are included in this review.

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

Welch, M.J.

Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy inmore » PET, and the futures of PET. 22 figs.« less

Molecular Imaging and Therapy of Prostate Cancer

DTIC Science & Technology

2015-10-01

arsenic-based, IGF1R-targeted radiopharmaceuticals can allow for PET imaging, IRT, and monitoring the therapeutic response of PCa. Specific Aims: Aim 1: To...models with PET imaging. Aim 3: To monitor the efficacy of 76As-based IRT of PCa with multimodality imaging.

[Principles of PET].

PubMed

Beuthien-Baumann, B

2018-05-01

Positron emission tomography (PET) is a procedure in nuclear medicine, which is applied predominantly in oncological diagnostics. In the form of modern hybrid machines, such as PET computed tomography (PET/CT) and PET magnetic resonance imaging (PET/MRI) it has found wide acceptance and availability. The PET procedure is more than just another imaging technique, but a functional method with the capability for quantification in addition to the distribution pattern of the radiopharmaceutical, the results of which are used for therapeutic decisions. A profound knowledge of the principles of PET including the correct indications, patient preparation, and possible artifacts is mandatory for the correct interpretation of PET results.

PET/CT study performed after an oral administration of 18F-fluoride.

PubMed

Zacchi, Samara Riguete; Valadares, Agnes Araújo; Duarte, Paulo Schiavom; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

2013-12-01

A 52-year-old woman with right breast cancer was referred for 18F-fluoride whole-body PET/CT for the assessment of bone metastases. The peripheral i.v. access was not obtained after multiple attempts. The radiopharmaceutical was administered by oral route.

Molecular SPECT Imaging: An Overview

PubMed Central

Khalil, Magdy M.; Tremoleda, Jordi L.; Bayomy, Tamer B.; Gsell, Willy

2011-01-01

Molecular imaging has witnessed a tremendous change over the last decade. Growing interest and emphasis are placed on this specialized technology represented by developing new scanners, pharmaceutical drugs, diagnostic agents, new therapeutic regimens, and ultimately, significant improvement of patient health care. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have their signature on paving the way to molecular diagnostics and personalized medicine. The former will be the topic of the current paper where the authors address the current position of the molecular SPECT imaging among other imaging techniques, describing strengths and weaknesses, differences between SPECT and PET, and focusing on different SPECT designs and detection systems. Radiopharmaceutical compounds of clinical as well-preclinical interest have also been reviewed. Moreover, the last section covers several application, of μSPECT imaging in many areas of disease detection and diagnosis. PMID:21603240

Radiopharmaceuticals drug interactions: a critical review.

PubMed

Santos-Oliveira, Ralph; Smith, Sheila W; Carneiro-Leão, Ana Maria A

2008-12-01

Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance) or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here,we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions.

Carbon-11 and fluorine-18 chemistry devoted to molecular probes for imaging the brain with positron emission tomography.

PubMed

Dollé, Frédéric

2013-01-01

Exploration of the living human brain in real-time and in a noninvasive way was for centuries only a dream, made, however, possible today with the remarkable development during the four last decades of powerful molecular imaging techniques, and especially positron emission tomography (PET). Molecular PET imaging relies, from a chemical point of view, on the use and preparation of a positron-emitting radiolabelled probe or radiotracer, notably compounds incorporating one of two short-lived radionuclides fluorine-18 (T1/2 : 109.8 min) and carbon-11 (T1/2 : 20.38 min). The growing availability and interest for the radiohalogen fluorine-18 in radiopharmaceutical chemistry undoubtedly results from its convenient half-life and the successful use in clinical oncology of 2-[(18) F]fluoro-2-deoxy-d-glucose ([(18) F]FDG). The special interest of carbon-11 is not only that carbon is present in virtually all biomolecules and drugs allowing therefore for isotopic labelling of their chemical structures but also that a given molecule could be radiolabelled at different functions or sites, permitting to explore (or to take advantage of) in vivo metabolic pathways. PET chemistry includes production of these short-lived radioactive isotopes via nuclear transmutation reactions using a cyclotron, and is directed towards the development of rapid synthetic methods, at the trace level, for the introduction of these nuclides into a molecule, as well as the use of fast purification, analysis and formulation techniques. PET chemistry is the driving force in molecular PET imaging, and this special issue of the Journal of Labelled Compounds and Radiopharmaceuticals, which is strongly chemistry and radiochemistry-oriented, aims at illustrating, be it in part only, the state-of-the-art arsenal of reactions currently available and its potential for the research and development of specific molecular probes labelled with the positron emitters carbon-11 and fluorine-18, with optimal imaging properties for PET exploration of the brain. Copyright © 2013 John Wiley & Sons, Ltd.

Dynamic neurotransmitter interactions measured with PET

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

Schiffer, W.K.; Dewey, S.L.

2001-04-02

Positron emission tomography (PET) has become a valuable interdisciplinary tool for understanding physiological, biochemical and pharmacological functions at a molecular level in living humans, whether in a healthy or diseased state. The utility of tracing chemical activity through the body transcends the fields of cardiology, oncology, neurology and psychiatry. In this, PET techniques span radiochemistry and radiopharmaceutical development to instrumentation, image analysis, anatomy and modeling. PET has made substantial contributions in each of these fields by providing a,venue for mapping dynamic functions of healthy and unhealthy human anatomy. As diverse as the disciplines it bridges, PET has provided insight intomore » an equally significant variety of psychiatric disorders. Using the unique quantitative ability of PET, researchers are now better able to non-invasively characterize normally occurring neurotransmitter interactions in the brain. With the knowledge that these interactions provide the fundamental basis for brain response, many investigators have recently focused their efforts on an examination of the communication between these chemicals in both healthy volunteers and individuals suffering from diseases classically defined as neurotransmitter specific in nature. In addition, PET can measure the biochemical dynamics of acute and sustained drug abuse. Thus, PET studies of neurotransmitter interactions enable investigators to describe a multitude of specific functional interactions in the human brain. This information can then be applied to understanding side effects that occur in response to acute and chronic drug therapy, and to designing new drugs that target multiple systems as opposed to single receptor types. Knowledge derived from PET studies can be applied to drug discovery, research and development (for review, see (Fowler et al., 1999) and (Burns et al., 1999)). Here, we will cover the most substantial contributions of PET to understanding biologically distinct neurochemical systems that interact to produce a variety of behaviors and disorders. Neurotransmitters are neither static nor isolated in their distribution. In fact, it is through interactions with other neurochemically distinct systems that the central nervous system (CNS) performs its vital role in sustaining life. Exclusive quantitative capabilities intrinsic to PET make this technology a suitable experimental tool to measure not only the regional distribution of specific receptors and their subtypes, but also the dynamic properties of neuroreceptors and their inherent influence on related neurotransmitter pathways. The ability to investigate dynamic properties in a non-invasive and reproducible manner provides a powerful tool that can extend our current knowledge of these interactions. Coupled with innovative paradigms including pharmacologic manipulations, physiologic models and reconstruction theories, knowledge derived from PET studies can greatly advance our understanding of normal and abnormal brain function.« less

Radiopharmaceuticals in the elderly cancer patient: Practical considerations, with a focus on prostate cancer therapy: A position paper from the International Society of Geriatric Oncology Task Force.

PubMed

Prior, John O; Gillessen, Silke; Wirth, Manfred; Dale, William; Aapro, Matti; Oyen, Wim J G

2017-05-01

Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e.g. myelosuppression). Since the introduction of Iodine-131 as a targeted therapy in thyroid cancer, several radiopharmaceuticals have been widely used. These include antibodies and peptides targeting specific epitopes on cancer cells. Among therapeutic bone seeking agents, radium-223 ( 223 Ra) stands out as it results in survival gains in patients with castration-resistant prostate cancer and symptomatic bone metastases. The therapeutic use of radiopharmaceuticals in elderly cancer patients specifically has received little attention. In elderly prostate cancer patients, there may be advantages in radionuclides' ease of use and relative lack of toxicity compared with cytotoxic and cytostatic drugs. When using radionuclide therapies, close coordination between oncology and nuclear medicine is needed to ensure safe and effective use. Bone marrow reserve has to be considered. As most radiopharmaceuticals are cleared renally, dose adjustment may be required in the elderly. However, compared with younger patients there is less, if any, concern about adverse long-term radiation effects such as radiation-induced second cancers. Issues regarding the safety of medical staff, care givers and the wider environment can be managed by current precautions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Nano-graphene oxide composite for in vivo imaging

PubMed Central

Oh, Seo Yeong; Vilian, AT Ezhil; Lee, Ilsong; Han, Young-Kyu; Park, Jeong Hoon; Roh, Changhyun; Huh, Yun Suk

2018-01-01

Introduction Positron emission tomography (PET) tracers has the potential to revolutionize cancer imaging and diagnosis. PET tracers offer non-invasive quantitative imaging in biotechnology and biomedical applications, but it requires radioisotopes as radioactive imaging tracers or radiopharmaceuticals. Method This paper reports the synthesis of 18F-nGO-PEG by covalently functionalizing PEG with nano-graphene oxide, and its excellent stability in physiological solutions. Using a green synthesis route, nGO is then functionalized with a biocompatible PEG polymer to acquire high stability in PBS and DMEM. Results and discussion The radiochemical safety of 18F-nGO-PEG was measured by a reactive oxygen species and cell viability test. The biodistribution of 18F-nGO-PEG could be observed easily by PET, which suggested the significantly high sensitivity tumor uptake of 18F-nGO-PEG and in a tumor bearing CT-26 mouse compared to the control. 18F-nGO-PEG was applied successfully as an efficient radiotracer or drug agent in vivo using PET imaging. This article is expected to assist many researchers in the fabrication of 18F-labeled graphene-based bio-conjugates with high reproducibility for applications in the biomedicine field. PMID:29379283

Imaging of Prostate Cancer Using Gallium-68-Labeled Bombesin.

PubMed

Sonni, Ida; Baratto, Lucia; Iagaru, Andrei

2017-04-01

Nuclear medicine can play an important role in evaluating prostate cancer combining anatomical and functional information with hybrid techniques. Various PET radiopharmaceuticals have been used for targeting specific biological markers in prostate cancer. Research is ideally oriented towards the development of radiopharmaceuticals targeting antigens overexpressed in prostate cancer, as opposed to normal prostate tissue. In this regard, gastrin-releasing peptide receptors (GRPR) are excellent candidates. Bombesin analogues targeting the GRPR have been investigated. Gallium-68 ( 68 Ga) is an interesting PET radioisotope due to several advantages, such as availability, ease of radiochemistry, half-life, and costs. The focus of this review is on 68 Ga-labeled bombesin analogues in prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Current activities in the ICRP concerning estimation of radiation doses to patients from radiopharmaceuticals for diagnostic use

NASA Astrophysics Data System (ADS)

Mattsson, S.; Johansson, L.; Leide-Svegborn, S.; Liniecki, J.; Nosske, D.; Riklund, K.; Stabin, M.; Taylor, D.

2011-09-01

A Task Group within the ICRP Committees 2 and 3 is continuously working to improve absorbed dose estimates to patients investigated with radiopharmaceuticals. The work deals with reviews of the literature, initiation of new or complementary studies of the biokinetics of a compound and dose estimates. Absorbed dose calculations for organs and tissues have up to now been carried out using the MIRD formalism. There is still a lack of necessary biokinetic data from measurements in humans. More time series obtained by nuclear medicine imaging techniques such as whole-body planar gamma-camera imaging, SPECT or PET are highly desirable for this purpose. In 2008, a new addendum to ICRP Publication 53 was published under the name of ICRP Publication 106 containing biokinetic data and absorbed dose information to organs and tissues of patients of various ages for radiopharmaceuticals in common use. That report also covers a number of generic models and realistic maximum models covering other large groups of substances (e.g. "123I-brain receptor substances"). Together with ICRP Publication 80, most radiopharmaceuticals in clinical use at the time of publication were covered except the radioiodine labeled compounds for which the ICRP dose estimates are still found in Publication 53. There is an increasing use of new radiopharmaceuticals, especially PET-tracers and the TG has recently finished its work with biokinetic and dosimetric data for 18F-FET, 18F-FLT and 18F-choline. The work continues now with new data for 11C-raclopride, 11C-PiB and 123I-ioflupan as well as re-evaluation of published data for 82Rb-chloride, 18F-fluoride and radioiodide. This paper summarises published ICRP-information on dose to patients from radiopharmaceuticals and gives some preliminary data for substances under review.

Preparation and biological evaluation of 64Cu-CB-TE2A-sst2-ANT, a somatostatin antagonist for PET imaging of somatostatin receptor-positive tumors.

PubMed

Wadas, Thaddeus J; Eiblmaier, Martin; Zheleznyak, Alexander; Sherman, Christopher D; Ferdani, Riccardo; Liang, Kexian; Achilefu, Samuel; Anderson, Carolyn J

2008-11-01

Recently, the somatostatin receptor subtype 2 (SSTR2) selective antagonist sst2-ANT was determined to have a high affinity for SSTR2. Additionally, 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-sst2-ANT showed high uptake in an SSTR2-transfected, tumor-bearing mouse model and suggested that radiolabeled SSTR2 antagonists may be superior to agonists for imaging SSTR2-positive tumors. This report describes the synthesis and evaluation of 64Cu-CB-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-sst2-ANT (64Cu-CB-TE2A-sst2-ANT) as a PET radiopharmaceutical for the in vivo imaging of SSTR2-positive tumors. Receptor-binding studies were performed to determine the dissociation constant of the radiopharmaceutical 64Cu-CB-TE2A-sst2-ANT using AR42J rat pancreatic tumor cell membranes. The internalization of 64Cu-CB-TE2A-sst2-ANT was compared with that of the 64Cu-labeled agonist 64Cu-CB-TE2A-tyrosine3-octreotate (64Cu-CB-TE2A-Y3-TATE) in AR42J cells. Both radiopharmaceuticals were also compared in vivo through biodistribution studies using healthy rats bearing AR42J tumors, and small-animal PET/CT of 64Cu-CB-TE2A-sst2-ANT was performed. The dissociation constant value for the radiopharmaceutical was determined to be 26 +/- 2.4 nM, and the maximum number of binding sites was 23,000 fmol/mg. 64Cu-CB-TE2A-sst2-ANT showed significantly less internalization than did 64Cu-CB-TE2A-Y3-TATE at time points from 15 min to 4 h. Biodistribution studies revealed that the clearance of 64Cu-CB-TE2A-sst2-ANT from the blood was rapid, whereas the clearance of 64Cu-CB-TE2A-sst2-ANT from the liver and kidneys was more modest at all time points. Tumor-to-blood and tumor-to-muscle ratios were determined to be better for 64Cu-CB-TE2A-sst2-ANT than those for 64Cu-CB-TE2A-Y3-TATE at the later time points, although liver and kidney uptake was significantly higher. Small-animal imaging using 64Cu-CB-TE2A-sst2-ANT revealed excellent tumor-to-background contrast at 4 h after injection, and standardized uptake values remained high even after 24 h. The PET radiopharmaceutical 64Cu-CB-TE2A-sst2-ANT is an attractive agent, worthy of future study as a PET radiopharmaceutical for the imaging of somatostatin receptor-positive tumors.

The use of positron emission tomography in pion radiotherapy.

PubMed

Goodman, G B; Lam, G K; Harrison, R W; Bergstrom, M; Martin, W R; Pate, B D

1986-10-01

The radioactive debris produced by pion radiotherapy can be imaged by the technique of Positron Emission Tomography (PET) as a method of non-invasive in situ verification of the pion treatment. This paper presents the first visualization of the pion stopping distribution within a tumor in a human brain using PET. Together with the tissue functional information provided by the standard PET scans using radiopharmaceuticals, the combination of pion with PET technique can provide a much better form of radiotherapy than the use of conventional radiation in both treatment planning and verification.

Re-thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals.

PubMed

Notni, Johannes; Wester, Hans-Jürgen

2018-03-01

The potential and future role of certain metal radionuclides, for example, 44 Sc, 89 Zr, 86 Y, 64 Cu, 68 Ga, 177 Lu, 225 Ac, and 213 Bi, and several terbium isotopes has been controversially discussed in the past decades. Furthermore, the possible benefits of "matched pairs" of isotopes for tandem applications of diagnostics and therapeutics (theranostics) have been emphasized, while such approaches still have not made their way into routine clinical practice. Analysis of bibliographical data illustrates how popularity of certain nuclides has been promoted by cycles of availability and applications. We furthermore discuss the different practical requirements for diagnostic and therapeutic radiopharmaceuticals and the resulting consequences for efficient development of clinically useful pairs of radionuclide theranostics, with particular emphasis on the underlying economical factors. Based on an exemplary assessment of overall production costs for 68 Ga and 18 F radiopharmaceuticals, we venture a look into the future of theranostics and predict that high-throughput PET applications, that is, diagnosis of frequent conditions, will ultimately rely on 18 F tracers. PET radiometals will occupy a niche in the clinical low-throughput sector (diagnosis of rare diseases), but above all, dominate preclinical research and clinical translation. Matched isotope pairs will be of lesser relevance for theranostics but may become important for future PET-based therapeutic dosimetry. Copyright © 2017 John Wiley & Sons, Ltd.

PET radiopharmaceuticals for imaging of tumor hypoxia: a review of the evidence

PubMed Central

Lopci, Egesta; Grassi, Ilaria; Chiti, Arturo; Nanni, Cristina; Cicoria, Gianfranco; Toschi, Luca; Fonti, Cristina; Lodi, Filippo; Mattioli, Sandro; Fanti, Stefano

2014-01-01

Hypoxia is a pathological condition arising in living tissues when oxygen supply does not adequately cover the cellular metabolic demand. Detection of this phenomenon in tumors is of the utmost clinical relevance because tumor aggressiveness, metastatic spread, failure to achieve tumor control, increased rate of recurrence, and ultimate poor outcome are all associated with hypoxia. Consequently, in recent decades there has been increasing interest in developing methods for measurement of oxygen levels in tumors. Among the image-based modalities for hypoxia assessment, positron emission tomography (PET) is one of the most extensively investigated based on the various advantages it offers, i.e., broad range of radiopharmaceuticals, good intrinsic resolution, three-dimensional tumor representation, possibility of semiquantification/quantification of the amount of hypoxic tumor burden, overall patient friendliness, and ease of repetition. Compared with the other non-invasive techniques, the biggest advantage of PET imaging is that it offers the highest specificity for detection of hypoxic tissue. Starting with the 2-nitroimidazole family of compounds in the early 1980s, a great number of PET tracers have been developed for the identification of hypoxia in living tissue and solid tumors. This paper provides an overview of the principal PET tracers applied in cancer imaging of hypoxia and discusses in detail their advantages and pitfalls. PMID:24982822

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.

Positron Emission Tomography in Breast Cancer

PubMed Central

Vercher-Conejero, Jose Luis; Pelegrí-Martinez, Laura; Lopez-Aznar, Diego; Cózar-Santiago, María del Puig

2015-01-01

Gradually, FDG-PET/CT has been strengthening within the diagnostic algorithms of oncological diseases. In many of these, PET/CT has shown to be useful at different stages of the disease: diagnosis, staging or re-staging, treatment response assessment, and recurrence. Some of the advantages of this imaging modality versus CT, MRI, bone scan, mammography, or ultrasound, are based on its great diagnostic capacity since, according to the radiopharmaceutical used, it reflects metabolic changes that often occur before morphological changes and therefore allows us to stage at diagnosis. Moreover, another advantage of this technique is that it allows us to evaluate the whole body so it can be very useful for the detection of distant disease. With regard to breast cancer, FDG-PET/CT has proven to be important when recurrence is suspected or in the evaluation of treatment response. The technological advancement of PET equipment through the development of new detectors and equipment designed specifically for breast imaging, and the development of more specific radiopharmaceuticals for the study of the different biological processes of breast cancer, will allow progress not only in making the diagnosis of the disease at an early stage but also in enabling personalized therapy for patients with breast cancer. PMID:26854143

Audits of radiopharmaceutical formulations

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

Castronovo, F.P. Jr.

A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expertmore » knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team.« less

Good manufacturing practice production of [68Ga]Ga-ABY-025 for HER2 specific breast cancer imaging

PubMed Central

Velikyan, Irina; Wennborg, Anders; Feldwisch, Joachim; Lindman, Henrik; Carlsson, Jörgen; Sörensen, Jens

2016-01-01

Therapies targeting human epidermal growth factor receptor type 2 (HER2) have revolutionized breast cancer treatment, but require invasive biopsies and rigorous histopathology for optimal patient stratification. A non-invasive and quantitative diagnostic method such as positron emission tomography (PET) for the pre-therapeutic determination of the presence and density of the HER2 would significantly improve patient management efficacy and treatment cost. The essential part of the PET methodology is the production of the radiopharmaceutical in compliance with good manufacturing practice (GMP). The use of generator produced positron emitting 68Ga radionuclide would provide worldwide accessibility of the agent. GMP compliant, reliable and highly reproducible production of [68Ga]Ga-ABY-025 with control over the product peptide concentration and amount of radioactivity was accomplished within one hour. Two radiopharmaceuticals were developed differing in the total peptide content and were validated independently. The specific radioactivity could be kept similar throughout the study, and it was 6-fold higher for the low peptide content radiopharmaceutical. Intrapatient comparison of the two peptide doses allowed imaging optimization. The high peptide content decreased the uptake in healthy tissue, in particular liver, improving image contrast. The later imaging time points enhanced the contrast. The combination of high peptide content radiopharmaceutical and whole-body imaging at 2 hours post injection appeared to be optimal for routine clinical use. PMID:27186441

76 FR 10602 - Medicare Program; Public Meetings in Calendar Year 2011 for All New Public Requests for Revisions...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

.../Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 2. Wednesday, May 18, 2011, 9 a.m. to 5 p.m. e.d.t. (Drugs/ Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 3. Tuesday, May 24, 2011, 9... not need the second day of Drugs/Biologicals/ Radiopharmaceuticals/Radiologic Imaging Agents Public...

75 FR 8971 - Medicare Program; Public Meetings in Calendar Year 2010 for All New Public Requests for Revisions...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

.../Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 2. Wednesday, May 5, 2010, 9 a.m. to 5 p.m., e.d.t. (Drugs/ Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 3. Tuesday, May 25, 2010, 9... not need the second day of Drugs/Biologicals/ Radiopharmaceuticals/Radiologic Imaging Agents Public...

Role of PET in medullary thyroid carcinoma.

PubMed

Rufini, V; Treglia, G; Perotti, G; Leccisotti, L; Calcagni, M L; Rubello, D

2008-06-01

In the diagnostic assessment of medullary thyroid carcinoma (MTC), nuclear medicine imaging provides its contribution mainly in the postoperative work-up to detect residual or recurrent tumor. With respect to scintigraphy with gamma-emitter radiopharmaceuticals, positron emission tomography (PET) offers interesting perspectives owing to its higher image quality, spatial resolution and speed. Moreover, the recent developments of hybrid machines allow to obtain images that simultaneously hold both anatomic (computed tomography) and functional (PET) information with great impact on diagnostic efficacy. (18)F-fluoro-deoxyglucose ((18)F-FDG) is the most frequently used PET tracer in oncology. Preliminary reports of FDG-PET in MTC patients show encouraging results with a higher sensitivity in detecting local recurrent and metastatic disease when compared with single photon emission tracers. However, (18)F-FDG uptake depends on lesion size and to some extent on the grade of differentiation and biologic aggressiveness of the tumor; so FDG-PET seems useful mainly in patients with very high calcitonin levels and high progression rate. Like other neuroendocrine tumors, MTC is characterized by the presence of amine uptake mechanism and/or peptide receptors at the cell membrane allowing the clinical use of specific radiopharmaceuticals that reflect the different metabolic pathways of MTC, and in particular the synthesis, storage and release of hormones ((18)F-dihydroxyphenilalanine, (18)F-DOPA and (18)F-fluorodopamine, (18)F-FDA) and the expression of receptors ((68)Ga-labeled somatostatin analogs). These tracers are currently under investigation and will further improve the diagnostic approach of MTC.

Ethanolic carbon-11 chemistry: the introduction of green radiochemistry.

PubMed

Shao, Xia; Fawaz, Maria V; Jang, Keunsam; Scott, Peter J H

2014-07-01

The principles of green chemistry have been applied to a radiochemistry setting. Eleven carbon-11 labeled radiopharmaceuticals have been prepared using ethanol as the only organic solvent throughout the entire manufacturing process. The removal of all other organic solvents from the process simplifies production and quality control (QC) testing, moving our PET Center towards the first example of a green radiochemistry laboratory. All radiopharmaceutical doses prepared are suitable for clinical use. Copyright © 2014 Elsevier Ltd. All rights reserved.

Positron emission tomography in oncology: the most sophisticated imaging technology.

PubMed

Lacić, M; Maisey, M N; Kusić, Z

1997-01-01

The primary aim of this paper is to present a new nuclear medicine technology, which has just recently crossed over the clinical-research barrier. Positron emission tomography (PET) has become one of the routine functional imaging techniques in the most developed countries. The biggest advantage of PET is the usage of short-lived positron emission radionuclides, e.g., fluorine-18 (F-18), carbon-11 (C-11), nitrogen-13, and oxygen-15 (0-15). These radionuclides could be incorporated (H2O15) or linked (F-18 fluorodeoxyglucose (FDG) to different metabolically active molecules. In this way, it is possible to image and quantify the metabolic activity of various disorders and diseases including different types of tumors. The authors have concentrated on the PET rule in oncology. FDG and C-11 methionine are the most widely used PET radiopharmaceuticals in tumor imaging today, thus the results of human PET studies with FDG and C-11 methionine in the evaluation of tumors have been reviewed. The facts about the mechanism of uptake of both metabolic PET radiopharmaceuticals as well as the kinetics of tracers in normal and tumor tissue are described. The problem of accumulation of these tracers in some benign lesions is also mentioned. PET could be used for the evaluation of tumor response to therapy and duration of therapeutic effects in follow-up studies. PET offers a unique possibility to fully quantify the tumor metabolic activity, although semi-quantitative approaches are clinically more convenient. At the end, comparative studies of FDG and C-11 methionine in tumor evaluation are analyzed. A double-tracer FDG and C-11 methionine scanning protocol has been suggested as very useful for the assessment of brain tumor. This finding was also supported by the authors' data.

Quantification of Kryptofix 2.2.2 in [18F]fluorine-labelled radiopharmaceuticals by rapid-resolution liquid chromatography.

PubMed

Lao, Yexing; Yang, Cuiping; Zou, Wei; Gan, Manquan; Chen, Ping; Su, Weiwei

2012-05-01

The cryptand Kryptofix 2.2.2 is used extensively as a phase-transfer reagent in the preparation of [18F]fluoride-labelled radiopharmaceuticals. However, it has considerable acute toxicity. The aim of this study was to develop and validate a method for rapid (within 1 min), specific and sensitive quantification of Kryptofix 2.2.2 at trace levels. Chromatographic separations were carried out by rapid-resolution liquid chromatography (Agilent ZORBAX SB-C18 rapid-resolution column, 2.1 × 30 mm, 3.5 μm). Tandem mass spectra were acquired using a triple quadrupole mass spectrometer equipped with an electrospray ionization interface. Quantitative mass spectrometric analysis was conducted in positive ion mode and multiple reaction monitoring mode for the m/z 377.3 → 114.1 transition for Kryptofix 2.2.2. The external standard method was used for quantification. The method met the precision and efficiency requirements for PET radiopharmaceuticals, providing satisfactory results for specificity, matrix effect, stability, linearity (0.5-100 ng/ml, r(2)=0.9975), precision (coefficient of variation < 5%), accuracy (relative error < ± 3%), sensitivity (lower limit of quantification=0.5 ng) and detection time (<1 min). Fluorodeoxyglucose (n=6) was analysed, and the Kryptofix 2.2.2 content was found to be well below the maximum permissible levels approved by the US Food and Drug Administration. The developed method has a short analysis time (<1 min) and high sensitivity (lower limit of quantification=0.5 ng/ml) and can be successfully applied to rapid quantification of Kryptofix 2.2.2 at trace levels in fluorodeoxyglucose. This method could also be applied to other [18F]fluorine-labelled radiopharmaceuticals that use Kryptofix 2.2.2 as a phase-transfer reagent.

Positron emission tomography in cardiology

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

Correia, J.A.; Alpert, N.M.

1985-12-01

This article reviews the basis of PET imaging and current applications to cardiology. Included is a discussion of physical principles, detectors, quantitative estimation of regional radioactivity concentrations, radiopharmaceuticals, and application to flow and metabolism measurements in the myocardium.

Radiopharmaceutical regulation and Food and Drug Administration policy.

PubMed

Rotman, M; Laven, D; Levine, G

1996-04-01

The regulatory policy of the Food and Drug Administration (FDA) on radiopharmaceuticals flows from a rigid, traditional, drug-like interpretation of the FDC Act on the licensing of radiopharmaceuticals. This contributes to significant delays in the drug-approval process for radiopharmaceuticals, which are very costly to the nuclear medicine community and the American public. It seems that radiopharmaceuticals would be better characterized as molecular devices. Good generic rule-making principles include: use of a risk/benefit/cost analysis; intent based on sound science; performance standards prepared by outside experts; a definite need shown by the regulatory agency; to live with the consequences of any erroneous cost estimates; and design individual credential requirements so that additional training results in enhanced professional responsibility. When these common elements are applied to current FDA policy, it seems that the agency is out of sync with the stated goals for revitalizing federal regulatory policies as deemed necessary by the Clinton administration. Recent FDA rulings on positron-emission tomography, Patient Package inserts, and on medical device service accentuate the degree of such asynchronization. Radiopharmaceutical review and licensing flexibility could be dramatically improved by excluding radiopharmaceuticals from the drug category and reviewing them as separate entities. This new category would take into account their excellent record of safety and their lack of pharmacological action. Additionally, their evaluation of efficacy should be based on their ability to provide useful scintiphotos, data, or responses of the physiological system it portends to image, quantitate, or describe. To accomplish the goal of transforming the FDA's rigid, prescriptive policy into a streamlined flexible performance-based policy, the Council on Radionuclides and Radiopharmaceuticals proposal has been presented. In addition, it is suggested that the United States Pharmacopeia write radiopharmaceutical review standards, that an independent scientific body review the data submitted, and that the FDA either accept or reject the recommendation.

Synthesis and Biodistribution of Lipophilic Monocationic Gallium Radiopharmaceuticals Derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine: Potential Agents for PET Myocardial Imaging with 68Ga

PubMed Central

Hsiao, Yui-May; Mathias, Carla J.; Wey, Shiaw-Pyng; Fanwick, Phillip E.; Green, Mark A.

2009-01-01

Introduction In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga-radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiologic processes. Methods The lipophilic, monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands, the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-methoxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6− salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates determined in rats following i.v. administration and compared to the biodistribution of [86Rb]rubidium chloride. Results The [Ga(4-MeOsal)2BAPDMEN]+PF6− complex exhibits the expected pseudo-octahedral N4O22− coordination sphere about the Ga3+ center with a trans-disposition of the phenolate oxygen atoms. All five of the 67Ga-radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart at both 1-minute and 2-hours post-injection and very high heart/non-target ratios (heart/blood ratios of 7.6 ± 1.0 and 54 ± 10 at 1-min and 120-min, respectively; heart/liver ratios of 1.8 ± 0.4 and 39 ± 3 at 1-min and 120-min, respectively). Conclusions Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicyaldimines) of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga. PMID:19181267

Technological advances in hybrid imaging and impact on dose.

PubMed

Mattsson, Sören; Andersson, Martin; Söderberg, Marcus

2015-07-01

New imaging technologies utilising X-rays and radiopharmaceuticals have developed rapidly. Clinical application of computed tomography (CT) has revolutionised medical imaging and plays an enormous role in medical care. Due to technical improvements, spatial, contrast and temporal resolutions have continuously improved. In spite of significant reduction of CT doses during recent years, CT is still a dominating source of radiation exposure to the population. Combinations with single photon emission computed tomography (SPECT) and positron emission tomography (PET) and especially the use of SPECT/CT and PET/CT, provide important additional information about physiology as well as cellular and molecular events. However, significant dose contributions from SPECT and PET occur, making PET/CT and SPECT/CT truly high dose procedures. More research should be done to find optimal activities of radiopharmaceuticals for various patient groups and investigations. The implementation of simple protocol adjustments, including individually based administration, encouraged hydration, forced diuresis and use of optimised voiding intervals, laxatives, etc., can reduce the radiation exposure to the patients. New data about staff doses to fingers, hands and eye lenses indicate that finger doses could be a problem, but not doses to the eye lenses and to the whole body. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

21 CFR 601.31 - Definition.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Definition. 601.31 Section 601.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Diagnostic Radiopharmaceuticals § 601.31 Definition. For purposes of this part,diagnostic radiopharmaceutical...

SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

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

Fernandes, F; Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia; Silva, D da

2015-06-15

Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: {sup 18}F (109,7 min, 249,8 keV), {sup 89}Zr (78,4 hs, 395,5 keV), {sup 11}C (20,4 min, 385,7 keV) and {sup 68}Ga (67,8 min, 836 keV). {sup 68}Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ({sup 18}F-FDG), lipogenesis ({sup 11}C-Choline and {sup 11}C-Acetate), amino acid transportmore » (Anti-{sup 18}F-FACBC), bone matrix ({sup 18}F-NaF), prostatespecific membrane antigen ({sup 68}Ga-PSMA and {sup 89}Zr-J591), CXCR receptors ({sup 89}Ga-Pentixafor), adrenal receptors ({sup 18}F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-{sup 18}FFACBC (liver) and {sup 18}F-FBDC (stomach wall) are the exception. Higher effective dose was seen {sup 18}F-NaF (27 μSv/MBq) while the lowest was {sup 11}CAcetate (3,5 μSv/MBq). Conclusion: Even though {sup 18}F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when {sup 18}F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider {sup 11}C or {sup 18}F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for {sup 18}F labeling. Anti-{sup 18}F-FACBC, {sup 68}Ga-PSMA and {sup 68}Ga-Pentixafor are demonstrating good results but more researches are needed. While PSMA imaging seems to be independent of PSA level, one choline limitation, anti-{sup 18}F-FACBC adds value because imaging any disease stage. {sup 68}Ga-Petixafor is being tested as theranostics marker integrating molecular image and therapy.« less

18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry.

PubMed

Wong, Dean F; Waterhouse, Rikki; Kuwabara, Hiroto; Kim, Jongho; Brašić, James R; Chamroonrat, Wichana; Stabins, Michael; Holt, Daniel P; Dannals, Robert F; Hamill, Terence G; Mozley, P David

2013-03-01

Identification of safe and valid PET radioligands for metabotropic glutamate receptor, type 5 (mGluR5), is essential to measure changes in brain mGluR5 in neuropsychiatric disorders, to confirm central mGluR5 occupancy of drug candidates, and to guide dose selection for obtaining an optimum therapeutic window. Here we present the results of a first-in-human study assessing the safety and effectiveness of a novel PET radiopharmaceutical, (18)F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ((18)F-FPEB), for quantifying regional brain concentrations of mGluR5. Quantification of whole-body biokinetics was conducted in 6 healthy adults (3 men and 3 women). The radiation safety profile was estimated with OLINDA/EXM software. Subsequently, pairs of dynamic brain scans were obtained for 11 healthy men to identify optimal methods for derivation of regional distribution volume and binding potential and to determine the repeatability of measurement. The whole-body effective radiation dose was approximately 17 μSv/MBq (62 mrem/mCi), with the gallbladder receiving the highest dose of 190 μSv/MBq. In brain studies, time-activity curves showed high accumulation in the insula/caudate nucleus, moderate uptake in the thalamus, and the lowest concentration in the cerebellum/pons. The plasma reference graphical analysis method appeared optimal for (18)F-FPEB; it showed acceptable test-retest variability of nondisplaceable binding potential (<10%) and identified the highest nondisplaceable binding potential values (from ∼0.5 in the globus pallidus to ∼3.5 in the insula) for target regions. Safety assessments revealed no clinically meaningful changes in vital signs, electrocardiogram, or laboratory values. (18)F-FPEB is safe and well tolerated, and its regional cerebral distribution is consistent with previous reports in the literature for metabotropic glutamate receptors. The repeatability of measurement suggests that (18)F-FPEB is suitable for quantifying mGluR5 in humans.

Low energy cyclotron production of multivalent transition metals for PET imaging and therapy

NASA Astrophysics Data System (ADS)

Avila-Rodriguez, Miguel Angel

Recent advances in high-resolution tomographs for small animals require the production of nonconventional long-lived positron emitters to label novel radiopharmaceuticals for PET-based molecular imaging. Radioisotopes with an appropriate half life to match the kinetics of slow biological processes will allow to researchers to study the phamacokinetics of PET ligands over several hours, or even days, on the same animal, with the injection of a single dose. In addition, radionuclides with a suitable half life can potentially be distributed from a central production site making them available in PET facilities that lack an in-house cyclotron. In the last few years there has been a growing interest in the use of PET ligands labeled with radiometals, particularly isotopes of copper, yttrium and zirconium. Future clinical applications of these tracers will require them to be produced reliably and efficiently. This thesis work deals with implementing and optimizing the production of the multivalent transition metals 61,64Cu, 86Y and 89Zr for molecular PET imaging and therapy. Our findings in the production of these radionuclides at high specific activity on an 11 MeV proton-only cyclotron are presented. Local applications of these tracers, including Cu-ATSM for in vivo quantification of hypoxia, synthesis of targeted radiopharmaceuticals using activated esters of DOTA, and a novel development of positron emitting resin microspheres, are also be discussed. As a result of this thesis work, metallic radionuclides are now efficiently produced on a weekly basis in sufficient quality and quantity for collaborating scientists at UW-Madison and external users in other Universities across the country.

Role of positron emission tomography/computed tomography in breast cancer.

PubMed

Bourgeois, Austin C; Warren, Lance A; Chang, Ted T; Embry, Scott; Hudson, Kathleen; Bradley, Yong C

2013-09-01

Although positron emission tomography (PET) imaging may not be used in the diagnosis of breast cancer, the use of PET/computed tomography is imperative in all aspects of breast cancer staging, treatment, and follow-up. PET will continue to be relevant in personalized medicine because accurate tumor status will be even more critical during and after the transition from a generic metabolic agent to receptor imaging. Positron emission mammography is an imaging proposition that may have benefits in lower doses, but its use is limited without new radiopharmaceuticals. Copyright © 2013 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.

Synthesis, isolation and purification of [11C]-choline

PubMed Central

Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

2016-01-01

[11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [11C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [11C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [11C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [11C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [11C]-target containing cyclotron. PMID:27660552

Applications of penetrating radiation for small animal imaging

NASA Astrophysics Data System (ADS)

Hasegawa, Bruce H.; Wu, Max C.; Iwata, Koji; Hwang, Andrew B.; Wong, Kenneth H.; Barber, William C.; Dae, Michael W.; Sakdinawat, Anne E.

2002-11-01

Researchers long have relied on research involving small animals to unravel scientific mysteries in the biological sciences, and to develop new diagnostic and therapeutic techniques in the medical and health sciences. Within the past 2 decades, new techniques have been developed to manipulate the genome of the mouse, allowing the development of transgenic and knockout models of mammalian and human disease, development, and physiology. Traditionally, much biological research involving small animals has relied on the use of invasive methods such as organ harvesting, tissue sampling, and autoradiography during which the animal was sacrificed to perform a single measurement. More recently, imaging techniques have been developed that assess anatomy and physiology in the intact animal, in a way that allows the investigator to follow the progression of disease, or to monitor the response to therapeutic interventions. Imaging techniques that use penetrating radiation at millimeter or submillimeter levels to image small animals include x-ray computed tomography (microCT), single-photon emission computed tomography (microSPECT), and imaging positron emission computed tomography (microPET). MicroCT generates cross-sectional slices which reveal the structure of the object with spatial resolution in the range of 50 to 100 microns. MicroSPECT and microPET are radionuclide imaging techniques in which a radiopharmaceutical is injected into the animal that is accumulated to metabolism, blood flow, bone remodeling, tumor growth, or other biological processes. Both microSPECT and microPET offer spatial resolutions in the range of 1-2 millimeters. However, microPET records annihilation photons produced by a positron-emitting radiopharmaceutical using electronic coincidence, and has a sensitivity approximately two orders of magnitude better than microSPECT, while microSPECT is compatible with gamma-ray emitting radiopharmaceuticals that are less expensive and more readily available than those used with microPET. High-resolution dual-modality imaging systems now are being developed that combine microPET or microSPECT with microCT in a way that facilitates more direct correlation of anatomy and physiology in the same animal. Small animal imaging allows researchers to perform experiments that are not possible with conventional invasive techniques, and thereby are becoming increasingly important tools for discovery of fundamental biological information, and development of new diagnostic and therapeutic techniques in the biomedical sciences.

MicroPET imaging and transgenic models: a blueprint for Alzheimer's disease clinical research.

PubMed

Zimmer, Eduardo R; Parent, Maxime J; Cuello, A Claudio; Gauthier, Serge; Rosa-Neto, Pedro

2014-11-01

Over the past decades, developments in neuroimaging have significantly contributed to the understanding of Alzheimer's disease (AD) pathophysiology. Specifically, positron emission tomography (PET) imaging agents targeting amyloid deposition have provided unprecedented opportunities for refining in vivo diagnosis, monitoring disease propagation, and advancing AD clinical trials. Furthermore, the use of a miniaturized version of PET (microPET) in transgenic (Tg) animals has been a successful strategy for accelerating the development of novel radiopharmaceuticals. However, advanced applications of microPET focusing on the longitudinal propagation of AD pathophysiology or therapeutic strategies remain in their infancy. This review highlights what we have learned from microPET imaging in Tg models displaying amyloid and tau pathology, and anticipates cutting-edge applications with high translational value to clinical research. Copyright © 2014 Elsevier Ltd. All rights reserved.

A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

PubMed

Barrio, Jorge R; Marcus, Carol S; Hung, Joseph C; Keppler, Jennifer S

2004-01-01

We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor compliance with existing US Pharmacopeia (USP) requirements. With abbreviated and more appropriate regulations, new PET molecular imaging probes for diagnostic use would be then rapidly incorporated into the mainstream diagnostic medicine. Equally importantly, this approach would facilitate the use of molecular imaging in drug discovery and development, which would substantially reduce the costs and time required to bring new therapeutic drugs to market.

Present assessment of myocardial viability by nuclear imaging.

PubMed

Saha, G B; MacIntyre, W J; Brunken, R C; Go, R T; Raja, S; Wong, C O; Chen, E Q

1996-10-01

Prospective delineation of viable from nonviable myocardium in patients with coronary artery disease in an important factor in deciding whether a patient should be revascularized or treated medically. Two common techniques--single-photon emission computed tomography (SPECT) and positron-emission computed tomography (PET)--are used in nuclear medicine using various radiopharmaceuticals for the detection of myocardial viability in patients. Thallium-201 (201Tl) and technetium-99m (99mTc)-sestamibi are the common radiopharmaceuticals used in different protocols using SPECT, whereas fluoride-18 (18F)-fluorodeoxyglucose (FDG) and rubidium-82 (82Rb) are most widely used in PET. The SPECT protocols involve stress/redistribution, stress/redistribution/reinjection, and rest/redistribution imaging techniques. Many studies have compared the results of 201Tl and (99mTc)-sestamibi SPECT with those of FDG PET; in some studies, concordant results have been found between delayed thallium and FDG results, indicating that 201Tl, although considered a perfusion agent, shows myocardial viability. Discordant results in a number of studies have been found between sestamibi and FDG, suggesting that the efficacy of sestamibi as a viability marker has yet to be established. Radiolabeled fatty acids such as iodine-123 (123I)-para-iodophenylpentadecanoic acid and carbon-11 (11C)-palmitic acid have been used for the assessment of myocardial viability with limited success. 11C-labeled acetate is a good marker of oxidative metabolism in the heart and has been used to predict the reversibility of wall motion abnormalities. (18F)-FDG is considered the marker of choice for myocardial viability, although variable results are obtained under different physiological conditions. Detection of myocardial viability can be greatly improved by developing new equipment and radiopharmaceuticals of better quality.

Electroplating targets for production of unique PET radionuclides

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

Bui, V.; Sheh, Y.; Finn, R.

1994-12-31

The past decade has witnessed the applications of Positron Emission Tomography (PET) evolving from a purely research endeavour to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules i.e. monoclonal antibodies and pepetides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing themore » Memorial Sloan-Kettering Cancer Center cyclotron are examples of target design and development applicable to many medical accelerators.« less

Electroplated targets for production of unique PET radionuclides

NASA Astrophysics Data System (ADS)

Bui, V.; Sheh, Y.; Finn, R.; Francesconi, L.; Cai, S.; Schlyer, D.; Wieland, B.

1995-12-01

The past decade has witnessed the applications of positron emission tomography (PET) evolving from a purely research endeavor to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in both medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules, i.e. monoclonal antibodies and peptides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing the Memorial Sloan-Kettering Cancer Center (MSKCC) cyclotron are examples of target design and development applicable to many medical accelerators.

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.

Rapid production of positron emitting labeled compounds for use in cardiology PET studies

NASA Astrophysics Data System (ADS)

Bolomey, Leonard

1985-05-01

Large scale clinical application of positron emission tomography requires a variety of short-lived positron emitting radionuclides to be produced in Curie quantities up to 20 times per day. Rapid routine production of these radiopharmaceuticals requires the collaboration of engineers and chemists to achieve production targetry compatible with high beam current (up to 100 μA) and radionuclide production in a chemical form compatible with the rapid radiochemical synthesis. Chemical processing is further complicated by the need to repeat the procedures several times per day and maintain sterility within the shielded area. At our cyclotron facility primary production targets for 11C, 13N, 15O, and 18F (half lives from 2 min to 2 h) are mounted on a vertical gantr that indexes to position the required target on the beam line. Target changes are handled under microprocessor control remotely from the control room such that all valves, cooling, evacuation of target manifold, and testing of interlocks are handled automatically. This system enables us to change targets, energy and particles in less than five minutes. Since the installation of the cyclotron up to fifteen batches of routine radiopharmaceuticals have been produced per day with very low radiation doses to all personnel involved. These radiopharmaceuticals will be used to measure perfusion, metabolism and other biochemical functions in man non invasively with PET.

Phosphinic acid functionalized polyazacycloalkane chelators for radiodiagnostics and radiotherapeutics: unique characteristics and applications.

PubMed

Notni, Johannes; Šimeček, Jakub; Wester, Hans-Jürgen

2014-06-01

Given the wide application of positron emission tomography (PET), positron-emitting metal radionuclides have received much attention recently. Of these, gallium-68 has become particularly popular, as it is the only PET nuclide commercially available from radionuclide generators, therefore allowing local production of PET radiotracers independent of an on-site cyclotron. Hence, interest in optimized bifunctional chelators for the elaboration of (68) Ga-labeled bioconjugates has been rekindled as well, resulting in the development of improved triazacyclononane-triphosphinate (TRAP) ligand structures. The most remarkable features of these ligands are unparalleled selectivity for Ga(III) , rapid Ga(III) complexation kinetics, extraordinarily high thermodynamic stability, and kinetic inertness of the respective Ga(III) chelates. As a result, TRAP chelators exhibit very favorable (68) Ga-labeling properties. Based on the scaffolds NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) and TRAP-Pr, tailored for convenient preparation of (68) Ga-labeled monomeric and multimeric bioconjugates, a variety of novel (68) Ga radiopharmaceuticals have been synthesized. These include bisphosphonates, somatostatin receptor ligands, prostate-specific membrane antigen (PSMA)-targeting peptides, and cyclic RGD pentapeptides, for in vivo PET imaging of bone, neuroendocrine tumors, prostate cancer, and integrin expression, respectively. Furthermore, TRAP-based (68) Ga-labeled gadolinium(III) complexes have been proposed as bimodal probes for PET/MRI, and a cyclen-based analogue of TRAP-Pr has been suggested for the elaboration of targeted radiotherapeutics comprising radiolanthanide ions. Thus, polyazacycloalkane-based polyphosphinic acid chelators are a powerful toolbox for pharmaceutical research, particularly for the development of (68) Ga radiopharmaceuticals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PET imaging in the assessment of normal and impaired cognitive function.

PubMed

Silverman, Daniel H S; Alavi, Abass

2005-01-01

PET has been used to directly quantify several processes relevant to the status of cerebral health and function, including cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism, and cerebral glucose use. Clinically, the most commonly performed PET studies of the brain are performed with fluorine-18-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic use in evaluating patients who have cognitive impairment, and in distinguishing among primary neurodegenerative dementias and other causes of cognitive decline. In certain pathologic circumstances, the normal coupling between blood flow and metabolic needs may be disturbed, and changes in oxygen extraction fraction can have significant prognostic value.

Analysis of non-conformity in continuous quality improvement in a Hospital Radiopharmacy Unit.

PubMed

Martinez, T; Contreras, J F

To perform an analysis of non-conformities (NC) registered between 2012 and 2015, as a part of the review process of the Quality Management System of our Radiopharmacy Unit. Non-conformities registered in the Radiopharmacy Unit in the period 2012-2015 are analyzed and sorted by their impact on the process (critical, major, and minor), cause/origin of the non-conformity, and nature of radiopharmaceutical (PET vs. SPECT). A decrease in the NC of 20% per year is observed, especially in PET radiopharmaceuticals. Non-conformities in SPECT make up about 62-84% of the total of the NC, mainly related to the high number of doses prepared and not administered, which is about 1.5-3% in the ratio of non-administered/administered per year. Analysis of the NC can be considered as a useful indicator in assessment of quality assurance, and in our particular case, the decrease in the registration of NC indicates effectiveness in the corrective and preventive actions implemented. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Diagnostic imaging to detect and evaluate response to therapy in bone metastases from prostate cancer: current modalities and new horizons.

PubMed

Evangelista, Laura; Bertoldo, Francesco; Boccardo, Francesco; Conti, Giario; Menchi, Ilario; Mungai, Francesco; Ricardi, Umberto; Bombardieri, Emilio

2016-07-01

Different therapeutic options for the management of prostate cancer (PC) have been developed, and some are successful in providing crucial improvement in both survival and quality of life, especially in patients with metastatic castration-resistant PC. In this scenario, diverse combinations of radiopharmaceuticals (for targeting bone, cancer cells and receptors) and nuclear medicine modalities (e.g. bone scan, SPECT, SPECT/CT, PET and PET/CT) are now available for imaging bone metastases. Some radiopharmaceuticals are approved, currently available and used in the routine clinical setting, while others are not registered and are still under evaluation, and should therefore be considered experimental. On the other hand, radiologists have other tools, in addition to CT, that can better visualize bone localization and medullary involvement, such as multimodal MRI. In this review, the authors provide an overview of current management of advanced PC and discuss the choice of diagnostic modality for the detection of metastatic skeletal lesions in different phases of the disease. In addition to detection of bone metastases, the evaluation of response to therapy is another critical issue, since it remains one of the most important open questions that a multidisciplinary team faces when optimizing the management of PC. The authors emphasize the role of nuclear modalities that can presently be used in clinical practice, and also look at future perspectives based on relevant clinical data with novel radiopharmaceuticals.

In vitro evaluation of the monoclonal antibody 64Cu-IgG M75 against human carbonic anhydrase IX and its in vivo imaging.

PubMed

Čepa, Adam; Ráliš, Jan; Král, Vlastimil; Paurová, Monika; Kučka, Jan; Humajová, Jana; Lázníček, Milan; Lebeda, Ondřej

2018-03-01

Specific oncology diagnostics requires new types of the selective radiopharmaceuticals, particularly those suitable for the molecular PET imaging. The aim of this work is to present a new, specific PET-immunodiagnostic radiopharmaceutical based on the monoclonal antibody IgG M75 targeting human carbonic anhydrase IX labelled with 64 Cu (T ½ = 12.70h) and its in vitro and in vivo evaluation. The antibody IgG M75 was conjugated with a non-commercial copper-specific chelator "phosphinate" and then labelled with the positron emitter 64 Cu. Stability of the labelled conjugated was tested in human serum. The immunoreactivity of the labelled conjugate was evaluated in vitro on a suitable cell cultures of the colorectal carcinoma (HT-29) and its imaging properties were estimated in vivo on a mouse model with inoculated colorectal carcinoma HT-29 imaged on a µPET/CT. The tested radioimmunoconjugate was obtained in a specific activity of 0.25-0.5 MBq/µg. In vitro uptake experiments revealed specific binding to the HT-29 cells (45 ± 2.8% of the total added activity) and the measured K D value was found to be 9.2nM. Imaging clearly demonstrated significant uptake of the labelled monoclonal antibody in the tumour at 18h post administration. The radioimmunoconjugate 64 Cu-PS-IgG M75 seems to be a suitable candidate for PET diagnostics of hypoxic tumours expressing human carbonic anhydrase IX. Copyright © 2017 Elsevier Ltd. All rights reserved.

Final Report 2007: DOE-FG02-87ER60561

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

Kilbourn, Michael R

2007-04-26

This project involved a multi-faceted approach to the improvement of techniques used in Positron Emission Tomography (PET), from radiochemistry to image processing and data analysis. New methods for radiochemical syntheses were examined, new radiochemicals prepared for evaluation and eventual use in human PET studies, and new pre-clinical methods examined for validation of biochemical parameters in animal studies. The value of small animal PET imaging in measuring small changes of in vivo biochemistry was examined and directly compared to traditional tissue sampling techniques. In human imaging studies, the ability to perform single experimental sessions utilizing two overlapping injections of radiopharmaceuticals wasmore » tested, and it was shown that valid biochemical measures for both radiotracers can be obtained through careful pharmacokinetic modeling of the PET emission data. Finally, improvements in reconstruction algorithms for PET data from small animal PET scanners was realized and these have been implemented in commercial releases. Together, the project represented an integrated effort to improve and extend all basic science aspects of PET imaging at both the animal and human level.« less

Management of radioactive waste gases from PET radiopharmaceutical synthesis using cost effective capture systems integrated with a cyclotron safety system.

PubMed

Stimson, D H R; Pringle, A J; Maillet, D; King, A R; Nevin, S T; Venkatachalam, T K; Reutens, D C; Bhalla, R

2016-09-01

The emphasis on the reduction of gaseous radioactive effluent associated with PET radiochemistry laboratories has increased. Various radioactive gas capture strategies have been employed historically including expensive automated compression systems. We have implemented a new cost-effective strategy employing gas capture bags with electronic feedback that are integrated with the cyclotron safety system. Our strategy is suitable for multiple automated 18 F radiosynthesis modules and individual automated 11 C radiosynthesis modules. We describe novel gas capture systems that minimize the risk of human error and are routinely used in our facility.

[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.

Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice.

PubMed

Silveira, Marina B; Ferreira, Soraya M Z M D; Nascimento, Leonardo T C; Costa, Flávia M; Mendes, Bruno M; Ferreira, Andrea V; Malamut, Carlos; Silva, Juliana B; Mamede, Marcelo

2016-10-01

[(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bench to bedside development of GMP grade Rhenium-188-HEDP, a radiopharmaceutical for targeted treatment of painful bone metastases.

PubMed

ter Heine, Rob; Lange, Rogier; Breukels, Oscar B; Bloemendal, Haiko J; Rummenie, Rob G; Wakker, Antoinette M; de Graaf, Hilly; Beekman, Freek J; van der Westerlaken, Monique M L; Malingré, Mirte M; Wielders, Jos P M; van den Berg, Leo; Hendrikse, N Harry; de Klerk, John M H

2014-04-25

Bone-targeting therapeutic radiopharmaceuticals are effective agents for treatment of painful bone metastases. Rhenium-188-HEDP is such a therapeutic radiopharmaceutical and has advantages over commercially available alternatives in terms of efficacy, safety and the ability to be produced on-site, allowing rapid treatment upon presentation of patients with pain. Unlike many other radiopharmaceuticals, there are no standardized preparation methods for Rhenium-188-HEDP. It is known, however, that drug composition may not only affect stability of the final drug product, but it may also influence bone affinity and, thus, efficacy. Furthermore, for support of clinical studies with Rhenium-188-HEDP as an investigational medicinal product, preparation of this radiopharmaceutical has to be performed under GMP conditions. To our knowledge, no group has reported on the preparation of Rhenium-188-HEDP under GMP conditions or on stock production of sterile non-radioactive starting materials. We present the production of GMP grade Rhenium-188-HEDP for application of this therapeutic radiopharmaceutical in routine clinical practice and for support of clinical studies. In addition, bio-distribution data of Rhenium-188-HEDP in mice and in patients with bone metastases originating from prostate cancer are presented. Copyright © 2014 Elsevier B.V. All rights reserved.

A PET Tracer for Renal Organic Cation Transporters, ¹¹C-Metformin: Radiosynthesis and Preclinical Proof-of-Concept Studies.

PubMed

Jakobsen, Steen; Busk, Morten; Jensen, Jonas Brorson; Munk, Ole Lajord; Zois, Nora Elisabeth; Alstrup, Aage K O; Jessen, Niels; Frøkiær, Jørgen

2016-04-01

Organic cation transporters (OCTs) in the kidney proximal tubule (PT) participate in renal excretion of drugs and endogenous compounds. PT function is commonly impaired in kidney diseases, and consequently quantitative measurement of OCT function may provide an important estimate of kidney function. Metformin is a widely used drug and targets OCT type 2 located in the PT. Thus, we hypothesized that (11)C-labeled metformin would be a suitable PET tracer for quantification of renal function. (11)C-metformin was prepared by (11)C-methylation of 1-methylbiguanide. In vitro cell uptake of (11)C-metformin was studied in LLC-PK1 cells in the presence of increasing doses of unlabeled metformin. In vivo small-animal PET studies in Sprague-Dawley rats were performed at baseline and after treatment with OCT inhibitors to evaluate renal uptake of (11)C-metformin. Kidney and liver pharmacokinetics of (11)C-metformin was investigated in vivo by dynamic (11)C-metformin PET/CT in 6 anesthetized pigs, and renal clearance of (11)C-metformin was compared with renal clearance of (51)Cr-ethylenediaminetetraacetic acid (EDTA). Formation of (11)C metabolites was investigated by analysis of blood and urine samples. The radiochemical yield of (11)C-metformin was 15% ± 3% (n= 40, decay-corrected), and up to 1.5 GBq of tracer were produced with a radiochemical purity greater than 95% in less than 30 min. Dose-dependent uptake of (11)C-metformin in LLC-PK1 cells was rapid. Rat small-animal PET images showed (11)C-metformin uptake in the kidney and liver, the kinetics of which were changed after challenging animals with OCT inhibitors. In pigs, 80% of the injected metformin dose was rapidly present in the kidney, and a high dose of metformin caused a delayed renal uptake and clearance compared with baseline consistent with transporter-mediated competition. Renal clearance of (11)C-metformin was approximately 3 times the renal clearance of (51)Cr-EDTA. We successfully synthesized an (11)C-metformin tracer, and PET studies in rats and pigs showed a rapid kidney uptake from the blood and excretion into the bladder similar to other radiopharmaceuticals developed for γ-camera renography. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Advances in PET/MR instrumentation and image reconstruction.

PubMed

Cabello, Jorge; Ziegler, Sibylle I

2018-01-01

The combination of positron emission tomography (PET) and MRI has attracted the attention of researchers in the past approximately 20 years in small-animal imaging and more recently in clinical research. The combination of PET/MRI allows researchers to explore clinical and research questions in a wide number of fields, some of which are briefly mentioned here. An important number of groups have developed different concepts to tackle the problems that PET instrumentation poses to the exposition of electromagnetic fields. We have described most of these research developments in preclinical and clinical experiments, including the few commercial scanners available. From the software perspective, an important number of algorithms have been developed to address the attenuation correction issue and to exploit the possibility that MRI provides for motion correction and quantitative image reconstruction, especially parametric modelling of radiopharmaceutical kinetics. In this work, we give an overview of some exemplar applications of simultaneous PET/MRI, together with technological hardware and software developments.

Cerenkov Radiation Energy Transfer (CRET) Imaging: A Novel Method for Optical Imaging of PET Isotopes in Biological Systems

PubMed Central

Dothager, Robin S.; Goiffon, Reece J.; Jackson, Erin; Harpstrite, Scott; Piwnica-Worms, David

2010-01-01

Background Positron emission tomography (PET) allows sensitive, non-invasive analysis of the distribution of radiopharmaceutical tracers labeled with positron (β+)-emitting radionuclides in small animals and humans. Upon β+ decay, the initial velocity of high-energy β+ particles can momentarily exceed the speed of light in tissue, producing Cerenkov radiation that is detectable by optical imaging, but is highly absorbed in living organisms. Principal Findings To improve optical imaging of Cerenkov radiation in biological systems, we demonstrate that Cerenkov radiation from decay of the PET isotopes 64Cu and 18F can be spectrally coupled by energy transfer to high Stokes-shift quantum nanoparticles (Qtracker705) to produce highly red-shifted photonic emissions. Efficient energy transfer was not detected with 99mTc, a predominantly γ-emitting isotope. Similar to bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), herein we define the Cerenkov radiation energy transfer (CRET) ratio as the normalized quotient of light detected within a spectral window centered on the fluorophore emission divided by light detected within a spectral window of the Cerenkov radiation emission to quantify imaging signals. Optical images of solutions containing Qtracker705 nanoparticles and [18F]FDG showed CRET ratios in vitro as high as 8.8±1.1, while images of mice with subcutaneous pseudotumors impregnated with Qtracker705 following intravenous injection of [18F]FDG showed CRET ratios in vivo as high as 3.5±0.3. Conclusions Quantitative CRET imaging may afford a variety of novel optical imaging applications and activation strategies for PET radiopharmaceuticals and other isotopes in biomaterials, tissues and live animals. PMID:20949021

Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems.

PubMed

Dothager, Robin S; Goiffon, Reece J; Jackson, Erin; Harpstrite, Scott; Piwnica-Worms, David

2010-10-11

Positron emission tomography (PET) allows sensitive, non-invasive analysis of the distribution of radiopharmaceutical tracers labeled with positron (β(+))-emitting radionuclides in small animals and humans. Upon β(+) decay, the initial velocity of high-energy β(+) particles can momentarily exceed the speed of light in tissue, producing Cerenkov radiation that is detectable by optical imaging, but is highly absorbed in living organisms. To improve optical imaging of Cerenkov radiation in biological systems, we demonstrate that Cerenkov radiation from decay of the PET isotopes (64)Cu and (18)F can be spectrally coupled by energy transfer to high Stokes-shift quantum nanoparticles (Qtracker705) to produce highly red-shifted photonic emissions. Efficient energy transfer was not detected with (99m)Tc, a predominantly γ-emitting isotope. Similar to bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), herein we define the Cerenkov radiation energy transfer (CRET) ratio as the normalized quotient of light detected within a spectral window centered on the fluorophore emission divided by light detected within a spectral window of the Cerenkov radiation emission to quantify imaging signals. Optical images of solutions containing Qtracker705 nanoparticles and [(18)F]FDG showed CRET ratios in vitro as high as 8.8±1.1, while images of mice with subcutaneous pseudotumors impregnated with Qtracker705 following intravenous injection of [(18)F]FDG showed CRET ratios in vivo as high as 3.5±0.3. Quantitative CRET imaging may afford a variety of novel optical imaging applications and activation strategies for PET radiopharmaceuticals and other isotopes in biomaterials, tissues and live animals.

New aspects of molecular imaging in prostate cancer.

PubMed

Ceci, Francesco; Castellucci, Paolo; Cerci, Juliano J; Fanti, Stefano

2017-11-01

Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging. PSMA, the glutamate carboxypeptidase II, is a membrane bound metallo-peptidase over-expressed in PCa cells. It has been shown that PSMA based imaging offers higher tumor detection rate compared to choline PET/CT and radiological conventional imaging, especially at very low PSA levels during biochemical recurrence. In addition PSMA, as theranostics agent, allows both radiolabeling with diagnostic (e.g. 68Ga, 18F) or therapeutic nuclides (e.g. 177Lu, 225Ac). Initial results show that PSMA-targeted radioligand therapy can potentially delay disease progression in metastatic castrate-resistant PCa. Despite still investigational, the bombesin-based radiotracers and antagonist of gastrin releasing-peptide receptor (GRP) (RM2) and anti1-amino-3-18Ffluorocyclobutane-1-carboxylic acid (18F-FACBC) are emerging as possible alternatives for investigating PCa. Considering the wide diffusion of PCa in the Europe and the United States, the presence of these new diagnostic techniques able to detect the disease with high sensitivity and specificity might have a clinical impact on the management of patients. PET/CT imaging with new radiopharmaceuticals can implement the patient management identifying lesion(s) not detectable with conventional imaging procedures. In this review article will be discussed the most promising new PET radiopharmaceuticals (68Ga-PSMA-11, 18F-FACBC, 68Ga-RM2) available at the moment, focusing the attention on their accuracy and their impact on treatment strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiopharmaceuticals 1994. Nil desperandum. European Association of Nuclear Medicine Committees on Radiopharmaceuticals and Positron Emission Tomography.

PubMed

Cox, P H; Meyer, G J

1995-06-01

On the basis of the discussions at a symposium held in Düsseldorf and attended by representatives of various interested bodies, European legislation as it affects radiopharmaceuticals is reviewed. Due consideration is given to the new, centralised and decentralised, registration procedures, effective since 1 January 1995. The dossier required to support an application for marketing authorisation is discussed, separate consideration being given to single-photon emitters, therapeutic radio-nuclides and positron-emitting radiopharmaceuticals. The role of the European Pharmacopoiea is also considered. It is concluded that the new, modified procedures for the registration of medicinal products in the European Union may actually inhibit free availability of radio-pharmaceuticals within the Community, and that there is a strong case for modification of the European Directives so that radiopharmaceuticals are placed in a separate category to therapeutic drugs, with less stringent registration requirements.

Which is the best strategy for diagnosing bronchial carcinoid tumours? The role of dual tracer PET/CT scan.

PubMed

Lococo, Filippo; Treglia, Giorgio

2014-01-01

Bronchial carcinoids (BC) are rare well-differentiated neuroendocrine tumours (NET) sub-classified into typical (TC) and atypical carcinoids (AC). A correct pathological identification in the pre-operative setting is a key element for planning the best strategy of care, considering the different biological behavior of TC and AC. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in BC. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (dotanoc, dotatoc or dotatate) labeled with gallium-68 ((68)Ga) in pulmonary NET. Based on information obtained by using different radiopharmaceuticals and different (68)Ga labeled somatostatin analogues in PET and PET/CT studies, we are able to diagnose BC. In conclusion, by using somatostatin receptor imaging and (18)F-FDG PET/CT scan, we can differentiate BC from benign pulmonary lesions and TC from AC by specific diagnostic patterns. Clinical trials on larger groups of patient would allow for a better and "tailored" therapeutic strategy in NET patients using dual-tracer PET/CT to identify BC and distinguish between TC and AC.

76 FR 34079 - Agency Information Collection Activities; Proposed Collection; Comment Request; Regulations for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

...] Agency Information Collection Activities; Proposed Collection; Comment Request; Regulations for In Vivo Radiopharmaceuticals Used for Diagnosis and Monitoring AGENCY: Food and Drug Administration, HHS. ACTION: Notice... collection for in vivo Radiopharmaceuticals Used for Diagnosis and Monitoring. DATES: Submit either...

78 FR 11202 - Medicare Program; Public Meetings in Calendar Year 2013 for All New Public Requests for Revisions...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

.../Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 2. Thursday, May 9, 2013, 9 a.m. to 5 p.m., e.d.t. (Drugs/ Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 3. Wednesday, May 29, 2013, 9 a.m...

Radiochemistry, PET Imaging, and the Internet of Chemical Things

PubMed Central

2016-01-01

The Internet of Chemical Things (IoCT), a growing network of computers, mobile devices, online resources, software suites, laboratory equipment, synthesis apparatus, analytical devices, and a host of other machines, all interconnected to users, manufacturers, and others through the infrastructure of the Internet, is changing how we do chemistry. While in its infancy across many chemistry laboratories and departments, it became apparent when considering our own work synthesizing radiopharmaceuticals for positron emission tomography (PET) that a more mature incarnation of the IoCT already exists. How does the IoCT impact our lives today, and what does it hold for the smart (radio)chemical laboratories of the future? PMID:27610410

Radiochemistry, PET Imaging, and the Internet of Chemical Things.

PubMed

Thompson, Stephen; Kilbourn, Michael R; Scott, Peter J H

2016-08-24

The Internet of Chemical Things (IoCT), a growing network of computers, mobile devices, online resources, software suites, laboratory equipment, synthesis apparatus, analytical devices, and a host of other machines, all interconnected to users, manufacturers, and others through the infrastructure of the Internet, is changing how we do chemistry. While in its infancy across many chemistry laboratories and departments, it became apparent when considering our own work synthesizing radiopharmaceuticals for positron emission tomography (PET) that a more mature incarnation of the IoCT already exists. How does the IoCT impact our lives today, and what does it hold for the smart (radio)chemical laboratories of the future?

Methods and applications of positron-based medical imaging

NASA Astrophysics Data System (ADS)

Herzog, H.

2007-02-01

Positron emission tomography (PET) is a diagnostic imaging method to examine metabolic functions and their disorders. Dedicated ring systems of scintillation detectors measure the 511 keV γ-radiation produced in the course of the positron emission from radiolabelled metabolically active molecules. A great number of radiopharmaceuticals labelled with 11C, 13N, 15O, or 18F positron emitters have been applied both for research and clinical purposes in neurology, cardiology and oncology. The recent success of PET with rapidly increasing installations is mainly based on the use of [ 18F]fluorodeoxyglucose (FDG) in oncology where it is most useful to localize primary tumours and their metastases.

Hybrid cardiac imaging using PET/MRI: a joint position statement by the European Society of Cardiovascular Radiology (ESCR) and the European Association of Nuclear Medicine (EANM).

PubMed

Nensa, Felix; Bamberg, Fabian; Rischpler, Christoph; Menezes, Leon; Poeppel, Thorsten D; la Fougère, Christian; Beitzke, Dietrich; Rasul, Sazan; Loewe, Christian; Nikolaou, Konstantin; Bucerius, Jan; Kjaer, Andreas; Gutberlet, Matthias; Prakken, Niek H; Vliegenthart, Rozemarijn; Slart, Riemer H J A; Nekolla, Stephan G; Lassen, Martin L; Pichler, Bernd J; Schlosser, Thomas; Jacquier, Alexis; Quick, Harald H; Schäfers, Michael; Hacker, Marcus

2018-05-02

Positron emission tomography (PET) and magnetic resonance imaging (MRI) have both been used for decades in cardiovascular imaging. Since 2010, hybrid PET/MRI using sequential and integrated scanner platforms has been available, with hybrid cardiac PET/MR imaging protocols increasingly incorporated into clinical workflows. Given the range of complementary information provided by each method, the use of hybrid PET/MRI may be justified and beneficial in particular clinical settings for the evaluation of different disease entities. In the present joint position statement, we critically review the role and value of integrated PET/MRI in cardiovascular imaging, provide a technical overview of cardiac PET/MRI and practical advice related to the cardiac PET/MRI workflow, identify cardiovascular applications that can potentially benefit from hybrid PET/MRI, and describe the needs for future development and research. In order to encourage its wide dissemination, this article is freely accessible on the European Radiology and European Journal of Hybrid Imaging web sites. • Studies and case-reports indicate that PET/MRI is a feasible and robust technology. • Promising fields of application include a variety of cardiac conditions. • Larger studies are required to demonstrate its incremental and cost-effective value. • The translation of novel radiopharmaceuticals and MR-sequences will provide exciting new opportunities.

Imaging Prostate Cancer with Positron Emission Tomography

DTIC Science & Technology

2014-07-01

critical role in tumor development. The purpose of this proposal is to utilize fibroblast activation protein alpha ( FAP ) expression on TAFs within...based cell lines, which stably express eGFP and FAP . Ongoing experiments are focused on the in vitro and in vivo evaluation of each radiopharmaceutical...and on understanding the growth characteristics of each transfected cell line in vivo. 15. SUBJECT TERMS PET, Prostate Cancer, FAP , molecular

21 CFR 315.6 - Evaluation of safety.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Evaluation of safety. 315.6 Section 315.6 Food and... USE DIAGNOSTIC RADIOPHARMACEUTICALS § 315.6 Evaluation of safety. (a) Factors considered in the safety...)(1) To establish the safety of a diagnostic radiopharmaceutical, FDA may require, among other...

Strategies of statistical windows in PET image reconstruction to improve the user’s real time experience

NASA Astrophysics Data System (ADS)

Moliner, L.; Correcher, C.; Gimenez-Alventosa, V.; Ilisie, V.; Alvarez, J.; Sanchez, S.; Rodríguez-Alvarez, M. J.

2017-11-01

Nowadays, with the increase of the computational power of modern computers together with the state-of-the-art reconstruction algorithms, it is possible to obtain Positron Emission Tomography (PET) images in practically real time. These facts open the door to new applications such as radio-pharmaceuticals tracking inside the body or the use of PET for image-guided procedures, such as biopsy interventions, among others. This work is a proof of concept that aims to improve the user experience with real time PET images. Fixed, incremental, overlapping, sliding and hybrid windows are the different statistical combinations of data blocks used to generate intermediate images in order to follow the path of the activity in the Field Of View (FOV). To evaluate these different combinations, a point source is placed in a dedicated breast PET device and moved along the FOV. These acquisitions are reconstructed according to the different statistical windows, resulting in a smoother transition of positions for the image reconstructions that use the sliding and hybrid window.

Elucidation of the Human Serum Albumin (HSA) Binding Site for the Cu-PTSM and Cu-ATSM Radiopharmaceuticals

PubMed Central

Basken, Nathan E.; Mathias, Carla J.; Green, Mark A.

2008-01-01

The Cu-PTSM (pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II)) and Cu-ATSM (diacetyl bis(N4-methylthiosemicarbazonato)copper(II)) radiopharmaceuticals exhibit strong, species-dependent binding to human serum albumin (HSA), while Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)) appears to only exhibit non-specific binding to human and animal serum albumins. This study examines the structural basis for HSA binding of Cu-PTSM and Cu-ATSM via competition with drugs having known albumin binding sites. Warfarin, furosemide, ibuprofen, phenylbutazone, benzylpenicillin, and cephmandole were added to HSA solutions at drug:HSA mole ratios from 0 to 8:1, followed by quantification of radiopharmaceutical binding to HSA by ultrafiltration. Warfarin, a site IIA drug, progressively displaced both [64Cu]Cu-PTSM and [64Cu]Cu-ATSM from HSA. At 8:1 warfarin:HSA mole ratios, free [64Cu]Cu-PTSM and [64Cu]Cu-ATSM levels increased 300–500%. This was in contrast to solutions containing ibuprofen, a site IIIA drug; no increase in free [64Cu]Cu-PTSM or [64Cu]Cu-ATSM was observed except at high ibuprofen:HSA ratios, where secondary ibuprofen binding to the IIA site may cause modest radiopharmaceutical displacement. By contrast, and consistent with earlier findings suggesting Cu-ETS exhibits only non-specific associations, [64Cu]Cu-ETS binding to HSA was unaffected by the addition of drugs that bind in either site. We conclude that the species-dependence of Cu-PTSM and Cu-ATSM albumin binding arises from interaction(s) with the IIA site of HSA. PMID:18937368

New horizons in cardiac innervation imaging: introduction of novel 18F-labeled PET tracers.

PubMed

Kobayashi, Ryohei; Chen, Xinyu; Werner, Rudolf A; Lapa, Constantin; Javadi, Mehrbod S; Higuchi, Takahiro

2017-12-01

Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11 C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18 F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18 F-labeled radiotracers along with their possible applications are reviewed.

SPECT and PET radiopharmaceuticals for molecular imaging of apoptosis: from bench to clinic

PubMed Central

Wang, Xiaobo; Feng, Han; Zhao, Shichao; Xu, Junling; Wu, Xinyu; Cui, Jing; Zhang, Ying; Qin, Yuhua; Liu, Zhiguo; Gao, Tang; Gao, Yongju; Zeng, Wenbin

2017-01-01

Owing to the central role of apoptosis in many human diseases and the wide-spread application of apoptosis-based therapeutics, molecular imaging of apoptosis in clinical practice is of great interest for clinicians, and holds great promises. Based on the well-defined biochemical changes for apoptosis, a rich assortment of probes and approaches have been developed for molecular imaging of apoptosis with various imaging modalities. Among these imaging techniques, nuclear imaging (including single photon emission computed tomography and positron emission tomography) remains the premier clinical method owing to their high specificity and sensitivity. Therefore, the corresponding radiopharmaceuticals have been a major focus, and some of them like 99mTc-Annexin V, 18F-ML-10, 18F-CP18, and 18F-ICMT-11 are currently under clinical investigations in Phase I/II or Phase II/III clinical trials on a wide scope of diseases. In this review, we summarize these radiopharmaceuticals that have been widely used in clinical trials and elaborate them in terms of radiosynthesis, pharmacokinetics and dosimetry, and their applications in different clinical stages. We also explore the unique features required to qualify a desirable radiopharmaceutical for imaging apoptosis in clinical practice. Particularly, a perspective of the impact of these clinical efforts, namely, apoptosis imaging as predictive and prognostic markers, early-response indicators and surrogate endpoints, is also the highlight of this review. PMID:28108738

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

Marsh, I; Otto, M; Weichert, J

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical {sup 131}I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the {sup 124}124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of {sup 124}I-CLR1404 were used to predict therapeutic doses from {sup 131}I-CLR1404 at each timemore » point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.« less

Clinical Evaluation of 68Ga-PSMA-II and 68Ga-RM2 PET Images Reconstructed With an Improved Scatter Correction Algorithm.

PubMed

Wangerin, Kristen A; Baratto, Lucia; Khalighi, Mohammad Mehdi; Hope, Thomas A; Gulaka, Praveen K; Deller, Timothy W; Iagaru, Andrei H

2018-06-06

Gallium-68-labeled radiopharmaceuticals pose a challenge for scatter estimation because their targeted nature can produce high contrast in these regions of the kidneys and bladder. Even small errors in the scatter estimate can result in washout artifacts. Administration of diuretics can reduce these artifacts, but they may result in adverse events. Here, we investigated the ability of algorithmic modifications to mitigate washout artifacts and eliminate the need for diuretics or other interventions. The model-based scatter algorithm was modified to account for PET/MRI scanner geometry and challenges of non-FDG tracers. Fifty-three clinical 68 Ga-RM2 and 68 Ga-PSMA-11 whole-body images were reconstructed using the baseline scatter algorithm. For comparison, reconstruction was also processed with modified sampling in the single-scatter estimation and with an offset in the scatter tail-scaling process. None of the patients received furosemide to attempt to decrease the accumulation of radiopharmaceuticals in the bladder. The images were scored independently by three blinded reviewers using the 5-point Likert scale. The scatter algorithm improvements significantly decreased or completely eliminated the washout artifacts. When comparing the baseline and most improved algorithm, the image quality increased and image artifacts were reduced for both 68 Ga-RM2 and for 68 Ga-PSMA-11 in the kidneys and bladder regions. Image reconstruction with the improved scatter correction algorithm mitigated washout artifacts and recovered diagnostic image quality in 68 Ga PET, indicating that the use of diuretics may be avoided.

75 FR 875 - Guidance for Industry on New Contrast Imaging Indication Considerations for Devices and Approved...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-06

... imaging devices for use with imaging contrast agents or radiopharmaceuticals. FDA intends this guidance to..., for medical imaging devices for use with imaging contrast agents or radiopharmaceuticals. Further, the...] Guidance for Industry on New Contrast Imaging Indication Considerations for Devices and Approved Drug and...

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.

Radiochemistry, PET Imaging, and the Internet of Chemical Things

DOE PAGES

Thompson, Stephen; Kilbourn, Michael R.; Scott, Peter J. H.

2016-08-16

The Internet of Chemical Things (IoCT), a growing network of computers, mobile devices, online resources, software suites, laboratory equipment, synthesis apparatus, analytical devices, and a host of other machines, all interconnected to users, manufacturers, and others through the infrastructure of the Internet, is changing how we do chemistry. While in its infancy across many chemistry laboratories and departments, it became apparent when considering our own work synthesizing radiopharmaceuticals for positron emission tomography (PET) that a more mature incarnation of the IoCT already exists. Finally, how does the IoCT impact our lives today, and what does it hold for the smartmore » (radio)chemical laboratories of the future?« less

Radiochemistry, PET Imaging, and the Internet of Chemical Things

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

Thompson, Stephen; Kilbourn, Michael R.; Scott, Peter J. H.

The Internet of Chemical Things (IoCT), a growing network of computers, mobile devices, online resources, software suites, laboratory equipment, synthesis apparatus, analytical devices, and a host of other machines, all interconnected to users, manufacturers, and others through the infrastructure of the Internet, is changing how we do chemistry. While in its infancy across many chemistry laboratories and departments, it became apparent when considering our own work synthesizing radiopharmaceuticals for positron emission tomography (PET) that a more mature incarnation of the IoCT already exists. Finally, how does the IoCT impact our lives today, and what does it hold for the smartmore » (radio)chemical laboratories of the future?« less

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

NASA Astrophysics Data System (ADS)

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

2014-11-01

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [11C ]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

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

Avendaño-Estrada, A., E-mail: avilarod@uwalumni.com; Lara-Camacho, V. M., E-mail: avilarod@uwalumni.com; Ávila-García, M. C., E-mail: avilarod@uwalumni.com

2014-11-07

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [{sup 11}C]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Application of fluorodeoxyglucose positron emission tomography in the management of head and neck cancers

PubMed Central

Siddiqui, Farzan; Yao, Min

2014-01-01

The use of fluorodeoxyglucose positron emission tomography (FDG PET) scan technology in the management of head and neck cancers continues to increase. We discuss the biology of FDG uptake in malignant lesions and also discuss the physics of PET imaging. The various parameters described to quantify FDG uptake in cancers including standardized uptake value, metabolic tumor volume and total lesion glycolysis are presented. PET scans have found a significant role in the diagnosis and staging of head and neck cancers. They are also being increasingly used in radiation therapy treatment planning. Many groups have also used PET derived values to serve as prognostic indicators of outcomes including loco-regional control and overall survival. FDG PET scans are also proving very useful in assessing the efficacy of treatment and management and follow-up of head and neck cancer patients. This review article focuses on the role of FDG-PET computed tomography scans in these areas for squamous cell carcinoma of the head and neck. We present the current state of the art and speculate on the future applications of this technology including protocol development, newer imaging methods such as combined magnetic resonance and PET imaging and novel radiopharmaceuticals that can be used to further study tumor biology. PMID:24976927

21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

Code of Federal Regulations, 2013 CFR

2013-04-01

... distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION... distribution of PET drug products? (a) Written distribution procedures. You must establish, maintain, and follow written procedures for the control of distribution of PET drug products shipped from the PET drug...

21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

Code of Federal Regulations, 2011 CFR

2011-04-01

... distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION... distribution of PET drug products? (a) Written distribution procedures. You must establish, maintain, and follow written procedures for the control of distribution of PET drug products shipped from the PET drug...

21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

Code of Federal Regulations, 2012 CFR

2012-04-01

... distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION... distribution of PET drug products? (a) Written distribution procedures. You must establish, maintain, and follow written procedures for the control of distribution of PET drug products shipped from the PET drug...

21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

Code of Federal Regulations, 2014 CFR

2014-04-01

... distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION... distribution of PET drug products? (a) Written distribution procedures. You must establish, maintain, and follow written procedures for the control of distribution of PET drug products shipped from the PET drug...

Deficiencies of product labeling directions for the preparation of radiopharmaceuticals.

PubMed

Hung, Joseph C; Ponto, James A; Gadient, Katie R; Frie, Julia A; Aksamit, Carolyn M; Enquist, Cassandra L; Carrels, Katie E

2004-01-01

To identify potential deficiencies in product labeling (package insert) instructions for the preparation of radiopharmaceuticals. Preparation instructions, which include both reconstitution and quality control (QC) directions, as stated in the package inserts were evaluated for all commercially available reconstituted radiopharmaceuticals. Reviews of the package inserts were initially performed by each author, and then all identified deficiencies were compiled and evaluated by all authors. The preparation scenario for each package insert evaluated was based on a centralized nuclear pharmacy operation assuming typical support personnel, standard operating equipment, and workload. The instructions as stated in each package insert for the preparation (including QC) were rated as inadequate if a satisfactory preparation could not be prepared by a nuclear pharmacist or physician when instructions were followed exactly. Identified deficiencies in package insert instructions for the preparation of radiopharmaceuticals fell into the following five categories: (1) absent or incomplete directions (especially with regard to QC procedures); (2) restrictive directions (e.g., specific requirement to use designated needles, chromatography solvents, counting devices), (3) inconsistent directions (e.g., different reconstituted volumes for the same final drug product, unworkable expiration times); (4) impractical directions (e.g., unrealistically low reconstituted activity limits, dangerously high number of radiolabeled particles); and (5) vague directions (e.g., use of the words "should," "may," "recommend"). Manufacturers' directions for the preparation of radiopharmaceuticals often contain deficiencies and should be viewed as standard guidance rather than as requirements. Just as physicians are permitted to use U.S. Food and Drug Administration (FDA)-approved drugs for off-label indications, nuclear pharmacists should be allowed to use alternative methods for preparing radiopharmaceuticals, provided those methods have been validated to be as good as the stated directions and that the nuclear pharmacists do not engage in activities that fall outside the normal practice of pharmacy. Manufacturers, FDA, nuclear pharmacists, and nuclear physicians should work together to address identified deficiencies in package insert directions.

[Extravasation of radiopharmaceuticals: preventive measures and management recommended by SoFRa (Société Française de Radiopharmacie)].

PubMed

Barré, E; Nguyen, M-L; Bruel, D; Fournel, C; Hosten, B; Lao, S; Vercellino, L; Rizzo-Padoin, N

2013-07-01

Radiopharmaceuticals extravasation is rare but may have serious clinical issues. Because no specific recommendations are being proposed to date, the goals of our working group created within the French Society of Radiopharmacy are to determine preventive measures and to establish a pragmatic management of extravasation of these drugs. Our preventive measures are to recognize the symptoms (erythema, venous discoloration, swelling), to know the risk factors (which are related to radiopharmaceutical, patient, site of injection, injection technique) and severity (from erythema to skin necrosis, depending on the radionuclide) and how to avoid them (training and awareness of staff, choice of injection site, route of drug administration test, use of a catheter for administration of therapeutic radiopharmaceuticals). Management should be immediate. It can be facilitated by a specific emergency kit. General measures recommended are the immediate cessation of injection, aspiration of fluid extravasation, delimitation of the extravasated area with an indelible pen, informing the doctor. Specific measures taking into account the radiotoxicity of the radionuclide and the type of radiopharmaceutical were also established. The patient should be informed by the doctor about the risks and how to take care of. Traceability of the incident must be ensured. A multidisciplinary reflexion is essential to manage the extravasation as early and effectively as possible. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Cerenkov luminescence imaging of medical isotopes

PubMed Central

Ruggiero, Alessandro; Holland, Jason P.; Lewis, Jason S.; Grimm, Jan

2011-01-01

The development of novel multimodality imaging agents and techniques represents the current frontier of research in the field of medical imaging science. However, the combination of nuclear tomography with optical techniques has yet to be established. Here, we report the use of the inherent optical emissions from the decay of radiopharmaceuticals for Cerenkov luminescence imaging (CLI) of tumors in vivo and correlate the results with those obtained from concordant immuno-PET studies. Methods In vitro phantom studies were used to validate the visible light emission observed from a range of radionuclides including the positron emitters 18F, 64Cu, 89Zr, and 124I; β-emitter 131I; and α-particle emitter 225Ac for potential use in CLI. The novel radiolabeled monoclonal antibody 89Zr-desferrioxamine B-[DFO-J591 for immuno-PET of prostate-specific membrane antigen (PSMA) expression was used to coregister and correlate the CLI signal observed with the immuno-PET images and biodistribution studies. Results Phantom studies confirmed that Cerenkov radiation can be observed from a range of positron-,β-, and α-emitting radionuclides using standard optical imaging devices. The change in light emission intensity versus time was concordant with radionuclide decay and was also found to correlate linearly with both the activity concentration and the measured PET signal (percentage injected dose per gram). In vivo studies conducted in male severe combined immune deficient mice bearing PSMA-positive, subcutaneous LNCaP tumors demonstrated that tumor-specific uptake of 89Zr-DFO-J591 could be visualized by both immuno-PET and CLI. Optical and immuno-PET signal intensities were found to increase over time from 24 to 96 h, and biodistribution studies were found to correlate well with both imaging modalities. Conclusion These studies represent the first, to our knowledge, quantitative assessment of CLI for measuring radiotracer uptake in vivo. Many radionuclides common to both nuclear tomographic imaging and radiotherapy have the potential to be used in CLI. The value of CLI lies in its ability to image radionuclides that do not emit either positrons or γ-rays and are, thus, unsuitable for use with current nuclear imaging modalities. Optical imaging of Cerenkov radiation emission shows excellent promise as a potential new imaging modality for the rapid, high-throughput screening of radiopharmaceuticals PMID:20554722

Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?

PubMed

Cecchin, Diego; Palombit, Alessandro; Castellaro, Marco; Silvestri, Erica; Bui, Franco; Barthel, Henryk; Sabri, Osama; Corbetta, Maurizio; Bertoldo, Alessandra

2017-12-01

In the last 20 years growing attention has been devoted to multimodal imaging. The recent literature is rich of clinical and research studies that have been performed using different imaging modalities on both separate and integrated positron emission tomography (PET) and magnetic resonance (MR) scanners. However, today, hybrid PET/MR systems measure signals related to brain structure, metabolism, neurochemistry, perfusion, and neuronal activity simultaneously, i.e. in the same physiological conditions. A frequently raised question at meeting and symposia is: "Do we really need a hybrid PET/MR system? Are there any advantages over acquiring sequential and separate PET and MR scans?" The present paper is an attempt to answer these questions specifically in relation to PET combined with functional magnetic resonance imaging (fMRI) and arterial spin labeling. We searched (last update: June 2017) the databases PubMed, PMC, Google Scholar and Medline. We also included additional studies if they were cited in the selected articles. No language restriction was applied to the search, but the reviewed articles were all in English. Among all the retrieved articles, we selected only those performed using a hybrid PET/MR system. We found a total of 17 papers that were selected and discussed in three main groups according to the main radiopharmaceutical used: 18F-fluorodeoxyglucose (18F-FDG) (N.=8), 15O-water (15O-H2O) (N.=3) and neuroreceptors (N.=6). Concerning studies using 18F-FDG, simultaneous PET/fMRI revealed that global aspects of functional organization (e.g. graph properties of functional connections) are partially associated with energy consumption. There are remarkable spatial and functional similarities across modalities, but also discrepant findings. More work is needed on this point. There are only a handful of papers comparing blood flow measurements with PET 15O-H2O and MR arterial spin label (ASL) measures, and they show significant regional CBF differences between these two modalities. However, at least in one study the correlation at the level of gray, white matter, and whole brain is rather good (r=0.94, 0.8, 0.81 respectively). Finally, receptor studies show that simultaneous PET/fMRI could be a useful tool to characterize functional connectivity along with dynamic neuroreceptor adaptation in several physiological (e.g. working memory) or pathological (e.g. pain) conditions, with or without drug administrations. The simultaneous acquisition of PET (using a number of radiotracers) and functional MRI (using a number of sequences) offers exciting opportunities that we are just beginning to explore. The results thus far are promising in the evaluation of cerebral metabolism/flow, neuroreceptor adaptation, and network's energetic demand.

Bringing New PET Drugs to Clinical Practice - A Regulatory Perspective

PubMed Central

Hung, Joseph C.

2013-01-01

The regulatory framework for radioactive drugs, in particular those used in positron emission tomography (PET) scans, has been gradually established since the release of the Food and Drug Administration Modernization Act in 1997. Various guidances specially tailored to accommodate special properties of PET drugs have been issued by the Food and Drug Administration (FDA) in order to ensure this valuable technology (i.e., PET molecular imaging) will continue to be available to patients and yet the safety and efficacy of PET drugs are well regulated so that public health will be protected. This article presents several key elements of this regulatory framework for PET drugs. New regulatory avenues proposed by the FDA to facilitate the research and development process to bring more new PET drugs to clinical practice, as well as to foster the opportunity of using “orphan” PET drugs in clinical practice are also discussed in this paper. PMID:24312157

Organometallic Radiopharmaceuticals

NASA Astrophysics Data System (ADS)

Alberto, Roger

Although molecular imaging agents have to be synthesized ultimately from aqueous solutions, organometallic complexes are becoming more and more important as flexible yet kinetically stable building blocks for radiopharmaceutical drug discovery. The diversity of ligands, targets, and targeting molecules related to these complexes is an essential base for finding novel, noninvasive imaging agents to diagnose and eventually treat widespread diseases such as cancer. This review article covers the most important findings toward these objectives accomplished during the past 3-4 years. The two major available organometallic building blocks will be discussed in the beginning together with constraints for market introduction as imposed by science and industry. Since targeting radiopharmaceuticals are a major focus of current research in molecular imaging, attempts toward so-called technetium essential radiopharmaceuticals will be briefly touched in the beginning followed by the main discussion about the labeling of targeting molecules such as folic acid, nucleosides, vitamins, carbohydrates, and fatty acids. At the end, some new strategies for drug discovery will be introduced together with results from organometallic chemistry in water. The majority of the new results have been achieved with the [99mTc(OH2)3(CO)3]+ complex which will, though not exclusively, be a focus of this review.

Design study of an ultra-compact superconducting cyclotron for isotope production

NASA Astrophysics Data System (ADS)

Smirnov, V.; Vorozhtsov, S.; Vincent, J.

2014-11-01

A 12.5 MeV, 25 μA, proton compact superconducting cyclotron for medical isotope production has been designed and is currently in fabrication. The machine is initially aimed at producing 13N ammonia for Positron Emission Tomography (PET) cardiology applications. With an ultra-compact size and cost-effective price point, this system will offer clinicians unprecedented access to the preferred radiopharmaceutical isotope for cardiac PET imaging. A systems approach that carefully balanced the subsystem requirements coupled to precise beam dynamics calculations was followed. The system is designed to irradiate a liquid target internal to the cyclotron and to minimize the need for radiation shielding. The main parameters of the cyclotron, its design, and principal steps of the development work are presented here.

Fluorine-18 Radiochemistry, Labeling Strategies and Synthetic Routes

PubMed Central

2015-01-01

Fluorine-18 is the most frequently used radioisotope in positron emission tomography (PET) radiopharmaceuticals in both clinical and preclinical research. Its physical and nuclear characteristics (97% β+ decay, 109.7 min half-life, 635 keV positron energy), along with high specific activity and ease of large scale production, make it an attractive nuclide for radiochemical labeling and molecular imaging. Versatile chemistry including nucleophilic and electrophilic substitutions allows direct or indirect introduction of 18F into molecules of interest. The significant increase in 18F radiotracers for PET imaging accentuates the need for simple and efficient 18F-labeling procedures. In this review, we will describe the current radiosynthesis routes and strategies for 18F labeling of small molecules and biomolecules. PMID:25473848

Technical Pitfall in 68Ga-Prostate Specific Membrane Antigen Imaging: Altered Biodistribution Caused by Free 68Ga-Citrate Due to Radiolysis Showing Increased Vascular Activity.

PubMed

Hod, Nir; Anconina, Reut; Levin, Daniel; Ezroh Kazap, Dina; Lantsberg, Sophie

2018-06-01

As with any new molecular imaging modality, accurate characterization of abnormalities on Ga-PSMA PET/CT imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants, and potential sources of false imaging findings. Altered biodistribution can have a significant impact on scan interpretation. Presented here is a rare case in which radiopharmaceutical radiolysis occurred causing excessive free Ga-citrate showing as an increased vascular activity. As Ga-PSMA PET/CT imaging is a relatively new imaging technique, it is important to be aware of such a potential technical pitfall in clinical practice in order to prevent scan misinterpretation.

21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

Code of Federal Regulations, 2013 CFR

2013-04-01

... PET drugs? 212.2 Section 212.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... TOMOGRAPHY DRUGS General Provisions § 212.2 What is current good manufacturing practice for PET drugs? Current good manufacturing practice for PET drugs is the minimum requirements for the methods to be used...

21 CFR 212.110 - How must I maintain records of my production of PET drugs?

Code of Federal Regulations, 2014 CFR

2014-04-01

... PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... EMISSION TOMOGRAPHY DRUGS Records § 212.110 How must I maintain records of my production of PET drugs? (a) Record availability. Records must be maintained at the PET drug production facility or another location...

21 CFR 212.110 - How must I maintain records of my production of PET drugs?

Code of Federal Regulations, 2012 CFR

2012-04-01

... PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... EMISSION TOMOGRAPHY DRUGS Records § 212.110 How must I maintain records of my production of PET drugs? (a) Record availability. Records must be maintained at the PET drug production facility or another location...

21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

Code of Federal Regulations, 2014 CFR

2014-04-01

... PET drugs? 212.2 Section 212.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... TOMOGRAPHY DRUGS General Provisions § 212.2 What is current good manufacturing practice for PET drugs? Current good manufacturing practice for PET drugs is the minimum requirements for the methods to be used...

21 CFR 212.110 - How must I maintain records of my production of PET drugs?

Code of Federal Regulations, 2013 CFR

2013-04-01

... PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... EMISSION TOMOGRAPHY DRUGS Records § 212.110 How must I maintain records of my production of PET drugs? (a) Record availability. Records must be maintained at the PET drug production facility or another location...

21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

Code of Federal Regulations, 2012 CFR

2012-04-01

... PET drugs? 212.2 Section 212.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... TOMOGRAPHY DRUGS General Provisions § 212.2 What is current good manufacturing practice for PET drugs? Current good manufacturing practice for PET drugs is the minimum requirements for the methods to be used...

The Beginning and Development of the Theranostic Approach in Nuclear Medicine, as Exemplified by the Radionuclide Pair 86Y and 90Y

PubMed Central

Rösch, Frank; Herzog, Hans; Qaim, Syed M.

2017-01-01

In the context of radiopharmacy and molecular imaging, the concept of theranostics entails a therapy-accompanying diagnosis with the aim of a patient-specific treatment. Using the adequate diagnostic radiopharmaceutical, the disease and the state of the disease are verified for an individual patient. The other way around, it verifies that the radiopharmaceutical in hand represents a target-specific and selective molecule: the “best one” for that individual patient. Transforming diagnostic imaging into quantitative dosimetric information, the optimum radioactivity (expressed in maximum radiation dose to the target tissue and tolerable dose to healthy organs) of the adequate radiotherapeutical is applied to that individual patient. This theranostic approach in nuclear medicine is traced back to the first use of the radionuclide pair 86Y/90Y, which allowed a combination of PET and internal radiotherapy. Whereas the β-emitting therapeutic radionuclide 90Y (t½ = 2.7 d) had been available for a long time via the 90Sr/90Y generator system, the β+ emitter 86Y (t½ = 14.7 h) had to be developed for medical application. A brief outline of the various aspects of radiochemical and nuclear development work (nuclear data, cyclotron irradiation, chemical processing, quality control, etc.) is given. In parallel, the paper discusses the methodology introduced to quantify molecular imaging of 86Y-labelled compounds in terms of multiple and long-term PET recordings. It highlights the ultimate goal of radiotheranostics, namely to extract the radiation dose of the analogue 90Y-labelled compound in terms of mGy or mSv per MBq 90Y injected. Finally, the current and possible future development of theranostic approaches based on different PET and therapy nuclides is discussed. PMID:28632200

99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

PubMed

Parisella, Maria; D'Alessandria, Calogero; van de Bossche, Bieke; Chianelli, Marco; Ronga, Giuseppe; Papini, Enrico; Mikolajczak, Renata; Letizia, Claudio; De Toma, Giorgio; Veneziani, Augusto; Scopinaro, Francesco; Signore, Alberto

2004-04-01

An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

Positron emission tomography in neurological diseases.

PubMed

Kumar, Sudhir; Rajshekher, G; Prabhakar, Subhashini

2005-06-01

Positron emission tomography (PET) is the study of human physiology by electronic detection of positron-emitting radiopharmaceuticals. It is one of the noninvasive technologies that can measure the metabolic and functional activity of living tissue. Positron emission tomography finds its clinical applications in broadly three specialties--oncology, cardiology, and neurology. The current review focuses on its indications in neurological diseases. Recently published literature on the use of PET in neurology has been thoroughly analyzed. Several reports regarding the usage of PET in epilepsy, stroke, dementia, and movement disorders are available. Positron emission tomography does not appear to be useful as a primary or sole imaging technique in these conditions. On the other hand, it is useful in very specific situations, which have been elaborated in the review. It is also noteworthy that PET is complementary to the computed tomography/magnetic resonance imaging findings and data obtained from combining these modalities can be valuable in situations such as localization of the epileptogenic focus in cases of refractory epilepsy or for prediction of the outcome after thrombolysis in acute ischemic stroke. The major handicaps in widespread use of PET appear to be its lack of availability and its relatively high cost. Nevertheless, a review such as this would be helpful in judiciously selecting those patients who would benefit from undergoing a PET scan, at a time when PET imaging facility is likely to be available soon in the Indian private sector.

Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma.

PubMed

Castaldi, P; Leccisotti, L; Bussu, F; Miccichè, F; Rufini, V

2013-02-01

The role of PET-CT imaging in head and neck squamous cell carcinoma during pre-treatment staging, radiotherapy planning, treatment response assessment and post-therapy follow-up is reviewed with focus on current evidence, controversial issues and future clinical applications. In staging, the role of (18)F-FDG PET-CT is well recognized for detecting cervical nodal involvement as well as for exclusion of distant metastases and synchronous primary tumours. In the evaluation of treatment response, the high negative predictive value of (18)F-FDG PET-CT performed at least 8 weeks from the end of radio-chemotherapy allows prevention of unnecessary diagnostic invasive procedures and neck dissection in many patients, with a significant impact on clinical outcome. On the other hand, in this setting, the low positive predictive value due to possible post-radiation inflammation findings requires special care before making a clinical decision. Controversial data are currently available on the role of PET imaging during the course of radio-chemotherapy. The prognostic role of (18)F-FDG PET-CT imaging in head and neck squamous cell carcinoma is recently emerging, in addition to the utility of this technique in evaluation of the tumour volume for planning radiation therapy. Additionally, new PET radiopharmaceuticals could provide considerable information on specific tumour characteristics, thus overcoming the limitations of (18)F-FDG.

Cage-like bifunctional chelators, copper-64 radiopharmaceuticals and PET imaging using the same

DOEpatents

Conti, Peter S.; Cai, Hancheng; Li, Zibo; Liu, Shuanglong

2016-08-02

Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.

Status of the cyclotron/P.E.T. facility at the State University of New York at Buffalo

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

Toorongian, S.A.; Haka, M.S.

1994-12-31

A new P.E.T./Cyclotron facility has been constructed on the Main St. campus of the State University of New York at Buffalo to service the needs of Nuclear Medicine departments in Buffalo and throughout the Western New York area. This facility is jointly funded and operated by S.U.N.Y. and the Veterans Administration. The cyclotron, as well as the research labs and a nuclear pharmacy to prepare non-positron emitting radiopharmaceuticals, are located in a newly constructed facility on campus. The P.E.T. scanner is located in the Veterans Administration Hospital adjacent to the campus. The two annexes are connected by a pneumatic transportmore » {open_quotes}rabbit{close_quotes} system. The cyclotron and all radiopharmaceutical synthesis apparatus have been purchased from Ion Beam Applications s.a. of Lovain-la-Neuve Belgium.« less

MA-NOTMP: A Triazacyclononane Trimethylphosphinate Based Bifunctional Chelator for Gallium Radiolabelling of Biomolecules.

PubMed

Poty, Sophie; Désogère, Pauline; Šimeček, Jakub; Bernhard, Claire; Goncalves, Victor; Goze, Christine; Boschetti, Frédéric; Notni, Johannes; Wester, Hans J; Denat, Franck

2015-09-01

In the past few years, gallium-68 has demonstrated significant potential as a radioisotope for positron emission tomography (PET), and the optimization of chelators for gallium coordination is a major goal in the development of radiopharmaceuticals. Methylaminotriazacyclononane trimethylphosphinate (MA-NOTMP), a new C-functionalized triazacyclononane derivative with phosphinate pendant arms, presents excellent coordination properties for (68) Ga (low ligand concentration, labelling at low pH even at room temperature). A "ready-to-be-grafted" bifunctional chelating agent (p-NCS-Bz-MA-NOTMP) was prepared to allow (68) Ga labelling of sensitive biological vectors. Conjugation to a bombesin(7-14) derivative was performed, and preliminary in vitro experiments demonstrated the potential of MA-NOTMP in the development of radiopharmaceuticals. This new chelator is therefore of major interest for labelling sensitive biomolecules, and further in vivo experiments will soon be performed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION... with labeling and packaging PET drug products? (a) A PET drug product must be suitably labeled and...

21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION... with labeling and packaging PET drug products? (a) A PET drug product must be suitably labeled and...

21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION... with labeling and packaging PET drug products? (a) A PET drug product must be suitably labeled and...

21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION... with labeling and packaging PET drug products? (a) A PET drug product must be suitably labeled and...

68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling.

PubMed

Young, Jennifer D; Abbate, Vincenzo; Imberti, Cinzia; Meszaros, Levente K; Ma, Michelle T; Terry, Samantha Y A; Hider, Robert C; Mullen, Greg E; Blower, Philip J

2017-08-01

The clinical impact and accessibility of 68 Ga tracers for the prostate-specific membrane antigen (PSMA) and other targets would be greatly enhanced by the availability of a simple, 1-step kit-based labeling process. Radiopharmacy staff are accustomed to such procedures in the daily preparation of 99m Tc radiopharmaceuticals. Currently, chelating agents used in 68 Ga radiopharmaceuticals do not meet this ideal. The aim of this study was to develop and evaluate preclinically a 68 Ga radiotracer for imaging PSMA expression that could be radiolabeled simply by addition of 68 Ga generator eluate to a cold kit. Methods: A conjugate of a tris(hydroxypyridinone) (THP) chelator with the established urea-based PSMA inhibitor was synthesized and radiolabeled with 68 Ga by adding generator eluate directly to a vial containing the cold precursors THP-PSMA and sodium bicarbonate, with no further manipulation. It was analyzed after 5 min by instant thin-layer chromatography and high-performance liquid chromatography. The product was subjected to in vitro studies to determine PSMA affinity using PSMA-expressing DU145-PSMA cells, with their nonexpressing analog DU145 as a control. In vivo PET imaging and ex vivo biodistribution studies were performed in mice bearing xenografts of the same cell lines, comparing 68 Ga-THP-PSMA with 68 Ga-HBED-CC-PSMA. Results: Radiolabeling was complete (>95%) within 5 min at room temperature, showing a single radioactive species by high-performance liquid chromatography that was stable in human serum for more than 6 h and showed specific binding to PSMA-expressing cells (concentration giving 50% inhibition of 361 ± 60 nM). In vivo PET imaging showed specific uptake in PSMA-expressing tumors, reaching 5.6 ± 1.2 percentage injected dose per cubic centimeter at 40-60 min and rapid clearance from blood to kidney and bladder. The tumor uptake, biodistribution, and pharmacokinetics were not significantly different from those of 68 Ga-HBED-CC-PSMA except for reduced uptake in the spleen. Conclusion: 68 Ga-THP-PSMA has equivalent imaging properties but greatly simplified radiolabeling compared with other 68 Ga-PSMA conjugates. THP offers the prospect of rapid, simple, 1-step, room-temperature syringe-and-vial radiolabeling of 68 Ga radiopharmaceuticals. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

Code of Federal Regulations, 2011 CFR

2011-04-01

... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

Code of Federal Regulations, 2013 CFR

2013-04-01

... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

Code of Federal Regulations, 2014 CFR

2014-04-01

... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

Code of Federal Regulations, 2012 CFR

2012-04-01

... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

21 CFR 212.90 - What actions must I take to control the distribution of PET drug products?

Code of Federal Regulations, 2010 CFR

2010-04-01

... distribution of PET drug products? 212.90 Section 212.90 Food and Drugs FOOD AND DRUG ADMINISTRATION... control the distribution of PET drug products? (a) Written distribution procedures. You must establish, maintain, and follow written procedures for the control of distribution of PET drug products shipped from...

21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

Code of Federal Regulations, 2010 CFR

2010-04-01

... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... What controls and acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining...

21 CFR 315.4 - Indications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Indications. 315.4 Section 315.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE... assessment; and (4) Diagnostic or therapeutic patient management. (b) Where a diagnostic radiopharmaceutical...

Development of an Isolator System for PET Drug Compounding with Sterilization and Dispensing Units.

PubMed

Waki, Atsuo; Hashimoto, Yuuki; Suzuki, Hisashi; Mizukawa, Yousuke; Kinoshita, Toshiaki; Ichihara, Hironobu; Kaneko, Izumi; Iwakuma, Kazuko; Kawamura, Kazuki; Zhang, Ming-Rong; Fujibayashi, Yasuhisa

2016-01-01

To maintain sterility of PET drug is the most important for in-house positron emission tomography (PET) drug manufacturing, and sanitary control of the laboratory to perform aseptic procedure is the key point for the sterility of PET drugs. However, rigorous sanitary control affects both the high cost and the low efficiency. To conquer those, we developed an isolator system especially for PET drug compounding including sterilization and dispensing units. This system consists of a HEPA unit for inlet and outlet, positive regulation of the ear inside isolator, a sterilizer with vapored hydrogen peroxide and a dispenser with self-shield for radiation. We set the materials for the dispenser through gloves, and the compounding such as sterilization and dispensing PET drugs to the containers is performed automatically without radiation. High level assurance of PET drug sterility is expected to be accomplished in the PET centers of the hospitals without high level sanitary control.

76 FR 7863 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... Eligibility of Drugs, Biologicals, and Radiopharmaceutical Agents for Transitional Pass-Through Status Under... physicians can apply for transitional pass-through payment for drugs and biologicals used with services...

76 FR 30944 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

... Determine Eligibility of Drugs, Biologicals, and Radiopharmaceutical Agents for Transitional Pass-Through... companies, and physicians can apply for transitional pass-through payment for drugs and biologicals used...

Position of nuclear medicine techniques in the diagnostic work-up of neuroendocrine tumors.

PubMed

Bombardieri, E; Seregni, E; Villano, C; Chiti, A; Bajetta, E

2004-06-01

In recent years nuclear medicine has contributed to the impressive development of the knowledge of neuroendocrine tumors in terms of biology (receptor scintigraphy), pharmacology (development of new tracers), and therapy (radiometabolic therapy). At present, it is impossible to plan the management of a patient affected by a neuroendocrine tumor without performing nuclear medicine examinations. The contribution of nuclear medicine had affected and improved the management of these patients by offering various important options that are part of the modern diagnosis and treatment protocols. The clinical experience and the literature confirm that, among the wide variety of tracers and nuclear medicine modalities available today, metaiodobenzylguanidine (MIBG) and DTPA-D-Phe-octreotide (pentetreotide) are the radiopharmaceuticals of current clinical use. Several new somatostatin analogues are under investigation. Positron emission tomography (PET) supplies a range of labelled compounds to be used for the visualization of tumor biochemistry. In addition to the first routinely used PET tracer in oncology, 18F-labelled deoxyglucose (FDG), a number of radiopharmaceuticals based on different precursors such as fluorodopamine and 5-hydroxytryptophan (5-HTP) are going to gain a clinical role. Of course, the diagnosis of neuroendocrine tumors has to be based on integrated information derived from different examinations including nuclear medicine studies. The clinical presentation of neuroendocrine tumors is highly variable: sometimes they manifest typical or atypical symptoms but they may also be detected by chance during an X-ray or ultrasound examination carried out for other reasons. At disease presentation nuclear medicine modalities are sometimes able to direct physicians towards the clinical diagnosis thanks to the specificity of their imaging mechanisms. They also play a role in disease staging and restaging, patient follow-up and treatment monitoring. In addition, the biological characterisation of neuroendocrine tissues (receptor status, glucose metabolism, differentiation, etc.) allows the interpretation of radiopharmaceutical uptake as a prognostic parameter and sometimes as a predictor of the response to treatment.

Effect of blood activity on dosimetric calculations for radiopharmaceuticals

NASA Astrophysics Data System (ADS)

Zvereva, Alexandra; Petoussi-Henss, Nina; Li, Wei Bo; Schlattl, Helmut; Oeh, Uwe; Zankl, Maria; Graner, Frank Philipp; Hoeschen, Christoph; Nekolla, Stephan G.; Parodi, Katia; Schwaiger, Markus

2016-11-01

The objective of this work was to investigate the influence of the definition of blood as a distinct source on organ doses, associated with the administration of a novel radiopharmaceutical for positron emission tomography-computed tomography (PET/CT) imaging—(S)-4-(3-18F-fluoropropyl)-L-glutamic acid (18F-FSPG). Personalised pharmacokinetic models were constructed based on clinical PET/CT images from five healthy volunteers and blood samples from four of them. Following an identifiability analysis of the developed compartmental models, person-specific model parameters were estimated using the commercial program SAAM II. Organ doses were calculated in accordance to the formalism promulgated by the Committee on Medical Internal Radiation Dose (MIRD) and the International Commission on Radiological Protection (ICRP) using specific absorbed fractions for photons and electrons previously derived for the ICRP reference adult computational voxel phantoms. Organ doses for two concepts were compared: source organ activities in organs parenchyma with blood as a separate source (concept-1); aggregate activities in perfused source organs without blood as a distinct source (concept-2). Aggregate activities comprise the activities of organs parenchyma and the activity in the regional blood volumes (RBV). Concept-1 resulted in notably higher absorbed doses for most organs, especially non-source organs with substantial blood contents, e.g. lungs (92% maximum difference). Consequently, effective doses increased in concept-1 compared to concept-2 by 3-10%. Not considering the blood as a distinct source region leads to an underestimation of the organ absorbed doses and effective doses. The pronounced influence of the blood even for a radiopharmaceutical with a rapid clearance from the blood, such as 18F-FSPG, suggests that blood should be introduced as a separate compartment in most compartmental pharmacokinetic models and blood should be considered as a distinct source in dosimetric calculations. Hence, blood samples should be included in all pharmacokinetic and dosimetric studies for new tracers if possible.

77 FR 71802 - Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

...] Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability... Positron Emission Tomography (PET) Drugs.'' The guidance is intended to assist manufacturers of PET drugs... ``Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs.'' The guidance summarizes the...

Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran.

PubMed

Jalilian, Amir Reza; Beiki, Davood; Hassanzadeh-Rad, Arman; Eftekhari, Arash; Geramifar, Parham; Eftekhari, Mohammad

2016-07-01

During past 3 decades, nuclear medicine has flourished as vibrant and independent medical specialty in Iran. Since that time, more than 200 nuclear physicians have been trained and now practicing in nearly 158 centers throughout the country. In the same period, Tc-99m generators and variety of cold kits for conventional nuclear medicine were locally produced for the first time. Local production has continued to mature in robust manner while fulfilling international standards. To meet the ever-growing demand at the national level and with international achievements in mind, work for production of other Tc-99m-based peptides such as ubiquicidin, bombesin, octreotide, and more recently a kit formulation for Tc-99m TRODAT-1 for clinical use was introduced. Other than the Tehran Research Reactor, the oldest facility active in production of medical radioisotopes, there is one commercial and three hospital-based cyclotrons currently operational in the country. I-131 has been one of the oldest radioisotope produced in Iran and traditionally used for treatment of thyrotoxicosis and differentiated thyroid carcinoma. Since 2009, (131)I-meta-iodobenzylguanidine has been locally available for diagnostic applications. Gallium-67 citrate, thallium-201 thallous chloride, and Indium-111 in the form of DTPA and Oxine are among the early cyclotron-produced tracers available in Iran for about 2 decades. Rb-81/Kr-81m generator has been available for pulmonary ventilation studies since 1996. Experimental production of PET radiopharmaceuticals began in 1998. This work has culminated with development and optimization of the high-scale production line of (18)F-FDG shortly after installation of PET/CT scanner in 2012. In the field of therapy, other than the use of old timers such as I-131 and different forms of P-32, there has been quite a significant advancement in production and application of therapeutic radiopharmaceuticals in recent years. Application of (131)I-meta-iodobenzylguanidine for treatment of neuroblastoma, pheochromocytoma, and other neuroendocrine tumors has been steadily increasing in major academic university hospitals. Also (153)Sm-EDTMP, (177)Lu-EDTMP, (90)Y-citrate, (90)Y-hydroxyapatite colloid, (188/186)Re-sulfur colloid, and (188/186)Re-HEDP have been locally developed and now routinely available for bone pain palliation and radiosynovectomy. Cu-64 has been available to the nuclear medicine community for some time. With recent reports in diagnostic and therapeutic applications of this agent especially in the field of oncology, we anticipate an expansion in production and availability. The initiation of the production line for gallium-68 generator is one of the latest exciting developments. We are proud that Iran would be joining the club of few nations with production lines for this type of generator. There are also quite a number of SPECT and PET tracers at research and preclinical stage of development preliminarily introduced for possible future clinical applications. Availability of fluorine-18 tracers and gallium-68 generators would no doubt allow rapid dissemination of PET/CT practices in various parts of our large country even far from a cyclotron facility. Also, local production and availability of therapeutic radiopharmaceuticals are going to open exciting horizons in the field of nuclear medicine therapy. Given the available manpower, local infrastructure of SPECT imaging, and rapidly growing population, the production of Tc-99m generators and cold kit would continue to flourish in Iran. Copyright © 2016 Elsevier Inc. All rights reserved.

21 CFR 601.33 - Indications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Indications. 601.33 Section 601.33 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING... assessment; and (4) Diagnostic or therapeutic patient management. (b) Where a diagnostic radiopharmaceutical...

Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P.

PubMed

Smilkov, Katarina; Janevik, Emilija; Guerrini, Remo; Pasquali, Micol; Boschi, Alessandra; Uccelli, Licia; Di Domenico, Giovanni; Duatti, Adriano

2014-09-01

New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N](2+) (M=(99m)Tc, (188)Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N](2+) core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N](2+) core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph. New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties. Copyright © 2014 Elsevier Ltd. All rights reserved.

PET Scans Obtained for Evaluation of Cognitive Dysfunction

PubMed Central

Silverman, Daniel H. S.; Mosconi, Lisa; Ercoli, Linda; Chen, W; Small, Gary W.

2015-01-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism with devastating neuropathologic, economic, social and clinical consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are carried out with [18F]fluorodeoxyglucose (FDG) as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility in evaluating patients with cognitive impairment, and in distinguishing among primary neurodegenerative disorders and other etiologies for cognitive decline. In addition to focusing upon the effects on cerebral metabolism examined with FDG PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact upon the enormous human toll exacted by these diseases. PMID:18514081

Clinical evaluation of the radiolanthanide terbium-152: first-in-human PET/CT with 152Tb-DOTATOC.

PubMed

Baum, Richard P; Singh, Aviral; Benešová, Martina; Vermeulen, Christiaan; Gnesin, Silvano; Köster, Ulli; Johnston, Karl; Müller, Dirk; Senftleben, Stefan; Kulkarni, Harshad R; Türler, Andreas; Schibli, Roger; Prior, John O; van der Meulen, Nicholas P; Müller, Cristina

2017-10-31

The existence of theragnostic pairs of radionuclides allows the preparation of radiopharmaceuticals for diagnostic and therapeutic purposes. Radiolanthanides, such as 177 Lu, are successfully used for therapeutic purposes; however, a perfect diagnostic match is currently not available for clinical use. A unique, multi-disciplinary study was performed using 152 Tb (T 1/2 = 17.5 h, Eβ + average = 1140 keV, Iβ + = 20.3%), which resulted in the first-in-human PET/CT images with this promising radionuclide. For this purpose, 152 Tb was produced via a spallation process followed by mass separation at ISOLDE, CERN. The chemical separation and quality control, performed at PSI, resulted in a pure product in sufficient yields. Clinical PET phantom studies revealed an increased image noise level, because of the smaller β + branching ratio of 152 Tb as compared to standard PET nuclides at matched activity concentrations; however, the expected recovery would be comparable at matched signal-to-noise ratios in clinical PET. 152 Tb was used for labeling DOTATOC, at Zentralklinik Bad Berka, and administered to a patient for a first-in-human clinical study. PET scans were performed over a period of 24 h, allowing the visualization of even small metastases with increased tumor-to-background contrast over time. Based on the results obtained in this work, it can be deduced that PET/CT imaging with 152 Tb-labeled targeting agents has promise for clinical application and may be particularly interesting for pre-therapeutic dosimetry.

[(68)Ga-labeled peptides for clinical trials - production according to the German Drug Act: the Göttingen experience].

PubMed

Meller, Birgit; Angerstein, C; Liersch, T; Ghadimi, M; Sahlmann, C-O; Meller, J

2012-01-01

The AMG implies far-reaching implications for the synthesis of new radiopharmaceuticals for clinical trials. As a part of the DFG-funded Clinical Research Group (KFO 179) a project designated "Immuno-PET for assessment of early response to radiochemotherapy of advanced rectal cancer" was initiated. This trial is focused on a trivalent bispecific humanized monoclonal antibody, and a 68Ga-labeled peptide. Following the new regulatory framework we established a GMP-compliant cleanroom laboratory and applied for a manufacturing permission. During the project constructural, personnel and organizational conditions for a successful application were established, including a quality management system. A GMP-conform cleanroom laboratory class C was constructed, equipped with a two-chamber lock. The actual manufacturing is performed in a closed system with subsequent sterile filtration. The manufacturing processes have been automatised and validated as well as the necessary quality controls. The manufacturing permission was granted after an official inspection. The new German Drug Act is considered as a break in the production practice of nuclear medicine. The early involvement and communication with the authorities avoids time-consuming and costly planning errors. It is much to be hoped that the new legal situation in Germany will not cause serious impairments in the realization of clinical trials in German nuclear medicine.

21 CFR 212.40 - How must I control the components I use to produce PET drugs and the containers and closures I...

Code of Federal Regulations, 2014 CFR

2014-04-01

... PET drugs and the containers and closures I package them in? 212.40 Section 212.40 Food and Drugs FOOD..., and Closures § 212.40 How must I control the components I use to produce PET drugs and the containers... not use in PET drug production any lot that does not meet its specifications, including any expiration...

21 CFR 212.40 - How must I control the components I use to produce PET drugs and the containers and closures I...

Code of Federal Regulations, 2013 CFR

2013-04-01

... PET drugs and the containers and closures I package them in? 212.40 Section 212.40 Food and Drugs FOOD..., and Closures § 212.40 How must I control the components I use to produce PET drugs and the containers... not use in PET drug production any lot that does not meet its specifications, including any expiration...

21 CFR 212.40 - How must I control the components I use to produce PET drugs and the containers and closures I...

Code of Federal Regulations, 2012 CFR

2012-04-01

... PET drugs and the containers and closures I package them in? 212.40 Section 212.40 Food and Drugs FOOD..., and Closures § 212.40 How must I control the components I use to produce PET drugs and the containers... not use in PET drug production any lot that does not meet its specifications, including any expiration...

21 CFR 212.40 - How must I control the components I use to produce PET drugs and the containers and closures I...

Code of Federal Regulations, 2011 CFR

2011-04-01

... PET drugs and the containers and closures I package them in? 212.40 Section 212.40 Food and Drugs FOOD..., and Closures § 212.40 How must I control the components I use to produce PET drugs and the containers... not use in PET drug production any lot that does not meet its specifications, including any expiration...

Preparation and preclinical evaluation of (66)Ga-DOTA-E(c(RGDfK))2 as a potential theranostic radiopharmaceutical.

PubMed

Lopez-Rodriguez, V; Gaspar-Carcamo, R E; Pedraza-Lopez, M; Rojas-Calderon, E L; Arteaga de Murphy, C; Ferro-Flores, G; Avila-Rodriguez, M A

2015-02-01

Integrin αvβ3 plays an important role in angiogenesis and is over-expressed in tumoral endothelial cells and some other tumor cells. RGD (Arg-Gly-Asn) peptides labeled with (68)Ga (t1/2=68min) have showed good characteristics for imaging of αvβ3 expression using positron emission tomography (PET). Gallium-66 has been proposed as a PET imaging alternative to (68)Ga and given the unique high energy of its emitted positrons (Emax 4.15MeV) it may also be useful for therapy. The aim of this research is to prepare [(66)Ga]DOTA-E-[c(RGDfK)]2 and evaluate in mice its potential as a new theranostic radiopharmaceutical. High specific activity (66)Ga was produced via the (66)Zn(p,n) reaction, and the labelling method of DOTA-E-[c(RGDfK)]2 with (66)Ga was optimized. Radiochemical purity was determined by TLC, and in vitro stability and protein binding were determined. Serial microPET imaging and biodistribution studies were carried out in nude mice bearing C6 xenografts. Radiation absorbed dose estimates were based on the biodistribution studies, where tumor and organs of interest were collected at 0.5, 1, 3, 5 and 24h post-injection of [(66)Ga]DOTA-E-[c(RGDfK)]2. Our results have shown that [(66)Ga]DOTA-E-[c(RGDfK)]2 can be prepared with high radiochemical purity (>97%), specific activity (36-67GBq/μmol), in vitro stability, and moderate protein binding. MicroPET imaging up to 24 post-injection showed contrasting tumors reflecting αvβ3-targeted tracer accumulation. Biodistribution studies and dosimetry estimations showed a stable tumor uptake, rapid blood clearance, and favorable tumor-to-tissue ratios. The peptide conjugated DOTA-E-[c(RGDfK)]2 labeled with (66)Ga may be attractive as a theranostic agent for tumors over-expressing αvβ3 integrins. Copyright © 2014 Elsevier Inc. All rights reserved.

75 FR 45769 - Medicare Program; Changes to the Hospital Outpatient Prospective Payment System and Ambulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... 2010 OPPS/ASC final rule, we estimated that pass-through spending for both drugs and biologicals and... pass through drugs and non-implantable biologicals, and device categories and the proportion of... and implantable biologicals), ``policy packaged'' drugs (diagnostic radiopharmaceuticals and contrast...

21 CFR 212.71 - What actions must I take if a batch of PET drug product does not conform to specifications?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false What actions must I take if a batch of PET drug... actions must I take if a batch of PET drug product does not conform to specifications? (a) Rejection of nonconforming product. You must reject a batch of a PET drug product that does not conform to specifications...

21 CFR 212.71 - What actions must I take if a batch of PET drug product does not conform to specifications?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false What actions must I take if a batch of PET drug... actions must I take if a batch of PET drug product does not conform to specifications? (a) Rejection of nonconforming product. You must reject a batch of a PET drug product that does not conform to specifications...

21 CFR 212.71 - What actions must I take if a batch of PET drug product does not conform to specifications?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false What actions must I take if a batch of PET drug... actions must I take if a batch of PET drug product does not conform to specifications? (a) Rejection of nonconforming product. You must reject a batch of a PET drug product that does not conform to specifications...

21 CFR 212.71 - What actions must I take if a batch of PET drug product does not conform to specifications?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false What actions must I take if a batch of PET drug... actions must I take if a batch of PET drug product does not conform to specifications? (a) Rejection of nonconforming product. You must reject a batch of a PET drug product that does not conform to specifications...

PET - radiopharmaceutical facilities at Washington University Medical School - an overview

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

Dence, C.S.; Welch, M.J.

1994-12-31

The PET program at Washington University has evolved over more than three decades of research and development in the use of positron-emitting isotopes in medicine and biology. In 1962 the installation of the first hospital cyclotron in the USA was accomplished. This first machine was an Allis Chalmers (AC) cyclotron and it was operated until July, 1990. Simultaneously with this cyclotron the authors also ran a Cyclotron Corporation (TCC) CS-15 cyclotron that was purchased in 1977. Both of these cyclotrons were maintained in-house and operated with a relatively small downtime (approximately 3.5%). After the dismantling of the AC machine inmore » 1990, a Japanese Steel Works 16/8 (JSW-16/8) cyclotron was installed in the vault. Whereas the AC cyclotron could only accelerate deuterons (6.2 MeV), the JSW - 16/8 machine can accelerate both protons and deuterons, so all of the radiopharmaceuticals can be produced on either of the two presently owned accelerators. At the end of May 1993, the medical school installed the first clinical Tandem Cascade Accelerator (TCA) a collaboration with Science Research Laboratories (SRL) of Somerville, MA. Preliminary target testing, design and development are presently under way. In 1973, the University installed the first operational PETT device in the country, and at present there is a large basic science and clinical research program involving more than a hundred staff in nuclear medicine, radiation sciences, neurology, neurosurgery, psychiatry, cardiology, pulmonary medicine, oncology, and surgery.« less

Trends of radiopharmaceutical use at Mayo Clinic Rochester.

PubMed

Mroczenski, Ashley A; Berent, Stephanie M; Hall, Alice A; Hung, Joseph C; Herold, Thomas J; Mullan, Brian P

2007-09-01

The field of radiology is continuously changing. The purpose of this study was to identify the effect of technologic advances on nuclear medicine during the past 15 y. The number of radiopharmaceutical doses dispensed at Mayo Clinic (Rochester, Minnesota) from 1990 through 2004 was tracked. The number of doses was equivalent to the number of scans performed. Since 1990, the number of bone scans decreased by 38%. Brain scans using (99m)Tc have increased by 166%. The number of cardiac doses dispensed increased 184% from 1990 through 1999 but decreased 3% between 2000 and 2004. The number of lung scans decreased 52% from 1992 through 1999 and increased 66% from 1999 through 2004. The number of kidney scans decreased 67% since 1990. Since its introduction in 1993, the use of (111)In-pentetreotide has increased 16-fold. PET data showed a 602% increase in the number of procedures from 2001 through 2004. The number of bone, lung, and kidney scans has decreased because of advances in other imaging modalities. Although the number of cardiac imaging scans increased during most of the study period, the recent rate of growth has declined, possibly because of the availability of alternative procedures such as stress echocardiography. The number of brain and lung scans performed has increased, partially because of the development of new protocols. PET and tumor imaging have shown a substantial increase because of increasing numbers of approved indications and Medicare reimbursement.

21 CFR 212.61 - What must I do to ensure the stability of my PET drug products through expiry?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false What must I do to ensure the stability of my PET... my PET drug products through expiry? (a) Stability testing program. You must establish, follow, and maintain a written testing program to assess the stability characteristics of your PET drug products. The...

21 CFR 212.61 - What must I do to ensure the stability of my PET drug products through expiry?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false What must I do to ensure the stability of my PET... my PET drug products through expiry? (a) Stability testing program. You must establish, follow, and maintain a written testing program to assess the stability characteristics of your PET drug products. The...

21 CFR 212.61 - What must I do to ensure the stability of my PET drug products through expiry?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What must I do to ensure the stability of my PET... the stability of my PET drug products through expiry? (a) Stability testing program. You must... PET drug products. The test methods must be reliable, meaningful, and specific. The samples tested for...

21 CFR 212.61 - What must I do to ensure the stability of my PET drug products through expiry?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false What must I do to ensure the stability of my PET... my PET drug products through expiry? (a) Stability testing program. You must establish, follow, and maintain a written testing program to assess the stability characteristics of your PET drug products. The...

21 CFR 212.61 - What must I do to ensure the stability of my PET drug products through expiry?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false What must I do to ensure the stability of my PET... my PET drug products through expiry? (a) Stability testing program. You must establish, follow, and maintain a written testing program to assess the stability characteristics of your PET drug products. The...

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

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

Highlights lecture EANM 2016: "Embracing molecular imaging and multi-modal imaging: a smart move for nuclear medicine towards personalized medicine".

PubMed

Aboagye, Eric O; Kraeber-Bodéré, Françoise

2017-08-01

The 2016 EANM Congress took place in Barcelona, Spain, from 15 to 19 October under the leadership of Prof. Wim Oyen, chair of the EANM Scientific Committee. With more than 6,000 participants, this congress was the most important European event in nuclear medicine, bringing together a multidisciplinary community involved in the different fields of nuclear medicine. There were over 600 oral and 1,200 poster or e-Poster presentations with an overwhelming focus on development and application of imaging for personalized care, which is timely for the community. Beyond FDG PET, major highlights included progress in the use of PSMA and SSTR receptor-targeted radiopharmaceuticals and associated theranostics in oncology. Innovations in radiopharmaceuticals for imaging pathologies of the brain and cardiovascular system, as well as infection and inflammation, were also highlighted. In the areas of physics and instrumentation, multimodality imaging and radiomics were highlighted as promising areas of research.

Diffusion processes in tumors: A nuclear medicine approach

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

Amaya, Helman, E-mail: haamayae@unal.edu.co

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 {sup 18}F-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 softwaremore » 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 {sup 18}F-FDG is necessary to include pharmacokinetic models, to make a correct interpretation of the gradient magnitude and Laplacian of counts images.« 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.

21 CFR 212.100 - What do I do if I receive a complaint about a PET drug product produced at my facility?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false What do I do if I receive a complaint about a PET... complaint about a PET drug product produced at my facility? (a) Written complaint procedures. You must... quality or purity of, or possible adverse reactions to, a PET drug product. (b) Complaint review. The...

21 CFR 212.100 - What do I do if I receive a complaint about a PET drug product produced at my facility?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false What do I do if I receive a complaint about a PET... complaint about a PET drug product produced at my facility? (a) Written complaint procedures. You must... quality or purity of, or possible adverse reactions to, a PET drug product. (b) Complaint review. The...

21 CFR 212.100 - What do I do if I receive a complaint about a PET drug product produced at my facility?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false What do I do if I receive a complaint about a PET... complaint about a PET drug product produced at my facility? (a) Written complaint procedures. You must... quality or purity of, or possible adverse reactions to, a PET drug product. (b) Complaint review. The...

21 CFR 212.100 - What do I do if I receive a complaint about a PET drug product produced at my facility?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false What do I do if I receive a complaint about a PET... complaint about a PET drug product produced at my facility? (a) Written complaint procedures. You must... quality or purity of, or possible adverse reactions to, a PET drug product. (b) Complaint review. The...

Activity-based costing evaluation of a [(18)F]-fludeoxyglucose positron emission tomography study.

PubMed

Krug, Bruno; Van Zanten, Annie; Pirson, Anne-Sophie; Crott, Ralph; Borght, Thierry Vander

2009-10-01

The aim of the study is to use the activity-based costing approach to give a better insight in the actual cost structure of a positron emission tomography procedure (FDG-PET) by defining the constituting components and by simulating the impact of possible resource or practice changes. The cost data were obtained from the hospital administration, personnel and vendor interviews as well as from structured questionnaires. A process map separates the process in 16 patient- and non-patient-related activities, to which the detailed cost data are related. One-way sensitivity analyses shows to which degree of uncertainty the different parameters affect the individual cost and evaluate the impact of possible resource or practice changes like the acquisition of a hybrid PET/CT device, the patient throughput or the sales price of a 370MBq (18)F-FDG patient dose. The PET centre spends 73% of time in clinical activities and the resting time after injection of the tracer (42%) is the single largest departmental cost element. The tracer cost and the operational time have the most influence on cost per procedure. The analysis shows a total cost per FDG-PET ranging from 859 Euro for a BGO PET camera to 1142 Euro for a 16 slices PET-CT system, with a distribution of the resource costs in decreasing order: materials (44%), equipment (24%), wage (16%), space (6%) and hospital overhead (10%). The cost of FDG-PET is mainly influenced by the cost of the radiopharmaceutical. Therefore, the latter rather than the operational time should be reduced in order to improve its cost-effectiveness.

Positron emission tomography molecular imaging of dopaminergic system in drug addiction.

PubMed

Hou, Haifeng; Tian, Mei; Zhang, Hong

2012-05-01

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Copyright © 2012 Wiley Periodicals, Inc.

21 CFR 212.100 - What do I do if I receive a complaint about a PET drug product produced at my facility?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What do I do if I receive a complaint about a PET... if I receive a complaint about a PET drug product produced at my facility? (a) Written complaint... concerning the quality or purity of, or possible adverse reactions to, a PET drug product. (b) Complaint...

Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: a concise overview and practical guidance for a risk-based approach.

PubMed

Lange, Rogier; ter Heine, Rob; Decristoforo, Clemens; Peñuelas, Iván; Elsinga, Philip H; van der Westerlaken, Monique M L; Hendrikse, N Harry

2015-05-01

Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations are not always adequate for their production. Strict compliance may have a huge resource impact, without further improving product quality. In this paper we give an overview of the applicable legislation and guidelines and propose a risk-based approach for their implementation. We focus on a few controversial Good Manufacturing Practice topics: cleanroom classification, air pressure regime, cleanroom qualification and microbiological monitoring. We have developed an algorithm to assess the combined risk of microbiological contamination of a radiopharmaceutical preparation process and propose corresponding Good Manufacturing Practice classification levels. In our opinion, the risk of carry-over of radiopharmaceuticals by individuals cannot be contained by pressure differences, and complicated regimes with underpressured rooms are not necessary in most situations. We propose a sterility assurance level of 10 for radiopharmaceuticals that are administered within a working day, irrespective of their use. We suggest the adoption of limits for environmental monitoring of microbial contamination, as proposed by Bruel and colleagues, on behalf of the French Society of Radiopharmacy. Recently launched regulatory documents seem to breathe a more liberal spirit than current legislation and recognize the need for the use of risk assessment. We argue that future legislation be further harmonized and state risk assessment as the gold standard for implementation of drug quality regulations for the preparation of unlicensed radiopharmaceuticals.

21 CFR 212.5 - To what drugs do the regulations in this part apply?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 210 and 211 of this chapter. (b) Investigational and research PET drugs. For investigational PET drugs... this chapter, and PET drugs produced with the approval of a Radioactive Drug Research Committee in... Biosciences Library, 10903 New Hampshire Ave., Silver Spring, MD, 20993-0002, 301-796-3504, or at the National...

21 CFR 212.5 - To what drugs do the regulations in this part apply?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 210 and 211 of this chapter. (b) Investigational and research PET drugs. For investigational PET drugs... this chapter, and PET drugs produced with the approval of a Radioactive Drug Research Committee in... Biosciences Library, 10903 New Hampshire Ave., Silver Spring, MD, 20993-0002, 301-796-3504, or at the National...

21 CFR 212.5 - To what drugs do the regulations in this part apply?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 210 and 211 of this chapter. (b) Investigational and research PET drugs. For investigational PET drugs... this chapter, and PET drugs produced with the approval of a Radioactive Drug Research Committee in... Biosciences Library, 10903 New Hampshire Ave., Silver Spring, MD, 20993-0002, 301-796-3504, or at the National...

21 CFR 212.5 - To what drugs do the regulations in this part apply?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 210 and 211 of this chapter. (b) Investigational and research PET drugs. For investigational PET drugs... this chapter, and PET drugs produced with the approval of a Radioactive Drug Research Committee in... Biosciences Library, 10903 New Hampshire Ave., Silver Spring, MD, 20993-0002, 301-796-3504, or at the National...

Automated Synthesis of 68Ga-DOTA-TOC: Methodological Aspects and Suitable Technical Solutions for a Cationic Purification System.

PubMed

Uccelli, Licia; Boschi, Alessandra; Cittanti, Corrado; Martini, Petra; Lodi, Luca; Zappaterra, Elisa; Romani, Simona; Zaccaria, Samanta; Cecconi, Davide; Rambaldi, Ilaria; Santi, Ivan; Panareo, Stefano; Giganti, Melchiore; Bartolomei, Mirco

2018-05-08

The PET Gallium-68 isotope has the advantage of being produced from a generator, so it is also available in nuclear medicine departments without a cyclotron. The preparation of Ga-68 DOTA-labelled compounds is actually performed by remotely controlled automated systems developed in order to assure production efficiency, reproducibility of the results, guarantee fast reaction time, to facilitate the synthesis and minimize the radiation exposure. Many automatic synthesis systems are available on the radiopharmaceutical market, and each of these requires the realization of some technical adaptations for routine use. We reported the Ga-68 DOTATOC production by automated cassette-based theranostic synthesizer system used in combination with a disposable GMP grade cassette system for cationic purification. The synthesizer is integrated with the 68Ge/68Ga generator systems and it allows to perform elution, eluate purification and radiolabeling in about 38 minutes. We have performed between January 2016 and January 2017 over 100 [68Ga]Ga-DOTA-TOC preparation and of these only three have failed. The average synthesis yield of radiopharmaceutical production was 54.4 ± 2.3 % and the average radiochemical purity was 96.94 ± 0.74 %. The methodology and the technical solutions adopted have allowed to obtain a high quality radiopharmaceutical product as required by the European Pharmacopoeia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Compartmental model of 18F-choline

NASA Astrophysics Data System (ADS)

Janzen, T.; Tavola, F.; Giussani, A.; Cantone, M. C.; Uusijärvi, H.; Mattsson, S.; Zankl, M.; Petoussi-Henß, N.; Hoeschen, C.

2010-03-01

The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies.

Development of 89Zr-Ontuxizumab for in vivo TEM-1/endosialin PET applications

PubMed Central

Lange, Sara E.S.; Zheleznyak, Alex; Studer, Matthew; O'Shannessy, Daniel J.; Lapi, Suzanne E.; Van Tine, Brian A.

2016-01-01

Purpose The complexity of sarcoma has led to the need for patient selection via in vivo biomarkers. Tumor endothelial marker-1 (TEM-1) is a cell surface marker expressed by the tumor microenvironment. Currently MORAb-004 (Ontuxizumab), an anti-TEM-1 humanized monoclonal antibody, is in sarcoma clinical trials. Development of positron emission tomography (PET) for in vivo TEM-1 expression may allow for stratification of patients, potentially enhancing clinical outcomes seen with Ontuxizumab. Results Characterization of cell lines revealed clear differences in TEM-1 expression. One high expressing (RD-ES) and one low expressing (LUPI) cell line were xenografted, and mice were injected with 89Zr-Ontuxizumab. PET imaging post-injection revealed that TEM-1 was highly expressed and readily detectable in vivo only in RD-ES. In vivo biodistribution studies confirmed high radiopharmaceutical uptake in tumor relative to normal organs. Experimental Design Sarcoma cell lines were characterized for TEM-1 expression. Ontuxizumab was labeled with 89Zr and evaluated for immunoreactivity preservation. 89Zr-Ontuxizumab was injected into mice with high or null expressing TEM-1 xenografts. In vivo PET imaging experiments were performed. Conclusion 89Zr-Ontuxizumab can be used in vivo to determine high versus low TEM-1 expression. Reliable PET imaging of TEM-1 in sarcoma patients may allow for identification of patients that will attain the greatest benefit from anti-TEM-1 therapy. PMID:26909615

Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

PubMed

Arsenault, Frédéric; Beauregard, Jean-Mathieu; Pouliot, Frédéric

2018-06-22

In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact management impacts of PSMA-targeted molecules are urgently needed.

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.

18F-FDOPA PET/CT imaging of MAX-related pheochromocytoma.

PubMed

Taïeb, David; Jha, Abhishek; Guerin, Carole; Pang, Ying; Adams, Karen T; Chen, Clara C; Romanet, Pauline; Roche, Philippe; Essamet, Wassim; Ling, Alexander; Quezado, Martha M; Castinetti, Frédéric; Sebag, Fréderic; Pacak, Karel

2018-03-08

MYC associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of approximately 40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO. The objective of this study was to present our experience with contrast-enhanced CT and 18F-FDOPA PET/CT imaging in 6 consecutive patients (4 at initial diagnosis and 2 at follow-up evaluation) with rare but clinically important MAX-related PHEOs. In 5 patients, 18F-FDOPA was also compared to other radiopharmaceuticals. Patients had 5 different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in-silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilateral and detected more adrenal and extradrenal lesions than CT (per lesion sensitivity 90.5% vs 52.4% for CT/MRI). The 2 missed PHEO on 18F-FDOPA PET/CT were <1cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTATATE PET/CT detected fewer lesions than 18F-FDOPA PET/CT in 1/3 patients and 18F-FDG PET/CT was only faintly positive in 2/4 patients with underestimation of extraadrenal lesions in 1 patient. MAX-related PHEO exihibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEO associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluation in these patients.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of (F18)fluorinated benzamides (dopamine D-2 receptor tracers), (F18)fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of (F18)-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Evaluation of 64Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer's Disease.

PubMed

Bandara, Nilantha; Sharma, Anuj K; Krieger, Stephanie; Schultz, Jason W; Han, Byung Hee; Rogers, Buck E; Mirica, Liviu M

2017-09-13

Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer's disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides 11 C (20.4 min) and 18 F (109.8 min) may limit the widespread use of these imaging agents. Therefore, we have begun to evaluate novel AD diagnostic agents that can be radiolabeled with 64 Cu, a radionuclide with a half-life of 12.7 h, ideal for PET imaging. Described herein are a series of bifunctional chelators (BFCs), L 1 -L 5 , that were designed to tightly bind 64 Cu and shown to interact with Aβ aggregates both in vitro and in transgenic AD mouse brain sections. Importantly, biodistribution studies show that these compounds exhibit promising brain uptake and rapid clearance in wild-type mice, and initial microPET imaging studies of transgenic AD mice suggest that these compounds could serve as lead compounds for the development of improved diagnostic agents for AD.

The Effect of the Prosthetic Group on the Pharmacologic Properties of 18F-labeled Rhodamine B, a Potential Myocardial Perfusion Agent for PET

PubMed Central

Bartholomä, Mark D.; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

2013-01-01

We recently reported the development of the 2-[18F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [18F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats, but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared 18F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of 18F-labeled compounds. They also support the value of continued investigation of 18F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging. PMID:23210516

Effect of the prosthetic group on the pharmacologic properties of 18F-labeled rhodamine B, a potential myocardial perfusion agent for positron emission tomography (PET).

PubMed

Bartholomä, Mark D; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H; Treves, S Ted; Packard, Alan B

2012-12-27

We recently reported the development of the 2-[(18)F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [(18)F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared (18)F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of (18)F-labeled compounds. They also support the value of continued investigation of (18)F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging.

Development of Candidates for Positron Emission Tomography (PET) Imaging of Ghrelin Receptor in Disease: Design, Synthesis, and Evaluation of Fluorine-Bearing Quinazolinone Derivatives.

PubMed

Hou, Jinqiang; Kovacs, Michael S; Dhanvantari, Savita; Luyt, Leonard G

2018-02-08

Molecular imaging with positron emission tomography (PET) is an attractive platform for noninvasive detection and assessment of disease. The development of a PET imaging agent targeting the ghrelin receptor (growth hormone secretagogue receptor type 1a or GHS-R1a) has the potential to lead to the detection and assessment of the higher than normal expression of GHS-R1a in diseases such as prostate, breast, and ovarian cancer. To enable the development of 18 F radiopharmaceuticals, we have designed and synthesized three series of quinazolinone derivatives, resulting in the identification of two compound (5i, 17) with subnanomolar binding affinity and one fluorine-bearing compound (10b) with picomolar binding affinity (20 pM), representing the highest binding affinity for GHS-R1a reported to date. Two lead compounds (5b, IC 50 = 20.6 nM; 5e, IC 50 = 9.3 nM) were successfully 18 F-radiolabeled with radiochemical purity of greater than 99%. Molecular modeling studies were performed to shed light on ligand-receptor interactions.

21 CFR 212.20 - What activities must I perform to ensure drug quality?

Code of Federal Regulations, 2014 CFR

2014-04-01

... operations. You must oversee production operations to ensure that each PET drug meets the requirements of the... of a PET drug. (c) Specifications and processes. You must approve or reject, before implementation..., and purity of a PET drug. You must demonstrate that any change does not adversely affect the identity...

21 CFR 212.20 - What activities must I perform to ensure drug quality?

Code of Federal Regulations, 2012 CFR

2012-04-01

... operations. You must oversee production operations to ensure that each PET drug meets the requirements of the... of a PET drug. (c) Specifications and processes. You must approve or reject, before implementation..., and purity of a PET drug. You must demonstrate that any change does not adversely affect the identity...

21 CFR 212.20 - What activities must I perform to ensure drug quality?

Code of Federal Regulations, 2013 CFR

2013-04-01

... operations. You must oversee production operations to ensure that each PET drug meets the requirements of the... of a PET drug. (c) Specifications and processes. You must approve or reject, before implementation..., and purity of a PET drug. You must demonstrate that any change does not adversely affect the identity...

Evolving role of FDG-PET/CT in prognostic evaluation of resectable gastric cancer

PubMed Central

De Raffele, Emilio; Mirarchi, Mariateresa; Cuicchi, Dajana; Lecce, Ferdinando; Cola, Bruno

2017-01-01

Gastric cancer (GC) remains a leading cause of cancer death worldwide. Radical gastrectomy is the only potentially curative treatment, and perioperative adjuvant therapies may improve the prognosis after curative resection. Prognosis largely depends on the tumour stage and histology, but the host systemic inflammatory response (SIR) to GC may contribute as well, as has been determined for other malignancies. In GC patients, the potential utility of positron emission tomography/computed tomography (PET/CT) with the imaging radiopharmaceutical 18F-fluorodeoxyglucose (FDG) is still debated, due to its lower sensitivity in diagnosing and staging GC compared to other imaging modalities. There is, however, growing evidence that FDG uptake in the primary tumour and regional lymph nodes may be efficient for predicting prognosis of resected patients and for monitoring tumour response to perioperative treatments, having prognostic value in that it can change therapeutic strategies. Moreover, FDG uptake in bone marrow seems to be significantly associated with SIR to GC and to represent an efficient prognostic factor after curative surgery. In conclusion, PET/CT technology is efficient in GC patients, since it is useful to integrate other imaging modalities in staging tumours and may have prognostic value that can change therapeutic strategies. With ongoing improvements, PET/CT imaging may gain further importance in the management of GC patients. PMID:29097864

Positron emission tomography scans obtained for the evaluation of cognitive dysfunction.

PubMed

Silverman, Daniel H S; Mosconi, Lisa; Ercoli, Linda; Chen, Wei; Small, Gary W

2008-07-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism, with devastating neuropathologic, clinical, social, and economic consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are performed with (18)F-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility for clinicians evaluating patients with cognitive impairment and in distinguishing among primary neurodegenerative disorders and other etiologies contributing to cognitive decline. In addition to focusing on the effects on cerebral metabolism examined with (18)F-fluorodeoxyglucose PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact on the enormous human toll exacted by these diseases.

Which metabolic imaging, besides bone scan with 99mTc-phosphonates, for detecting and evaluating bone metastases in prostatic cancer patients? An open discussion.

PubMed

Bombardieri, E; Setti, L; Kirienko, M; Antunovic, L; Guglielmo, P; Ciocia, G

2015-12-01

Prostate cancer bone metastases occur frequently in advanced cancer and this is matter of particular attention, due to the great impact on patient's management and considering that a lot of new emerging therapeutic options have been recently introduced. Imaging bone metastases is essential to localize lesions, to establish their size and number, to study characteristics and changes during therapy. Besides radiological imaging, nuclear medicine modalities can image their features and offer additional information about their metabolic behaviour. They can be classified according to physical characteristics, type of detection, mechanism of uptake, availability for daily use. The physiopathology of metastases formation and the mechanisms of tracer uptake are essential to understand the interpretation of nuclear medicine images. Therefore, radiopharmaceuticals for bone metastases can be classified in agents targeting bone (99mTc-phosphonates, 18F-fluoride) and those targeting prostatic cancer cells (18F-fluoromethylcholine, 11C-choline, 18F-fluorodeoxyglucose). The modalities using the first group of tracers are planar bone scan, SPECT or SPECT/CT with 99mTc-diphosphonates, and 18F-fluoride PET/CT, while the modalities using the second group include 18F/11C-choline derivatives PET/CT, 18F-FDG PET/CT and PET/CT scans with several other radiopharmaceuticals described in the literature, such as 18F/11C-acetate derivatives, 18F-fluoro-5α-dihydrotestosterone (FDHT), 18F-anti-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), 18F-2'-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) and 68Ga-labeled-prostate specific membrane antigen (PMSA) PET/TC. However, since data on clinical validation for these last novel modalities are not conclusive and/or are not still sufficient in number, at present they can be still considered as promising tools under evaluation. The present paper considers the nuclear modalities today available for the clinical routine. This overview wants to discuss the opportunities and the drawbacks of these current diagnostic tests in a scenario where planar scintigraphy and/or SPECT with phosphonates, is the only metabolic imaging recommended by the most important Guidelines of the Scientific Societies dealing with prostate cancer. Other nuclear medicine modalities are in very few cases just cited, never recommended except in rare situations. Is there space for agents other than 99mTc-phosphonates to image bone lesions from prostate cancer?

Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans.

PubMed

Herrero, Pilar; Laforest, Richard; Shoghi, Kooresh; Zhou, Dong; Ewald, Gregory; Pfeifer, John; Duncavage, Eric; Krupp, Kitty; Mach, Robert; Gropler, Robert

2012-06-01

Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Two groups were studied-a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time-activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Both AUMC at 10 min (P < 0.05) and tissue iNOS (P < 0.0001) were higher in patients exhibiting rejection than in those without rejection. Moreover, the (18)F-NOS AUMC at 10 min correlated positively with tissue iNOS at 10 min (R(2) = 0.42, P < 0.05). (18)F-NOS activity was cleared by the hepatobiliary system. The critical organ was the bladder wall, with a dose of 95.3 μGy/MBq, and an effective dose of 15.9 μSv/MBq was calculated. Myocardial (18)F-NOS activity is increased in organ rejection (a condition associated with increased iNOS levels) and correlates with tissue iNOS measurements with acceptable radiation exposure. Although further modifications to improve the performance of (18)F-NOS are needed, these data show the feasibility of PET of iNOS in the heart and other tissues.

[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.

Measurements and evaluation of the risks due to external radiation exposures and to intake of activated elements for operational staff engaged in the maintenance of medical cyclotrons.

PubMed

Calandrino, R; del Vecchio, A; Parisi, R; Todde, S; De Felice, P; Savi, A; Pepe, A; Mrskova, A

2010-06-01

The aim of this paper is to assess the activation phenomena and to evaluate the risk of external exposure and intake doses for the maintenance staff of two medical cyclotrons. Two self-shielded cyclotrons are currently operating in the facility for the routine production of (11)C and (18)F. Four radiochemistry laboratories are linked to the cyclotrons by means of shielded radioisotope delivery lines. Radiopharmaceuticals are prepared both for the PET Diagnostic Department, where four CT-PET scanners are operating with a mean patient workload of 40 d(-1) and for [(18)F]FDG external distribution, to provide radiopharmaceuticals for other institutions. In spite of the fact that air contamination inside the radiochemistry laboratories during the synthesis represents the largest 'slice of the pie' in the evaluation of annual intake dose, potential contamination due to the activated particulate, generated during cyclotron irradiation by micro-corrosion of targets and other components potentially struck by the proton beam and generated neutrons, should be considered. In this regard, the most plausible long-lived (T(1/2) > 30 d) radioisotopes formed are: (97)Tc, (56)Co, (57)Co, (58)Co, (60)Co, (49)V, (55)Fe, (109)Cd, (65)Zn and (22)Na. The results for the operating personnel survey has revealed only low-level contamination for (65)Zn in one test, together with minor (18)F intake, probably due to the environmental dispersion of the radioisotope during the [(18)F]FDG synthesis.

Disclosure of positron emission tomography amyloid imaging results: A preliminary study of safety and tolerability.

PubMed

Lim, Yen Ying; Maruff, Paul; Getter, Christine; Snyder, Peter J

2016-04-01

Three (18)F-labeled radiopharmaceuticals have been Food and Drug Administration-approved for the identification of cortical amyloidosis in clinical settings. Although there has been strong debate among professionals as to the ethical and social consequences of disclosing such information, increasing numbers of participants are being recruited into secondary prevention trials for which they are likely to, and/or desire to, receive their positron emission tomography (PET) imaging results. Healthy older adults (n = 63, mean age = 62 years) enrolled in a preclinical Alzheimer's disease (AD) biomarkers trial, and 11 requested disclosure of PET amyloid imaging results to their treating neurologist, per institutional review board-approved study protocol. These individuals completed a follow-up psychoeducational program and structured interviews to assess impact of disclosure on several key psychological factors. Four of 11 subjects demonstrated increased amyloid aggregation and reported that they were not surprised, particularly given their family histories and subjective memory concerns. All indicated that they had shared this information with pertinent significant others; they were satisfied with their level of social support, and the imaging results had motivated them to change their lifestyle by exercising more, changing their diet, and planning ahead. Amyloid-positive participants showed little change in levels of depressive, anxiety, and stress symptoms, subjective sense of memory impairment, or on measures of intrusion, avoidance, and hyperarousal, and reported risk of self-harm. Disclosure of PET amyloid status did not significantly impact mood, subjective sense of memory impairment, or perceived risk of developing AD; nor was this associated with significant emotional impact, irrespective of actual amyloid burden status. Those subjects with increased amyloid burden were more likely than those without significant amyloidosis to make positive changes to their lifestyle (e.g., engaging in more exercise and changing their diet). Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

[Nationwide survey on radioactive waste management related to positron emission tomography in Japan].

PubMed

Nagaoka, Hiroaki; Watanabe, Hiroshi; Yamaguchi, Ichiro; Fujibuchi, Toshioh; Kida, Tetsuo; Tanaka, Shinji

2009-12-20

A clearance system for medical radioactive solid waste has not yet been implemented in Japan. Since 2004 new regulations have allowed institutions using positron emission tomography(PET)to handle totally decayed radioactive waste as non-radioactive waste after decay-in-storage. It was expected that this new regulation would mediate the installation of clearance systems in Japan. In order to assess the current situation of radiation safety management in PET institutions, we conducted a nationwide survey. The study design was a cross-sectional descriptive study conducted by questionnaire. The subjects of this survey were all the PET institutions in Japan. Among 224 institutes, 128 institutes are equipped with cyclotrons and 96 institutes are not. The number of returned questionnaires was 138. Among institutes that are using delivered radiopharmaceuticals, 80% treat their waste as non-radioactive according to the new regulation. The impact of new regulations for reducing radioactive waste in PET institutes without a cyclotron was estimated at about $400 thousand per year. The main concern of medical institutes was assessment of the contamination caused by by-products of radioactive nuclides generated in target water during the operation of a cyclotron. It was thought that a rational rule based on scientific risk management should be established because these by-products of radioactive nuclides are negligible for radiation safety. New regulation has had a good influence on medical PET institutes, and it is expected that a clearance system for medical radioactive waste will be introduced in the near future, following these recent experiences in PET institutes.

In vivo spatial correlation between (18)F-BPA and (18)F-FDG uptakes in head and neck cancer.

PubMed

Kobayashi, Kazuma; Kurihara, Hiroaki; Watanabe, Yoshiaki; Murakami, Naoya; Inaba, Koji; Nakamura, Satoshi; Wakita, Akihisa; Okamoto, Hiroyuki; Umezawa, Rei; Takahashi, Kana; Igaki, Hiroshi; Ito, Yoshinori; Yoshimoto, Seiichi; Shigematsu, Naoyuki; Itami, Jun

2016-09-01

Borono-2-(18)F-fluoro-phenylalanine ((18)F-BPA) has been used to estimate the therapeutic effects of boron neutron capture therapy (BNCT), while (18)F-fluorodeoxyglucose ((18)F-FDG) is the most commonly used positron emission tomography (PET) radiopharmaceutical in a routine clinical use. The aim of the present study was to evaluate spatial correlation between (18)F-BPA and (18)F-FDG uptakes using a deformable image registration-based technique. Ten patients with head and neck cancer were recruited from January 2014 to December 2014. All patients underwent whole-body (18)F-BPA PET/computed tomography (CT) and (18)F-FDG PET/CT within a 2-week period. For each patient, (18)F-BPA PET/CT and (18)F-FDG PET/CT images were aligned based on a deformable image registration framework. The voxel-by-voxel spatial correlation of standardized uptake value (SUV) within the tumor was analyzed. Our image processing framework achieved accurate and validated registration results for each PET/CT image. In 9/10 patients, the spatial distribution of SUVs between (18)F-BPA and (18)F-FDG showed a significant, positive correlation in the tumor volume. Deformable image registration-based voxel-wise analysis demonstrated a spatial correlation between (18)F-BPA and (18)F-FDG uptakes in the head and neck cancer. A tumor sub-volume with a high (18)F-FDG uptake may predict high accumulation of (18)F-BPA. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Current Status of Human Resource Training Program for Fostering RIBiomics Professionals

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

Lee, Dong-Eun; Jang, Beom-Su; Choi, Dae Seong

RI-Biomics is a state-of-the-art radiation fusion technology for evaluating in-vivo dynamics such as absorption, distribution, metabolism and excretion (ADME) of new drug candidates and biomaterials using radioisotope (RI), and quantitative evaluation of their efficacy via molecular imaging techniques and animal models. The RI-Biomics center is the sole comprehensive research and experiment complex in Korea that can simultaneously perform the radio-synthesis of drug candidate with radioisotope, analysis, and molecular imaging evaluation with animal model. Molecular imaging techniques, including nuclear imaging (SPECT and PET), near-infrared fluorescent (NIRF) imaging, and magnetic resonance imaging (MRI), are the cutting-edge technologies for evaluating drug candidates. Sincemore » they allow in vivo real-time imaging of the diseased site, monitoring the biodistribution of drug and determining the optimal therapeutic efficacy following treatments, we have integrated RI-ADME and molecular imaging to provide useful information for drug evaluation and to accelerate the development of new drugs and biomaterials. The RI-Biomics center was established with total investment of 18 million $ during four years from 2009 to 2012 in order to develop a comprehensive analyzing system using RI for new drug development as an axis for national growth in the next generation. The RI-Biomics center has labeling synthesis facility for the radiosynthesis of drug candidate with radioisotope such as Tc-99m, I-125, I-131, F-18, H-3 and C-14 using hot cell. It also includes RI-general analysis facilities, such as Radio-HPLC, LC/MS, GC/MS, gamma counter that can analyzing the radio-synthesized materials, and animal image analysis facilities that developed small animal imaging equipment such as SPECT/PET/CT, 7 T MRI, in-vivo optical imaging system and others. In order to achieve the system to verify safety and effectiveness of the new drugs using RI, it is necessary to establish a human resource training program for fostering RI-Biomics professionals in the following key fields; (1) Radio-pharmaceuticals synthesis and labeled compound development, (2) Development of RI-ADME in the living object and image assessment technology. Personnel training program that carries out theoretical education and practical training in the field related to RI-Biomics in parallel is being conducted. Internship training for university students has been administered twice already while educational program for the existing professionals in the RI-Biomics field will be carried out during the summer of 2014. The human resource training program for combination of RIADME and different molecular imaging techniques can offer synergistic advantages to facilitate understanding RIADME and fostering RI-ADME professionals. (authors)« less

First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study.

PubMed

Singh, Aviral; van der Meulen, Nicholas P; Müller, Cristina; Klette, Ingo; Kulkarni, Harshad R; Türler, Andreas; Schibli, Roger; Baum, Richard P

2017-05-01

44 Sc is a promising positron emission tomography (PET) radionuclide (T 1/2  = 4.04 hours, E β+average  = 632 keV) and can be made available, using a cyclotron production route, in substantial quantities as a highly pure product. Herein, the authors report on a first-in-human PET/CT study using 44 Sc-DOTATOC prepared with cyclotron-produced 44 Sc. The production of 44 Sc was carried out through the 44 Ca(p,n) 44 Sc nuclear reaction at Paul Scherrer Institut, Switzerland. After separation, 44 Sc was shipped to Zentralklinik Bad Berka, Germany, where radiolabeling was performed, yielding radiochemically pure 44 Sc-DOTATOC. Two patients, currently followed up after peptide receptor radionuclide therapy of metastatic neuroendocrine neoplasms, participated in this proof-of-concept study. Blood sampling was performed before and after application of 44 Sc-DOTATOC. PET/CT acquisitions, performed at different time points after injection of 44 Sc-DOTATOC, allowed detection of even very small lesions on delayed scans. No clinical adverse effects were observed and the laboratory hematological, renal, and hepatic profiles remained unchanged. In this study, cyclotron-produced 44 Sc was used in the clinic for the first time. It is attractive for theranostic application with 177 Lu, 90 Y, or 47 Sc as therapeutic counterparts. 44 Sc-based radiopharmaceuticals will be of particular value for PET facilities without radiopharmacy, to which they can be shipped from a centralized production site.

New Mexico Center for Isotopes in Medicine

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

Burchiel, Scott W.

2012-12-13

The purpose of the New Mexico Center for Isotopes in Medicine (NMCIM) is to support research, education and service missions of the UNM College of Pharmacy Radiopharmaceutical Sciences Program (COP RSP) and the Cancer Research and Treatment Center (CRTC). NMCIM developed and coordinated unique translational research in cancer radioimaging and radiotherapy agents based on novel molecules developed at UNM and elsewhere. NMCIM was the primary interface for novel radioisotopes and radiochemistries developed at the Los Alamos National Laboratory (LANL) for SPECT/PET imaging and therapy. NMCIM coordinated the use of the small animal imaging facility with the CRTC provided support servicesmore » to assist investigators in their studies. NMCIM developed education and training programs that benefited professional, graduate, and postdoctoral students that utilized its unique facilities and technologies. UNM COP RSP has been active in writing research and training grants, as well as supporting contract research with industrial partners. The ultimate goal of NMCIM is to bring new radiopharmaceutical imaging and therapeutic agents into clinical trials that will benefit the health and well being of cancer and other patients in New Mexico and the U.S.« less

Synthesis, Characterization and Biological Studies of 99mTc and 188Re Peptides

NASA Astrophysics Data System (ADS)

Sanders, Vanessa

Radiopharmaceuticals are very powerful diagnostic tools for evaluation of a host of medical conditions. These drugs are labeled with radioactive isotopes, which are utilized to create pictures of areas of interest through absorption of the drug. They are currently in high demand due to their ability to image areas that traditional imaging devices cannot. The radioisotope 99mTc, with a half-life of 6.01 hours and a 140 keV gamma emission, is central to many radiopharmaceutical compounds. This isotope is easily obtained from a 99Mo-99mTc generator, through beta decay and column chromatography separations. Very little technetium, less than 6 ng, is needed to label the pharmaceuticals for use in-vivo. Another radioisotope 188Re is also important due to its ability to be used for therapy while being tracked throughout the body. Radiotherapy gives radiopharmaceuticals a huge advantage by their ability to destroy rapidly growing cells. One of the main reasons there is interest in rhenium pharmaceuticals is the chemical similarity between it and technetium. The 188Re isotope also has a considerably short half-life of approximately 17 hours and has emission energy of 155 keV. The 188Re isotope is separated from 188W-188Re generator, analogously to the 99Mo-99mTc generator. The ligand used in this work is a pentapepetide macrocyclic ligand. This ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for imaging and therapeutic in vivo agents. Ligands are chosen based on their in-situ biological behavior, and are used in the complexation with technetium and rhenium. Understanding and exploiting technetium and rhenium chemistry can provide insight into the reaction mechanisms and coordination chemistry of these compounds. The exploration of various oxidation states as a function of the ligands used and the reaction conditions can help develop novel radiopharmaceuticals. The investigations of the manipulation of oxidation states have the possible application to simplify the synthesis of the pharmaceutical. The versatility of the oxidation states of these metals leads to numerous possibilities in developing new radiopharmaceuticals. The coordination chemistry and reaction mechanisms must be efficiently characterized to ensure the reproducibility of the radiopharmaceutical. The current study focuses on technetium and rhenium complexes with peptides. These complexes have become increasing interesting for their use in diagnostic and therapeutic radiopharmaceuticals. The characterization of the complexation of Tc(V), and Rh(V) with the pentapeptide KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine) will be discussed. Complexes will be characterized by High Performance Liquid Chromatography (HPLC), UV-Visible Spectroscopy, Proton NMR, Circular Dichroism (CD), and Electrospray Ionization Mass Spectroscopy, to compare them to current radiopharmaceuticals. Information on the underlying reactions and coordination will be discussed.

21 CFR 212.50 - What production and process controls must I have?

Code of Federal Regulations, 2012 CFR

2012-04-01

... must have adequate production and process controls to ensure the consistent production of a PET drug... all steps in the PET drug production process. The master production and control records must include the following information: (1) The name and strength of the PET drug; (2) If applicable, the name and...

21 CFR 212.50 - What production and process controls must I have?

Code of Federal Regulations, 2014 CFR

2014-04-01

... must have adequate production and process controls to ensure the consistent production of a PET drug... all steps in the PET drug production process. The master production and control records must include the following information: (1) The name and strength of the PET drug; (2) If applicable, the name and...

21 CFR 212.50 - What production and process controls must I have?

Code of Federal Regulations, 2013 CFR

2013-04-01

... must have adequate production and process controls to ensure the consistent production of a PET drug... all steps in the PET drug production process. The master production and control records must include the following information: (1) The name and strength of the PET drug; (2) If applicable, the name and...

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science). Progress report, January 1, 1992--December 31, 1992

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of [F18]fluorinated benzamides (dopamine D-2 receptor tracers), [F18]fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of [F18]-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling.

PubMed

Tsionou, Maria Iris; Knapp, Caroline E; Foley, Calum A; Munteanu, Catherine R; Cakebread, Andrew; Imberti, Cinzia; Eykyn, Thomas R; Young, Jennifer D; Paterson, Brett M; Blower, Philip J; Ma, Michelle T

2017-10-24

Gallium-68 ( 68 Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68 Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68 Ga 3+ . Ideally, the chelator will rapidly, quantitatively and stably coordinate 68 Ga 3+ at room temperature, near neutral pH and low chelator concentration, allowing for simple routine radiopharmaceutical formulation. Identification of chelators that fulfil these requirements will facilitate development of kit-based 68 Ga radiopharmaceuticals. Herein the reaction of a range of widely used macrocyclic and acyclic chelators with 68 Ga 3+ is reported. Radiochemical yields have been measured under conditions of varying chelator concentrations, pH (3.5 and 6.5) and temperature (25 and 90 °C). These chelators are: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups at the amine, bis(2-hydroxybenzyl)ethylenediaminediacetic acid (HBED), a tris(hydroxypyridinone) containing three 1,6-dimethyl-3-hydroxypyridin-4-one groups (THP) and the hexadentate tris(hydroxamate) siderophore desferrioxamine-B (DFO). Competition studies have also been undertaken to assess relative complexation efficiencies of each chelator for 68 Ga 3+ under different pH and temperature conditions. Performing radiolabelling reactions at pH 6.5, 25 °C and 5-50 μM chelator concentration resulted in near quantitative radiochemical yields for all chelators, except DOTA. Radiochemical yields either decreased or were not substantially improved when the reactions were undertaken at lower pH or at higher temperature, except in the case of DOTA. THP and DFO were the most effective 68 Ga 3+ chelators at near-neutral pH and 25 °C, rapidly providing near-quantitative radiochemical yields at very low chelator concentrations. NOTP and HBED were only slightly less effective under these conditions. In competition studies with all other chelators, THP demonstrated highest reactivity for 68 Ga 3+ complexation under all conditions. These data point to THP possessing ideal properties for rapid, one-step kit-based syntheses of 68 Ga-biomolecules for molecular PET imaging. LC-MS and 1 H, 13 C{ 1 H} and 71 Ga NMR studies of HBED complexes of Ga 3+ showed that under the analytical conditions employed in this study, multiple HBED-bound Ga complexes exist. X-ray diffraction data indicated that crystals isolated from these solutions contained octahedral [Ga(HBED)(H 2 O)], with HBED coordinated in a pentadentate N 2 O 3 mode, with only one phenolic group coordinated to Ga 3+ , and the remaining coordination site occupied by a water molecule.

21 CFR 212.60 - What requirements apply to the laboratories where I test components, in-process materials, and...

Code of Federal Regulations, 2012 CFR

2012-04-01

... I test components, in-process materials, and finished PET drug products? 212.60 Section 212.60 Food... finished PET drug products? (a) Testing procedures. Each laboratory used to conduct testing of components, in-process materials, and finished PET drug products must have and follow written procedures for the...

21 CFR 212.60 - What requirements apply to the laboratories where I test components, in-process materials, and...

Code of Federal Regulations, 2010 CFR

2010-04-01

... I test components, in-process materials, and finished PET drug products? 212.60 Section 212.60 Food... materials, and finished PET drug products? (a) Testing procedures. Each laboratory used to conduct testing of components, in-process materials, and finished PET drug products must have and follow written...

21 CFR 212.60 - What requirements apply to the laboratories where I test components, in-process materials, and...

Code of Federal Regulations, 2014 CFR

2014-04-01

... I test components, in-process materials, and finished PET drug products? 212.60 Section 212.60 Food... finished PET drug products? (a) Testing procedures. Each laboratory used to conduct testing of components, in-process materials, and finished PET drug products must have and follow written procedures for the...

21 CFR 212.60 - What requirements apply to the laboratories where I test components, in-process materials, and...

Code of Federal Regulations, 2013 CFR

2013-04-01

... I test components, in-process materials, and finished PET drug products? 212.60 Section 212.60 Food... finished PET drug products? (a) Testing procedures. Each laboratory used to conduct testing of components, in-process materials, and finished PET drug products must have and follow written procedures for the...

21 CFR 212.60 - What requirements apply to the laboratories where I test components, in-process materials, and...

Code of Federal Regulations, 2011 CFR

2011-04-01

... I test components, in-process materials, and finished PET drug products? 212.60 Section 212.60 Food... finished PET drug products? (a) Testing procedures. Each laboratory used to conduct testing of components, in-process materials, and finished PET drug products must have and follow written procedures for the...

Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

PubMed Central

2015-01-01

Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for 89Zr4+; however, accumulation of 89Zr in the bones of mice suggests that 89Zr4+ is released from DFO in vivo. An improved chelator for 89Zr4+ could eliminate the release of osteophilic 89Zr4+ and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of 89Zr-HOPO matched or surpassed that of 89Zr-DFO in every experiment. In healthy mice, 89Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents. PMID:24814511

Static and dynamic (18) FDG-PET in normal hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Souza, Marcy J; Wall, Jonathan S; Stuckey, Alan; Daniel, Gregory B

2011-01-01

Positron emission tomography (PET) is often used to stage and monitor human cancer and has recently been used in a similar fashion in veterinary medicine. The most commonly used radiopharmaceutical is 2-Deoxy-2-[(18) F]-Fluoro-d-glucose ((18) F-FDG), which is concentrated and trapped within cells that use glucose as their energy substrate. We characterized the normal distribution of (18) F-FDG in 10 healthy Hispaniolan Amazon parrots (Amazona ventralis) by performing whole body PET scans at steady state, 60min after injection. Significant variability was found in the intestinal activity. Avian species are known to reflux fluid and electrolytes from their cloaca into their colon. To evaluate reflux as the cause of variability in intestinal distribution of (18) F-FDG, dynamic PET scans were performed on the coelomic cavity of six Hispaniolan Amazon parrots from time 0 to 60min postinjection of radiotracer. Reflux of radioactive material from the cloaca into the colon occurred in all birds to varying degrees and occurred before 60min. To evaluate the intestinal tract of clinical avian patients, dynamic scans must be performed starting immediately after injection so that increased radioactivity due to metabolism or hypermetabolic lesions such as cancer can be differentiated from increased radioactivity due to reflux of fluid from the cloaca. © 2010 Veterinary Radiology & Ultrasound.

Probing neurodegeneration and aging: A PET approach

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

VanBrocklin, H.F.

1995-12-31

Positron Emission Tomography (PET) imaging has received wide application to the study of the aging brain and its diseases, most notably Parkinson`s Disease (PD) and Alzheimer`s Disease (AD). Basic neurological processes such as blood flow and glucose metabolism have been most often measured. Radioligands developed for specific neurochemical systems have amplified the flow and metabolism studies by more precisely defining the changes associated with degenerative processes. Our present research focuses on two additional applications of radiopharmaceutical development and PET imaging - (1) investigating the fundamental mechanisms of neurodegeneration and aging, and (2) assessing novel therapeutic intervention for PD with PETmore » imaging. We have synthesized fluorine-18 labeled analogs of rotenone, a natural product that possesses high affinity to Complex I of the mitochondrial electron transport chain, and evaluated their potential to study changes in neuronal mitochondrial density and function. A large body evidence points to mitochondrial dysfunction as a key factor in aging and neurodegeneration. We are also currently evaluating the use of genetically transfected cells to treat PD. Primates are being imaged with [{sup 18}F]flouro-m-L-tyrosine before and after MPTP Parkinsonian type lesioning and following implantation of genetically altered cells capable of secreting tyrosine hydroxylase into the lesioned area. The ability to develop and apply PET probes has significantly enhanced the understanding of normal, aging, and degenerative processes of the brain.« less

Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role

PubMed Central

Kettenbach, Kathrin; Reffert, Laura M.; Schieferstein, Hanno; Pektor, Stefanie; Eckert, Raphael; Miederer, Matthias; Rösch, Frank

2018-01-01

Within the last decade, several folate-based radiopharmaceuticals for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been evaluated; however, there is still a lack of suitable 18F-folates for clinical PET imaging. Herein, we report the synthesis and evaluation of two novel 18F-folates employing strain-promoted and copper-catalyzed click chemistry. Furthermore, the influence of both click-methods on lipophilicity and pharmacokinetics of the 18F-folates was investigated. 18F-Ala-folate and 18F-DBCO-folate were both stable in human serum albumin. In vitro studies proved their high affinity to the folate receptor (FR). The lipophilic character of the strain-promoted clicked 18F-DBCO-folate (logD = 0.6) contributed to a higher non-specific binding in cell internalization studies. In the following in vivo PET imaging studies, FR-positive tumors could not be visualized in a maximum intensity projection images. Compared with 18F-DBCO-folate, 18F-Ala-folate (logD = −1.4), synthesized by the copper-catalyzed click reaction, exhibited reduced lipophilicity, and as a result an improved in vivo performance and a clear-cut visualization of FR-positive tumors. In view of high radiochemical yield, radiochemical purity and favorable pharmacokinetics, 18F-Ala-folate is expected to be a promising candidate for FR-PET imaging. PMID:29562610

21 CFR 212.30 - What requirements must my facilities and equipment meet?

Code of Federal Regulations, 2014 CFR

2014-04-01

... could reasonably be expected to adversely affect the identity, strength, quality, or purity of a PET..., in-process materials, or PET drugs are not reactive, additive, or absorptive so as to alter the quality of PET drugs. ...

21 CFR 212.30 - What requirements must my facilities and equipment meet?

Code of Federal Regulations, 2012 CFR

2012-04-01

... could reasonably be expected to adversely affect the identity, strength, quality, or purity of a PET..., in-process materials, or PET drugs are not reactive, additive, or absorptive so as to alter the quality of PET drugs. ...

21 CFR 212.30 - What requirements must my facilities and equipment meet?

Code of Federal Regulations, 2013 CFR

2013-04-01

... could reasonably be expected to adversely affect the identity, strength, quality, or purity of a PET..., in-process materials, or PET drugs are not reactive, additive, or absorptive so as to alter the quality of PET drugs. ...

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma

PubMed Central

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUVaverage for MM lesions was 11.9 and mean SUVmax was 23.2. Respectively, SUVaverage and SUVmax for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18F-NaF revealed the following mean values for MM lesions: K1 = 0.248 (1/min), k3 = 0.359 (1/min), influx (Ki) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K1 = 0.169 (1/min), k3 = 0.422 (1/min), influx (Ki) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUVaverage, SUVmax, K1, k3 and influx (Ki) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18F-NaF PET/CT in the diagnostic workup of MM. PMID:28913153

Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: Single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM

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

Mathias, C.J.; Welch, M.J.; Raichle, M.E.

1990-03-01

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM andmore » Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of (64Cu)-Cu-PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and (64Cu)-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that (62Cu)-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.« less

Fluorinase: a tool for the synthesis of ¹⁸F-labeled sugars and nucleosides for PET.

PubMed

Onega, Mayca; Winkler, Margit; O'Hagan, David

2009-08-01

There is an increasing interest in the preparation of (18)F-labeled radiopharmaceuticals with potential applications in PET for medicinal imaging. Appropriate synthetic methods require a quick and efficient route in which to incorporate the (18)F into a ligand, due to the relatively short half-life of the (18)F isotope. Enzymatic methods are rare in this area; however, the discovery of a fluorinating enzyme from Streptomyces cattleya (EC 2.5.1.63) has opened up the possibility of the enzymatic synthesis and formation of C-(18)F bonds from the [(18)F]fluoride ion. In this article, the development of enzymatic preparations of (18)F-labeled sugars and nucleosides as potential radiotracers using the fluorinase from S. cattleya for PET applications is reviewed. Enzymatic reactions are not traditional in PET synthesis, but this enzyme has some attractive features. The enzyme is available in an overexpressed form from Escherichia coli and it is relatively stable and can be easily purified and manipulated. Most notably, it utilizes [(18)F] fluoride, the form of the isotope normally generated by the cyclotron and usually in very high specific radioactivity. The disadvantage with the enzyme is that it is substrate specific; however, when the fluorinase is used in combination biotransformations with a second or third enzyme, then a range of radiolabeled nucleosides and ribose sugars can be prepared. The fluorinase enzyme has emerged as a curiosity from biosynthesis studies, but it now has some potential as a new catalyst for (18)F incorporation for PET syntheses. The focus is now on delivering a user-friendly catalyst to the PET synthesis community and establishing a clinical role for some of the (18)F-labeled molecules available using this technology.

Why are investors not interested in my radiotracer? The industrial and regulatory constraints in the development of radiopharmaceuticals.

PubMed

Zimmermann, Richard G

2013-02-01

Four criteria are essential in the acceptance by investors of new radiopharmaceuticals: the existence of a market and a medical need, the quality of the science and technology behind the new molecule, the feasibility and compliance with regulations and the limited competitive landscape. Potential investors need to get more convincing market evidence, largely beyond the nice preclinical data generated to the point of first discussion. A properly protected compound not jeopardized by earlier published results is a must. A guarantee of an easy and secured source of the ligand is obvious. A safe access to the radionuclide in volumes corresponding to the targeted market is rarely taken into account, but of utmost importance. The evaluation of new drugs by investors will include the evaluation of the real market size for the targeted indication and the position of the drug in the healthcare environment at the time to market. This includes the potential competition with other radiopharmaceuticals, but also with conventional drugs or competitive modalities also at time to market. Both criteria are usually not easily accessible to researchers whose acquaintance remains limited to the scientific and technical part. Starting from this set of information, a first business plan can be deduced based on a best estimate for price per dose and a rough evaluation about the chance and level of reimbursement. In the following most of the events are covered that could jeopardize the development of the drug, focusing on the industrial, economic and regulatory aspects, comprehending the detailed analysis of the currently best available radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

Preparation of [(68)Ga]PSMA-11 for PET-CT imaging using a manual synthesis module and organic matrix based (68)Ge/(68)Ga generator.

PubMed

Nanabala, Raviteja; Anees, Muhammed K; Sasikumar, Arun; Joy, Ajith; Pillai, M R A

2016-08-01

[(68)Ga]PSMA-11 is a relatively recently introduced radiopharmaceutical for PET-CT imaging of prostate cancer patients. The availability of (68)Ge/(68)Ga generator and PSMA-11 ligand from commercial sources is facilitating the production of the radiopharmaceutical in-house. This paper describes our experience on the preparation of ~200 batches of [(68)Ga]PSMA-11 for conducting PET-CT imaging in patients suspected/suffering from prostate cancer. The radiosynthesis of [(68)Ga]PSMA-11 was done in a hospital based nuclear medicine department using (68)Ge/(68)Ga generator and a manual synthesis module, both supplied by Isotope Technologies Garching (ITG), Germany. The production involved the reaction of 5μg (5.3nmol) of PSMA-11 ligand in 1 ml of 0.25M sodium acetate buffer with 4ml of (68)GaCl3 in 0.05M HCl for 5min at 105°C; followed by purification in a C18 cartridge and collection through a 0.22μm pore size filter. The radiochemical yields obtained were consistently high, 93.19%±3.76%, and there was hardly any batch failure. The radiochemical purity of the product was >99% and the product was stable for over 2h; however it was used in patients immediately after preparation. About 200 batches of [(68)Ga]PSMA-11 were prepared during the period and more than 300 patients received the tracer during the 14months of study. No adverse reaction was observed in any of the patients and the image qualities were consistent with literature reports. [(68)Ga]PSMA-11 with high radiochemical and radionuclidic purity is conveniently prepared by using a (68)Ge/(68)Ga generator and manual synthesis module. The radiochemical yields are very high; and activity sufficient for 3-4 patients can be prepared in a single batch; multiple batches can be done on the same day and when needed after a gap of 1.5-2h. Copyright © 2016 Elsevier Inc. All rights reserved.

21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false What is current good manufacturing practice for PET drugs? 212.2 Section 212.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION...

Molecular Imaging of Transporters with Positron Emission Tomography

NASA Astrophysics Data System (ADS)

Antoni, Gunnar; Sörensen, Jens; Hall, Håkan

Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a really useful PET ligand for NET still remains to be identified. The most promising tracer to date is (S,S)-[18F]FMeNER-D2. The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditions related to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands based on cocaine were not selective, but more recently several selective tracers such as [11C]PE2I have been characterized and shown to be suitable as PET radioligands. Although there are a large number of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when [11C]McN5652 was synthesized, that this transporter was studied using PET. New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASB and [11C]MADAM and their analogues are today the most promising ligands. The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheral and central drug-Pgp interactions, although [11C]verapamil and [18F]fluoropaclitaxel are probably restricted to use in studies of the blood-brain barrier. The vesicular monoamine transporter 2 (VMAT2) is another interesting target for diagnostic imaging and [11C]DTBZ is a promising tracer. The noninvasive imaging of transporter density as a function of disease progression or availability following interaction with blocking drugs is highlighted, including the impact on both development of new therapies and the process of developing new drugs. Although CNS-related work focusing on psychiatric disorders is the main focus of this review, other applications of PET ligands, such as diagnosis of cancer, diabetes research, and drug interactions with efflux systems, are also discussed. The use of PET especially in terms of tracer development is briefly described. Finally, it can be concluded that there is an urgent need for new, selective radioligands for the study of the transporter systems in the human brain using PET.

Gallium-68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience.

PubMed

Aslani, Alireza; Snowdon, Graeme M; Bailey, Dale L; Schembri, Geoffrey P; Bailey, Elizabeth A; Roach, Paul J

2014-01-01

Gallium-68 (Ga-68) is an ideal research and hospital-based PET radioisotope. Currently, the main form of Ga-68 radiopharmaceutical that is being synthesised in-house is Ga-68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga-68 DOTATATE. The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerised system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in-. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC-SG and HPLC methods. A total of 500 Ga-68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga-68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer's expected value of approximately 70%. Germanium breakthrough averaged 8.6×10(-6)% of total activity which is well below the recommended level of 0.001%. The average ITLC-measured radiochemical purity was above 98.5% and the average HPLC-measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga-68 DOTATATE output with high labelling efficiency and purity. There is minimal operator intervention and radiation exposure. The system is GMP-compliant and has low maintenance and acceptable running costs. This system together with the recommended (68)Ge/(68)Ga generator is well suited for use in a hospital-based radiopharmacy.

Overview of positron emission tomography chemistry: clinical and technical considerations and combination with computed tomography.

PubMed

Koukourakis, G; Maravelis, G; Koukouraki, S; Padelakos, P; Kouloulias, V

2009-01-01

The concept of emission and transmission tomography was introduced by David Kuhl and Roy Edwards in the late 1950s. Their work later led to the design and construction of several tomographic instruments at the University of Pennsylvania. Tomographic imaging techniques were further developed by Michel Ter-Pogossian, Michael E. Phelps and others at the Washington University School of Medicine. Positron emission tomography (PET) is a nuclear medicine imaging technique which produces a 3-dimensional image or map of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Images of tracer concentration in 3-dimensional space within the body are then reconstructed by computer analysis. In modern scanners, this reconstruction is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine. If the biologically active molecule chosen for PET is 18F-fluorodeoxyglucose (FDG), an analogue of glucose, the concentrations of tracer imaged give tissue metabolic activity in terms of regional glucose uptake. Although use of this tracer results in the most common type of PET scan, other tracer molecules are used in PET to image the tissue concentration of many other types of molecules of interest. The main role of this article was to analyse the available types of radiopharmaceuticals used in PET-CT along with the principles of its clinical and technical considerations.

Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography.

PubMed

Elmaleh, D R; Fischman, A J; Tawakol, A; Zhu, A; Shoup, T M; Hoffmann, U; Brownell, A-L; Zamecnik, P C

2006-10-24

Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)-monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.

Fast and cost-effective cyclotron production of 61Cu using a natZn liquid target: an opportunity for radiopharmaceutical production and R&D.

PubMed

do Carmo, S J C; Alves, V H P; Alves, F; Abrunhosa, A J

2017-10-31

Following our previous work on the production of radiometals, such as 64 Cu and 68 Ga, through the irradiation of liquid targets using a medical cyclotron, we describe in this paper a technique to produce 61 Cu through the irradiation of natural zinc using a liquid target. The proposed method is very cost-effective, as it avoids the use of expensive enriched material, and is fast, as a purified solution of 61 CuCl 2 is obtained in less than 30 min after the end of beam. Considering its moderate half-life of 3.33 h and favourable decay properties as a positron emitter, 61 Cu is a very attractive nuclide for the labelling of PET tracers for pre-clinical and clinical use with PET as well as to support the intense R&D programmes being carried out worldwide by taking advantage of the rich and versatile chemistry of copper.

Discovery of a highly selective glycogen synthase kinase-3 inhibitor (PF-04802367) that modulates tau phosphorylation in brain: Translation for PET neuroimaging

PubMed Central

Liang, Steven H.; Chen, Jinshan Michael; Normandin, Marc D.; Chang, Jeanne S.; Chang, George C.; Taylor, Christine K.; Trapa, Patrick; Plummer, Mark S.; Para, Kimberly S.; Conn, Edward L.; Lopresti-Morrow, Lori; Lanyon, Lorraine F.; Cook, James M.; Richter, Karl E. G.; Nolan, Charlie E.; Schachter, Joel B.; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Lefker, Bruce A.; Enerson, Bradley E.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas; Patnaik, Debasis; Wagner, Florence F.; Perlis, Roy; Holson, Edward B.; Haggarty, Stephen J.; Fakhri, Georges El

2016-01-01

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology and neurology. We have identified N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. We demonstrated its efficacy in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A 11C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding. PMID:27355874

The development of a personalized patient education tool for decision making for postmenopausal women with osteoporosis.

PubMed

Hiligsmann, M; Ronda, G; van der Weijden, T; Boonen, A

2016-08-01

A personalized patient education tool for decision making (PET) for postmenopausal women with osteoporosis was developed by means of a systematic development approach. A prototype was constructed and refined by involving various professionals and patients. Professionals and patients expressed a positive attitude towards the use of the PET. The purpose was to systematically develop a paper-based personalized PET to assist postmenopausal women with osteoporosis in selecting a treatment in line with their personal values and preferences. The development of the PET was based on a systematic process including scope, design, development of a prototype, and alpha testing among professionals and patients by semi-structured interviews. The design and development resulted in a four-page PET prototype together with a one-page fact sheet of the different drug options. The prototype PET provided the personal risk factors, the estimated individualized risk for a future major osteoporotic fracture and potential reduction with drugs, and a summary of advantages and disadvantages whether or not to start drugs. The drug fact sheet presents five attributes of seven drugs in a tabular format. The alpha testing with professionals resulted in some adaptations, e.g., inclusion of the possibility to calculate fracture risk based on various individual risk scoring methods. Important results from the alpha testing with patients were differences in the fracture risk percentage which was seen as worthwhile to start drugs, the importance of an overview of side effects, and of the timing of the PET into the patient pathway. All women indicated that the PET could be helpful for their decision to select a treatment. Physicians and patients expressed a positive attitude towards the use of the proposed PET. Further research would be needed to test the effects of the PET on feasibility in clinical workflow and on patient outcomes.

21 CFR 212.110 - How must I maintain records of my production of PET drugs?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON...

21 CFR 212.110 - How must I maintain records of my production of PET drugs?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON...

21 CFR 212.80 - What are the requirements associated with labeling and packaging PET drug products?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What are the requirements associated with labeling and packaging PET drug products? 212.80 Section 212.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

[CNS metabolism in high-risk drug abuse, German version : Insights gained from 1H- and 31P MRS and PET].

PubMed

Bodea, S V

2017-06-01

High-risk drug consumption is a considerable problem for public health actors in industrialised countries. The latest trends show a market tendency towards diversification and increasing demand for high-purity synthetic drugs. Whilst most consumers seek medical help after cannabis use, it is high-risk drugs like cocaine, heroin and amphetamines that account for most of the 1000 drug-related deaths that occur in Germany every year. This article presents the most prominent in vivo cerebral metabolic information in cocaine, heroin and methamphetamine users provided by MRI spectroscopy and PET imaging. We reviewed the literature reporting neuroimaging studies of in vivo metabolic data for methamphetamine, cocaine and heroin consumption published up to March 2017. The search was conducted using PubMed with the following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET. MRI and PET are indispensable tools in gauging brain metabolic response to illegal drug abuse. Future breakthroughs in this field will most likely come from the investigation of novel neurotransmitter systems in PET and imaging phosphorus and carbon metabolites in MRI.

Development of peptide and protein based radiopharmaceuticals.

PubMed

Wynendaele, Evelien; Bracke, Nathalie; Stalmans, Sofie; De Spiegeleer, Bart

2014-01-01

Radiolabelled peptides and proteins have recently gained great interest as theranostics, due to their numerous and considerable advantages over small (organic) molecules. Developmental procedures of these radiolabelled biomolecules start with the radiolabelling process, greatly defined by the amino acid composition of the molecule and the radionuclide used. Depending on the radionuclide selection, radiolabelling starting materials are whether or not essential for efficient radiolabelling, resulting in direct or indirect radioiodination, radiometal-chelate coupling, indirect radiofluorination or (3)H/(14)C-labelling. Before preclinical investigations are performed, quality control analyses of the synthesized radiopharmaceutical are recommended to eliminate false positive or negative functionality results, e.g. changed receptor binding properties due to (radiolabelled) impurities. Therefore, radionuclidic, radiochemical and chemical purity are investigated, next to the general peptide attributes as described in the European and the United States Pharmacopeia. Moreover, in vitro and in vivo stability characteristics of the peptides and proteins also need to be explored, seen their strong sensitivity to proteinases and peptidases, together with radiolysis and trans-chelation phenomena of the radiopharmaceuticals. In vitro biomedical characterization of the radiolabelled peptides and proteins is performed by saturation, kinetic and competition binding assays, analyzing KD, Bmax, kon, koff and internalization properties, taking into account the chemical and metabolic stability and adsorption events inherent to peptides and proteins. In vivo biodistribution can be adapted by linker, chelate or radionuclide modifications, minimizing normal tissue (e.g. kidney and liver) radiation, and resulting in favorable dosimetry analyses. Finally, clinical trials are initiated, eventually leading to the marketing of radiolabelled peptides and proteins for PET/SPECT-imaging and therapy of different clinical diseases.

76 FR 54473 - Guidance on Positron Emission Tomography Drug Applications-Content and Format for New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... (formerly Docket No. 00D-0892)] Guidance on Positron Emission Tomography Drug Applications-- Content and... the availability of a guidance for industry entitled ``PET Drug Applications--Content and Format for... guidance for industry entitled ``PET Drug Applications--Content and Format for NDAs and ANDAs.'' The...

21 CFR 212.5 - To what drugs do the regulations in this part apply?

Code of Federal Regulations, 2010 CFR

2010-04-01

... requirements in parts 210 and 211 of this chapter. (b) Investigational and research PET drugs. For... part 312 of this chapter, and PET drugs produced with the approval of a Radioactive Drug Research... Drug Administration Biosciences Library, 10903 New Hampshire Ave., Silver Spring, MD, 20993-0002, 301...

75 FR 43990 - Agency Information Collection Activities; Proposed Collection; Comment Request; Pet Event...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... outbreaks in companion animals or contamination incidents concerning pet food or animals feed, which they... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 2010-N-0368... Network--State, Federal Cooperation to Prevent Spread of Pet Food Related Diseases AGENCY: Food and Drug...

Improved synthesis of no-carrier-added p-[124I]iodo-L-phenylalanine and p-[131I]iodo-L-phenylalanine for nuclear medicine applications in malignant gliomas.

PubMed

Israel, Ina; Brandau, Wolfgang; Farmakis, Georgios; Samnick, Samuel

2008-04-01

This work describes the synthesis and the tumor affinity testing of no-carrier-added (n.c.a.) p-[(124)I]iodo-L-phenyalanine ([(124)I]IPA) and n.c.a. p-[(131)I]iodo-l-phenyalanine ([(131)I]IPA) as radiopharmaceuticals for imaging brain tumors with PET and for radionuclid-based therapy, respectively. Parameters for labeling were optimized with regard to the amount of precursor, temperature and time. Thereafter, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were investigated in rat F98 glioma and in primary human A1207 and HOM-T3868 glioblastoma cells in vitro, followed by an in vivo evaluation in CD1 nu/nu mice engrafted with human glioblastoma. No-carrier-added [(124)I]IPA and n.c.a. [(131)I]IPA were obtained in 90+/-6% radiochemical yield and >99% radiochemical purity by iododestannylation of N-Boc-4-(tri-n-butylstannyl)-L-phenylalanine methylester in the presence of chloramine-T, followed by hydrolysis of the protecting groups. The total synthesis time, including the HPLC separation and pharmacological formulation, was less than 60 min and compatible with a clinical routine production. Both amino acid tracers accumulated intensively in rat and in human glioma cells. The radioactivity incorporation in tumor cells following a 15-min incubation at 37 degrees C/pH 7.4 varied from 25% to 42% of the total loaded activity per 10(6) tumor cells (296-540 cpm/1000 cells). Inhibition experiments confirmed that n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA were taken up into tumor by the sodium-independent L- and ASC-type transporters. Biodistribution and whole-body imaging by a gamma-camera and a PET scanner demonstrated a high targeting level and a prolonged retention of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA within the xenotransplanted human glioblastoma and a primarily renal excretion. However, an accurate delineation of the tumors in mice was not possible by our imaging systems. Radioactivity accumulation in the thyroid and in the stomach as a secondary indication of deiodination was less than 1% of the injected dose at 24h p.i., confirming the high in vivo stability of the radiopharmaceuticals. In conclusion, n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA are new promising radiopharmaceuticals, which can now be prepared in high radiochemical yields and high purity for widespread clinical applications. The specific and high-level targeting of n.c.a. [(124)I]IPA and n.c.a. [(131)I]IPA to glioma cells in vitro and to glioblastoma engrafts in vivo encourages further in vivo validations to ascertain their clinical potential as agent for imaging and quantitation of gliomas with PET, and for radionuclid-based therapy, respectively.

Clinical applications with the HIDAC positron camera

NASA Astrophysics Data System (ADS)

Frey, P.; Schaller, G.; Christin, A.; Townsend, D.; Tochon-Danguy, H.; Wensveen, M.; Donath, A.

1988-06-01

A high density avalanche chamber (HIDAC) positron camera has been used for positron emission tomographic (PET) imaging in three different human studies, including patients presenting with: (I) thyroid diseases (124 cases); (II) clinically suspected malignant tumours of the pharynx or larynx (ENT) region (23 cases); and (III) clinically suspected primary malignant and metastatic tumours of the liver (9 cases, 19 PET scans). The positron emitting radiopharmaceuticals used for the three studies were Na 124I (4.2 d half-life) for the thyroid, 55Co-bleomycin (17.5 h half-life) for the ENT-region and 68Ga-colloid (68 min half-life) for the liver. Tomographic imaging was performed: (I) 24 h after oral Na 124I administration to the thyroid patients, (II) 18 h after intraveneous administration of 55Co-bleomycin to the ENT patients and (III) 20 min following the intraveneous injection of 68Ga-colloid to the liver tumour patients. Three different imaging protocols were used with the HIDAC positron camera to perform appropriate tomographic imaging in each patient study. Promising results were obtained in all three studies, particularly in tomographic thyroid imaging, where a significant clinical contribution is made possible for diagnosis and therapy planning by the PET technique. In the other two PET studies encouraging results were obtained for the detection and precise localisation of malignant tumour disease including an estimate of the functional liver volume based on the reticulo-endothelial-system (RES) of the liver, obtained in vivo, and the three-dimensional display of liver PET data using shaded graphics techniques. The clinical significance of the overall results obtained in both the ENT and the liver PET study, however, is still uncertain and the respective role of PET as a new imaging modality in these applications is not yet clearly established. To appreciate the clinical impact made by PET in liver and ENT malignant tumour staging needs further investigation, and more detailed data on a larger number of clinical and experimental PET scans will be necessary for definitive evaluation. Nevertheless, the HIDAC positron camera may be used for clinical PET imaging in well-defined patient cases, particularly in situations where both high spatial resolution is desired in the reconstructed image of the examined pathological condition and at the same time "static" PET imaging may be adequate, as is the case in thyroid-, ENT- and liver tomographic imaging using the HIDAC positron camera.

[18F]FDG labeling of neural stem cells for in vivo cell tracking with positron emission tomography: inhibition of tracer release by phloretin.

PubMed

Stojanov, Katica; de Vries, Erik F J; Hoekstra, Dick; van Waarde, Aren; Dierckx, Rudi A J O; Zuhorn, Inge S

2012-02-01

The introduction of neural stem cells into the brain has promising therapeutic potential for the treatment of neurodegenerative diseases. To monitor the cellular replacement therapy, that is, to determine stem cell migration, survival, and differentiation, in vivo tracking methods are needed. Ideally, these tracking methods are noninvasive. Noninvasive tracking methods that have been successfully used for the visualization of blood-derived progenitor cells include magnetic resonance imaging and radionuclide imaging using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The SPECT tracer In-111-oxine is suitable for stem cell labeling, but for studies in small animals, the higher sensitivity and facile quantification that can be obtained with PET are preferred. Here the potential of 2'-[18F]fluoro-2'-deoxy-D-glucose ([18F]-FDG), a PET tracer, for tracking of neural stem cell (NSCs) trafficking toward an inflammation site was investigated. [18F]-FDG turns out to be a poor radiopharmaceutical to label NSCs owing to the low labeling efficiency and substantial release of radioactivity from these cells. Efflux of [18F]-FDG from NSCs can be effectively reduced by phloretin in vitro, but inhibition of tracer release is insufficient in vivo for accurate monitoring of stem cell trafficking.

76 FR 6143 - Draft Guidance on Positron Emission Tomography Drug Applications-Content and Format for New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

... fludeoxyglucose (FDG) 18 injection, ammonia N 13 injection, and sodium fluoride F 18 injection used in PET imaging... assist the manufacturers of certain PET drugs--fludeoxyglucose (FDG) F 18 injection, ammonia N 13...

Role of (18)F-FDG PET-CT in Monitoring the Cyclophosphamide Induced Pulmonary Toxicity in Patients with Breast Cancer - 2 Case Reports.

PubMed

Taywade, Sameer Kamalakar; Kumar, Rakesh; Bhethanabhotla, Sainath; Bal, Chandrasekhar

2016-09-01

Drug induced pulmonary toxicity is not uncommon with the use of various chemotherapeutic agents. Cyclophosphamide is a widely used chemotherapeutic drug in the treatment of breast cancer. Although rare, lung toxicity has been reported with cyclophosphamide use. Detection of bleomycin induced pulmonary toxicity and pattern of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in lungs on fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) has been elicited in literature in relation to lymphoma. However, limited data is available regarding the role of (18)F-FDG PET-CT in monitoring drug induced pulmonary toxicity in breast cancer. We here present two cases of cyclophosphamide induced drug toxicity. Interim (18)F-FDG PET-CT demonstrated diffusely increased tracer uptake in bilateral lung fields in both these patients. Subsequently there was resolution of lung uptake on (18)F-FDG PET-CT scan post completion of chemotherapy. These patients did not develop significant respiratory symptoms during chemotherapy treatment and in follow up.

Improving radiopharmaceutical supply chain safety by implementing bar code technology.

PubMed

Matanza, David; Hallouard, François; Rioufol, Catherine; Fessi, Hatem; Fraysse, Marc

2014-11-01

The aim of this study was to describe and evaluate an approach for improving radiopharmaceutical supply chain safety by implementing bar code technology. We first evaluated the current situation of our radiopharmaceutical supply chain and, by means of the ALARM protocol, analysed two dispensing errors that occurred in our department. Thereafter, we implemented a bar code system to secure selected key stages of the radiopharmaceutical supply chain. Finally, we evaluated the cost of this implementation, from overtime, to overheads, to additional radiation exposure to workers. An analysis of the events that occurred revealed a lack of identification of prepared or dispensed drugs. Moreover, the evaluation of the current radiopharmaceutical supply chain showed that the dispensation and injection steps needed to be further secured. The bar code system was used to reinforce product identification at three selected key stages: at usable stock entry; at preparation-dispensation; and during administration, allowing to check conformity between the labelling of the delivered product (identity and activity) and the prescription. The extra time needed for all these steps had no impact on the number and successful conduct of examinations. The investment cost was reduced (2600 euros for new material and 30 euros a year for additional supplies) because of pre-existing computing equipment. With regard to the radiation exposure to workers there was an insignificant overexposure for hands with this new organization because of the labelling and scanning processes of radiolabelled preparation vials. Implementation of bar code technology is now an essential part of a global securing approach towards optimum patient management.

Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography

PubMed Central

Elmaleh, D. R.; Fischman, A. J.; Tawakol, A.; Zhu, A.; Shoup, T. M.; Hoffmann, U.; Brownell, A.-L.; Zamecnik, P. C.

2006-01-01

Diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and its analog P2,P3-monochloromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P2,P3-[18F]monofluoromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate ([18F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [18F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [18F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [18F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [18F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [18F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation. PMID:17038498

Effective dose to staff members in a positron emission tomography/CT facility using zirconium-89

PubMed Central

2013-01-01

Objective: Positron emission tomography (PET) using zirconium-89 (89Zr) is complicated by its complex decay scheme. In this study, we quantified the effective dose from 89Zr and compared it with fluorine-18 fludeoxyglucose (18F-FDG). Methods: Effective dose distribution in a PET/CT facility in Riyadh was calculated by Monte Carlo simulations using MCNPX. The positron bremsstrahlung, the annihilation photons, the delayed gammas from 89Zr and those emissions from 18F-FDG were modelled in the simulations but low-energy characteristic X-rays were ignored. Results: On the basis of injected activity, the dose from 89Zr was higher than that of 18F-FDG. However, the dose per scan from 89Zr became less than that from 18F-FDG near the patient, owing to the difference in injected activities. In the corridor and control rooms, the 89Zr dose was much higher than 18F-FDG, owing to the difference in attenuation by the shielding materials. Conclusion: The presence of the high-energy photons from 89Zr-labelled immuno-PET radiopharmaceuticals causes a significantly higher effective dose than 18F-FDG to the staff outside the patient room. Conversely, despite the low administered activity of 89Zr, it gives rise to a comparable or even lower dose than 18F-FDG to the staff near the patient. This interesting result raises apparently contradictory implications in the radiation protection considerations of a PET/CT facility. Advances in knowledge: To the best of our knowledge, radiation exposure to staff and public in the PET/CT unit using 89Zr has not been investigated. The ultimate output of this study will lead to the optimal design of the facility for routine use of 89Zr. PMID:23934963

Positron emission tomography imaging as a key enabling technology in drug development.

PubMed

McCarthy, T J

2007-01-01

The use of positron emission tomography (PET) in drug development has become more common in the pharmaceutical industry in recent years. One of the biggest challenges to gaining acceptance of this technology is for project teams to understand when to use PET. This chapter reviews the usage of PET in drug development in the context of target, mechanism and efficacy biomarkers. Examples are drawn from a number of therapeutic areas, but we also show that the relative penetration of this technology beyond CNS and oncology applications has been relatively small. However, with the increasing availability of PET and development of novel radiotracers it is expected that the utilization will be much broader in future years, with the additional expectation that the use of PET as an efficacy biomarker will also become more evident.

Improving cancer treatment with cyclotron produced radionuclides. Progress report

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

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

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

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

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Grafting of [(64)Cu]-TPPF20 porphyrin complex on Functionalized nano-porous MCM-41 silica as a potential cancer imaging agent.

PubMed

Fazaeli, Yousef; Feizi, Shahzad; Jalilian, Amir R; Hejrani, Ali

2016-06-01

Mesoporous silica, MCM-41, functionalized with 3-aminopropyltriethoxysilane (APTES) was investigated as a potential drug delivery system, using [(64)Cu]-5, 10, 15, 20-tetrakis penta fluorophenyl porphyrin complex. [(64)Cu]-TPPF20 complex was grafted on functionalized MCM-41. The product was characterized by paper chromatography, FTIR spectroscopy, low angle X-ray diffraction, CHN and TGA/DTA analyses and atomic force microscopy. The biological evaluations of the grafted complex, [(64)Cu]-TPPF20@NH2-MCM-41, were done in Fibrosarcoma tumor-bearing Sprague-Dawley rats using scarification studies and Sopha DST-XL Dual-Head SPECT system. The actual loading amount of aminopropyl groups was found about 1.6mmol per gram of final silica. The specific activity of the final compound was found to be 3Ci/g. Amine functionalized MCM-41 was found to be a good platform for theranostic radiopharmaceuticals such as copper-64 complexes. Considering the accumulation of the tracer in tumor cells, fast wash-out from normal tissues, the short half-life copper-64 and less imposed radiation doses to patients, [(64)Cu]-TPPF20@NH2-MCM-41 can potentially be a suitable candidate for tumor imaging applications and future PET studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Imaging in Central Nervous System Drug Discovery.

PubMed

Gunn, Roger N; Rabiner, Eugenii A

2017-01-01

The discovery and development of central nervous system (CNS) drugs is an extremely challenging process requiring large resources, timelines, and associated costs. The high risk of failure leads to high levels of risk. Over the past couple of decades PET imaging has become a central component of the CNS drug-development process, enabling decision-making in phase I studies, where early discharge of risk provides increased confidence to progress a candidate to more costly later phase testing at the right dose level or alternatively to kill a compound through failure to meet key criteria. The so called "3 pillars" of drug survival, namely; tissue exposure, target engagement, and pharmacologic activity, are particularly well suited for evaluation by PET imaging. This review introduces the process of CNS drug development before considering how PET imaging of the "3 pillars" has advanced to provide valuable tools for decision-making on the critical path of CNS drug development. Finally, we review the advances in PET science of biomarker development and analysis that enable sophisticated drug-development studies in man. Copyright © 2017 Elsevier Inc. All rights reserved.

The Production of PET Tracers Utilizing Small Accelerators.

NASA Astrophysics Data System (ADS)

Votaw, John Ralph

The goal of positron emission tomographic (PET) studies is to utilize radiotracers to provide fundamental information that will lead to a better understanding of the physiology in both diseased and healthy tissue. In order for PET to become a viable clinical modality, these tracers must be produced reliably and efficiently. Work has concentrated on developing a cyclotron laboratory dedicated to the efficient production of the most commonly used PET tracers. Considerable effort has been directed towards understanding the subtleties of all of the subprocedures involved. As a result of this work, the success rate of delivering radiopharmaceuticals on demand to the nuclear medicine clinic is now above 95%. In order to further facilitate performing PET studies with minimal professional support, a time-of-flight detector system has been developed to noninvasively measure input functions that are required in applying compartmental models to the data. Its potential utility has been demonstrated with phantoms; testing and evaluation is currently being studied in human patients. The feasibility of producing PET tracers in a manner consistent with the operation of a clinical PET center has been demonstrated. Since FDG is the tracer in highest demand (over 50% of all studies), the effort has concentrated on the production of this model compound. As a result of this work, the amount of FDG that may be produced in a single synthesis at the University of Wisconsin-Madison has increased by a factor of 25 in the last five years. During the same period, the number of man-hours needed to perform a FDG synthesis has decreased by a factor of 10 and the radiation dose received by the chemist per mCi of starting material has decreased by a factor of 100. In addition to these advances, the number of successful syntheses between failures has increased by a factor of 20. This improvement has been made possible by a thorough understanding of all aspects of the production of PET tracers and by intelligent monitoring of the parameters that have the greatest effect on the outcome of the synthesis.

PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience.

PubMed

Calabria, Ferdinando; Chiaravalloti, Agostino; Cicciò, Carmelo; Gangemi, Vincenzo; Gullà, Domenico; Rocca, Federico; Gallo, Gianpasquale; Cascini, Giuseppe Lucio; Schillaci, Orazio

2017-08-01

The 11 C/ 18 F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11 C/ 18 F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18 F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18 F-choline bio-distribution in the female body. We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18 F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18 F-choline PET/CT in 5 female patients. 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. The accurate knowledge of 18 F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18 F-choline uptake in the exocrine glands. Our results confirm the possibility of 18 F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18 F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a better patient quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma.

PubMed

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18 F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18 F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18 F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18 F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUV average for MM lesions was 11.9 and mean SUV max was 23.2. Respectively, SUV average and SUV max for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18 F-NaF revealed the following mean values for MM lesions: K 1 = 0.248 (1/min), k 3 = 0.359 (1/min), influx (K i ) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K 1 = 0.169 (1/min), k 3 = 0.422 (1/min), influx (K i ) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUV average , SUV max , K 1 , k 3 and influx (K i ) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18 F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18 F-NaF PET/CT in the diagnostic workup of MM.

What have positron emission tomography and 'Zippy' told us about the neuropharmacology of drug addiction?

PubMed

Cumming, Paul; Caprioli, Daniele; Dalley, Jeffrey W

2011-08-01

Translational molecular imaging with positron emission tomography (PET) and allied technologies offer unrivalled applications in the discovery of biomarkers and aetiological mechanisms relevant to human disease. Foremost among clinical PET findings during the past two decades of addiction research is the seminal discovery of reduced dopamine D(2/3) receptor expression in the striatum of drug addicts, which could indicate a predisposing factor and/or compensatory reaction to the chronic abuse of stimulant drugs. In parallel, recent years have witnessed significant improvements in the performance of small animal tomographs (microPET) and a refinement of animal models of addiction based on clinically relevant diagnostic criteria. This review surveys the utility of PET in the elucidation of neuropharmacological mechanisms underlying drug addiction. It considers the consequences of chronic drug exposure on regional brain metabolism and neurotransmitter function and identifies those areas where further research is needed, especially concerning the implementation of PET tracers targeting neurotransmitter systems other than dopamine, which increasingly have been implicated in the pathophysiology of drug addiction. In addition, this review considers the causal effects of behavioural traits such as impulsivity and novelty/sensation-seeking on the emergence of compulsive drug-taking. Previous research indicates that spontaneously high-impulsive rats--as exemplified by 'Zippy'--are pre-disposed to escalate intravenous cocaine self-administration, and subsequently to develop compulsive drug taking tendencies that endure despite concurrent adverse consequences of such behaviour, just as in human addiction. The discovery using microPET of pre-existing differences in dopamine D(2/3) receptor expression in the striatum of high-impulsive rats suggests a neural endophenotype that may likewise pre-dispose to stimulant addiction in humans. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Positron Emission Tomography Image-Guided Drug Delivery: Current Status and Future Perspectives

PubMed Central

2015-01-01

Positron emission tomography (PET) is an important modality in the field of molecular imaging, which is gradually impacting patient care by providing safe, fast, and reliable techniques that help to alter the course of patient care by revealing invasive, de facto procedures to be unnecessary or rendering them obsolete. Also, PET provides a key connection between the molecular mechanisms involved in the pathophysiology of disease and the according targeted therapies. Recently, PET imaging is also gaining ground in the field of drug delivery. Current drug delivery research is focused on developing novel drug delivery systems with emphasis on precise targeting, accurate dose delivery, and minimal toxicity in order to achieve maximum therapeutic efficacy. At the intersection between PET imaging and controlled drug delivery, interest has grown in combining both these paradigms into clinically effective formulations. PET image-guided drug delivery has great potential to revolutionize patient care by in vivo assessment of drug biodistribution and accumulation at the target site and real-time monitoring of the therapeutic outcome. The expected end point of this approach is to provide fundamental support for the optimization of innovative diagnostic and therapeutic strategies that could contribute to emerging concepts in the field of “personalized medicine”. This review focuses on the recent developments in PET image-guided drug delivery and discusses intriguing opportunities for future development. The preclinical data reported to date are quite promising, and it is evident that such strategies in cancer management hold promise for clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in enhanced quality of life for cancer patients. PMID:24865108

Eleventh international symposium on radiopharmaceutical chemistry

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

NONE

This document contains abstracts of papers which were presented at the Eleventh International Symposium on Radiopharmaceutical Chemistry. Sessions included: radiopharmaceuticals for the dopaminergic system, strategies for the production and use of labelled reactive small molecules, radiopharmaceuticals for measuring metabolism, radiopharmaceuticals for the serotonin and sigma receptor systems, labelled probes for molecular biology applications, radiopharmaceuticals for receptor systems, radiopharmaceuticals utilizing coordination chemistry, radiolabelled antibodies, radiolabelling methods for small molecules, analytical techniques in radiopharmaceutical chemistry, and analytical techniques in radiopharmaceutical chemistry.

[18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging.

PubMed

Lemoine, Laëtitia; Verdurand, Mathieu; Vacher, Bernard; Blanc, Elodie; Le Bars, Didier; Newman-Tancredi, Adrian; Zimmer, Luc

2010-03-01

The serotonin-1A (5-HT(1A)) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT(1A) receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT(1A) receptors. Since all clinical PET 5-HT(1A) radiopharmaceuticals are antagonists, it is of great interest to develop a( 18)F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT(1A) receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT(1A) receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [(18)F]MPPF, a validated 5-HT(1A) antagonist radiopharmaceutical. The chemical and radiochemical purities of [(18)F]F15599 were >98%. In vitro [(18)F]F15599 binding was consistent with the known 5-HT(1A) receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [(18)F]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [(18)F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT(1A) antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer readily entered the rat and the cat brain and generated few brain radioactive metabolites. Remarkably, in microPET studies, [(18)F]F15599 notably displayed a pattern of brain labelling that did not correlate with in vitro observations. Thus, in cat, the highest binding was observed in dorsal raphe and cingulate cortex with little binding in other cortical regions and none in hippocampus. In vivo binding was abolished by WAY100635, indicating specific labelling of 5-HT(1A) receptors. [(18)F]F15599 is a radiofluorinated agonist presenting interesting characteristics for probing in vitro and in vivo the high-affinity states of the 5-HT(1A) receptors. Its differential labelling of 5-HT(1A) receptors in vitro and in vivo may result from its reported preferential interaction with receptors coupled to specific G-protein subtypes.

21 CFR 212.40 - How must I control the components I use to produce PET drugs and the containers and closures I...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false How must I control the components I use to produce PET drugs and the containers and closures I package them in? 212.40 Section 212.40 Food and Drugs FOOD... GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Control of...

21 CFR 601.35 - Evaluation of safety.

Code of Federal Regulations, 2010 CFR

2010-04-01

... established, low-risk profile). Upon reviewing the relevant product characteristics and safety information..., carrier, or ligand; (3) The risks of an incorrect diagnostic determination; (4) The adverse reaction profile of the drug; (5) Results of human experience with the radiopharmaceutical for other uses; and (6...

68Ga-DOTA-TATE PET vs. 123I-MIBG in identifying malignant neural crest tumours.

PubMed

Naji, Meeran; Zhao, Chunlei; Welsh, Sarah J; Meades, Richard; Win, Zarni; Ferrarese, Annalisa; Tan, Tricia; Rubello, Domenico; Al-Nahhas, Adil

2011-08-01

We aimed to compare imaging with (123)I-MIBG and (68)Ga-DOTA-TATE in neural crest tumours (NCT) to see if the latter could offer more advantage in detecting extra lesions and have higher sensitivity for malignant lesions. We retrospectively reviewed 12 patients (M = 10, F = 2; age range 20-71 years) with NCT (phaeochromocytomas = 7, paragangliomas = 4, medullary thyroid cancer = 1) who underwent both (68)Ga-DOTA-TATE positron emission tomography (PET) or PET/computed tomography (CT) and (123)I-MIBG single-photon emission computed tomography within 6 months. Visual assessment of all lesions and measurement of target/non-target (T/N) ratio in selected lesions were performed. Five patients (aged 50 or less) had SDHB screening results correlated with imaging results of both radiopharmaceuticals. All patients had contrast-enhanced CT and/or other cross-sectional imaging. (68)Ga-DOTA-TATE PET showed tumour lesions in ten out of 12 patients with confirmed disease, while (123)I-MIBG showed lesions in five out of 12 patients. In one patient, both (68)Ga-DOTA-TATE PET and (123)I-MIBG were negative, but CT, magnetic resonance imaging, and 2-deoxy-2-[(18)F]fluoro-D-glucose PET scans identified a lesion in the thorax. (68)Ga-DOTA-TATE and (123)I-MIBG detected a total of 30 lesions, of which 29/30 were positive with (68)Ga-DOTA-TATE and 7/30 with (123)I-MIBG. We also found higher incidence of SDHB positive results in patients with positive (68)Ga-DOTA-TATE. Our limited data suggest that (68)Ga-DOTA-TATE is a better imaging agent for NCT and detects significantly more lesions with higher T/N ratio compared to (123)I-MIBG. (68)Ga-DOTA-TATE was more likely to detect malignant lesions as indicated by correlating imaging results with SDHB screening.

Recent Trends in Soft Tissue Infection Imaging

PubMed Central

Petruzzi, Nicholas; Shanthly, Nylla; Thakur, Mathew

2009-01-01

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, CNS, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of 18F-FDG PET and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to monitor the therapeutic response in a variety of conditions. Current studies suggest PET should be considered the most accurate quantitative method. Scintigraphy has much to offer in localizing abdominal infection as well as inflammation. We may begin to see a gradual increase in the usage of FDG PET in detecting occult abdominal infections. Commonly used modalities for imaging inflammatory bowel disease are scintigraphy with 111In-oxine/99mTc-HMPAO labeled autologous white blood cells. The literature on CNS infection imaging is relatively scarce. Few clinical studies have been performed and numerous new agents have been developed for this use with varying results. Further studies are needed to more clearly delineate the future direction of this field. In evaluating the post-operative spine, 99mTc-ciprofloxacin SPECT was reported to be >80% sensitive in patients more than 6 months post-surgery. FDG PET has also been suggested for this purpose and may play a larger role than originally thought. It appears PET/CT is gaining support, especially in imaging those with fever of unknown origin or nonfunctional immune systems. While an infection specific agent is lacking, the development of one would greatly advance our ability to detect, localize, and quantify infections. Overall, imaging such an agent via SPECT/CT or PET/CT will pave the way for greater clinical reliability in the localization of infection. PMID:19187804

Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer.

PubMed

Sevcenco, Sabina; Klingler, Hans Christoph; Eredics, Klaus; Friedl, Alexander; Schneeweiss, Jenifer; Knoll, Peter; Kunit, Thomas; Lusuardi, Lukas; Mirzaei, Siroos

2018-06-01

The high diagnostic potential of 64 Cu-PSMA PET-CT imaging was clinically investigated in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local disease. The aim of our study is to assess the uptake behavior in the clinical setting of 64Copper Prostate-Specific Membrane Antigen ( 64 Cu PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) in prostate cancer. A retrospective study was performed in 23 patients with intermediate, high risk and progressive disease at primary staging of prostate cancer. All patients underwent 64 Cu-PSMA PET. Overall, 250 MBq (4 MBq per kg bodyweight, range 230-290 MBq) of 64 Cu-NODAGA PSMA was intravenously applied. PET images were performed 30 min (pelvis and abdomen) and 1-2 h post-injection (skull base to mid-thigh). Maximum standardized uptake values (SUVmax) were measured in the organs with high physiological uptake such as liver and kidney, and, additionally, background activity was measured in the gluteal area and in suspected tumor lesions using a HERMES workstation. PSMA uptake was detected in prostate bed in nine patients, in six patients in distant metastases (bone, lung and liver) and in nine patients in lymph nodes. Of 23 patients, 5 (20.8%) did not show any focal pathological uptake in the whole body. The number of sites (prostate bed, lymph nodes, distant metastases) with positive PSMA uptake was significantly associated with PSA values before imaging (P = 0.0032). The 64 Cu PSMA uptake increased significantly from 30 min to 1-3 h post-injection (Wilcoxon signed rank test, P = 0.002). 64 Cu NODAGA-PSMA PET is a promising imaging tool in the detection of residual disease in patients with recurrent or primary progressive prostate cancer. Furthermore, the increased tracer uptake over time indicates in vivo stability of the diagnostic radiopharmaceutical.

78 FR 17215 - Agency Information Collection Activities: Proposed Collection; Comment Request; Current Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0242... (CGMP) for positron emission tomography (PET) drugs. DATES: Submit either electronic or written comments... product. FDA's CGMP regulations at 21 CFR part 212 are intended to ensure that PET drug products meet the...

Automatic, sterile, and apyrogenic delivery of PET radiotracers from the cyclotron to the patient

NASA Astrophysics Data System (ADS)

Votaw, J. R.; Cashion, D. B.; Clanton, J. A.

1991-05-01

An automatic delivery remote injection system has been developed to administer either 13N-labelled ammonia, or 15O-labelled water or 18F-labelled FDG to patients. Automation increases the throughout and efficiency of the PET center, and remote dose administration ensures patient safety and reduces the radiation exposure to the technologist supervising the radiopharmaceutical injection. The remote dose administration apparatus utilizes a syringe pump to transfer liquid activity and a solenoid three-way valve to switch between lines connected to a patient and a receiving vial. To ensure apyrogenicity and sterility of the injected product, the entire system is washed with sterile water before it is used. Since the tracer is delivered in an ~ 8 ml bolus of water, the next delivery through the system is considered safe for injection if pyrogens are not detected at a threshold of 3 endotoxin units per ml (EU/ml) in the wash. Time delayed tests shows that the system may be left unused for up to 6 h before the wash must be repeated.

Nuclear Imaging in Sarcoidosis.

PubMed

Piekarski, Eve; Benali, Khadija; Rouzet, François

2018-05-01

Sarcoidosis is a multisystem granulomatosis which may result in a wide variety of clinical and biological presentations. Symptoms are often nonspecific, and incidental abnormal findings on chest radiography is rather common. Although sarcoidosis resolves favorably in most cases, some localizations can provoke functional impairment or even impact on patients' prognosis. The diagnosis is based on a pathological hallmark which is the non-necrotizing epithelioid-cell rich granuloma. Owing to the ability to detect inflammation throughout the body with a high sensibility, FDG-PET/CT gained a central role in sarcoidosis because it can suggest the diagnosis in certain clinical context, guide biopsy, evaluate the extent of the disease, help assess the prognosis, and monitor immunosuppressive therapy. This review will briefly describe clinical and typical findings of conventional imaging according to organ involvement, in order to highlight the additional information provided by nuclear imaging. In the future, we can expect to further improve diagnostic performance of imaging in some indications through the availability of more specific radiopharmaceuticals and the wider use of combined PET/MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

Prostate-specific membrane antigen as a target for cancer imaging and therapy

PubMed Central

KIESS, A. P.; BANERJEE, S. R.; MEASE, R. C.; ROWE, S. P.; RAO, A.; FOSS, C. A.; CHEN, Y.; YANG, X.; CHO, S. Y.; NIMMAGADDA, S.; POMPER, M. G.

2016-01-01

The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers. PMID:26213140

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

Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP.

PubMed

Lange, R; de Klerk, J M H; Bloemendal, H J; Ramakers, R M; Beekman, F J; van der Westerlaken, M M L; Hendrikse, N H; Ter Heine, R

2015-05-01

(188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration. We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice. The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP. For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 μmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs. Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo. The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthesis, 68Ga-Radiolabeling, and Preliminary In Vivo Assessment of a Depsipeptide-Derived Compound as a Potential PET/CT Infection Imaging Agent

PubMed Central

Mokaleng, Botshelo B.; Ebenhan, Thomas; Ramesh, Suhas; Govender, Thavendran; Kruger, Hendrik G.; Hazari, Puja P.; Mishra, Anil K.; Marjanovic-Painter, Biljana; Zeevaart, Jan R.; Sathekge, Mike M.

2015-01-01

Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. µPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs (P = 0.322) > forearm muscles (P = 0.092) > background (P = 0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101's capacity as targeting vector. PMID:25699267

INVESTIGATION OF PARTIAL VOLUME EFFECT IN DIFFERENT PET/CT SYSTEMS: A COMPARISON OF RESULTS USING THE MADEIRA PHANTOM AND THE NEMA NU-2 2001 PHANTOM.

PubMed

Chipiga, L; Sydoff, M; Zvonova, I; Bernhardsson, C

2016-06-01

Positron emission tomography combined with computed tomography (PET/CT) is a quantitative technique used for diagnosing various diseases and for monitoring treatment response for different types of tumours. However, the accuracy of the data is limited by the spatial resolution of the system. In addition, the so-called partial volume effect (PVE) causes a blurring of image structures, which in turn may cause an underestimation of activity of a structure with high-activity content. In this study, a new phantom, MADEIRA (Minimising Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations) for activity quantification in PET and single photon emission computed tomography (SPECT) was used to investigate the influence on the PVE by lesion size and tumour-to-background activity concentration ratio (TBR) in four different PET/CT systems. These measurements were compared with data from measurements with the NEMA NU-2 2001 phantom. The results with the MADEIRA phantom showed that the activity concentration (AC) values were closest to the true values at low ratios of TBR (<10) and reduced to 50 % of the actual AC values at high TBR (30-35). For all scanners, recovery of true values became closer to 1 with an increasing diameter of the lesion. The MADEIRA phantom showed good agreement with the results obtained from measurements with the NEMA NU-2 2001 phantom but allows for a wider range of possibilities in measuring image quality parameters. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

On the use of positron counting for radio-Assay in nuclear pharmaceutical production.

PubMed

Maneuski, D; Giacomelli, F; Lemaire, C; Pimlott, S; Plenevaux, A; Owens, J; O'Shea, V; Luxen, A

2017-07-01

Current techniques for the measurement of radioactivity at various points during PET radiopharmaceutical production and R&D are based on the detection of the annihilation gamma rays from the radionuclide in the labelled compound. The detection systems to measure these gamma rays are usually variations of NaI or CsF scintillation based systems requiring costly and heavy lead shielding to reduce background noise. These detectors inherently suffer from low detection efficiency, high background noise and very poor linearity. They are also unable to provide any reasonably useful position information. A novel positron counting technique is proposed for the radioactivity assay during radiopharmaceutical manufacturing that overcomes these limitations. Detection of positrons instead of gammas offers an unprecedented level of position resolution of the radiation source (down to sub-mm) thanks to the nature of the positron interaction with matter. Counting capability instead of charge integration in the detector brings the sensitivity down to the statistical limits at the same time as offering very high dynamic range and linearity from zero to any arbitrarily high activity. This paper reports on a quantitative comparison between conventional detector systems and the proposed positron counting detector. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination

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

Mossine, Andrew V.; Brooks, Allen F.; Ichiishi, Naoko

In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET radiochemistry landscape. These reactions have enabled the radiofluorination of a wide range of substrates, facilitating access to radiopharmaceuticals that were challenging to synthesize using traditional fluorine-18 radiochemistry. However, the process of adapting these new reactions for automated radiopharmaceutical production has revealed limitations in fitting them into the confines of traditional radiochemistry systems. In particular, the presence of bases (e.g. K 2CO 3) and/or phase transfer catalysts (PTC) (e.g. kryptofix 2.2.2) associated with fluorine-18 preparation has been found to be detrimental to reaction yields. We hypothesizedmore » that these limitations could be addressed through the development of alternate techniques for preparing [18F]fluoride. This approach also opens the possibility that an eluent can be individually tailored to meet the specific needs of a metal-catalyzed reaction of interest. In this communication, we demonstrate that various solutions of copper salts, bases, and ancillary ligands can be utilized to elute [ 18F]fluoride from ion exchange cartridges. The new procedures we present here are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.« less

Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination

DOE PAGES

Mossine, Andrew V.; Brooks, Allen F.; Ichiishi, Naoko; ...

2017-03-22

In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET radiochemistry landscape. These reactions have enabled the radiofluorination of a wide range of substrates, facilitating access to radiopharmaceuticals that were challenging to synthesize using traditional fluorine-18 radiochemistry. However, the process of adapting these new reactions for automated radiopharmaceutical production has revealed limitations in fitting them into the confines of traditional radiochemistry systems. In particular, the presence of bases (e.g. K 2CO 3) and/or phase transfer catalysts (PTC) (e.g. kryptofix 2.2.2) associated with fluorine-18 preparation has been found to be detrimental to reaction yields. We hypothesizedmore » that these limitations could be addressed through the development of alternate techniques for preparing [18F]fluoride. This approach also opens the possibility that an eluent can be individually tailored to meet the specific needs of a metal-catalyzed reaction of interest. In this communication, we demonstrate that various solutions of copper salts, bases, and ancillary ligands can be utilized to elute [ 18F]fluoride from ion exchange cartridges. The new procedures we present here are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.« less

Development and Validation of a High-Pressure Liquid Chromatography Method for the Determination of Chemical Purity and Radiochemical Purity of a [68Ga]-Labeled Glu-Urea-Lys(Ahx)-HBED-CC (Positron Emission Tomography) Tracer

PubMed Central

2017-01-01

Background: Prostate-specific membrane antigen (PSMA) has gained high attention as a useful biomarker in the imaging evaluation of prostate cancer with positron emission tomography (PET) during recent years. [68Ga]-labeled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]-PSMA-HBED-CC) is a novel PSMA inhibitor radiotracer which has demonstrated its suitability in detecting prostate cancer. Preparation conditions may influence the quality and in vivo behavior of this tracer, and no standard procedure for the quality control (QC) is available. The aim of this study was to develop a new rapid and simple high-pressure liquid chromatography method of analysis for the routine QCs of [68Ga]-PSMA-HBED-CC to guarantee the high quality of the radiopharmaceutical product before release. Methods: A stepwise approach was used based on the quality by design concept of the International Conference of Harmonisation Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of European Association of Nuclear Medicine, Society of Nuclear Medicine, International Atomic Energy Agency, World Health Organization, and Italian Association of Nuclear Medicine and Molecular Imaging. The developed analytical test method was validated because a specific monograph in the pharmacopoeia is not available for [68Ga]-PSMA-HBED-CC. Results: The purity and quality of the radiopharmaceutical obtained according to the proposed method resulted high enough to safely administrate it to patients. An excellent linearity was found between 0.8 and 5 μg/mL, with a detection limit of 0.2 μg/mL. Assay imprecision (% CV) was <2%. Conclusions: The developed method to assess the radiochemical and chemical purity of [68Ga]-PSMA-HBED-CC is rapid, accurate, and reproducible, allowing routinely the use of this PET tracer as a diagnostic tool for imaging prostate cancer and also assuring patient safety. PMID:29520394

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes.

PubMed

Janssen, Ingo; Chen, Clara C; Zhuang, Zhenping; Millo, Corina M; Wolf, Katherine I; Ling, Alexander; Lin, Frank I; Adams, Karen T; Herscovitch, Peter; Feelders, Richard A; Fojo, Antonio T; Taieb, David; Kebebew, Electron; Pacak, Karel

2017-08-01

Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene. Recently, mutations in the prolyl hydroxylase gene ( PHD ) 1 and 2 and in the hypoxia-inducible factor 2 α ( HIF2A ) were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered. Because the functional imaging signature of patients with PPGL-polycythemia syndromes is still unknown, and because these tumors (in most patients) are multiple, recurrent, and metastatic, the goal of our study was to assess the optimal imaging approach using 4 different PET radiopharmaceuticals and CT/MRI in these patients. Methods: Fourteen patients (10 women, 4 men) with confirmed PPGL and polycythemia prospectively underwent 68 Ga-DOTATATE (13 patients), 18 F-FDG (13 patients), 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) (14 patients), 18 F-fluorodopamine ( 18 F-FDA) (11 patients), and CT/MRI (14 patients). Detection rates of PPGL lesions were compared between all imaging studies and stratified between the underlying mutations. Results: 18 F-FDOPA and 18 F-FDA PET/CT showed similar combined lesion-based detection rates of 98.7% (95% confidence interval [CI], 92.7%-99.8%) and 98.3% (95% CI, 90.9%-99.7%), respectively. The detection rates for 68 Ga-DOTATATE (35.3%; 95% CI, 25.0%-47.2%), 18 F-FDG (42.3; 95% CI, 29.9%-55.8%), and CT/MRI (60.3%; 95% CI, 48.8%-70.7%) were significantly lower ( P < 0.01), irrespective of the mutation status. Conclusion: 18 F-FDOPA and 18 F-FDA are superior to 18 F-FDG, 68 Ga-DOTATATE, and CT/MRI and should be the radiopharmaceuticals of choice in this rare group of patients. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy.

PubMed

Naganawa, Mika; Gallezot, Jean-Dominique; Rossano, Samantha; Carson, Richard E

2017-12-11

Positron emission tomography, an imaging tool using radiolabeled tracers in humans and preclinical species, has been widely used in recent years in drug development, particularly in the central nervous system. One important goal of PET in drug development is assessing the occupancy of various molecular targets (e.g., receptors, transporters, enzymes) by exogenous drugs. The current linear mathematical approaches used to determine occupancy using PET imaging experiments are presented. These algorithms use results from multiple regions with different target content in two scans, a baseline (pre-drug) scan and a post-drug scan. New mathematical estimation approaches to determine target occupancy, using maximum likelihood, are presented. A major challenge in these methods is the proper definition of the covariance matrix of the regional binding measures, accounting for different variance of the individual regional measures and their nonzero covariance, factors that have been ignored by conventional methods. The novel methods are compared to standard methods using simulation and real human occupancy data. The simulation data showed the expected reduction in variance and bias using the proper maximum likelihood methods, when the assumptions of the estimation method matched those in simulation. Between-method differences for data from human occupancy studies were less obvious, in part due to small dataset sizes. These maximum likelihood methods form the basis for development of improved PET covariance models, in order to minimize bias and variance in PET occupancy studies.

Potential clinical impact of radionuclide imaging technologies: highlights of the ITBS 2003 meeting

NASA Astrophysics Data System (ADS)

Itti, Roland

2004-07-01

Radiopharmaceuticals are major determinants of progress in Nuclear Medicine. Besides 18FDG, the most common PET tracer, several other molecules are under evaluation, such as 18F-fluoride for bone studies, numerous ligands for neurotransmission, 18F-DOPA for neuro-endocrine tumors or generator produced 68Ga-peptides for various cancers. Nuclear medicine gradually changes for "molecular imaging" and medical imaging, which was at the beginning mainly anatomic, has progressed in the direction of functional and metabolic imaging. The present challenge is to achieve some degree of "in vivo" biochemistry or even histology or genetics. The importance of anatomic/functional image fusion justifies the development of combined PET-CT instrumentation, whose objectives have to be discussed in terms of anatomical landmarks and/or additional clinical information. The question of "hard" or "soft" image co-registration remains open, involving not only CT, but also SPECT or MRI. Development of dedicated imaging devices, whether single photon or positron, is of major interest for breast imaging, allowing optimal imaging conditions, with results definitely superior to classical gamma-cameras or PET. The patient population concerned with scintimammography is still controversial, as well as the imaging modalities: FDG or sestaMIBI, planar or tomographic, scintillators or semi-conductors, and the research field remains open. This is also valid for external or per-operative probe systems for tumor or lymph nodes localization.

Dosimetric evaluation of the staff working in a PET/CT department

NASA Astrophysics Data System (ADS)

Dalianis, K.; Malamitsi, J.; Gogou, L.; Pagou, M.; Efthimiadou, R.; Andreou, J.; Louizï, A.; Georgiou, E.

2006-12-01

The dosimetric literature data concerning the medical personnel working in positron emission tomography/computed tomography (PET/CT) departments are limited. Therefore, we measured the radiation dose of the staff working in the first PET/CT department in Greece at the Diagnostic and Therapeutic Center of Athens HYGEIA—Harvard Medical International. As, for the time being, only 2-deoxy-2-[ 18F]fluoro-d-glucose (FDG) PET studies are performed, radiation dose measurements concern those derived from dispensing of the radiopharmaceutical as well as from the patients undergoing FDG-PET imaging. Our aim is to develop more effective protective measures against radionuclide exposure. To estimate the effective dose from external exposure, all seven members of the staff (two nurses, two medical physicists, two technologists, one secretary) had TLD badges worn at the upper pocket of their overall, TLD rings on the right hand and digital dosimeters at their upper side pocket. In addition, isodose curves were measured with thermoluminescence detectors for distances of 20, 50, 70 and 100 cm away from patients who had been injected with 18F-FDG. Dose values of the PET/CT staff were measured with digital detectors, TLD badges and TLD rings over the first 8 months for a total of 160 working days of the department's operation, consisting of a workload of about 10-15 patients/week who received 250-420 MBq of 18F-FDG each. Whole - body collective doses and hand doses for the staff were the following: Nurse #1 received 1.6 mSv as a whole body dose and 2,1 as a hand dose, Nurse #2 received 1.9 and 2.4 mSv respectively. For medical physicist #1 the dose values were 1.45 mSv whole body and 1.7 mSv hand dose, for medical physicist #2 1.67 mSv wholebody dose and 1.55 mSv hand dose and for technologists #1 & #2 the whole body doses were 0.7 and 0.64 mSv respectively. Lastly, the secretary received 0.1 mSv whole body dose. These preliminary data have shown that the dose levels of our PET/CT staff are within acceptable limits.

Meditative music listening to reduce state anxiety in patients during the uptake phase before positron emission tomography (PET) scans

PubMed Central

Lee, Wen-Li; Liu, Shu-Hsin; Chang, Shu-Min

2017-01-01

Objective: This study examines the effects of listening to meditative music on state anxiety and heart rate variability (HRV) of patients during the uptake phase before positron emission tomography (PET) scans. Methods: A two-group randomized experimental design was used. Eligible patients were randomly assigned to either the experimental or control group. All patients received baseline assessments of state anxiety using Spielberger State-Trait Anxiety Inventory (STAI-S) and HRV before receiving an intravenous injection of radiopharmaceutical fluorine-18 fludeoxyglucose in the uptake room. The experimental group (n = 35) listened individually to 30 min of meditative music, integrating Chinese “Chi” and western frequency resonation in the uptake room. The control group (n = 37) lay on bed quietly for 40 min in the uptake room without music. All patients were assessed for their anxiety level and HRV again, before receiving PET scanning as post-test. Results: The results indicated that patients in the experimental group showed a significant reduction in state anxiety and heart rate, and increase on high frequency norm of HRV (p < 0.001). There was a statistically significant reduction on anxiety level (p < 0.001), heart rate (p < 0.001) and high frequency norm (p = 0.001) in the experimental group compared with those of the control group. Conclusion: Listening to meditative music as a non-invasive and cost-effective strategy can help maximize efforts to promote comfort and relaxation for patients awaiting stressful procedures, such as PET scans. Meditative music can be effective in alleviating state anxiety of patients during the uptake phase before PET scans. Advances in knowledge: The study provides scientific evidence of the effects of listening to meditative music for reducing state anxiety in patients during the uptake phase before PET scans. It may have the potential to lower the risk of unwanted false-positive fluorine-18 fludeoxyglucose uptake in normal organs and to further improve image quality and image interpretation. Listening to meditative music is a safe and inexpensive intervention which can be incorporated into routine procedures to reduce anxiety of patients undergoing PET scans. PMID:27897034

Meditative music listening to reduce state anxiety in patients during the uptake phase before positron emission tomography (PET) scans.

PubMed

Lee, Wen-Li; Sung, Huei-Chuan; Liu, Shu-Hsin; Chang, Shu-Min

2017-02-01

This study examines the effects of listening to meditative music on state anxiety and heart rate variability (HRV) of patients during the uptake phase before positron emission tomography (PET) scans. A two-group randomized experimental design was used. Eligible patients were randomly assigned to either the experimental or control group. All patients received baseline assessments of state anxiety using Spielberger State-Trait Anxiety Inventory (STAI-S) and HRV before receiving an intravenous injection of radiopharmaceutical fluorine-18 fludeoxyglucose in the uptake room. The experimental group (n = 35) listened individually to 30 min of meditative music, integrating Chinese "Chi" and western frequency resonation in the uptake room. The control group (n = 37) lay on bed quietly for 40 min in the uptake room without music. All patients were assessed for their anxiety level and HRV again, before receiving PET scanning as post-test. The results indicated that patients in the experimental group showed a significant reduction in state anxiety and heart rate, and increase on high frequency norm of HRV (p < 0.001). There was a statistically significant reduction on anxiety level (p < 0.001), heart rate (p < 0.001) and high frequency norm (p = 0.001) in the experimental group compared with those of the control group. Listening to meditative music as a non-invasive and cost-effective strategy can help maximize efforts to promote comfort and relaxation for patients awaiting stressful procedures, such as PET scans. Meditative music can be effective in alleviating state anxiety of patients during the uptake phase before PET scans. Advances in knowledge: The study provides scientific evidence of the effects of listening to meditative music for reducing state anxiety in patients during the uptake phase before PET scans. It may have the potential to lower the risk of unwanted false-positive fluorine-18 fludeoxyglucose uptake in normal organs and to further improve image quality and image interpretation. Listening to meditative music is a safe and inexpensive intervention which can be incorporated into routine procedures to reduce anxiety of patients undergoing PET scans.

21 CFR 315.6 - Evaluation of safety.

Code of Federal Regulations, 2011 CFR

2011-04-01

... information, the following types of data: (i) Pharmacology data, (ii) Toxicology data, (iii) Clinical adverse... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Evaluation of safety. 315.6 Section 315.6 Food and... USE DIAGNOSTIC RADIOPHARMACEUTICALS § 315.6 Evaluation of safety. (a) Factors considered in the safety...

99mTc: Labeling Chemistry and Labeled Compounds

NASA Astrophysics Data System (ADS)

Alberto, R.; Abram, U.

This chapter reviews the radiopharmaceutical chemistry of technetium related to the synthesis of perfusion agents and to the labeling of receptor-binding biomolecules. To understand the limitations of technetium chemistry imposed by future application of the complexes in nuclear medicine, an introductory section analyzes the compulsory requirements to be considered when facing the incentive of introducing a novel radiopharmaceutical into the market. Requirements from chemistry, routine application, and market are discussed. In a subsequent section, commercially available 99mTc-based radiopharmaceuticals are treated. It covers the complexes in use for imaging the most important target organs such as heart, brain, or kidney. The commercially available radiopharmaceuticals fulfill the requirements outlined earlier and are discussed with this background. In a following section, the properties and perspectives of the different generations of radiopharmaceuticals are described in a general way, covering characteristics for perfusion agents and for receptor-specific molecules. Technetium chemistry for the synthesis of perfusion agents and the different labeling approaches for target-specific biomolecules are summarized. The review comprises a general introduction to the common approaches currently in use, employing the N x S4-x , [3+1] and 2-hydrazino-nicotinicacid (HYNIC) method as well as more recent strategies such as the carbonyl and the TcN approach. Direct labeling without the need of a bifunctional chelator is briefly reviewed as well. More particularly, recent developments in the labeling of concrete targeting molecules, the second generation of radiopharmaceuticals, is then discussed and prominent examples with antibodies/peptides, neuroreceptor targeting small molecules, myocardial imaging agents, vitamins, thymidine, and complexes relevant to multidrug resistance are given. In addition, a new approach toward peptide drug development is described. The section has a focus on coordination and labeling chemistry, but biological results are briefly summarized as well. The last (and shortest) section finally intends to give a (subjective) outlook for the future role of 99mTc-based radiopharmaceuticals. Critical comments are spread over the whole article but are concentrated in this section. Despite the increasing competition of diagnostic radiopharmacy by other commonly applied methods in medicine such as magnetic resonance imaging (MRI) or ultrasound, the authors are convinced that 99mTc will play a key role also in future if novel approaches are added and the requirements from chemistry biology and the market considered in research to a stronger extent.

10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or equivalent Agreement... State requirements; or (ii) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or...

10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or equivalent Agreement... State requirements; or (ii) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or...

10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or equivalent Agreement... State requirements; or (ii) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or...

10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or equivalent Agreement... State requirements; or (ii) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or...

10 CFR 35.63 - Determination of dosages of unsealed byproduct material for medical use.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or equivalent Agreement... State requirements; or (ii) A PET radioactive drug producer licensed under § 30.32(j) of this chapter or...

Cold Kit for Prostate-Specific Membrane Antigen (PSMA) PET Imaging: Phase 1 Study of 68Ga-Tris(Hydroxypyridinone)-PSMA PET/CT in Patients with Prostate Cancer.

PubMed

Hofman, Michael S; Eu, Peter; Jackson, Price; Hong, Emily; Binns, David; Iravani, Amir; Murphy, Declan; Mitchell, Catherine; Siva, Shankar; Hicks, Rodney J; Young, Jennifer D; Blower, Philip J; Mullen, Gregory E

2018-04-01

68 Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as 68 Ga-labeled N , N '-bis(2-hydroxybenzyl)ethylenediamine- N , N '-diacetic acid (HBED)-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical, 68 Ga-labeled tris(hydroxypyridinone) (THP)-PSMA, has a simplified design for single-step kit-based radiolabeling. It features the THP ligand, which forms complexes with 68 Ga 3+ rapidly at a low concentration, at room temperature, and over a wide pH range, enabling direct elution from a 68 Ge/ 68 Ga generator into a lyophilized radiopharmaceutical kit in 1 step without manipulation. The aim of this phase 1 study was to assess the safety and biodistribution of 68 Ga-THP-PSMA. Methods: Cohort A comprised 8 patients who had proven prostate cancer and were scheduled to undergo prostatectomy; they had Gleason scores of 7-10 and a mean prostate-specific antigen level of 7.8 μg/L (range, 5.4-10.6 μg/L). They underwent PET/CT after the administration of 68 Ga-THP-PSMA. All patients proceeded to prostatectomy (7 with pelvic nodal dissection). Dosimetry from multi-time-point PET imaging was performed with OLINDA/EXM. Cohort B comprised 6 patients who had positive 68 Ga-HBED-PSMA-11 PET/CT scanning results and underwent comparative 68 Ga-THP-PSMA scanning. All patients were monitored for adverse events. Results: No adverse events occurred. In cohort A, 6 of 8 patients had focal uptake in the prostate (at 2 h: average SUV max , 5.1; range, 2.4-9.2) and correlative 3+ staining of prostatectomy specimens on PSMA immunohistochemistry. The 2 68 Ga-THP-PSMA scans with negative results had only 1+/2+ staining. The mean effective dose was 2.07E-02 mSv/MBq. In cohort B, 68 Ga-THP-PSMA had lower physiologic background uptake than 68 Ga-HBED-PSMA-11 (in the parotid glands, the mean SUV max for 68 Ga-THP-PSMA was 3.6 [compared with 19.2 for 68 Ga-HBED-PSMA-11]; the respective corresponding values in the liver were 2.7 and 6.3, and those in the spleen were 2.7 and 10.5; P < 0.001 for all). In 5 of 6 patients, there was concordance in the number of metastases identified with 68 Ga-HBED-PSMA-11 and 68 Ga-THP-PSMA. Thirteen of 15 nodal abnormalities were subcentimeter. In 22 malignant lesions, the tumor-to-liver contrast with 68 Ga-THP-PSMA was similar to that with 68 Ga-HBED-PSMA (4.7 and 5.4, respectively; P = 0.15), despite a higher SUV max for 68 Ga-HBED-PSMA than for 68 Ga-THP-PSMA (30.3 and 10.7, respectively; P < 0.01). Conclusion: 68 Ga-THP-PSMA is safe and has a favorable biodistribution for clinical imaging. Observed focal uptake in the prostate was localized to PSMA-expressing malignant tissue on histopathology. Metastatic PSMA-avid foci were also visualized with 68 Ga-THP-PSMA PET. Single-step production from a Good Manufacturing Practice cold kit may enable rapid adoption. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

[Microdose clinical trial--impact of PET molecular imaging].

PubMed

Yano, Tsuneo; Watanabe, Yasuyoshi

2010-10-01

Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

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

Reduction-responsive PEtOz-SS-PCL micelle with tailored size to overcome blood-brain barrier and enhance doxorubicin antiglioma effect.

PubMed

Li, Yuling; Baiyang, Li; Leran, Bu; Zhen, Wang; Yandong, Xie; Baixiang, Du; Dandan, Zhu; Yufu, Zhu; Jun, Liang; Rutong, Yu; Hongmei, Liu

2017-11-01

A series of novel reduction-responsive micelles with tailored size were designed and prepared to release doxorubicin (DOX) for treating glioma, which were developed based on amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-b-poly (ε-caprolactone) (PEtOz-SS-PCL) and the micelle size could be regulated by designing the polymer structure. The DOX-loaded PEtOz-SS-PCL micelles had small size and rapid drug release in reductive intracellular environments. Biodistribution and in vivo imaging studies in C6 glioma mice tumor model showed that DOX loaded PEtOz-SS-PCL43 micelles with the smallest size had superior accumulation and fast drug release in tumor sites. In vivo antitumor activity demonstrated that DOX-loaded PEtOz-SS-PCL43 micelles improved antitumor efficacy in contrast to PEtOz-SS-PCL micelles with larger size toward the orthotopic C6-Luci cells-bearing mice. This study shows great potential in tailoring the micelle size and introducing the responsive bonds or compartment for intracellular drug delivery and release in glioma treatment by designing the architecture of the polymer.

75 FR 80825 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... pet food, and that FDA conducts inspections of pet food manufacturing establishments. However, USDA is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0368... Request; Pet Event Tracking Network--State, Federal Cooperation To Prevent Spread of Pet Food Related...

Prospective Evaluation of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging.

PubMed

Minamimoto, Ryogo; Sonni, Ida; Hancock, Steven; Vasanawala, Shreyas; Loening, Andreas; Gambhir, Sanjiv S; Iagaru, Andrei

2018-05-01

68 Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 ( 68 Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptor (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer (PCa). We present data from the use of 68 Ga-RM2 in patients with biochemical recurrence (BCR) of PCa and negative findings on conventional imaging. Methods: We enrolled 32 men with BCR of PCa, who were 59-83 y old (mean ± SD, 68.7 ± 6.4 y). Imaging started at 40-69 min (mean, 50.5 ± 6.8 min) after injection of 133.2-151.7 MBq (mean, 140.6 ± 7.4 MBq) of 68 Ga-RM2 using a time-of-flight-enabled simultaneous PET/MRI scanner. T1-weighted, T2-weighted, and diffusion-weighted images were acquired. Results: All patients had a rising level of prostate-specific antigen (PSA) (range, 0.3-119.0 ng/mL; mean, 10.1 ± 21.3 ng/mL) and negative findings on conventional imaging (CT or MRI, and a 99m Tc-methylene diphosphonate bone scan) before enrollment. The observed 68 Ga-RM2 PET detection rate was 71.8%. 68 Ga-RM2 PET identified recurrent PCa in 23 of the 32 participants, whereas the simultaneous MRI scan identified findings compatible with recurrent PCa in 11 of the 32 patients. PSA velocity was 0.32 ± 0.59 ng/mL/y (range, 0.04-1.9 ng/mL/y) in patients with negative PET findings and 2.51 ± 2.16 ng/mL/y (range, 0.13-8.68 ng/mL/y) in patients with positive PET findings ( P = 0.006). Conclusion: 68 Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR of PCa. High uptake in multiple areas compatible with cancer lesions suggests that 68 Ga-RM2 is a promising PET radiopharmaceutical for localization of disease in patients with BCR of PCa and negative findings on conventional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

PET measurement of receptor occupancy as a tool to guide dose selection in neuropharmacology: are we asking the right questions?

PubMed

Barrett, Jeffrey S; McGuire, Jennifer; Vezina, Heather; Spitsin, Serguei; Douglas, Steven D

2013-12-01

Receptor occupancy studies are becoming commonplace for verifying drug mechanism of action and selecting early development candidates. Positron emission tomography (PET) has been applied to pharmacodynamic (PD) studies in several therapeutic areas including neurology, cardiology, and oncology. Prospective use of PET to define dosing requirements has been proposed particularly for central nervous system (CNS)-targeted drugs; however, correlations with clinical outcomes have been mostly anecdotal and not causally established.

Matched pairs dosimetry: 124I/131I metaiodobenzylguanidine and 124I/131I and 86Y/90Y antibodies.

PubMed

Lopci, Egesta; Chiti, Arturo; Castellani, Maria Rita; Pepe, Giovanna; Antunovic, Lidija; Fanti, Stefano; Bombardieri, Emilio

2011-05-01

The technological advances in imaging and production of radiopharmaceuticals are driving an innovative way of evaluating the targets for antineoplastic therapies. Besides the use of imaging to better delineate the volume of external beam radiation therapy in oncology, modern imaging techniques are able to identify targets for highly specific medical therapies, using chemotherapeutic drugs and antiangiogenesis molecules. Moreover, radionuclide imaging is able to select targets for radionuclide therapy and to give the way to in vivo dose calculation to target tissues and to critical organs. This contribution reports the main studies published on matched pairs dosimetry with (124)I/(131)I- and (86)Y/(90)Y-labelled radiopharmaceuticals, with an emphasis on metaiodobenzylguanidine (MIBG) and monoclonal antibodies.

Attenuation correction for the large non-human primate brain imaging using microPET.

PubMed

Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R

2010-04-21

Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a (57)Co transmission point source with a 4% energy window. The optimal energy window for a (68)Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for (57)Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [(18)F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass (57)Co (4% energy window) or (68)Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

Attenuation correction for the large non-human primate brain imaging using microPET

NASA Astrophysics Data System (ADS)

Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

2010-04-01

Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

PubMed

Lin, Kun-Ju; Hsu, Wen-Chuin; Hsiao, Ing-Tsung; Wey, Shiaw-Pyng; Jin, Lee-Way; Skovronsky, Daniel; Wai, Yau-Yau; Chang, Hsiu-Ping; Lo, Chuan-Wei; Yao, Cheng Hsiang; Yen, Tzu-Chen; Kung, Mei-Ping

2010-05-01

The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application. (c) 2010 Elsevier Inc. All rights reserved.

Effective dose to immuno-PET patients due to metastable impurities in cyclotron produced zirconium-89

NASA Astrophysics Data System (ADS)

Alfuraih, Abdulrahman; Alzimami, Khalid; Ma, Andy K.; Alghamdi, Ali; Al Jammaz, Ibrahim

2014-11-01

Immuno-PET is a nuclear medicine technique that combines positron emission tommography (PET) with radio-labeled monoclonal antibodies (mAbs) for tumor characterization and therapy. Zirconium-89 (89Zr) is an emerging radionuclide for immuno-PET imaging. Its long half-life (78.4 h) gives ample time for the production, the administering and the patient uptake of the tagged radiopharmaceutical. Furthermore, the nuclides will remain in the tumor cells after the mAbs are catabolized so that time series studies are possible without incurring further administration of radiopharmarceuticals. 89Zr can be produced in medical cyclotrons by bombarding an yttrium-89 (89Y) target with a proton beam through the 89Y(p,n)89Zr reaction. In this study, we estimated the effective dose to the head and neck cancer patients undergoing 89Zr-based immune-PET procedures. The production of 89Zr and the impurities from proton irradiation of the 89Y target in a cyclotron was calculated with the Monte Carlo code MCNPX and the nuclear reaction code TALYS. The cumulated activities of the Zr isotopes were derived from real patient data in literature and the effective doses were estimated using the MIRD specific absorbed fraction formalism. The estimated effective dose from 89Zr is 0.5±0.2 mSv/MBq. The highest organ dose is 1.8±0.2 mSv/MBq in the liver. These values are in agreement with those reported in literature. The effective dose from 89mZr is about 0.2-0.3% of the 89Zr dose in the worst case. Since the ratio of 89mZr to 89Zr depends on the cooling time as well as the irradiation details, contaminant dose estimation is an important aspect in optimizing the cyclotron irradiation geometry, energy and time.

Detection of muscarinic receptors in the human lung using PET.

PubMed

Visser, T J; van Waarde, A; van der Mark, T W; Kraan, J; Ensing, K; Willemsen, A T; Elsinga, P H; Vaalburg, W

1999-08-01

The characterization of pulmonary muscarinic receptors with PET is still in its infancy. Because approximately 70% of the lungs consists of air and pulmonary muscarinic receptor densities are low, ligands with high receptor affinity are required to obtain reasonable signal-to-noise ratios on PET images. Therefore, the potent 11C-labeled muscarinic antagonist N-methyl-piperidin-4-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate methiodide ([R]-VC-002) was developed. We administered this radioligand to four healthy human volunteers to examine its suitability for studying pulmonary muscarinic receptors in vivo. [11C]VC-002 (185 MBq, specific activity > 7.4 TBq/mmol) was intravenously injected on 2 separate days, with an interval of at least 1 wk. On the first day the volunteers were not pretreated, but on the second day they received the anticholinergic glycopyrronium bromide (Robinul; 2 x 0.1 mg intravenous) 25 and 30 min before the injection of the radiopharmaceutical. C[15O]O scans (approximately 740 MBq [20 mCi] by inhalation) were acquired before the receptor scan to calculate pulmonary blood volume. On PET images of the thorax, the lungs were clearly visible. After the volunteer was pretreated with glycopyrronium bromide, pulmonary uptake of the radioligand was reduced to 32%+/-12% of the control value at 60 min postinjection and the lungs could no longer be seen. (R)-[11C]-VC-002 was rapidly cleared from plasma and was slowly metabolized during the time course (60 min) of the PET scan. The fraction of radioligand representing parent compound decreased from 99.9% at the time of injection to 82% at 40-60 min postinjection, both in the presence and absence of Robinul. Pulmonary tissue-to-plasma ratios, calculated on a count-per-minute-per-gram basis, reached a plateau value of 17.8+/-1.2 at 40-50 min postinjection. [11C]VC-002 appears to be suitable for in vivo studies of pulmonary cholinoceptors.

Sub-millimetre DOI detector based on monolithic LYSO and digital SiPM for a dedicated small-animal PET system.

PubMed

Marcinkowski, Radosław; Mollet, Pieter; Van Holen, Roel; Vandenberghe, Stefaan

2016-03-07

The mouse model is widely used in a vast range of biomedical and preclinical studies. Thanks to the ability to detect and quantify biological processes at the molecular level in vivo, PET has become a well-established tool in these investigations. However, the need to visualize and quantify radiopharmaceuticals in anatomic structures of millimetre or less requires good spatial resolution and sensitivity from small-animal PET imaging systems.In previous work we have presented a proof-of-concept of a dedicated high-resolution small-animal PET scanner based on thin monolithic scintillator crystals and Digital Photon Counter photosensor. The combination of thin monolithic crystals and MLE positioning algorithm resulted in an excellent spatial resolution of 0.7 mm uniform in the entire field of view (FOV). However, the limitation of the scanner was its low sensitivity due to small thickness of the lutetium-yttrium oxyorthosilicate (LYSO) crystals (2 mm).Here we present an improved detector design for a small-animal PET system that simultaneously achieves higher sensitivity and sustains a sub-millimetre spatial resolution. The proposed detector consists of a 5 mm thick monolithic LYSO crystal optically coupled to a Digital Photon Counter. Mean nearest neighbour (MNN) positioning combined with depth of interaction (DOI) decoding was employed to achieve sub-millimetre spatial resolution. To evaluate detector performance the intrinsic spatial resolution, energy resolution and coincidence resolving time (CRT) were measured. The average intrinsic spatial resolution of the detector was 0.60 mm full-width-at-half-maximum (FWHM). A DOI resolution of 1.66 mm was achieved. The energy resolution was 23% FWHM at 511 keV and CRT of 529 ps were measured. The improved detector design overcomes the sensitivity limitation of the previous design by increasing the nominal sensitivity of the detector block and retains an excellent intrinsic spatial resolution.

What have positron emission tomography and ‘Zippy’ told us about the neuropharmacology of drug addiction?

PubMed Central

Cumming, Paul; Caprioli, Daniele; Dalley, Jeffrey W

2011-01-01

Translational molecular imaging with positron emission tomography (PET) and allied technologies offer unrivalled applications in the discovery of biomarkers and aetiological mechanisms relevant to human disease. Foremost among clinical PET findings during the past two decades of addiction research is the seminal discovery of reduced dopamine D2/3 receptor expression in the striatum of drug addicts, which could indicate a predisposing factor and/or compensatory reaction to the chronic abuse of stimulant drugs. In parallel, recent years have witnessed significant improvements in the performance of small animal tomographs (microPET) and a refinement of animal models of addiction based on clinically relevant diagnostic criteria. This review surveys the utility of PET in the elucidation of neuropharmacological mechanisms underlying drug addiction. It considers the consequences of chronic drug exposure on regional brain metabolism and neurotransmitter function and identifies those areas where further research is needed, especially concerning the implementation of PET tracers targeting neurotransmitter systems other than dopamine, which increasingly have been implicated in the pathophysiology of drug addiction. In addition, this review considers the causal effects of behavioural traits such as impulsivity and novelty/sensation-seeking on the emergence of compulsive drug-taking. Previous research indicates that spontaneously high-impulsive rats – as exemplified by ‘Zippy’– are pre-disposed to escalate intravenous cocaine self-administration, and subsequently to develop compulsive drug taking tendencies that endure despite concurrent adverse consequences of such behaviour, just as in human addiction. The discovery using microPET of pre-existing differences in dopamine D2/3 receptor expression in the striatum of high-impulsive rats suggests a neural endophenotype that may likewise pre-dispose to stimulant addiction in humans. LINKED ARTICLES This article is part of a themed section on Imaging. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.163.issue-8BJP has previously published an Imaging in Pharmacology themed section, edited by A Davenport and C Daly. To view this section visit http://dx.doi.org/10.1111/bph.2010.159.issue-4 PMID:20846139

Clinical trials of the prototype Rutherford Appleton Laboratory MWPC positron camera at the Royal Marsden Hospital

NASA Astrophysics Data System (ADS)

Flower, M. A.; Ott, R. J.; Webb, S.; Leach, M. O.; Marsden, P. K.; Clack, R.; Khan, O.; Batty, V.; McCready, V. R.; Bateman, J. E.

1988-06-01

Two clinical trials of the prototype RAL multiwire proportional chamber (MWPC) positron camera were carried out prior to the development of a clinical system with large-area detectors. During the first clinical trial, the patient studies included skeletal imaging using 18F, imaging of brain glucose metabolism using 18F FDG, bone marrow imaging using 52Fe citrate and thyroid imaging with Na 124I. Longitudinal tomograms were produced from the limited-angle data acquisition from the static detectors. During the second clinical trial, transaxial, coronal and sagittal images were produced from the multiview data acquisition. A more detailed thyroid study was performed in which the volume of the functioning thyroid tissue was obtained from the 3D PET image and this volume was used in estimating the radiation dose achieved during radioiodine therapy of patients with thyrotoxicosis. Despite the small field of view of the prototype camera, and the use of smaller than usual amounts of activity administered, the PET images were in most cases comparable with, and in a few cases visually better than, the equivalent planar view using a state-of-the-art gamma camera with a large field of view and routine radiopharmaceuticals.

New imaging systems in nuclear medicine. Final report, January 1, 1993--December 31, 1995

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

NONE

1995-12-31

The aim of this program has been to improve the performance of positron emission tomography (PET) to achieve high resolution with high sensitivity. Towards this aim, the authors have carried out the following studies: (1) explored new techniques for detection of annihilation radiation including new detector materials and system geometries, specific areas that they have studied include--exploration of factors related to resolution and sensitivity of PET instrumentation including geometry, detection materials and coding, and the exploration of technique to improve the image quality by use of depth of interaction and increased sampling; (2) complete much of the final testing ofmore » PCR-II, an analog-coded cylindrical positron tomograph, developed and constructed during the current funding period; (3) developed the design of a positron microtomograph with mm resolution for quantitative studies in small animals, a single slice version of this device has been designed and studied by use of computer simulation; (4) continued and expanded the program of biological studies in animal models. Current studies have included imaging of animal models of Parkinson`s and Huntington`s disease and cancer. These studies have included new radiopharmaceuticals and techniques involving molecular biology.« less

Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology.

PubMed

Tamaki, Nagara; Yoshinaga, Keiichiro

2011-02-01

With the rapid growth of molecular biology, in vivo imaging of such molecular process (i.e., molecular imaging) has been well developed. The molecular imaging has been focused on justifying advanced treatments and for assessing the treatment effects. Most of molecular imaging has been developed using PET camera and suitable PET radiopharmaceuticals. However, this technique cannot be widely available and we need alternative approach. ¹²³I-labeled compounds have been also suitable for molecular imaging using single-photon computed tomography (SPECT) ¹²³I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity of heart failure and prognosis. In addition, it has a potential role to predict fatal arrhythmia, particularly for those who had and are planned to receive implantable cardioverter-defibrillator treatment. ¹²³I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying ischemia at rest, based on the unique capability to represent persistent metabolic alteration after recovery of ischemia, so called ischemic memory. Since BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it may permit risk analysis in CAD patients, particularly for those with chronic kidney disease and/or hemodialysis patients. This review will discuss about recent development of these important iodinated compounds.

Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology

PubMed Central

Yoshinaga, Keiichiro

2010-01-01

With the rapid growth of molecular biology, in vivo imaging of such molecular process (i.e., molecular imaging) has been well developed. The molecular imaging has been focused on justifying advanced treatments and for assessing the treatment effects. Most of molecular imaging has been developed using PET camera and suitable PET radiopharmaceuticals. However, this technique cannot be widely available and we need alternative approach. 123I-labeled compounds have been also suitable for molecular imaging using single-photon computed tomography (SPECT) 123I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity of heart failure and prognosis. In addition, it has a potential role to predict fatal arrhythmia, particularly for those who had and are planned to receive implantable cardioverter-defibrillator treatment. 123I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying ischemia at rest, based on the unique capability to represent persistent metabolic alteration after recovery of ischemia, so called ischemic memory. Since BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it may permit risk analysis in CAD patients, particularly for those with chronic kidney disease and/or hemodialysis patients. This review will discuss about recent development of these important iodinated compounds. PMID:21082300

21 CFR 212.1 - What are the meanings of the technical terms used in these regulations?

Code of Federal Regulations, 2010 CFR

2010-04-01

... active pharmaceutical ingredient. In-process material means any material fabricated, compounded, blended...-process material, packaging material, or labeling in the production of a PET drug. PET means positron... the Federal Food, Drug, and Cosmetic Act, as amended (21 U.S.C. 321 et seq.). Active pharmaceutical...

PSA-stratified detection rates for [68Ga]THP-PSMA, a novel probe for rapid kit-based 68Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer.

PubMed

Derlin, Thorsten; Schmuck, Sebastian; Juhl, Cathleen; Zörgiebel, Johanna; Schneefeld, Sophie M; Walte, Almut C A; Hueper, Katja; von Klot, Christoph A; Henkenberens, Christoph; Christiansen, Hans; Thackeray, James T; Ross, Tobias L; Bengel, Frank M

2018-06-01

[ 68 Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68 Ga 3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68 Ge/ 68 Ga-generator. We evaluated the clinical detection rates of [ 68 Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy. Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [ 68 Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging. At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [ 68 Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to <10 ng/mL, 54.5% for a PSA value of 1 to <2 ng/mL, 14.3% for a PSA value of 0.5 to <1 ng/mL, 20.0% for a PSA value of >0.2 to <0.5, and 22.2% for a PSA value of 0.01 to 0.2 ng/mL. [ 68 Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [ 68 Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003). In this study, [ 68 Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in patients with low PSA levels to evaluate the relative performance of different PSMA ligands.

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

Not Available

C-11 hydroxy ephedrine, introduced as the first clinically usable norepinephrine analogue, studies employing normal volunteers and patients with various cardiac disorders was found to valuable as a nonadreneric tracer. Simultaneously, animal studies been used to assess its use following ischemic injury in order to define neuronal damage. Current research focuses on the comparison of C-11 hydroxyephedrine with other neurotransmitters such as C-11 epinephrine and C-11 threohydroxyephedrine. Epinephrine is primarily stored in vesicles of the nerve terminal, while threo-hydroxyephedrine is only substrate to uptake I mechanism. Such a combination of radiotracers may allow the dissection of uptake I mechanism as wellmore » as vesicular storage. In parallel to the refinement of presynaptic tracers for the sympathetic nervous system, we are developing radiopharmaceuticals to delineate the adrenergic receptors in the heart. The combined evaluation of pre- and postsynaptic nerve function will improve our ability to identify abnormalides. We are currently developing a new radiosynthesis of the hydrophilic adrenergic receptor antagonist C-11 CGP-12177 which has been used by others for the visualization of adrenergic receptors in the heart. We are developing radiopharmaceuticals, for the delineation of presynaptic cholinergic nerve terminals. Derivatives of benzovesamicol have been labeled in our institution and are currently under investigation. The most promising agent is F-18 benzovesamicol (FEBOBV) which allows the visualization of parasympathetic nerve terminals in the canine heart as demonstrated by, preliminary PET data.« less

TH-AB-206-01: Advances in Radionuclide Therapy - From Radioiodine to Nanoparticles

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

Humm, J.

In the past few decades, the field of nuclear medicine has made long strides with the continued advancement of related sciences and engineering and the availability of diagnostic and therapeutic radionuclides. Leveraging these advancements while combining the advantages of therapeutic and diagnostic radionuclides into one radiopharmaceutical has also created a new subfield “theranostics” in nuclear medicine that has the potential to further propel the field into the future. This session is composed of two talks; one focused on the physics principles of theranostics from properties of beta and alpha emitting radionuclides to dosimetric models and quantification; while the second describesmore » preclinical and clinical applications of theranostics and discusses the challenges and opportunities of bringing them to the clinic. At the end of the session the listener should be able to identify: The different properties of beta and alpha emitting radionuclides Which radionuclides are selected for which nuclear medicine therapies and why How PET can be used to accurately quantify the uptake of tumor targeting molecules How individualized dosimetry can be performed from the management of thyroid cancer to novel radiolabeled antibody therapies Promising pre-clinical radiopharmaceutical pairs in prostate cancer and melanoma. Promising clinical Theranostics in neuroendocrine cancers. Challenges of bringing Theranostics to the clinic. E. Delpassand, RITA Foundation -Houston; SBIR Grant; CEO and share holder of RadioMedix.« less

TH-AB-206-00: Challenges and Opportunities for Nuclear Medicine Theranostics

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

NONE

In the past few decades, the field of nuclear medicine has made long strides with the continued advancement of related sciences and engineering and the availability of diagnostic and therapeutic radionuclides. Leveraging these advancements while combining the advantages of therapeutic and diagnostic radionuclides into one radiopharmaceutical has also created a new subfield “theranostics” in nuclear medicine that has the potential to further propel the field into the future. This session is composed of two talks; one focused on the physics principles of theranostics from properties of beta and alpha emitting radionuclides to dosimetric models and quantification; while the second describesmore » preclinical and clinical applications of theranostics and discusses the challenges and opportunities of bringing them to the clinic. At the end of the session the listener should be able to identify: The different properties of beta and alpha emitting radionuclides Which radionuclides are selected for which nuclear medicine therapies and why How PET can be used to accurately quantify the uptake of tumor targeting molecules How individualized dosimetry can be performed from the management of thyroid cancer to novel radiolabeled antibody therapies Promising pre-clinical radiopharmaceutical pairs in prostate cancer and melanoma. Promising clinical Theranostics in neuroendocrine cancers. Challenges of bringing Theranostics to the clinic. E. Delpassand, RITA Foundation -Houston; SBIR Grant; CEO and share holder of RadioMedix.« less

TH-AB-206-02: Nuclear Medicine Theronostics: Wave of the Future; Pre-Clinical and Clinical Opportunities

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

Delpassand, E.

In the past few decades, the field of nuclear medicine has made long strides with the continued advancement of related sciences and engineering and the availability of diagnostic and therapeutic radionuclides. Leveraging these advancements while combining the advantages of therapeutic and diagnostic radionuclides into one radiopharmaceutical has also created a new subfield “theranostics” in nuclear medicine that has the potential to further propel the field into the future. This session is composed of two talks; one focused on the physics principles of theranostics from properties of beta and alpha emitting radionuclides to dosimetric models and quantification; while the second describesmore » preclinical and clinical applications of theranostics and discusses the challenges and opportunities of bringing them to the clinic. At the end of the session the listener should be able to identify: The different properties of beta and alpha emitting radionuclides Which radionuclides are selected for which nuclear medicine therapies and why How PET can be used to accurately quantify the uptake of tumor targeting molecules How individualized dosimetry can be performed from the management of thyroid cancer to novel radiolabeled antibody therapies Promising pre-clinical radiopharmaceutical pairs in prostate cancer and melanoma. Promising clinical Theranostics in neuroendocrine cancers. Challenges of bringing Theranostics to the clinic. E. Delpassand, RITA Foundation -Houston; SBIR Grant; CEO and share holder of RadioMedix.« less

Recent trends in soft-tissue infection imaging.

PubMed

Petruzzi, Nicholas; Shanthly, Nylla; Thakur, Mathew

2009-03-01

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, central nervous system, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection-specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory tract infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to monitor the therapeutic response in a variety of conditions. Current studies suggest PET should be considered the most accurate quantitative method. Scintigraphy has much to offer in localizing abdominal infection as well as inflammation. We may begin to see a gradual increase in the usage of (18)F-FDG-PET in detecting occult abdominal infections. Commonly used modalities for imaging inflammatory bowel disease are scintigraphy with (111)In-oxine/(99m)Tc-HMPAO labeled autologous white blood cells. The literature on central nervous system infection imaging is relatively scarce. Few clinical studies have been performed and numerous new agents have been developed for this use with varying results. Further studies are needed to more clearly delineate the future direction of this field. In evaluating the postoperative spine, (99m)Tc-ciprofloxacin single-photon emission computed tomography (SPECT) was reported to be >80% sensitive in patients more than 6 months after surgery. FDG-PET has also been suggested for this purpose and may play a larger role than originally thought. It appears PET/computed tomography (CT) is gaining support, especially in imaging those with fever of unknown origin or nonfunctional immune systems. Although an infection-specific agent is lacking, the development of one would greatly advance our ability to detect, localize, and quantify infections. Overall, imaging such an agent via SPECT/CT or PET/CT will pave the way for greater clinical reliability in the localization of infection.

Strengthening radiopharmacy practice in IAEA Member States.

PubMed

Duatti, Adriano; Bhonsle, Uday

2013-05-01

Radiopharmaceuticals are essential components of nuclear medicine procedures. Without radiopharmaceuticals nuclear medicine procedures cannot be performed. Therefore it could be said that 'No radiopharmaceutical-no nuclear medicine.' A good radiopharmacy practice supports nuclear medicine activities by producing radiopharmaceuticals that are safe and are of the required quality in a consistent way. As with any medicinal product, radiopharmaceuticals are required to be produced under carefully controlled conditions and are tested for their quality, prior to the administration to patients, using validated standard operating procedures. These procedures are based on the principles of Good Manufacturing Practice (GMP). The GMP principles are based on scientific knowledge and applicable regulatory requirements and guidance related to radiopharmaceutical productions and use. The International Atomic Energy Agency (IAEA) is committed to promote, in the Member States (MS), a rational and practical approach for the implementation of GMP for compounding or manufacturing of diagnostic or therapeutic radiopharmaceuticals. To pursue this goal the IAEA has developed various mechanisms and collaborations with individual experts in the field and with relevant national and international institutions or organizations. IAEA's activities in promoting radiopharmaceutical science include commissioning expert advice in the form of publications on radiopharmaceutical production, quality control and usage, producing technical guidance on production and regulatory aspects related to new radiopharmaceuticals, creating guidance documentation for self or internal audits of radiopharmaceutical production facilities, producing guidance on implementation of Quality Management System and GMP in radiopharmacy, assisting in creation of specific radiopharmaceutical monographs for the International Pharmacopoeia, and developing radiopharmacy-related human resource capabilities in MS through individual and regional training courses and education programs. IAEA strongly supports development of clinical nuclear medicine services by assisting MS in setting up reliable Radiopharmaceutical production facilities for single photon emission computed tomography, positron emission tomography, and for therapeutic applications. Copyright © 2013 Elsevier Inc. All rights reserved.

Feasibility of in situ, high-resolution correlation of tracer uptake with histopathology by quantitative autoradiography of biopsy specimens obtained under 18F-FDG PET/CT guidance.

PubMed

Fanchon, Louise M; Dogan, Snjezana; Moreira, Andre L; Carlin, Sean A; Schmidtlein, C Ross; Yorke, Ellen; Apte, Aditya P; Burger, Irene A; Durack, Jeremy C; Erinjeri, Joseph P; Maybody, Majid; Schöder, Heiko; Siegelbaum, Robert H; Sofocleous, Constantinos T; Deasy, Joseph O; Solomon, Stephen B; Humm, John L; Kirov, Assen S

2015-04-01

Core biopsies obtained using PET/CT guidance contain bound radiotracer and therefore provide information about tracer uptake in situ. Our goal was to develop a method for quantitative autoradiography of biopsy specimens (QABS), to use this method to correlate (18)F-FDG tracer uptake in situ with histopathology findings, and to briefly discuss its potential application. Twenty-seven patients referred for a PET/CT-guided biopsy of (18)F-FDG-avid primary or metastatic lesions in different locations consented to participate in this institutional review board-approved study, which complied with the Health Insurance Portability and Accountability Act. Autoradiography of biopsy specimens obtained using 5 types of needles was performed immediately after extraction. The response of autoradiography imaging plates was calibrated using dummy specimens with known activity obtained using 2 core-biopsy needle sizes. The calibration curves were used to quantify the activity along biopsy specimens obtained with these 2 needles and to calculate the standardized uptake value, SUVARG. Autoradiography images were correlated with histopathologic findings and fused with PET/CT images demonstrating the position of the biopsy needle within the lesion. Logistic regression analysis was performed to search for an SUVARG threshold distinguishing benign from malignant tissue in liver biopsy specimens. Pearson correlation between SUVARG of the whole biopsy specimen and average SUVPET over the voxels intersected by the needle in the fused PET/CT image was calculated. Activity concentrations were obtained using autoradiography for 20 specimens extracted with 18- and 20-gauge needles. The probability of finding malignancy in a specimen is greater than 50% (95% confidence) if SUVARG is greater than 7.3. For core specimens with preserved shape and orientation and in the absence of motion, one can achieve autoradiography, CT, and PET image registration with spatial accuracy better than 2 mm. The correlation coefficient between the mean specimen SUVARG and SUVPET was 0.66. Performing QABS on core-biopsy specimens obtained using PET/CT guidance enables in situ correlation of (18)F-FDG tracer uptake and histopathology on a millimeter scale. QABS promises to provide useful information for guiding interventional radiology procedures and localized therapies and for in situ high-spatial-resolution validation of radiopharmaceutical uptake. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model.

PubMed

Song, In Ho; Lee, Tae Sup; Park, Yong Serk; Lee, Jin Sook; Lee, Byung Chul; Moon, Byung Seok; An, Gwang Il; Lee, Hae Won; Kim, Kwang Il; Lee, Yong Jin; Kang, Joo Hyun; Lim, Sang Moo

2016-07-01

Immuno-PET provides valuable information about tumor location, phenotype, susceptibility to therapy, and treatment response, especially to targeted radioimmunotherapy. In this study, we prepared antiepidermal growth factor receptor (EGFR) antibody via identical chelator, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-trience-3,6,9,-triacetic acid (PCTA), labeled with (64)Cu or (177)Lu to evaluate the EGFR expression levels using immuno-PET and the feasibility of radioimmunotherapy in an esophageal squamous cell carcinoma (ESCC) model. Cetuximab was conjugated with p-SCN-Bn-PCTA and radiolabeled with (64)Cu or (177)Lu. In vitro EGFR expression levels were determined and compared using flow cytometry and cell binding assay. In vivo EGFR expression levels were evaluated via immuno-PET imaging of (64)Cu-cetuximab and biodistribution analysis. Micro-SPECT/CT imaging, biodistribution, and radioimmunotherapy studies of (177)Lu-cetuximab were performed in the ESCC model. Therapeutic responses were monitored using (18)F-FDG PET and immunohistochemical staining. (64)Cu- or (177)Lu-labeled antibodies showed high radiolabeling yield (>98%), stability (>90%), and favorable immunoreactivity. In vitro EGFR status measured by cell binding assay was correlated with the flow cytometry data. Immuno-PET, micro-SPECT/CT, and biodistribution demonstrated specific uptake in ESCC tumors depending on the EGFR expression levels. Tumor accumulation of (64)Cu- and (177)Lu-cetuximab was peaked at 48 and 120 h, respectively. Radioimmunotherapy with (177)Lu-cetuximab showed significant inhibition of tumor growth (P < 0.01) and marked reduction of (18)F-FDG SUV compared with that of control (P < 0.05). Terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity and Ki-67 staining indices increased and decreased, respectively, in the radioimmunotherapy group compared with other groups (P < 0.01). (64)Cu-cetuximab immuno-PET represented EGFR expression levels in ESCC tumors, and (177)Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. The diagnostic and therapeutic convergence radiopharmaceutical (64)Cu-/(177)Lu-PCTA-cetuximab may be useful as a diagnostic tool in patient selection and a potent radioimmunotherapy agent in EGFR-positive ESCC tumors. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide.

PubMed

Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Traub-Weidinger, Tatjana; Uprimny, Christian; von Guggenberg, Elisabeth; Decristoforo, Clemens; Warwitz, Boris; Widmann, Gerlig; Virgolini, Irene Johanna

2013-02-01

The aim of this study was to evaluate the impact of (68)Ga-labelled DOTA(0)-lanreotide ((68)Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or (68)Ga-labelled DOTA(0),Tyr(3)-octreotide ((68)Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or (68)Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent (68)Ga-DOTA-LAN PET to evaluate a treatment option with (90)Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 ± 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. (68)Ga-DOTA-LAN and (68)Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of (68)Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for (68)Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. (68)Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV(max)) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to (68)Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. (68)Ga-DOTA-TOC revealed more tumour sites than (68)Ga-DOTA-LAN (106 vs 53). The tumour to background ratios for tumour and liver calculated from SUV(max) measurements were significantly higher for (68)Ga-DOTA-TOC than (68)Ga-DOTA-LAN (p < 0.02). (68)Ga-DOTA-TOC PET imaging is an established imaging procedure for accurate staging of NET patients. (68)Ga-DOTA-LAN should only be considered as a PET tracer of second choice in patients with no pathologic tracer uptake on (68)Ga-DOTA-TOC PET. In these patients, (68)Ga-DOTA-LAN PET can provide valuable information when evaluating PRRT as the treatment option, as a broader spectrum of human SSTR subtypes can be detected.

Molecular Imaging of the Kidneys

PubMed Central

Szabo, Zsolt; Alachkar, Nada; Xia, Jinsong; Mathews, William B.; Rabb, Hamid

2010-01-01

Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms in order to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive and accurate diagnosis. The most recent imaging technology, PET, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H215O, 82RbCl, and [64Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype AT1R using in vivo PET imaging. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc-99m MAG3 as well as some novel radiopharmaceuticals such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands have been utilized for molecular renal imaging. Additionally, other radioligands that interact with the organic cation transporters or peptide transporters have developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule- 1 (KIM-1) that is highly expressed in kidney injury and renal cancer but not in normal kidneys. While pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on upregulated molecules in response to tissue stress resulted from obstruction will be of great implication. Monocyte chemoattractant protein -1 (MCP-1) is a well-suited molecule in this case. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [18F]FDG, other radioligands such as [11C]acetate and anti-[18F]FACBC have emerged. Radioimmuno-imaging with [124I]G250 could lead to radioimmunotherapy for renal cancer. Considering the increasing age of general population, the incidence of kidney diseases such as atherosclerosis, diabetic nephropathy, and cancer is expected to increase. Successful management of these diseases offers an opportunity and a challenge for development of novel molecular imaging technologies. PMID:21111857

Evaluation of 209At as a theranostic isotope for 209At-radiopharmaceutical development using high-energy SPECT

NASA Astrophysics Data System (ADS)

Crawford, J. R.; Robertson, A. K. H.; Yang, H.; Rodríguez-Rodríguez, C.; Esquinas, P. L.; Kunz, P.; Blinder, S.; Sossi, V.; Schaffer, P.; Ruth, T. J.

2018-02-01

The development of alpha-emitting radiopharmaceuticals using 211At requires quantitative determination of the time-dependent nature of the 211At biodistribution. However, imaging-based methods for acquiring this information with 211At have not found wide-spread use because of its low abundance of decay emissions suitable for external detection. In this publication we demonstrate the theranostic abilities of the 211At/209At isotope pair and present the first-ever 209At SPECT images. The VECTor microSPECT/PET/CT scanner was used to image 209At with a collimator suitable for the 511 keV annihilation photons of PET isotopes. Data from distinct photopeaks of the 209At energy spectrum (195 keV (22.6%), 239 keV (12.4 %), 545 keV (91.0 %), a combined 782/790 keV peak (147 %), and 209Po x-rays (139.0 %)) were independently evaluated for use in image reconstructions using Monte Carlo (GATE) simulations and phantom studies. 209At-imaging in vivo was demonstrated in a healthy mouse injected with 10 MBq of free [209At]astatide. Image-based measurements of 209At uptake in organs of interest—acquired in 5 min intervals—were compared to ex vivo gamma counter measurements of the same organs. Simulated and measured data indicated that—due to the large amount of scatter from high energy (>750 keV) gammas—reconstructed images using the x-ray peak outperformed those obtained from other peaks in terms of image uniformity and spatial resolution, determined to be  <0.85 mm. 209At imaging using the x-ray peak revealed a biodistribution that matched the known distribution of free astatide, and in vivo image-based measurements of 209At uptake in organs of interest matched ex vivo measurements within 10%. We have acquired the first 209At SPECT images and demonstrated the ability of quantitative SPECT imaging with 209At to accurately determine astatine biodistributions with high spatial and temporal resolution.

Method for preparing radiopharmaceutical complexes

DOEpatents

Jones, Alun G.; Davison, Alan; Abrams, Michael J.

1989-05-02

A method for preparing radiopharmaceutical complexes that are substantially free of the reaction materials used to produce the radiopharmaceutical complex is disclosed. The method involves admixing in a suitable first solvent in a container a target seeking ligand or salt or metal adduct thereof, a radionuclide label, and a reducing agent for said radionuclide, thereby forming said radiopharmaceutical complex; coating the interior walls of the container with said pharmaceutical complex; discarding the solvent containing by-products and unreacted starting reaction materials; and removing the radiopharmaceutical complex from said walls by dissolving it in a second solvent, thereby obtaining said radiopharmaceutical complex substantially free of by-products and unreacted starting materials.

Targeted and Nontargeted α-Particle Therapies.

PubMed

McDevitt, Michael R; Sgouros, George; Sofou, Stavroula

2018-06-04

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease.

Targeted and Nontargeted α-Particle Therapies

PubMed Central

McDevitt, Michael R.; Sgouros, George; Sofou, Stavroula

2018-01-01

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease. PMID:29345977

Minimizing human error in radiopharmaceutical preparation and administration via a bar code-enhanced nuclear pharmacy management system.

PubMed

Hakala, John L; Hung, Joseph C; Mosman, Elton A

2012-09-01

The objective of this project was to ensure correct radiopharmaceutical administration through the use of a bar code system that links patient and drug profiles with on-site information management systems. This new combined system would minimize the amount of manual human manipulation, which has proven to be a primary source of error. The most common reason for dosing errors is improper patient identification when a dose is obtained from the nuclear pharmacy or when a dose is administered. A standardized electronic transfer of information from radiopharmaceutical preparation to injection will further reduce the risk of misadministration. Value stream maps showing the flow of the patient dose information, as well as potential points of human error, were developed. Next, a future-state map was created that included proposed corrections for the most common critical sites of error. Transitioning the current process to the future state will require solutions that address these sites. To optimize the future-state process, a bar code system that links the on-site radiology management system with the nuclear pharmacy management system was proposed. A bar-coded wristband connects the patient directly to the electronic information systems. The bar code-enhanced process linking the patient dose with the electronic information reduces the number of crucial points for human error and provides a framework to ensure that the prepared dose reaches the correct patient. Although the proposed flowchart is designed for a site with an in-house central nuclear pharmacy, much of the framework could be applied by nuclear medicine facilities using unit doses. An electronic connection between information management systems to allow the tracking of a radiopharmaceutical from preparation to administration can be a useful tool in preventing the mistakes that are an unfortunate reality for any facility.

The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?

PubMed Central

Ferreri, Florian; Drapier, Dominique; Baloche, Emmanuelle; Ouzid, Mehemed; Zimmer, Luc; Llorca, Pierre-Michel

2018-01-01

Abstract Background The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule’s relevant modes of action. Materials and Methods Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145, and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate. Results In cell cultures, the measured Kb confirmed high affinity of loxapine for the D2; intermediate affinity for the D1, D4, D5, 5-HT2C receptorsl and a lack of affinity toward D3, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors. In brain tissue, PET autoradiographies showed a radiopharmaceutical displacement at low concentrations of loxapine on D2 and 5-HT2A receptors. Conclusion This preclinical study reveals that loxapine receptorial spectrum is close to an “atypical” profile (D2/5HT2A ratio, 1.14). Loxapine is rightly classified as a DS-RAn agent in the Neuroscience Based Nomenclature classification. PMID:29106549

Dual-modality imaging

NASA Astrophysics Data System (ADS)

Hasegawa, Bruce; Tang, H. Roger; Da Silva, Angela J.; Wong, Kenneth H.; Iwata, Koji; Wu, Max C.

2001-09-01

In comparison to conventional medical imaging techniques, dual-modality imaging offers the advantage of correlating anatomical information from X-ray computed tomography (CT) with functional measurements from single-photon emission computed tomography (SPECT) or with positron emission tomography (PET). The combined X-ray/radionuclide images from dual-modality imaging can help the clinician to differentiate disease from normal uptake of radiopharmaceuticals, and to improve diagnosis and staging of disease. In addition, phantom and animal studies have demonstrated that a priori structural information from CT can be used to improve quantification of tissue uptake and organ function by correcting the radionuclide data for errors due to photon attenuation, partial volume effects, scatter radiation, and other physical effects. Dual-modality imaging therefore is emerging as a method of improving the visual quality and the quantitative accuracy of radionuclide imaging for diagnosis of patients with cancer and heart disease.

Therapeutic Contraindications in Exotic Pets.

PubMed

Petritz, Olivia A; Chen, Sue

2018-05-01

The selection and dosing of medications for exotic pets are often challenging because most drugs are used in an extralabel manner without pharmacokinetic and pharmacodynamic studies. Doses are often extrapolated from common domestic animals and safety data are often lacking in exotic species. Just as the bioavailability and therapeutic levels are different for each species, what may be a safe and commonly used medication in one species can be deadly in another. Various drugs with documented contraindications in certain exotic pet species are outlined in this review and the pathophysiology, clinical signs, and treatment options are described when applicable. Copyright © 2018 Elsevier Inc. All rights reserved.

The bifunctional liposomes constructed by poly(2-ethyl-oxazoline)-cholesteryl methyl carbonate: an effectual approach to enhance liposomal circulation time, pH-sensitivity and endosomal escape.

PubMed

Xu, Huan; Zhang, Wei; Li, Yan; Ye, Fei F; Yin, Peng P; Yu, Xiu; Hu, Mei N; Fu, Yuan S; Wang, Che; Shang, De J

2014-11-01

A novel bifunctional liposome with long-circulating and pH-sensitive properties was constructed using poly(2-ethyl-oxazoline)-cholesteryl methyl carbonate (PEtOz-CHMC) in this study. PEtOz-CHMC was synthesized and characterized by TLC, IR and (1)H-NMR. The obtained PEtOz lipid was inserted into liposomes by the post-insertion method. Through a series of experiments, such as drug release, tumor cell uptake, cytotoxicity, calcium-induced aggregation, pharmacokinetic experiments, etc., the pH-sensitive and long-circulating properties of PEtOzylated liposomes was identified. PEtOz-CHMC modified liposomes (PEtOz-L) showed increased calcein release at low pH. Flow cytometric analysis results showed that the fusion and cellular uptake of PEtOz-L could be promoted significantly at pH 6.4 compared with those at pH 7.4. Confocal laser scanning microscope observations revealed that PEtOz-L could respond to low endosomal pH and directly released the fluorescent tracer into the cytoplasm. MTT assays in HeLa cells demonstrated that doxorubicin hydrochloride (DOX) loaded PEtOz-L exhibited stronger anti-tumor activity in a medium at pH 6.4 than in a medium pH 7.4. PEtOz-L remained stable when these liposomes were incubated in calcium chloride solution. The cumulative calcein release rate of PEtOz-L was significantly lower than that of CL when the liposomes were dialysed in PBS. The pharmacokinetic experiments of liposomes in rats showed that t 1/2 and AUC of PEtOz-L were 4.13 times and 4.71 times higher than those of CL. PEtOzylated liposomes exhibits excellent long-circulating and pH-sensitive properties. Our results suggest that PEtOz is a promising biomaterial for the modification of liposome in drug delivery.

Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review.

PubMed

van der Pol, Jochem; Vöö, Stefan; Bucerius, Jan; Mottaghy, Felix M

2017-07-01

Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents. A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords "misadministration", "extravasation", "paravascular infiltration", combined with "tracer", "radionuclide", "radiopharmaceutical", and a list of keywords referring to clinically used tracers (i.e. "Technetium-99m", "Yttrium-90"). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised. Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature. Extravasation of diagnostic radiopharmaceuticals is common. 99m Tc, 123 I, 18 F, and 68 Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation.

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.

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

Comparison of 99mTc-HYNIC-TOC and HYNIC-TATE octreotide scintigraphy with FDG PET and 99mTc-MIBI in local recurrent or distant metastatic thyroid cancers.

PubMed

Sager, Sait; Kabasakal, Levent; Halac, Metin; Maecke, Helmut; Uslu, Lebriz; Önsel, Çetin; Kanmaz, Bedii

2013-05-01

There have been various studies for early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study is to evaluate the clinical utility of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE, octreotide derivatives, to detect recurrences or distant metastases in 131I-negative thyroglobulin positive thyroid cancer patients and to compare the lesions with FDG PET and 99mTc-MIBI studies in the same patient group. Twenty differentiated thyroid cancer patients, 7 male and 13 female, mean age 54.6 ± 15.3 (range 13-78 years), were included in this study. Eighteen patients had papillary thyroid cancer and 2 had follicular thyroid cancer. Fifteen patients received HYNIC-TOC and 5 patients received HYNIC-TATE as a radiopharmaceutical. All patients underwent whole-body scan 1 and 4 hours after injection of octreotide derivatives and SPECT imagings were performed from the suspicious sites. The lesions that were seen in 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE studies were compared with 99mTc-MIBI and FDG-PET studies. Among 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE scintigraphies, 15 patient studies were evaluated as true positive (75%) and 5 were false negative (25%). The total number of lesions in octreotide scintigraphy was 48 in 20 patients. Of 20 patients, 19 had FDG-PET study, 15 of them were evaluated as true positive (78.9%), and 4 them were evaluated as false negative (21.1%). Total number of lesions in FDG PET was 74. 99mTc-MIBI study was positive in 11 patients (55%) and negative in 9 patients (45%). Total number of lesions in 99mTc-MIBI was 25. Technetium-labeled somatostatin receptor scintigraphy analogues HYNIC-TOC and HYNIC-TATE are useful imaging alternatives in somatostatin receptor expressing thyroid cancer patients. Radiolabeling is easy and they are readily available for routine use.

Correlation of PET and AMS analyses for early kinetics of 2-fluoro-2-deoxyglucose (FDG)

NASA Astrophysics Data System (ADS)

Minamimoto, Ryogo; Hamabe, Yoshimi; Miyaoka, Teiji; Theeraladanon, Chumpol; Oka, Takashi; Matsui, Takao; Inoue, Tomio

2010-04-01

The draft of the guidelines for microdosing in clinical trials was published in Japan in 2008 following the guidelines of the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA). It recommends utilizing accelerator mass spectrometry (AMS), liquid chromatography/mass spectrometry (LC/MS/MS), and positron emission tomography (PET) for monitoring drug metabolites in preclinical studies. In this study, we clarified the correlation in measuring result between PET and AMS. The AMS measurement was undergone by using AMS system of Institute of Accelerator Analysis Ltd. (IAA, Kawasaki, Japan). First the back ground 14C level of blood in mice was measured by AMS. Second, we clarified the relationship between AMS and PET by using 2-fluoro-2-deoxyglucose (FDG). The correlation coefficient ( r) of the measurements using PET ( 18F-FDG) and AMS ( 14C-FDG) were quite high at 0.97 ( Y = 7.54 E - 05 X + 0.02, p < 0.001). The blood clearance profile of 18F-FDG was nearly identical with that of 14C-FDG. These results indicate that the AMS analysis has excellent correlation with the PET method.

Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

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

Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi

There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[ 18F] fluoro-2-deoxy-d-glucose ( 18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modificationmore » of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.« less

Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

DOE PAGES

Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi; ...

2014-05-28

There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[ 18F] fluoro-2-deoxy-d-glucose ( 18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modificationmore » of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.« less

PET and SPECT imaging of a radiolabeled minigastrin analogue conjugated with DOTA, NOTA, and NODAGA and labeled with (64)Cu, (68)Ga, and (111)In.

PubMed

Roosenburg, S; Laverman, P; Joosten, L; Cooper, M S; Kolenc-Peitl, P K; Foster, J M; Hudson, C; Leyton, J; Burnet, J; Oyen, W J G; Blower, P J; Mather, S J; Boerman, O C; Sosabowski, J K

2014-11-03

Cholecystokinin-2 (CCK-2) receptors, overexpressed in cancer types such as small cell lung cancers (SCLC) and medullary thyroid carcinomas (MTC), may serve as targets for peptide receptor radionuclide imaging. A variety of CCK and gastrin analogues has been developed, but a major drawback is metabolic instability or high kidney uptake. The minigastrin analogue PP-F11 has previously been shown to be a promising peptide for imaging of CCK-2 receptor positive tumors and was therefore further evaluated. The peptide was conjugated with one of the macrocyclic chelators DOTA, NOTA, or NODAGA. The peptide conjugates were then radiolabeled with either (68)Ga, (64)Cu, or (111)In. All (radio)labeled compounds were evaluated in vitro (IC50) and in vivo (biodistribution and PET/CT and SPECT/CT imaging). IC50 values were in the low nanomolar range for all compounds (0.79-1.51 nM). In the biodistribution studies, (68)Ga- and (111)In-labeled peptides showed higher tumor-to-background ratios than the (64)Cu-labeled compounds. All tested radiolabeled compounds clearly visualized the CCK2 receptor positive tumor in PET or SPECT imaging. The chelator did not seem to affect in vivo behavior of the peptide for (111)In- and (68)Ga-labeled peptides. In contrast, the biodistribution of the (64)Cu-labeled peptides showed high uptake in the liver and in other organs, most likely caused by high blood levels, probably due to dissociation of (64)Cu from the chelator and subsequent transchelation to proteins. Based on the present study, (68)Ga-DOTA-PP-F11 might be a promising radiopharmaceutical for PET/CT imaging of CCK2 receptor expressing tumors such as MTC and SCLC. Clinical studies are warranted to investigate the potential of this tracer.

Dual-Tracer PET Using Generalized Factor Analysis of Dynamic Sequences

PubMed Central

Fakhri, Georges El; Trott, Cathryn M.; Sitek, Arkadiusz; Bonab, Ali; Alpert, Nathaniel M.

2013-01-01

Purpose With single-photon emission computed tomography, simultaneous imaging of two physiological processes relies on discrimination of the energy of the emitted gamma rays, whereas the application of dual-tracer imaging to positron emission tomography (PET) imaging has been limited by the characteristic 511-keV emissions. Procedures To address this limitation, we developed a novel approach based on generalized factor analysis of dynamic sequences (GFADS) that exploits spatio-temporal differences between radiotracers and applied it to near-simultaneous imaging of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) (brain metabolism) and 11C-raclopride (D2) with simulated human data and experimental rhesus monkey data. We show theoretically and verify by simulation and measurement that GFADS can separate FDG and raclopride measurements that are made nearly simultaneously. Results The theoretical development shows that GFADS can decompose the studies at several levels: (1) It decomposes the FDG and raclopride study so that they can be analyzed as though they were obtained separately. (2) If additional physiologic/anatomic constraints can be imposed, further decomposition is possible. (3) For the example of raclopride, specific and nonspecific binding can be determined on a pixel-by-pixel basis. We found good agreement between the estimated GFADS factors and the simulated ground truth time activity curves (TACs), and between the GFADS factor images and the corresponding ground truth activity distributions with errors less than 7.3±1.3 %. Biases in estimation of specific D2 binding and relative metabolism activity were within 5.9±3.6 % compared to the ground truth values. We also evaluated our approach in simultaneous dual-isotope brain PET studies in a rhesus monkey and obtained accuracy of better than 6 % in a mid-striatal volume, for striatal activity estimation. Conclusions Dynamic image sequences acquired following near-simultaneous injection of two PET radiopharmaceuticals can be separated into components based on the differences in the kinetics, provided their kinetic behaviors are distinct. PMID:23636489

Companion Diagnostic 64Cu-Liposome Positron Emission Tomography Enables Characterization of Drug Delivery to Tumors and Predicts Response to Cancer Nanomedicines.

PubMed

Lee, Helen; Gaddy, Daniel; Ventura, Manuela; Bernards, Nicholas; de Souza, Raquel; Kirpotin, Dmitri; Wickham, Thomas; Fitzgerald, Jonathan; Zheng, Jinzi; Hendriks, Bart S

2018-01-01

Deposition of liposomal drugs into solid tumors is a potentially rate-limiting step for drug delivery and has substantial variability that may influence probability of response. Tumor deposition is a shared mechanism for liposomal therapeutics such that a single companion diagnostic agent may have utility in predicting response to multiple nanomedicines. Methods: We describe the development, characterization and preclinical proof-of-concept of the positron emission tomography (PET) agent, MM-DX-929, a drug-free untargeted 100 nm PEGylated liposome stably entrapping a chelated complex of 4-DEAP-ATSC and 64 Cu (copper-64). MM-DX-929 is designed to mimic the biodistribution of similarly sized therapeutic agents and enable quantification of deposition in solid tumors. Results: MM-DX-929 demonstrated sufficient in vitro and in vivo stability with PET images accurately reflecting the disposition of liposome nanoparticles over the time scale of imaging. MM-DX-929 is also representative of the tumor deposition and intratumoral distribution of three different liposomal drugs, including targeted liposomes and those with different degrees of PEGylation. Furthermore, stratification using a single pre-treatment MM-DX-929 PET assessment of tumor deposition demonstrated that tumors with high MM-DX-929 deposition predicted significantly greater anti-tumor activity after multi-cycle treatments with different liposomal drugs. In contrast, MM-DX-929 tumor deposition was not prognostic in untreated tumor-bearing xenografts, nor predictive in animals treated with small molecule chemotherapeutics. Conclusions: These data illustrate the potential of MM-DX-929 PET as a companion diagnostic strategy to prospectively select patients likely to respond to liposomal drugs or nanomedicines of similar molecular size.

Poly(2-ethyl-2-oxazoline) as matrix excipient for drug formulation by hot melt extrusion and injection molding.

PubMed

Claeys, Bart; Vervaeck, Anouk; Vervaet, Chris; Remon, Jean Paul; Hoogenboom, Richard; De Geest, Bruno G

2012-10-15

Here we evaluate poly(2-ethyl-2-oxazoline)s (PEtOx) as a matrix excipient for the production of oral solid dosage forms by hot melt extrusion (HME) followed by injection molding (IM). Using metoprolol tartrate as a good water-soluble model drug we demonstrate that drug release can be delayed by HME/IM, with the release rate controlled by the molecular weight of the PEtOx. Using fenofibrate as a lipophilic model drug we demonstrate that relative to the pure drug the dissolution rate is strongly enhanced by formulation in HME/IM tablets. For both drug molecules we find that solid solutions, i.e. molecularly dissolved drug in a polymeric matrix, are obtained by HME/IM. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multimodality Molecular Imaging of [18F]-Fluorinated Carboplatin Derivative Encapsulated in [111In]-Labeled Liposomes

NASA Astrophysics Data System (ADS)

Lamichhane, Narottam

Platinum based chemotherapy is amongst the mainstream DNA-damaging agents used in clinical cancer therapy today. Agents such as cisplatin, carboplatin are clinically prescribed for the treatment of solid tumors either as single agents, in combination, or as part of multi-modality treatment strategy. Despite the potent anti-tumor activity of these drugs, overall effectiveness is still hampered by inadequate delivery and retention of drug in tumor and unwanted normal tissue toxicity, induced by non-selective accumulation of drug in normal cells and tissues. Utilizing molecular imaging and nanoparticle technologies, this thesis aims to contribute to better understanding of how to improve the profile of platinum based therapy. By developing a novel fluorinated derivative of carboplatin, incorporating a Flourine-18 (18F) moiety as an inherent part of the molecule, quantitative measures of drug concentration in tumors and normal tissues can be directly determined in vivo and within the intact individual environment. A potential impact of this knowledge will be helpful in predicting the overall response of individual patients to the treatment. Specifically, the aim of this project, therefore, is the development of a fluorinated carboplatin drug derivative with an inherent positron emission tomography (PET) imaging capability, so that the accumulation of the drug in the tumor and normal organs can be studied during the course of therapy . A secondary objective of this research is to develop a proof of concept for simultaneous imaging of a PET radiolabeled drug with a SPECT radiolabeled liposomal formulation, enabling thereby bi-modal imaging of drug and delivery vehicle in vivo. The approach is challenging because it involves development in PET radiochemistry, PET and SPECT imaging, drug liposomal encapsulation, and a dual-modal imaging of radiolabeled drug and radiolabeled vehicle. The principal development is the synthesis of fluorinated carboplatin 19F-FCP using 2-(5-fluoro-pentyl)-2-methyl malonic acid as the labeling agent to coordinate with the cisplatin aqua complex. It was then used to treat various cell lines and compared with cisplatin and carboplatin at different concentrations ranging from 0.001 microM to 100 microM for 72 hrs and 96 hrs. IC50 values calculated from cell viability indicated that 19F-FCP is a more potent drug than Carboplatin. Manual radiosynthesis and characterization of [18F]-FCP was performed using [18F]-2-(5-fluoro-pentyl)-2-methyl malonic acid with coordination with cisplatin aqua complex. Automated radiosynthesis of [18F]-FCP was optimized using the manual synthetic procedures and using them as macros for the radiosynthesizer. [18F]-FCP was evaluated in vivo with detailed biodistribution studies and PET imaging in normal and KB 3-1 and KB 8-5 tumor xenograft bearing nude mice. The biodistribution studies and PET imaging of [18F]-FCP showed major uptake in kidneys which attributes to the renal clearance of radiotracer. In vivo plasma and urine stability demonstrated intact [18F]-FCP. [ 111In]-Labeled Liposomes was synthesized and physiochemical properties were assessed with DLS. [111In]-Labeled Liposome was evaluated in vivo with detailed pharmacokinetic studies and SPECT imaging. The biodistribution and ROI analysis from SPECT imaging showed the spleen and liver uptake of [111In]-Labeled Liposome and subsequent clearance of activity with time. [18F]-FCP encapsulated [111In]-Labeled Liposome was developed and physiochemical properties were characterized with DLS. [18F]-FCP encapsulated [111In]-Labeled Liposome was used for in vivo dual tracer PET and SPECT imaging from the same nanoconstruct in KB 3-1 (sensitive) and COLO 205 (resistant) tumor xenograft bearing nude mice. PET imaging of [18F]-FCP in KB 3-1 (sensitive) and COLO 205 (resistant) tumor xenograft bearing nude mice was performed. Naked [18F]-FCP and [18F]-FCP encapsulated [ 111In]-Labeled Liposome showed different pharmacokinetic profiles. PET imaging of [18F]-FCP showed major uptake in kidneys and bladder. However, [18F]-FCP encapsulated [111In]-Labeled Liposome showed major uptake in RES in both PET and SPECT images. ROI analysis of SPECT image enabled by 111In corresponded with PET image enabled by 18F demonstrating the feasibility of dual tracer imaging from the single nanoconstruct. Future work involves the intensive in vitro characterization of [18F]-FCP encapsulated [ 111In]-Labeled Liposome and detailed in vivo evaluation of [ 18F]-FCP encapsulated [111In]-Labeled Liposome in various tumor models.

Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson's disease patients.

PubMed

Hsiao, Ing-Tsung; Weng, Yi-Hsin; Lin, Wey-Yil; Hsieh, Chia-Ju; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Kung, Mei-Ping; Lu, Chin-Song; Lin, Kun-Ju

2014-04-01

(99m)Tc-TRODAT-1 is the first clinical routine (99m)Tc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). (18)F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects. Eighteen subjects (8 HC and 10 PD) were recruited for (99m)Tc-TRODAT-1 SPECT, (18)F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts-1). The nonparametric Mann-Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities. The SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p<0.001), and showed significant different between HC and PD subjects. Of note, the (18)F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to (99m)Tc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from (18)F-AV-133 image as compared to (99m)Tc-TRODAT-1 especially at the substantia nigra region. (18)F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical characteristics than that of (99m)Tc-TRODAT-1 SPECT. (18)F-AV-133 PET also showed additional information in substantia nigra integrity in PD subjects by voxelwise analysis. Collectively, (18)F-AV-133 could be a promising and better tracer for clinical use to detect monoaminergic terminal reduction in PD patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiopharmaceuticals in nuclear medicine practice

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

Kowalsky, R.J.; Perry, J.R.

1987-01-01

This book discusses the basic principles and clinical applications of radiopharmaceuticals. Topics include atomic physics as applied to radiopharmaceuticals, radionuclide generator function, nuclear pharmacy and safety, and radiopharmaceutical use in evaluating the major organ systems of the body. For each body system the author explains rationale for use, typical procedures, current agents of choice, and interpretation of results. Images, tables, and graphs illustrate normal and abnormal studies.

Influence of Storage Temperature on Radiochemical Purity of 99mTc-Radiopharmaceuticals.

PubMed

Uccelli, Licia; Boschi, Alessandra; Martini, Petra; Cittanti, Corrado; Bertelli, Stefania; Bortolotti, Doretta; Govoni, Elena; Lodi, Luca; Romani, Simona; Zaccaria, Samanta; Zappaterra, Elisa; Farina, Donatella; Rizzo, Carlotta; Giganti, Melchiore; Bartolomei, Mirco

2018-03-15

The influence of effective room temperature on the radiochemical purity of 99m Tc-radiopharmaceuticals was reported. This study was born from the observation that in the isolators used for the preparation of the 99m Tc-radiopharmaceuticals the temperatures can be higher than those reported in the commercial illustrative leaflets of the kits. This is due, in particular, to the small size of the work area, the presence of instruments for heating, the continuous activation of air filtration, in addition to the fact that the environment of the isolator used for the 99m Tc-radiopharmaceuticals preparation and storage is completely isolated and not conditioned. A total of 244 99m Tc-radiopharmaceutical preparations (seven different types) have been tested and the radiochemical purity was checked at the end of preparation and until the expiry time. Moreover, we found that the mean temperature into the isolator was significantly higher than 25 °C, the temperature, in general, required for the preparation and storage of 99m Tc-radiopharmaceuticals. Results confirmed the radiochemical stability of radiopharmaceutical products. However, as required in the field of quality assurance, the impact that different conditions than those required by the manufacturer on the radiopharmaceuticals quality have to be verified before human administration.

Trends in radiopharmaceutical dispensing in a regional nuclear pharmacy

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

Basmadjian, G.P.; Johnston, J.; Barker, K.

1982-11-01

Dispensing trends for radiopharmaceuticals at a regional nuclear pharmacy over a 51-month period were studied. dispensing records of a regional nuclear pharmacy were analyzed with a forecasting procedure that uses univariate time data to produce time trends and autoregressive models. The overall number of prescriptions increased from 3500 to 5500 per quarter. Radiopharmaceuticals used in nuclear cardiology studies increased from less than 0.1% to 17.5% of total prescriptions dispensed, while radiopharmaceuticals used for brain imaging showed a steady decline from 29% to 11% of total prescriptions dispensed. The demand for other radiopharmaceuticals increased in areas such as renal studies, bonemore » studies, lung studies, liver-function studies, and /sup 67/Ga tumor-uptake studies, and declined slightly for static liver studies. Changes in dispensing trends for radiopharmaceuticals will continue as the practice of nuclear medicine concentrates more on functional studies and as newer imaging techniques become used for other purposes.« less

Cyclotron produced radiopharmaceuticals

NASA Astrophysics Data System (ADS)

Kopička, K.; Fišer, M.; Hradilek, P.; Hanč, P.; Lebeda, O.

2003-01-01

Some of the cyclotron-produced radionuclides may serve as important materials for the production of radiopharmaceuticals. This lecture deals with basic information relating to various aspects of these compounds. In comparison with radionuclides/compounds used for non-medical purposes, radiopharmaceuticals are subject to a broader scale of regulations, both from the safety and efficacy point of view; besides that, there are both radioactive and medical aspects that must be taken into account for any radiopharmaceutical. According to the regulations and in compliance with general rules of work with radioactivity, radiopharmaceuticals should only be prepared/manufactured under special conditions, using special areas and special equipment and applying special procedures (e.g. sterilisation, disinfection, aseptic work). Also, there are special procedures for cleaning and maintenance. Sometimes the requirements for the product safety clash with those for the safety of the personnel; several examples of solutions pertaining to these cases are given in the lecture. Also, the specific role of cyclotron radiopharmaceuticals is discussed.

Improving the Imaging Contrast of 68Ga-PSMA-11 by Targeted Linker Design: Charged Spacer Moieties Enhance the Pharmacokinetic Properties.

PubMed

Baranski, Ann-Christin; Schäfer, Martin; Bauder-Wüst, Ulrike; Wacker, Anja; Schmidt, Jana; Liolios, Christos; Mier, Walter; Haberkorn, Uwe; Eisenhut, Michael; Kopka, Klaus; Eder, Matthias

2017-09-20

68 Ga-Glu-urea-Lys-(Ahx)-HBED-CC ( 68 Ga-PSMA-11) represents a successful radiopharmaceutical for PET/CT imaging of prostate cancer. Further optimization of the tumor-to-background contrast might significantly enhance the sensitivity of PET/CT imaging and the probability of detecting recurrent prostate cancer at low PSA values. This study describes the advantage of histidine (H)/glutamic acid (E) and tryptophan (W)/glutamic acid (E) containing linkers on the pharmacokinetic properties of 68 Ga-PSMA-11. The tracers were obtained by a combination of standard Fmoc-based solid-phase synthesis and copper(I)-catalyzed azide-alkyne cycloaddition. Their 68 Ga complexes were compared to the clinical reference 68 Ga-PSMA-11 with respect to cell binding, effective internalization, and tumor targeting properties in LNCaP-bearing balb/c nu/nu mice. The introduction of (HE) i (i = 1-3) or (WE) i (i = 1-3) into PSMA-11 resulted in a significantly changed biodistribution profile. The uptake values in kidneys, spleen, liver, and other background organs were reduced for (HE) 3 while the tumor uptake was not affected. For (HE) 1 the tumor uptake was significantly increased. The introduction of tryptophan-containing linkers also modulated the organ distribution profile. The results clearly indicate that histidine is of essential impact in order to improve the tumor-to-organ contrast. Hence, the histidine/glutamic acid linker modifications considerably improved the pharmacokinetic properties of 68 Ga-PSMA-11 leading to a reduced uptake in dose limiting organs and a significantly enhanced tumor-to-background contrast. Glu-urea-Lys-(HE) 3 -HBED-CC represents a promising 68 Ga complex ligand for PET/CT-imaging of prostate cancer.

Validation of 64Cu-DOTA-rituximab injection preparation under good manufacturing practices: a PET tracer for imaging of B-cell non-Hodgkin lymphoma.

PubMed

Natarajan, Arutselvan; Arksey, Natasha; Iagaru, Andrei; Chin, Frederick T; Gambhir, Sanjiv Sam

2015-01-01

Manufacturing of 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-rituximab injection under good manufacturing practices (GMP) was validated for imaging of patients with CD20+ B-cell non-Hodgkin lymphoma. Rituximab was purified by size exclusion high performance liquid chromatography (HPLC) and conjugated to DOTA-mono-(N-hydroxysuccinimidyl) ester. 64CuCl2, buffers, reagents, and other raw materials were obtained as high-grade quality. Following a semi-automated synthesis of 64Cu-DOTA-rituximab, a series of quality control tests was performed. The product was further tested in vivo using micro-positron emission tomography/computed tomography (PET/CT) to assess targeting ability towards human CD20 in transgenic mice. Three batches of 64Cu-DOTA-rituximab final product were prepared as per GMP specifications. The radiolabeling yield from these batches was 93.1 ± 5.8%; these provided final product with radiopharmaceutical yield, purity, and specific activity of 59.2 ± 5.1% (0.9 ± 0.1 GBq of 64Cu), > 95% (by HPLC and radio-thin layer chromatography), and 229.4 ± 43.3 GBq/µmol (or 1.5 ± 0.3 MBq/µg), respectively. The doses passed apyrogenicity and human serum stability specifications, were sterile up to 14 days, and retained > 60% immunoreactivity. In vivo micro-PET/CT mouse images at 24 hours postinjection showed that the tracer targeted the intended sites of human CD20 expression. Thus, we have validated the manufacturing of GMP grade 64Cu-DOTA-rituximab for injection in the clinical setting.

Nuclear oncology, a fast growing field of nuclear medicine

NASA Astrophysics Data System (ADS)

Olivier, Pierre

2004-07-01

Nuclear Medicine in oncology has been for a long time synonymous with bone scintigraphy, the first ever whole body imaging modality, and with treatment of thyroid cancer with iodine-131. More recently, somatostatin receptor scintigraphy (SRS) using peptides such as 111In-labelled octreotide became a reference imaging method in the detection and staging of neuroendocrine tumors while 131I- and 123I-MIBG remain the tracers of reference for pheochromocytomas and neuroblastomas. Lymphoscintigraphic imaging based on peritumoral injection of 99mTc-labelled colloids supports, in combination with per operative detection, the procedure of sentinel node identification in breast cancers and melanomas. Positron Emission Tomography (PET) is currently experiencing a considerable growth in oncology based on the use of 18F-FDG (fluorodeoxyglucose), a very sensitive, although non-specific, tumor tracer. Development of instrumentation is crucial in this expansion of PET imaging with new crystals being more sensitive and hybrid imagers that permit to reduce the acquisition time and offer fused PET-CT images. Current developments in therapy can be classified into three categories. Radioimmunotherapy (RIT) based on monoclonal antibodies (or fragments) labelled with beta-emitters. This technique has recently made its entrance in clinical practice with a 90Y-labelled anti-CD20 antibody ( 90Y-ibritumomab tiuxetan (Zevalin ®)) approved in US for the treatment of some subtypes of non-Hodgkin's lymphoma. Radionuclide-bone pain palliation has experienced developments with 153Sm-EDTMP, 186Re-HEDP or 89Sr, efficient in patients with widespread disease. Last, the same peptides, as those used in SRS, are being developed for therapy, labelled with 90Y, 111In or 177Lu in patients who failed to respond to other treatments. Overall, nuclear oncology is currently a fast growing field thanks to the combined developments of radiopharmaceuticals and instrumentation.

Synthesis of [11C]palmitic acid for PET imaging using a single molecular sieve 13X cartridge for reagent trapping, radiolabeling and selective purification.

PubMed

Amor-Coarasa, Alejandro; Kelly, James M; Babich, John W

2015-08-01

Radiolabeled fatty acids are valuable metabolic tracers for PET imaging. Carbon-11 is widely used in clinical PET studies due to the prevalence of facile techniques enabling the incorporation of [(11)C]CO2 and [(11)C]CH3 into molecules and a short half-life (20.4 min) that translates into low patient dose. However, the short half-life considerably limits the time for radiosynthesis. Furthermore, the majority of the syntheses of [(11)C]palmitic acid in common use employ high starting [(11)C]CO2 activities and/or expensive equipment. [(11)C]CO2 was trapped with greater than 99.99% efficiency by a three stage cartridge packed with molecular sieve 13X, 100-120 mesh. The labeling of n-pentadecylmagnesium bromide took place in 5 min in the cartridge, and the [(11)C]palmitic acid product was selectively eluted in ethanol following alkaline and acidic washes of the column. The system reliably produced more than 925 MBq (25 mCi) of [(11)C]palmitic acid suitable for human use from 7.4 GBq (200 mCi) of [(11)C]CO2 in 8 min from end-of-bombardment. We have exploited the properties of the inexpensive molecular sieve 13X to develop a miniature, disposable and leak tight "gas capture" system for the rapid labeling and purification of [(11)C]fatty acids in good yield and >99% radiochemical purity. The rapidity of the synthesis and purification allows small [(11)C]CO2 starting activities to be used, and with no requirement for expensive synthesis equipment or facilities, the system can be implemented in any radiopharmaceutical center. Copyright © 2015 Elsevier Inc. All rights reserved.

Is Overeating Behavior Similar to Drug Addiction? (427th Brookhaven Lecture)

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

Wang, Gene-Jack

2007-09-27

The increasing number of obese individuals in the U.S. and other countries world-wide adds urgency to the need to understand the mechanisms underlying pathological overeating. Research by the speaker and others at Brookhaven National Laboratory and elsewhere is compiling evidence that the brain circuits disrupted in obesity are similar to those involved in drug addiction. Using positron emission tomography (PET), the speaker and his colleagues have implicated brain dopamine in the normal and the pathological intake of food by humans. During the 427th Brookhaven Lecture, speaker will review the findings and implications of PET studies of obese subjects and thenmore » compare them to PET research involving drug-addicted individuals. For example, in pathologically obese subjects, it was found that reductions in striatal dopamine D2 receptors are similar to those observed in drug-addicted subjects. The speaker and his colleagues have postulated that decreased levels of dopamine receptors predisposed subjects to search for strongly rewarding reinforcers, be it drugs for the drug-addicted or food for the obese, as a means to compensate for decreased sensitivity of their dopamine-regulated reward circuits. As the speaker will summarize, multiple but similar brain circuits involved in reward, motivation, learning and inhibitory control are disrupted both in drug addiction and obesity, resulting in the need for a multimodal approach to the treatment of obesity.« less

The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

PubMed

Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

2018-04-01

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

(Coordinated research of chemotherapeutic agents and radiopharmaceuticals)

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

Srivastava, P.C.

1991-01-14

The traveler received a United Nations Development Program (UNDP) Award for Distinguished Scientists to visit Indian Research Institutions including Central Drug Research Institute (CDRI), Lucknow, the host institution, in cooperation with the Council of Scientific and Industrial Research (CSIR) of India. At CDRI, the traveler had meetings to discuss progress and future directions of on-going collaborative research work on nucleosides and had the opportunity to initiate new projects with the divisions of pharmacology, biopolymers, and membrane biology. As a part of this program, the traveler also visited Sanjay Gandhi Post Graduate Institute (SGPI) of Medical Sciences, Lucknow; Board of Radiationmore » and Isotope Technology (BRIT) and Bhabha Atomic Research Center (BARC), Bombay; Variable Energy Cyclotron Center (VECC) and Indian Institute of Chemical Biology, Calcutta. He also attended the Indo-American Society of Nuclear Medicine Meeting held in Calcutta. The traveler delivered five seminars describing various aspects of radiopharmaceutical development at the Oak Ridge National Laboratory (ORNL) and discussed the opportunities for exchange visits to ORNL by Indian scientists.« less

PET evaluation of the dopamine system of the human brain

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

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

1996-07-01

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson`s disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors,more » dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of change in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson`s disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurochemical parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research. 254 refs., 7 figs., 3 tabs.« less

A new automated high pressure reaction vessel for preparation of radiopharmaceuticals

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

Ropchan, J.R.; Ricci, T.; Low, J.

A continual growth in positron emission tomography (PET) has placed an increasing need for routine production of radiopharmaceuticals with minimization of radiation exposure to the chemist. The authors have developed the first remote, completely automated stainless-steel reaction vessel (SSRV) for the high temperature and pressure syntheses of any radiolabeled organic compounds (i.e. amino acids). The SSRV is composed of six major parts: (1) a top plate, which contains the four ports for the addition and withdrawal of solutions (2) a rotating inner disc, which controls the opening and closing of the four ports (3) a housing unit, for the O-ringsmore » and rotating disc (4) a fluid chamber, (5) a stepping motor, which drives the rotating disc and (6) a push-button control box, which operates the entire system. After cyclotron production of the radiolabeled precursor, activation of the appropriate buttons on the control box advance the rotating disc to the desired ports in the sequence of events where the reagents are added or withdrawn from the SSRV. Heating is supplied by a specially made hot plate mounted on an electrically operated jack. The SSRV is cooled via an external cooling system (nitrogen gas cooled in liquid nitrogen). The present system is easily adaptable to a microprocessing unit. This SSRV is successfully employed in the preparation of pure C-11 labeled DL-leucine, DL-alanine and DL-phenylalanine with high radiochemical yields (50-75%) and activities (typical activity in the final product(s) 240-400 mCi).« less

A study of shape-dependent partial volume correction in pet imaging using ellipsoidal phantoms fabricated via rapid prototyping

NASA Astrophysics Data System (ADS)

Mille, Matthew M.

Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is being increasingly recognized as an important tool for quantitative assessment of tumor response because of its ability to capture functional information about the tumor's metabolism. However, despite many advances in PET technology, measurements of tumor radiopharmaceutical uptake in PET are still challenged by issues of accuracy and consistency, thereby compromising the use of PET as a surrogate endpoint in clinical trials. One limiting component of the overall uncertainty in PET is the relatively poor spatial resolution of the images which directly affects the accuracy of the tumor radioactivity measurements. These spatial resolution effects, colloquially known as the partial volume effect (PVE), are a function of the characteristics of the scanner as well as the tumor being imaged. Previous efforts have shown that the PVE depends strongly on the tumor volume and the background-to-tumor activity concentration ratio. The PVE is also suspected to be a function of tumor shape, although to date no systematic study of this effect has been performed. This dissertation seeks to help fill the gap in the current knowledge about the shape-dependence of the PVE by attempting to quantify, through both theoretical calculation and experimental measurement, the magnitude of the shape effect for ellipsoidal tumors. An experimental investigation of the tumor shape effect necessarily requires tumor phantoms of multiple shapes. Hence, a prerequisite for this research was the design and fabrication of hollow tumor phantoms which could be filled uniformly with radioactivity and imaged on a PET scanner. The phantom fabrication was achieved with the aid of stereolithography and included prolate ellipsoids of various axis ratios. The primary experimental method involved filling the tumor phantoms with solutions of 18F whose activity concentrations were known and traceable to primary radioactivity standards held by the National Institute of Standards and Technology (NIST). The tumor phantoms were then placed inside a Jaszczak cylinder (representing the human body) and imaged on a PET scanner located at NIST. This experimental approach allowed for the testing of: (1) The relative difference between tumors phantoms of different shapes, but same volume; (2) The overall accuracy of the PET measurements in terms of a ground truth reference value. Theoretical calculations of the tumor shape effect were also performed by mathematically convolving the phantom shapes with a 3D Gaussian point-spread function, and the results of the calculations were compared with the experimental data. The data show that the shape effect in PET tumor imaging can be as large as 15% for ellipsoid phantoms with axis ratios of 2:1, volume of 1.15 cm 3, and tumor-to-background activity concentration ratio of 9:1. This is explained by a greater loss of counts along the minor axis direction in the ellipsoid tumors compared to that of spheres of the same volume. The results of this PhD research confirm the existence of a tumor shape effect PET imaging. However, except in the case of ellipsoids with major-to-minor axis ratio greater than 2:1, a correction for the effect using recovery coefficients is expected to be challenging because its magnitude is comparable to the repeatability of the PET measurements.

Intelligent MoS2 Nanotheranostic for Targeted and Enzyme-/pH-/NIR-Responsive Drug Delivery To Overcome Cancer Chemotherapy Resistance Guided by PET Imaging.

PubMed

Dong, Xinghua; Yin, Wenyan; Zhang, Xiao; Zhu, Shuang; He, Xiao; Yu, Jie; Xie, Jiani; Guo, Zhao; Yan, Liang; Liu, Xiangfeng; Wang, Qing; Gu, Zhanjun; Zhao, Yuliang

2018-01-31

Chemotherapy resistance remains a major hurdle for cancer therapy in clinic because of the poor cellular uptake and insufficient intracellular release of drugs. Herein, an intelligent, multifunctional MoS 2 nanotheranostic (MoS 2 -PEI-HA) ingeniously decorated with biodegradable hyaluronic acid (HA) assisted by polyethyleneimine (PEI) is reported to combat drug-resistant breast cancer (MCF-7-ADR) after loading with the chemotherapy drug doxorubicin (DOX). HA can not only target CD44-overexpressing MCF-7-ADR but also be degraded by hyaluronidase (HAase) that is concentrated in the tumor microenvironment, thus accelerating DOX release. Furthermore, MoS 2 with strong near-infrared (NIR) photothermal conversion ability can also promote the release of DOX in the acidic tumor environment at a mild 808 nm laser irradiation, achieving a superior antitumor activity based on the programmed response to HAase and NIR laser actuator. Most importantly, HA targeting combined with mild NIR laser stimuli, rather than using hyperthermia, can potently downregulate the expression of drug-resistance-related P-glycoprotein (P-gp), resulting in greatly enhanced intracellular drug accumulation, thus achieving drug resistance reversal. After labeled with 64 Cu by a simple chelation strategy, MoS 2 was employed for real-time positron emission tomography (PET) imaging of MCF-7-ADR tumor in vivo. This multifunctional nanoplatform paves a new avenue for PET imaging-guided spatial-temporal-controlled accurate therapy of drug-resistant cancer.

UCLA Translational Biomarker Development Program (UTBD)

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

Czernin, Johannes

2014-09-01

The proposed UTBD program integrates the sciences of diagnostic nuclear medicine and (radio)chemistry with tumor biology and drug development. UTBD aims to translate new PET biomarkers for personalized medicine and to provide examples for the use of PET to determine pharmacokinetic (PK) and pharmacodynamic (PD) drug properties. The program builds on an existing partnership between the Ahmanson Translational Imaging Division (ATID) and the Crump Institute of Molecular Imaging (CIMI), the UCLA Department of Chemistry and the Division of Surgical Oncology. ATID provides the nuclear medicine training program, clinical and preclinical PET/CT scanners, biochemistry and biology labs for probe and drugmore » development, radiochemistry labs, and two cyclotrons. CIMI provides DOE and NIH-funded training programs for radio-synthesis (START) and molecular imaging (SOMI). Other participating entities at UCLA are the Department of Chemistry and Biochemistry and the Division of Surgical Oncology. The first UTBD project focuses on deoxycytidine kinase, a rate-limiting enzyme in nucleotide metabolism, which is expressed in many cancers. Deoxycytidine kinase (dCK) positive tumors can be targeted uniquely by two distinct therapies: 1) nucleoside analog prodrugs such as gemcitabine (GEM) are activated by dCK to cytotoxic antimetabolites; 2) recently developed small molecule dCK inhibitors kill tumor cells by starving them of nucleotides required for DNA replication and repair. Since dCK-specific PET probes are now available, PET imaging of tumor dCK activity could improve the use of two different classes of drugs in a wide variety of cancers.« less

Can pets function as family members?

PubMed

Cohen, Susan Phillips

2002-10-01

This exploratory study investigated how clients of a large urban veterinary center viewed the role of their pet in the famil and how they compared this role to that of humans. In Phase 1, randomly selected clients (N = 201) completed a questionnaire containing scales delineating family relationships and pet attachment. Being either a man or a college graduate was associated with lesser feelings of psychological kinship and intimacy, both with pets and people. Neither living with a partner norhaving a child affected the strength of pet relationships. In Phase 2, 16 participants from Phase I completed a social network instrument and answered questions about family roles and boundaries. Thirteen of the 16 respondents said that there were circumstances in which they would give a scarce drug to their pet in preference to a person outside the family.

How to design PET experiments to study neurochemistry: application to alcoholism.

PubMed

Morris, Evan D; Lucas, Molly V; Petrulli, J Ryan; Cosgrove, Kelly P

2014-03-01

Positron Emission Tomography (PET) (and the related Single Photon Emission Computed Tomography) is a powerful imaging tool with a molecular specificity and sensitivity that are unique among imaging modalities. PET excels in the study of neurochemistry in three ways: 1) It can detect and quantify neuroreceptor molecules; 2) it can detect and quantify changes in neurotransmitters; and 3) it can detect and quantify exogenous drugs delivered to the brain. To carry out any of these applications, the user must harness the power of kinetic modeling. Further, the quality of the information gained is only as good as the soundness of the experimental design. This article reviews the concepts behind the three main uses of PET, the rationale behind kinetic modeling of PET data, and some of the key considerations when planning a PET experiment. Finally, some examples of PET imaging related to the study of alcoholism are discussed and critiqued.

How to Design PET Experiments to Study Neurochemistry: Application to Alcoholism

PubMed Central

Morris, Evan D.; Lucas, Molly V.; Petrulli, J. Ryan; Cosgrove, Kelly P.

2014-01-01

Positron Emission Tomography (PET) (and the related Single Photon Emission Computed Tomography) is a powerful imaging tool with a molecular specificity and sensitivity that are unique among imaging modalities. PET excels in the study of neurochemistry in three ways: 1) It can detect and quantify neuroreceptor molecules; 2) it can detect and quantify changes in neurotransmitters; and 3) it can detect and quantify exogenous drugs delivered to the brain. To carry out any of these applications, the user must harness the power of kinetic modeling. Further, the quality of the information gained is only as good as the soundness of the experimental design. This article reviews the concepts behind the three main uses of PET, the rationale behind kinetic modeling of PET data, and some of the key considerations when planning a PET experiment. Finally, some examples of PET imaging related to the study of alcoholism are discussed and critiqued. PMID:24600335

Pitfalls and Limitations of Radionuclide Planar and Hybrid Bone Imaging.

PubMed

Agrawal, Kanhaiyalal; Marafi, Fahad; Gnanasegaran, Gopinath; Van der Wall, Hans; Fogelman, Ignac

2015-09-01

The radionuclide (99m)Tc-MDP bone scan is one of the most commonly performed nuclear medicine studies and helps in the diagnosis of different pathologies relating to the musculoskeletal system. With its increasing utility in clinical practice, it becomes more important to be aware of various limitations of this imaging modality to avoid false interpretation. It is necessary to be able to recognize various technical, radiopharmaceutical, and patient-related artifacts that can occur while carrying out a bone scan. Furthermore, several normal variations of tracer uptake may mimic pathology and should be interpreted cautiously. There is an important limitation of a bone scan in metastatic disease evaluation as the inherent mechanism of tracer uptake is not specific for tumor but primarily relies on an osteoblastic response. Thus, it is crucial to keep in mind uptake in benign lesions, which can resemble malignant pathologies. The utility of a planar bone scan in benign orthopedic diseases, especially at sites with complex anatomy, is limited owing to lack of precise anatomical information. SPECT/CT has been significantly helpful in these cases. With wider use of PET/CT and reintroduction of the (18)F-fluoride bone scan, increasing knowledge of potential pitfalls on an (18)F-fluoride bone scan and (18)F-FDG-PET/CT will help in improving the accuracy of clinical reports. Copyright © 2015 Elsevier Inc. All rights reserved.

[Evaluation of therapies in oncology by positron emission tomography: towards therapeutical personalization].

PubMed

Bonardel, G; Vedrine, L; Aupee, O; Gontier, E; Le Garlantezec, P; Soret, M; Foehrenbach, H

2009-02-01

Recently introduced into clinical practice, positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has proven its utility for diagnosis and staging of malignant diseases on account of its ability for tissue identification. Its utilization is now moving toward the evaluation of anti-tumoral effects of anticancer therapy, because of the correlation between the uptake of a metabolic tracer and malignant cells viability. Metabolic effects of chemotherapy are first observed in cells and this is the explanation for the precocity of scintigraphic visualisation of therapeutic activity. However, monitoring response with FDG-PET requires rigorous method and needs to take into account the limitations of SUV. Moreover, in order to go beyond the limitations of FDG, new tracers are developed and their main indication could be precisely the monitoring of therapy response. The properties of positron emitters allow us to foresee the labelling of the therapeutic molecules themselves in order to try them in vivo before their utilization for a given patient. These prospects are the ground for real treatment personalization in oncology. They open up a wide field of clinical research but the means for image acquisition and radioactive tracers production will be mandatory for anyone who wants to contribute to this work. Due to the current performances of the imaging systems, the critical point will be availability of equipment allowing the designing and synthesis of the radiopharmaceuticals of the future.

Functional analysis of [methyl-(3)H]choline uptake in glioblastoma cells: Influence of anti-cancer and central nervous system drugs.

PubMed

Taguchi, Chiaki; Inazu, Masato; Saiki, Iwao; Yara, Miki; Hara, Naomi; Yamanaka, Tsuyoshi; Uchino, Hiroyuki

2014-04-01

Positron emission tomography (PET) and PET/computed tomography (PET-CT) studies with (11)C- or (18)F-labeled choline derivatives are used for PET imaging in glioblastoma patients. However, the nature of the choline transport system in glioblastoma is poorly understood. In this study, we performed a functional characterization of [methyl-(3)H]choline uptake and sought to identify the transporters that mediate choline uptake in the human glioblastoma cell lines A-172 and U-251MG. In addition, we examined the influence of anti-cancer drugs and central nervous system drugs on the transport of [methyl-(3)H]choline. High- and low-affinity choline transport systems were present in A-172 cells, U-251MG cells and astrocytes, and these were Na(+)-independent and pH-dependent. Cell viability in A-172 cells was not affected by choline deficiency. However, cell viability in U-251MG cells was significantly inhibited by choline deficiency. Both A-172 and U-251MG cells have two different choline transporters, choline transporter-like protein 1 (CTL1) and CTL2. In A-172 cells, CTL1 is predominantly expressed, whereas in U-251MG cells, CTL2 is predominantly expressed. Treatment with anti-cancer drugs such as cisplatin, etoposide and vincristine influenced [methyl-(3)H]choline uptake in U-251MG cells, but not A-172 cells. Central nervous system drugs such as imipramine, fluvoxamine, paroxetine, reboxetine, citalopram and donepezil did not affect cell viability or [methyl-(3)H]choline uptake. The data presented here suggest that CTL1 and CTL2 are functionally expressed in A-172 and U-251MG cells and are responsible for [methyl-(3)H]choline uptake that relies on a directed H(+) gradient as a driving force. Furthermore, while anti-cancer drugs altered [methyl-(3)H]choline uptake, central nervous system drugs did not affect [methyl-(3)H]choline uptake. Copyright © 2014 Elsevier Inc. All rights reserved.

Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

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

Russell, J.R.; Stabin, M.G.; Sparks, R.B.

The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper, after identification of radiopharmaceuticals often administered to women of childbearing age, the most recent data available on the placental crossover of these radiopharmaceuticals was used (with standard kinetic models describing the maternal distribution and retention and with the best available physical models) to obtain fetal dose estimates for these radiopharmaceuticals were identified as those most commonly administered to women of childbearing years.more » The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. Radiation dose estimates are presented in early pregnancy and at 3-, 6-, and 9-months gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose). 46 refs., 1 fig., 5 tabs.« less

An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats.

PubMed

Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

2011-01-01

Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-⁹⁹m (⁹⁹mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na⁹⁹mTcO₄)in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na⁹⁹mTcO₄ and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na⁹⁹mTcO₄ in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na⁹⁹mTcO₄ are conducted in patients who are using senna extract.

An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

PubMed Central

Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; de Souza da Fonseca, Adenilson; Bernardo-Filho, Mario

2011-01-01

ABSTRACT Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract. PMID:21552677

Understanding regulations affecting pet foods.

PubMed

Dzanis, David A

2008-08-01

In the United States, pet foods are subject to regulation at both the federal and the state levels. The US Food and Drug Administration has jurisdiction over all animal feeds (including pet foods, treats, chews, supplements, and ingredients) in interstate commerce, which includes imported products. Many states adopt and enforce at least in part the Association of American Feed Control Officials Model Bill and Model Regulations for Pet Food and Specialty Pet Food. Thus, all pet foods in multi-state distribution are subject to a host of labeling requirements covering aspects such as product names, ingredient lists, nutrient content guarantees, and nutritional adequacy statements. Ingredients must be GRAS (generally recognized as safe) substances, approved food additives, or defined by Association of American Feed Control Officials for their intended use. Pet food labels may not bear claims that are false or misleading or that state or imply use for the treatment or prevention of disease. Pet foods that are found to be adulterated or misbranded may be subject to seizure or other enforcement actions.

Convenient and Efficient Method for Quality Control Analysis of 18F-Fluorocholine: For a Small Scale GMP-based Radiopharmaceuticals Laboratory Set-up.

PubMed

Hassan, Hishar; Abu Bakar, Suharzelim; Halim, Khairul Najah Che A; Idris, Jaleezah; Nordin, Abdul Jalil

2016-01-01

Prostate cancer continues to be the most prevalent cancer in men in Malaysia. As time progresses, the prospect of PET imaging modality in diagnosis of prostate cancer is promising, with on-going improvement on novel tracers. Among all tracers, 18F-Fluorocholine is reported to be a reputable tracer and reliable diagnostic technique for prostate imaging. Nonetheless, only 18F-Fluorodeoxyglucose (18F-FDG) is available and used in most oncology cases in Malaysia. With a small scale GMP-based radiopharmaceuticals laboratory set-up, initial efforts have been taken to put Malaysia on 18F-Fluorocholine map. This article presents a convenient, efficient and reliable method for quality control analysis of 18F-Fluorocholine. Besides, the aim of this research work is to assist local GMP radiopharmaceuticals laboratories and local authority in Malaysia for quality control analysis of 18F-Fluorocholine guideline. In this study, prior to synthesis, quality control analysis method for 18F-Fluorocholine was developed and validated, by adapting the equipment set-up used in 18F-Fluorodeoxyglucose (18FFDG) routine production. Quality control on the 18F-Fluorocholine was performed by means of pH, radionuclidic identity, radio-high performance liquid chromatography equipped with ultraviolet, radio- thin layer chromatography, gas chromatography and filter integrity test. Post-synthesis; the pH of 18F-Fluorocholine was 6.42 ± 0.04, with half-life of 109.5 minutes (n = 12). The radiochemical purity was consistently higher than 99%, both in radio-high performance liquid chromatography equipped with ultraviolet (r-HPLC; SCX column, 0.25 M NaH2PO4: acetonitrile) and radio-thin layer chromatography method (r-TLC). The calculated relative retention time (RRT) in r-HPLC was 1.02, whereas the retention factor (Rf) in r-TLC was 0.64. Potential impurities from 18F-Fluorocholine synthesis such as ethanol, acetonitrile, dimethylethanolamine and dibromomethane were determined in gas chromatography. Using our parameters, (capillary column: DB-200, 30 m x 0.53 mm x 1 um) and oven temperature of 35°C (isothermal), all compounds were well resolved and eluted within 3 minutes. Level of ethanol and acetonitrile in 18F-Fluorocholine were detected below threshold limit; less than 5 mg/ml and 0.41 mg/ml respectively. Meanwhile, dimethylethanolamine and dibromomethane were undetectable. A convenient, efficient and reliable quality control analysis work-up procedure for 18FFluorocholine has been established and validated to comply all the release criteria. The convenient method of quality control analysis may provide a guideline to local GMP radiopharmaceutical laboratories to start producing 18F-Fluorocholine as a tracer for prostate cancer imaging.

Therapeutic Strategies for Bone Metastases and Their Clinical Sequelae in Prostate Cancer

PubMed Central

Autio, Karen A.; Scher, Howard I.

2013-01-01

Opinion statement Skeletal metastases threaten quality of life, functionality, and longevity in patients with metastatic castration-resistant prostate cancer (mCRPC). Therapeutic strategies for bone metastases in prostate cancer can palliate pain, delay/prevent skeletal complications, and prolong survival. Pharmacologic agents representing several drug classes have demonstrated the ability to achieve these treatment goals in men with mCRPC. Skeletal-related events such as fracture and the need for radiation can be delayed using drugs that target the osteoclast/osteoblast pathway. Cancer-related bone pain can be palliated using beta-emitting bone-seeking radiopharmaceuticals such as samarium-153 EDTMP and strontium-89. Also, prospective randomized studies have demonstrated that cytotoxic chemotherapy can palliate bone pain. For the first time, bone-directed therapy has been shown to prolong survival using the novel alpha-emitting radiopharmaceutical radium-223. Given these multifold clinical benefits, treatments targeting bone metabolism, tumor-bone stromal interactions, and bone metastases themselves are now central elements of routine clinical care. Decisions about which agents, alone or in combination, will best serve the patient’s and clinician’s clinical goals is contingent on the treatment history to date, present disease manifestations, and symptomatology. Clinical trials exploring novel agents such as those targeting c-Met and Src are under way, using endpoints that directly address how patients feel, function, and survive. PMID:22528368

[Experimental study of infrasonic phonophoresis].

PubMed

Filatov, V V

2001-01-01

A new method of drug administration, infrared phonophoresis, was experimentally studied. The method has no analogs in the world. The study was carried out on 20 Chinchilla rabbits. Water applications impregnated with equal volumes of the radiopharmaceutical (RP) were placed into the conjunctival cavities of both eyes. The right eye was control and the left was treated by infrasound (experiment). The information was recorded in live animals after removal of the application and thorough washing of the conjunctival cavity immediately, 30 min, and 1 h after infrasound phonophoresis session. Radioactivity measurements at all terms indicate its stable increase in the experimental eye and a progressive decrease in the control eye. Hence, infrasound promoted long accumulation of the RP in the eye at anterior route of the drug delivery without preliminary injection of the drug into ocular vessels.

Magnetic field effect corroborated with docking study to explore photoinduced electron transfer in drug-protein interaction.

PubMed

Chakraborty, Brotati; Roy, Atanu Singha; Dasgupta, Swagata; Basu, Samita

2010-12-30

Conventional spectroscopic tools such as absorption, fluorescence, and circular dichroism spectroscopy used in the study of photoinduced drug-protein interactions can yield useful information about ground-state and excited-state phenomena. However, photoinduced electron transfer (PET) may be a possible phenomenon in the drug-protein interaction, which may go unnoticed if only conventional spectroscopic observations are taken into account. Laser flash photolysis coupled with an external magnetic field can be utilized to confirm the occurrence of PET and authenticate the spin states of the radicals/radical ions formed. In the study of interaction of the model protein human serum albumin (HSA) with acridine derivatives, acridine yellow (AY) and proflavin (PF(+)), conventional spectroscopic tools along with docking study have been used to decipher the binding mechanism, and laser flash photolysis technique with an associated magnetic field (MF) has been used to explore PET. The results of fluorescence study indicate that fluorescence resonance energy transfer takes place from the protein to the acridine-based drugs. Docking study unveils the crucial role of Ser 232 residue of HSA in explaining the differential behavior of the two drugs towards the model protein. Laser flash photolysis experiments help to identify the radicals/radical ions formed in the due course of PET (PF(•), AY(•-), TrpH(•+), Trp(•)), and the application of an external MF has been used to characterize their initial spin-state. Owing to its distance dependence, MF effect gives an idea about the proximity of the radicals/radical ions during interaction in the system and also helps to elucidate the reaction mechanisms. A prominent MF effect is observed in homogeneous buffer medium owing to the pseudoconfinement of the radicals/radical ions provided by the complex structure of the protein.

Drug transport across the blood–brain barrier

PubMed Central

Pardridge, William M

2012-01-01

The blood–brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. This property arises from the epithelial-like tight junctions within the brain capillary endothelium. The BBB is anatomically and functionally distinct from the blood–cerebrospinal fluid barrier at the choroid plexus. Certain small molecule drugs may cross the BBB via lipid-mediated free diffusion, providing the drug has a molecular weight <400 Da and forms <8 hydrogen bonds. These chemical properties are lacking in the majority of small molecule drugs, and all large molecule drugs. Nevertheless, drugs can be reengineered for BBB transport, based on the knowledge of the endogenous transport systems within the BBB. Small molecule drugs can be synthesized that access carrier-mediated transport (CMT) systems within the BBB. Large molecule drugs can be reengineered with molecular Trojan horse delivery systems to access receptor-mediated transport (RMT) systems within the BBB. Peptide and antisense radiopharmaceuticals are made brain-penetrating with the combined use of RMT-based delivery systems and avidin–biotin technology. Knowledge on the endogenous CMT and RMT systems expressed at the BBB enable new solutions to the problem of BBB drug transport. PMID:22929442

76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-17

... a larger amount of the drug substance than what is intended to be delivered to the patient. This... patient, but also to others, including family members, caregivers, children, and pets. For example...

Fast Metabolic Response to Drug Intervention through Analysis on a Miniaturized, Highly Integrated Molecular Imaging System

PubMed Central

Wang, Jun; Hwang, Kiwook; Braas, Daniel; Dooraghi, Alex; Nathanson, David; Campbell, Dean O.; Gu, Yuchao; Sandberg, Troy; Mischel, Paul; Radu, Caius; Chatziioannou, Arion F.; Phelps, Michael E.; Christofk, Heather; Heath, James R.

2014-01-01

We report on a radiopharmaceutical imaging platform designed to capture the kinetics of cellular responses to drugs. Methods A portable in vitro molecular imaging system, comprised of a microchip and a beta-particle imaging camera, permits routine cell-based radioassays on small number of either suspension or adherent cells. We investigate the response kinetics of model lymphoma and glioblastoma cancer cell lines to [18F]fluorodeoxyglucose ([18F]FDG) uptake following drug exposure. Those responses are correlated with kinetic changes in the cell cycle, or with changes in receptor-tyrosine kinase signaling. Results The platform enables radioassays directly on multiple cell types, and yields results comparable to conventional approaches, but uses smaller sample sizes, permits a higher level of quantitation, and doesn’t require cell lysis. Conclusion The kinetic analysis enabled by the platform provides a rapid (~1 hour) drug screening assay. PMID:23978446

Design and evaluation of pH-sensitive liposomes constructed by poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate for doxorubicin delivery.

PubMed

Xu, Huan; Hu, Meina; Yu, Xiu; Li, Yan; Fu, Yuanshan; Zhou, Xiaoxia; Zhang, Di; Li, Jianying

2015-04-01

In this study, a novel material, poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate (PEtOz-CHEMS), was synthesized to construct pH-sensitive liposomes. The structure of PEtOz-CHEMS was confirmed by thin-layer chromatography, Fourier transform infrared spectroscopy, and (1)H NMR. Anticancer fluorescent drug doxorubicin (DOX) was encapsulated into the liposomes. Compared with conventional liposomes (CL), CHEMS modified liposomes (CH-L) and PEGylated liposomes (PEG-L), the PEtOzylated liposomes (PEtOz-L) showed an acidic pH-induced increase in particle size. At pH 6.4, the heme release of PEtOz-L group was close to that of the positive control group, whereas that of CL, CH-L and PEG-L was close to that of the negative control group. In vitro drug release studies demonstrated that DOX was released from PEtOz-L in a pH-dependent manner, and the release of DOX from conventional DOX liposomes (CL-DOX), DOX loaded CH-L (CH-DOX-L) and PEGylated DOX liposomes (PEG-DOX-L) had no pronounced differences under each pH medium. In vitro cellular uptake assays showed that PEtOz-DOX-L indicated a significant fluorescence intensity at pH 6.4 compared with at pH 7.4. CL-DOX, CH-DOX-L and PEG-DOX-L did not achieve any obvious diversity at different pH conditions. Confocal laser scanning microscopy images showed that PEtOz-DOX-L can fuse with the endosomal membrane under acidic conditions of endosome, release DOX into the cytoplasm, then gather into the nucleus. Therefore, PEtOz can help liposomes achieve "endosomal escape". The in vitro cytotoxicity experiment results on A375 cells showed that PEtOz-DOX-L resulted in lower cell viability than CL-DOX, CH-DOX-L and PEG-DOX-L under low pH conditions. These results confirm that the pH-responsive PEtOz was a promising material for intracellular targeted delivery system and might be used for overcoming the "PEG dilemma". Copyright © 2015 Elsevier B.V. All rights reserved.

Joint CDRH (Center for Devices and Radiological Health) and state quality-assurance surveys in nuclear medicine: Phase 2 - radiopharmaceuticals

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

Hamilton, D.R.; Evans, C.D.

The report discusses survey results on aspects of the quality assurance of radio-pharmaceuticals from 180 nuclear-medicine facilities in the United States. Data were collected from facilities in 8 states. Demographic information about nuclear-medicine operations and quality-assurance programs was gathered by state radiation-control-program personnel. The data collected from the survey show an incomplete acceptance of quality-assurance practices for radiopharmaceuticals. Most of the facilities in the survey indicated that, because an inferior radiopharmaceutical was prepared so infrequently, they did not believe it was cost-effective to perform extensive quality-assurance testing. The Center for Devices and Radiological Health hopes that the information from themore » survey will stimulate nuclear-medicine professionals and their organizations to encourage appropriate testing of all radiopharmaceuticals.« 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.

PET-Based Human Dosimetry of the Dimeric αvβ3 Integrin Ligand 68Ga-DOTA-E-[c(RGDfK)]2, a Potential Tracer for Imaging Tumor Angiogenesis.

PubMed

López-Rodríguez, Victoria; Galindo-Sarco, Carlos; García-Pérez, Francisco O; Ferro-Flores, Guillermina; Arrieta, Oscar; Ávila-Rodríguez, Miguel A

2016-03-01

Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvβ3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from (68)Ga-DOTA-E-[c(RGDfK)]2 using whole-body PET scans in humans. Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/EXM software was applied to calculate human radiation doses using the reference adult model. The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 μSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively. Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with (68)Ga and (18)F. Therefore, (68)Ga-DOTA-E-[c(RGDfK)]2 can safely be used for imaging integrin αVβ3 expression. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Nuclear Medicine in Pediatric Cardiology.

PubMed

Milanesi, Ornella; Stellin, Giovanni; Zucchetta, Pietro

2017-03-01

Accurate cardiovascular imaging is essential for the successful management of patients with congenital heart disease (CHD). Echocardiography and angiography have been for long time the most important imaging modalities in pediatric cardiology, but nuclear medicine has contributed in many situations to the comprehension of physiological consequences of CHD, quantifying pulmonary blood flow symmetry or right-to-left shunting. In recent times, remarkable improvements in imaging equipments, particularly in multidetector computed tomography and magnetic resonance imaging, have led to the progressive integration of high resolution modalities in the clinical workup of children affected by CHD, reducing the role of diagnostic angiography. Technology has seen a parallel evolution in the field of nuclear medicine, with the advent of hybrid machines, as SPECT/CT and PET/CT scanners. Improved detectors, hugely increased computing power, and new reconstruction algorithms allow for a significant reduction of the injected dose, with a parallel relevant decrease in radiation exposure. Nuclear medicine retains its distinctive capability of exploring at the tissue level many functional aspects of CHD in a safe and reproducible way. The lack of invasiveness, the limited need for sedation, the low radiation burden, and the insensitivity to body habitus variations make nuclear medicine an ideal complement of echocardiography. This is particularly true during the follow-up of patients with CHD, whose increasing survival represent a great medical success and a challenge for the health system in the next decades. Metabolic imaging using 18 FDG PET/CT has expanded its role in the management of infection and inflammation in adult patients, particularly in cardiology. The same expansion is observed in pediatric cardiology, with an increasing rate of studies on the use of FDG PET for the evaluation of children with vasculitis, suspected valvular infection or infected prosthetic devices. The introduction in the clinical practice of the first integrated PET/MR scanners and the development of new radiopharmaceuticals, as fluorinated compounds for the study of myocardial perfusion, open new perspectives in the use of nuclear medicine techniques in pediatric cardiology, offering the potential of a detailed noninvasive morphofunctional characterization in many types of CHD. Copyright © 2017. Published by Elsevier Inc.

21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What is current good manufacturing practice for... HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) General Provisions § 212.2 What is current good manufacturing practice for...

77 FR 21783 - Guidance on Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0691...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... manufacturers of PET drugs meet the requirements for the Agency's current good manufacturing practice...

76 FR 60847 - Draft Guidance on Media Fills for Validation of Aseptic Preparations for Positron Emission...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0691... Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and... manufacturing practice regulations for PET drugs. DATES: Although you can comment on any guidance at any time...

Hospital Nuclear Pharmacy Survey: Preliminary Aspects In Brazil

PubMed Central

Brasil, Marcelo Pau; de Barros, Marcio Paes; Antunes, Leila Jorge; Santos-Oliveira, Ralph

2012-01-01

Radiopharmaceuticals are special drugs that in the composition preserve one or more radionuclides which can be used as diagnostic or therapeutic tools in Nuclear Medicine Units. This study evaluated hospitals and clinics which have nuclear medicines services at the city of Rio de Janeiro from August to November 2010. The data were obtained through a longitudinal research. The results showed that most of the hospitals (>80%) did not have pharmacist and all them (100%) considered that a pharmacist in the nuclear pharmacy is not required. PMID:23493051

Radiolabeling of Nanoparticles and Polymers for PET Imaging

PubMed Central

Stockhofe, Katharina; Postema, Johannes M.; Schieferstein, Hanno; Ross, Tobias L.

2014-01-01

Nanomedicine has become an emerging field in imaging and therapy of malignancies. Nanodimensional drug delivery systems have already been used in the clinic, as carriers for sensitive chemotherapeutics or highly toxic substances. In addition, those nanodimensional structures are further able to carry and deliver radionuclides. In the development process, non-invasive imaging by means of positron emission tomography (PET) represents an ideal tool for investigations of pharmacological profiles and to find the optimal nanodimensional architecture of the aimed-at drug delivery system. Furthermore, in a personalized therapy approach, molecular imaging modalities are essential for patient screening/selection and monitoring. Hence, labeling methods for potential drug delivery systems are an indispensable need to provide the radiolabeled analog. In this review, we describe and discuss various approaches and methods for the labeling of potential drug delivery systems using positron emitters. PMID:24699244

Novel multifunctional theranostic liposome drug delivery system: construction, characterization, and multimodality MR, near-infrared fluorescent, and nuclear imaging.

PubMed

Li, Shihong; Goins, Beth; Zhang, Lujun; Bao, Ande

2012-06-20

Liposomes are effective lipid nanoparticle drug delivery systems, which can also be functionalized with noninvasive multimodality imaging agents with each modality providing distinct information and having synergistic advantages in diagnosis, monitoring of disease treatment, and evaluation of liposomal drug pharmacokinetics. We designed and constructed a multifunctional theranostic liposomal drug delivery system, which integrated multimodality magnetic resonance (MR), near-infrared (NIR) fluorescent and nuclear imaging of liposomal drug delivery, and therapy monitoring and prediction. The premanufactured liposomes were composed of DSPC/cholesterol/Gd-DOTA-DSPE/DOTA-DSPE with the molar ratio of 39:35:25:1 and having ammonium sulfate/pH gradient. A lipidized NIR fluorescent tracer, IRDye-DSPE, was effectively postinserted into the premanufactured liposomes. Doxorubicin could be effectively postloaded into the multifunctional liposomes. The multifunctional doxorubicin-liposomes could also be stably radiolabeled with (99m)Tc or (64)Cu for single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging, respectively. MR images displayed the high-resolution micro-intratumoral distribution of the liposomes in squamous cell carcinoma of head and neck (SCCHN) tumor xenografts in nude rats after intratumoral injection. NIR fluorescent, SPECT, and PET images also clearly showed either the high intratumoral retention or distribution of the multifunctional liposomes. This multifunctional drug carrying liposome system is promising for disease theranostics allowing noninvasive multimodality NIR fluorescent, MR, SPECT, and PET imaging of their in vivo behavior and capitalizing on the inherent advantages of each modality.

Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

PubMed Central

Mohammadi, Saman; Jones, Lyndon; Gorbet, Maud

2014-01-01

In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes. PMID:25207851

Consensus nomenclature rules for radiopharmaceutical chemistry — Setting the record straight

DOE PAGES

Coenen, Heinz H.; Gee, Antony D.; Adam, Michael; ...

2017-10-21

Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of ‘self-invented’ terms. Here, in order to address these concerns, an international Working Group on ‘Nomenclature in Radiopharmaceutical Chemistry and related areas’ was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field. Upon open consultation, the following consensus guidelines were agreed, which aim to: Provide a reference source for nomenclature good practice in the radiopharma-ceutical sciences; Clarify themore » use of terms and rules concerning exclusively radiopharmaceutical terminology, i.e. nuclear- and radiochemical terms, symbols and expressions; Address gaps and inconsistencies in existing radiochemistry nomenclature rules; Provide source literature for further harmonisation beyond our immediate peer group (publishers, editors, IUPAC, pharmacopoeias, etc.).« less

Consensus nomenclature rules for radiopharmaceutical chemistry — Setting the record straight

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

Coenen, Heinz H.; Gee, Antony D.; Adam, Michael

Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of ‘self-invented’ terms. Here, in order to address these concerns, an international Working Group on ‘Nomenclature in Radiopharmaceutical Chemistry and related areas’ was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field. Upon open consultation, the following consensus guidelines were agreed, which aim to: Provide a reference source for nomenclature good practice in the radiopharma-ceutical sciences; Clarify themore » use of terms and rules concerning exclusively radiopharmaceutical terminology, i.e. nuclear- and radiochemical terms, symbols and expressions; Address gaps and inconsistencies in existing radiochemistry nomenclature rules; Provide source literature for further harmonisation beyond our immediate peer group (publishers, editors, IUPAC, pharmacopoeias, etc.).« less

Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method

PubMed Central

Mueller, Dirk; Breeman, Wouter A P; Klette, Ingo; Gottschaldt, Michael; Odparlik, Andreas; Baehre, Manfred; Tworowska, Izabela; Schultz, Michael K

2017-01-01

Gallium-68 (68Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize 68Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system, 68Ga3+ of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3–4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of 68Ga radiopharmaceuticals (12–16 min). PMID:27172166

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.

Radiolabeling of DOTA-like conjugated peptides with generator-produced (68)Ga and using NaCl-based cationic elution method.

PubMed

Mueller, Dirk; Breeman, Wouter A P; Klette, Ingo; Gottschaldt, Michael; Odparlik, Andreas; Baehre, Manfred; Tworowska, Izabela; Schultz, Michael K

2016-06-01

Gallium-68 ((68)Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize (68)Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system,(68)Ga(3+) of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3-4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of (68)Ga radiopharmaceuticals (12-16 min).

21 CFR 212.71 - What actions must I take if a batch of PET drug product does not conform to specifications?

Code of Federal Regulations, 2010 CFR

2010-04-01

... product to avoid mix-ups. You must have and follow procedures to investigate the cause(s) of the... product does not conform to specifications? 212.71 Section 212.71 Food and Drugs FOOD AND DRUG... PRACTICE FOR POSITRON EMISSION TOMOGRAPHY DRUGS (Eff. 12-12-2011) Finished Drug Product Controls and...

Development, validation, and implementation of a patient-specific Monte Carlo 3D internal dosimetry platform

NASA Astrophysics Data System (ADS)

Besemer, Abigail E.

Targeted radionuclide therapy is emerging as an attractive treatment option for a broad spectrum of tumor types because it has the potential to simultaneously eradicate both the primary tumor site as well as the metastatic disease throughout the body. Patient-specific absorbed dose calculations for radionuclide therapies are important for reducing the risk of normal tissue complications and optimizing tumor response. However, the only FDA approved software for internal dosimetry calculates doses based on the MIRD methodology which estimates mean organ doses using activity-to-dose scaling factors tabulated from standard phantom geometries. Despite the improved dosimetric accuracy afforded by direct Monte Carlo dosimetry methods these methods are not widely used in routine clinical practice because of the complexity of implementation, lack of relevant standard protocols, and longer dose calculation times. The main goal of this work was to develop a Monte Carlo internal dosimetry platform in order to (1) calculate patient-specific voxelized dose distributions in a clinically feasible time frame, (2) examine and quantify the dosimetric impact of various parameters and methodologies used in 3D internal dosimetry methods, and (3) develop a multi-criteria treatment planning optimization framework for multi-radiopharmaceutical combination therapies. This platform utilizes serial PET/CT or SPECT/CT images to calculate voxelized 3D internal dose distributions with the Monte Carlo code Geant4. Dosimetry can be computed for any diagnostic or therapeutic radiopharmaceutical and for both pre-clinical and clinical applications. In this work, the platform's dosimetry calculations were successfully validated against previously published reference doses values calculated in standard phantoms for a variety of radionuclides, over a wide range of photon and electron energies, and for many different organs and tumor sizes. Retrospective dosimetry was also calculated for various pre-clinical and clinical patients and large dosimetric differences resulted when using conventional organ-level methods and the patient-specific voxelized methods described in this work. The dosimetric impact of various steps in the 3D voxelized dosimetry process were evaluated including quantitative imaging acquisition, image coregistration, voxel resampling, ROI contouring, CT-based material segmentation, and pharmacokinetic fitting. Finally, a multi-objective treatment planning optimization framework was developed for multi-radiopharmaceutical combination therapies.

Clinical translation of a PSMA inhibitor for 99mTc-based SPECT.

PubMed

Ferro-Flores, Guillermina; Luna-Gutiérrez, Myrna; Ocampo-García, Blanca; Santos-Cuevas, Clara; Azorín-Vega, Erika; Jiménez-Mancilla, Nallely; Orocio-Rodríguez, Emmanuel; Davanzo, Jenny; García-Pérez, Francisco O

2017-05-01

Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68 Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare 99m Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ( 99m Tc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the 99m Tc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer. 99m Tc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous 68 Ga-PSMA-617scan) were acquired at 1h and 3h after 99m Tc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%. In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of 99m Tc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as 68 Ga-PSMA-617 does. The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of 99m Tc-EDDA/HYNIC-iPSMA. Copyright © 2017 Elsevier Inc. All rights reserved.

Sixth international radiopharmaceutical dosimetry symposium: Proceedings. Volume 2

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

S.-Stelson, A.T.; Stabin, M.G.; Sparks, R.B.

1999-01-01

This conference was held May 7--10 in Gatlinburg, Tennessee. The purpose of this conference was to provide a multidisciplinary forum for exchange of state-of-the-art information on radiopharmaceutical dosimetry. Attention is focused on the following: quantitative analysis and treatment planning; cellular and small-scale dosimetry; dosimetric models; radiopharmaceutical kinetics and dosimetry; and animal models, extrapolation, and uncertainty.

ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody-Drug Conjugate Treatment.

PubMed

Lamberts, Laetitia E; Menke-van der Houven van Oordt, Catharina W; ter Weele, Eva J; Bensch, Frederike; Smeenk, Michiel M; Voortman, Johannes; Hoekstra, Otto S; Williams, Simon P; Fine, Bernard M; Maslyar, Daniel; de Jong, Johan R; Gietema, Jourik A; Schröder, Carolien P; Bongaerts, Alphons H H; Lub-de Hooge, Marjolijn N; Verheul, Henk M W; Sanabria Bohorquez, Sandra M; Glaudemans, Andor W J M; de Vries, Elisabeth G E

2016-04-01

Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an (89)Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody-drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole-body distribution, and relation between uptake, response to treatment, and MSLN expression. Before DMOT4039A treatment, patients received 37 MBq (89)Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days postinjection. Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue. Eleven patients were included, 7 with pancreatic and 4 with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days postinjection. Tumor tracer uptake occurred in 37 lesions with mean SUVmax of 13.1 (±7.5) on PET 4 days postinjection, with 11.5 (±7.5) in (N= 17) pancreatic and 14.5 (±8.7) in (N= 20) ovarian cancer lesions. Within patients, a mean 2.4-fold (±1.10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen, and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to IHC. Best response to DMOT4039A was partial response in one patient. With (89)Zr-MMOT0530A-PET, pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment. ©2015 American Association for Cancer Research.

PET/MR in oncology: an introduction with focus on MR and future perspectives for hybrid imaging

PubMed Central

Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin; Zamogilnaya, Yanna; Højgaard, Liselotte; Fischer, Barbara M

2012-01-01

After more than 20 years of research, a fully integrated PET/MR scanner was launched in 2010 enabling simultaneous acquisition of PET and MR imaging. Currently, no clinical indication for combined PET/MR has been established, however the expectations are high. In this paper we will discuss some of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number of different MRI techniques, such as DWI-MR (diffusion weighted imaging MR), DCE-MR (dynamic contrast enhanced MR), MRS (MR spectroscopy) and MR for attenuation correction of PET. All MR techniques presented in this paper have shown promising results in the treatment of patients with solid tumors and could be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new tracers and drugs will be discussed. PMID:23145362

Stray cats are more frequently infected with zoonotic protists than pet cats.

PubMed

Kvac, Martin; Hofmannova, Lada; Ortega, Ynes; Holubova, Nikola; Horcickova, Michaela; Kicia, Marta; Hlaskova, Lenka; Kvetonova, Dana; Sak, Bohumil; McEvoy, John

2017-12-06

Faecal samples were collected from cats kept as pets (n = 120) and stray cats (n = 135) in Central Europe (Czech Republic, Poland and Slovakia) and screened for the presence of Cryptosporidium spp., Giardia intestinalis (Kunstler, 1882), Encephalitozoon spp. and Enterocytozoon bieneusi Desportes, Le Charpentier, Galian, Bernard, Cochand-Priollet, Lavergne, Ravisse et Modigliani, 1985 by PCR analysis of the small-subunit of rRNA (Cryptosporidium spp. and G. intestinalis) and ITS (microsporidia) genes. Sequence analysis of targeted genes revealed the presence of C. felis Iseki, 1979, G. intestinalis assemblage F, E. cuniculi Levaditi, Nicolau et Schoen, 1923 genotype II, and E. bieneusi genotype D. There was no correlation between the occurrence of detected parasites and sex, presence of diarrhoea or drug treatment (drug containing pyrantel and praziquantel). Compared to pet cats (7%), stray cats (30%) were statistically more frequently infected with protist parasites and overall may present a greater risk to human health.

Doses to medical workers operating in a PET/CT department after the use of new dynamic techniques.

NASA Astrophysics Data System (ADS)

Dalianis, K.; Kollias, G.; Malamitsi, J.; Euthimiadou, R.; Andreou, J.; Georgiou, E.; Prassopoulos, V.

2015-09-01

Since new radiopharmaceuticals are used like [18F]-fluoro-3'-deoxy-3'-L- fluorothymidine and 18F fluoromethylcholine, also new dynamic techniques of imaging are used, measurements concerning the doses to medical staff are needed. The aim of this study was to measure the effective whole body dose of the personnel and compare them with the oldest. Estimation of equivalent dose for all members of the staff was monitored with the use of TLDs badges and electronic dosimeters. The duration of the study was year 2011 (983 patients).Concerning the nurses, we measured 10% increase in the wholebody doses and that is due to the longer time they spent near the patient (dynamic protocol). For technologist we measure 15-21% increase for they come near the patient immediately after administration. We can observe that there is an increase of the doses for technologists and nurses the numbers are significantly lower than the recommended annual dose limit by Euratrom 97/43.

Nuclear Cardiology: Are We Using the Right Protocols and Tracers the Right Way?

PubMed

Dondi, Maurizio; Pascual, Thomas; Paez, Diana; Einstein, Andrew J

2017-12-01

The field of nuclear cardiology has changed considerably over recent years, with greater attention paid to safety and radiation protection issues. The wider usage of technetium-99m (Tc-99m)-labeled radiopharmaceuticals for single-photon emission computed tomography (SPECT) imaging using gamma cameras has contributed to better quality studies and lower radiation exposure to patients. Increased availability of tracers and scanners for positron emission tomography (PET) will help further improve the quality of studies and quantify myocardial blood flow and myocardial flow reserve, thus enhancing the contribution of non-invasive imaging to the management of coronary artery disease. The introduction of new instrumentation such as solid state cameras and new software will help reduce further radiation exposure to patients undergoing nuclear cardiology studies. Results from recent studies, focused on assessing the relationship between best practices and radiation risk, provide useful insights on simple measures to improve the safety of nuclear cardiology studies without compromising the quality of results.

Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging

PubMed Central

Pike, Victor W.

2017-01-01

The development of reversibly binding radioligands for imaging brain proteins in vivo, such as enzymes, neurotransmitter transporters, receptors and ion channels, with positron emission tomography (PET) is keenly sought for biomedical studies of neuropsychiatric disorders and for drug discovery and development, but is recognized as being highly challenging at the medicinal chemistry level. This article aims to compile and discuss the main considerations to be taken into account by chemists embarking on programs of radioligand development for PET imaging of brain protein targets. PMID:27087244

[11C]choline uptake in regenerating liver after partial hepatectomy or CCl4-administration.

PubMed

Sasaki, Toru

2004-02-01

To characterize [methyl-(11)C]choline ([(11)C]choline) as an oncologic PET radiopharmaceutical, [(11)C]choline uptake in regenerating livers after partial hepatectomy as a model of typical proliferating tissue and after CCl(4) insult as that of proliferating tissue with inflammation, was studied in rats. [(11)C]Choline, [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and [2-(14)C]thymidine ([(14)C]TdR) uptake was studied in regenerating rat liver after 70% partial hepatectomy or CCl(4)-administration. [(11)C]Choline uptake in regenerating liver after partial hepatectomy was significantly increased with [(14)C]TdR uptake as a marker of DNA synthesis at 18 hours after surgery. On the other hand, the uptake was not accelerated by CCl(4)-administration, though it significantly increased [(14)C]TdR uptake. There were no differences of [(11)C]choline uptake acceleration following partial hepatectomy among the three parts of the regenerating liver. [(18)F]FDG uptake was accelerated in the regenerating liver on either partial hepatectomy or CCl(4)-administration. The magnitude of the increase in [(18)F]FDG uptake in the regenerating liver induced by partial hepatectomy was greater than that for [(11)C]choline. [(11)C]Choline uptake in the liver was accelerated by partial hepatectomy, but not by CCl(4)-administration. This might be expected given that the differentiation between proliferating tissues such as tumor and inflammatory tissue was possible by [(11)C]choline-PET.

Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

NASA Astrophysics Data System (ADS)

Qin, Zhengtao

Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and 99mTc. Chapter 5 introduces a 68Ga metal chelating bioorthogonal tetrazine dextran probe for multistep imaging of a colon cancer. Chapter 6 presents the synthesis and in vivo evaluation of a Hepatocellular Carcinoma targeting PET probe 68Ga-Insulin-Dextran. Chapter 7 discusses a novel method to prepare silicon nanoparticles with great yield and size control. The last chapter 8 concludes all probes developed in this thesis and their clinical relevance.

Theranostics Using Antibodies and Antibody-Related Therapeutics.

PubMed

Moek, Kirsten L; Giesen, Danique; Kok, Iris C; de Groot, Derk Jan A; Jalving, Mathilde; Fehrmann, Rudolf S N; Lub-de Hooge, Marjolijn N; Brouwers, Adrienne H; de Vries, Elisabeth G E

2017-09-01

In theranostics, radiolabeled compounds are used to determine a treatment strategy by combining therapeutics and diagnostics in the same agent. Monoclonal antibodies (mAbs) and antibody-related therapeutics represent a rapidly expanding group of cancer medicines. Theranostic approaches using these drugs in oncology are particularly interesting because antibodies are designed against specific targets on the tumor cell membrane and immune cells as well as targets in the tumor microenvironment. In addition, these drugs are relatively easy to radiolabel. Noninvasive molecular imaging techniques, such as SPECT and PET, provide information on the whole-body distribution of radiolabeled mAbs and antibody-related therapeutics. Molecular antibody imaging can potentially elucidate drug target expression, tracer uptake in the tumor, tumor saturation, and heterogeneity for these parameters within the tumor. These data can support drug development and may aid in patient stratification and monitoring of the treatment response. Selecting a radionuclide for theranostic purposes generally starts by matching the serum half-life of the mAb or antibody-related therapeutic and the physical half-life of the radionuclide. Furthermore, PET imaging allows better quantification than the SPECT technique. This information has increased interest in theranostics using PET radionuclides with a relatively long physical half-life, such as 89 Zr. In this review, we provide an overview of ongoing research on mAbs and antibody-related theranostics in preclinical and clinical oncologic settings. We identified 24 antibodies or antibody-related therapeutics labeled with PET radionuclides for theranostic purposes in patients. For this approach to become integrated in standard care, further standardization with respect to the procedures involved is required. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

A Novel Multifunctional Theranostic Liposome Drug Delivery System: Construction, Characterization, and Multimodality MR, Near-infrared Fluorescent and Nuclear Imaging

PubMed Central

Li, Shihong; Goins, Beth; Zhang, Lujun; Bao, Ande

2012-01-01

Liposomes are effective lipid nanoparticle drug delivery systems, which can also be functionalized with non-invasive multimodality imaging agents with each modality providing distinct information and having synergistic advantages in diagnosis, monitoring of disease treatment, and evaluation of liposomal drug pharmacokinetics. We designed and constructed a multifunctional theranostic liposomal drug delivery system, which integrated multimodality magnetic resonance (MR), near-infrared (NIR) fluorescent and nuclear imaging of liposomal drug delivery, and therapy monitoring and prediction. The pre-manufactured liposomes were composed of DSPC/cholesterol/Gd-DOTADSPE/DOTA-DSPE with the molar ratio of 39:35:25:1 and having ammonium sulfate/pH gradient. A lipidized NIR fluorescent tracer, IRDye-DSPE, was effectively post-inserted into the pre-manufactured liposomes. Doxorubicin could be effectively post-loaded into the multifunctional liposomes. The multifunctional doxorubicin-liposomes could also be stably radiolabeled with 99mTc or 64Cu for single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging, respectively. MR images displayed the high resolution micro-intratumoral distribution of the liposomes in squamous cell carcinoma of head and neck (SCCHN) tumor xenografts in nude rats after intratumoral injection. NIR fluorescent, SPECT and PET images also clearly showed either the high intratumoral retention or distribution of the multifunctional liposomes. This multifunctional drug carrying liposome system is promising for disease theranostics allowing non-invasive multimodality NIR fluorescent, MR, SPECT and PET imaging of their in vivo behavior and capitalizing on the inherent advantages of each modality. PMID:22577859

The good laboratory practice and good clinical practice requirements for the production of radiopharmaceuticals in clinical research.

PubMed

De Vos, Filip J; De Decker, Mario; Dierckx, Rudi A

2005-07-01

Radiopharmaceuticals account for more than 95% of the group of sterile pharmaceutical products and should therefore be handled and produced with care. Since the introduction of the European directive, all pharmaceuticals used in clinical studies must be prepared under good manufacturing practice (GMP) conditions. This review aims to give an overview of the basic principles and guidelines for the preparation of radiopharmaceuticals. Special attention is given to the production area environment and personnel, the two basic requirements for GMP productions. Especially for the production area, two philosophies have to be combined: the cascade system of over-pressure for the production of pharmaceuticals and the under pressure system for the manufacturing of radioisotopes. Personnel should be selected based on education and regularly given special training for the handling of radioactive material. Compared to pharmaceuticals, radiopharmaceuticals have their own labels, taking into account their specific nature. Besides the standard quality control, other items for quality control of radiopharmaceuticals are also discussed in this article.

The development, past achievements, and future directions of brain PET

PubMed Central

Jones, Terry; Rabiner, Eugenii A

2012-01-01

The early developments of brain positron emission tomography (PET), including the methodological advances that have driven progress, are outlined. The considerable past achievements of brain PET have been summarized in collaboration with contributing experts in specific clinical applications including cerebrovascular disease, movement disorders, dementia, epilepsy, schizophrenia, addiction, depression and anxiety, brain tumors, drug development, and the normal healthy brain. Despite a history of improving methodology and considerable achievements, brain PET research activity is not growing and appears to have diminished. Assessments of the reasons for decline are presented and strategies proposed for reinvigorating brain PET research. Central to this is widening the access to advanced PET procedures through the introduction of lower cost cyclotron and radiochemistry technologies. The support and expertize of the existing major PET centers, and the recruitment of new biologists, bio-mathematicians and chemists to the field would be important for such a revival. New future applications need to be identified, the scope of targets imaged broadened, and the developed expertize exploited in other areas of medical research. Such reinvigoration of the field would enable PET to continue making significant contributions to advance the understanding of the normal and diseased brain and support the development of advanced treatments. PMID:22434067

Poly(2-ethyl-2-oxazoline) conjugates with doxorubicin for cancer therapy: In vitro and in vivo evaluation and direct comparison to poly[N-(2-hydroxypropyl)methacrylamide] analogues.

PubMed

Sedlacek, Ondrej; Monnery, Bryn D; Mattova, Jana; Kucka, Jan; Panek, Jiri; Janouskova, Olga; Hocherl, Anita; Verbraeken, Bart; Vergaelen, Maarten; Zadinova, Marie; Hoogenboom, Richard; Hruby, Martin

2017-11-01

We designed and synthesized a new delivery system for the anticancer drug doxorubicin based on a biocompatible hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) carrier with linear architecture and narrow molar mass distribution. The drug is connected to the polymer backbone via an acid-sensitive hydrazone linker, which allows its triggered release in the tumor. The in vitro studies demonstrate successful cellular uptake of conjugates followed by release of the cytostatic cargo. In vivo experiments in EL4 lymphoma bearing mice revealed prolonged blood circulation, increased tumor accumulation and enhanced antitumor efficacy of the PEtOx conjugate having higher molecular weight (40 kDa) compared to the lower molecular weight (20 kDa) polymer. Finally, the in vitro and in vivo anti-cancer properties of the prepared PEtOx conjugates were critically compared with those of the analogous system based on the well-established PHPMA carrier. Despite the relatively slower intracellular uptake of PEtOx conjugates, resulting also in their lower cytotoxicity, there are no substantial differences in in vivo biodistribution and anti-cancer efficacy of both classes of polymer-Dox conjugates. Considering the synthetic advantages of poly(2-alkyl-2-oxazoline)s, the presented study demonstrates their potential as a versatile alternative to well-known PEO- or PHPMA-based materials for construction of drug delivery systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inductively coupled plasma mass-spectrometric determination of platinum in excretion products of client-owned pet dogs.

PubMed

Janssens, T; Brouwers, E E M; de Vos, J P; de Vries, N; Schellens, J H M; Beijnen, J H

2015-06-01

Residues of antineoplastic drugs in canine excretion products may represent exposure risks to veterinary personnel, owners of pet dogs and other animal care-takers. The aim of this study was to measure the extent and duration of platinum (Pt) excretion in pet dogs treated with carboplatin. Samples were collected before and up to 21 days after administration of carboplatin. We used validated, ultra-sensitive, inductively coupled plasma-mass spectrometry assays to measure Pt in canine urine, faeces, saliva, sebum and cerumen. Results showed that urine is the major route of elimination of Pt in dogs. In addition, excretion occurs via faeces and saliva, with the highest amounts eliminated during the first 5 days. The amount of excreted Pt decreased over time but was still quantifiable at 21 days after administration of carboplatin. In conclusion, increased Pt levels were found in all measured excretion products up to 21 days after administration of carboplatin to pet dogs, with urine as the main route of excretion. These findings may be used to further adapt current veterinary guidelines on safe handling of antineoplastic drugs and treated animals. © 2013 Blackwell Publishing Ltd.

Biodistribution and radiation dosimetry of LMI1195: first-in-human study of a novel 18F-labeled tracer for imaging myocardial innervation.

PubMed

Sinusas, Albert J; Lazewatsky, Joel; Brunetti, Jacqueline; Heller, Gary; Srivastava, Ajay; Liu, Yi-Hwa; Sparks, Richard; Puretskiy, Andrey; Lin, Shu-fei; Crane, Paul; Carson, Richard E; Lee, L Veronica

2014-09-01

A novel (18)F-labeled ligand for the norepinephrine transporter (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine [LMI1195]) is in clinical development for mapping cardiac nerve terminals in vivo using PET. Human safety, whole-organ biodistribution, and radiation dosimetry of LMI1195 were evaluated in a phase 1 clinical trial. Twelve healthy subjects at 3 clinical sites were injected intravenously with 150-250 MBq of LMI1195. Dynamic PET images were obtained over the heart for 10 min, followed by sequential whole-body images for approximately 5 h. Blood samples were obtained, and heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. Residence times were determined from multiexponential regression of organ region-of-interest data normalized by administered activity (AA). Radiation dose estimates were calculated using OLINDA/EXM. Myocardial, lung, liver, and blood-pool standardized uptake values were determined at different time intervals. No adverse events due to LMI1195 were seen. Blood radioactivity cleared quickly, whereas myocardial uptake remained stable and uniform throughout the heart over 4 h. Liver and lung activity cleared relatively rapidly, providing favorable target-to-background ratios for cardiac imaging. The urinary bladder demonstrated the largest peak uptake (18.3% AA), followed by the liver (15.5% AA). The mean effective dose was 0.026 ± 0.0012 mSv/MBq. Approximately 1.6% AA was seen in the myocardium initially, remaining above 1.5% AA (decay-corrected) through 4 h after injection. The myocardium-to-liver ratio was approximately unity initially, increasing to more than 2 at 4 h. These preliminary data suggest that LMI1195 is well tolerated and yields a radiation dose comparable to that of other commonly used PET radiopharmaceuticals. The kinetics of myocardial and adjacent organ activity suggest that cardiac imaging should be possible with acceptable patient radiation dose. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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.

21 CFR 601.30 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... intended for therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account...

21 CFR 601.30 - Scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... intended for therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account...

21 CFR 601.30 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... intended for therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account...

21 CFR 601.30 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... intended for therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account...

21 CFR 601.30 - Scope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... intended for therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account...

Monoamine oxidase: Radiotracer chemistry and human studies

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

Fowler, Joanna S.; Logan, Jean; Shumay, Elena

Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variablesmore » which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.« less

Monoamine oxidase: Radiotracer chemistry and human studies

DOE PAGES

Fowler, Joanna S.; Logan, Jean; Shumay, Elena; ...

2015-03-01

Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variablesmore » which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.« less

Microwave and continuous flow technologies in drug discovery.

PubMed

Sadler, Sara; Moeller, Alexander R; Jones, Graham B

2012-12-01

Microwave and continuous flow microreactors have become mainstream heating sources in contemporary pharmaceutical company laboratories. Such technologies will continue to benefit from design and engineering improvements, and now play a key role in the drug discovery process. The authors review the applications of flow- and microwave-mediated heating in library, combinatorial, solid-phase, metal-assisted, and protein chemistries. Additionally, the authors provide a description of the combination of microwave and continuous flow platforms, with applications in the preparation of radiopharmaceuticals and in drug candidate development. Literature reviewed is chiefly 2000 - 2012, plus key citations from earlier reports. With the advent of microwave irradiation, reactions that normally took days to complete can now be performed in a matter of minutes. Coupled with the introduction of continuous flow microreactors, pharmaceutical companies have an easy way to improve the greenness and efficiency of many synthetic operations. The combined force of these technologies offers the potential to revolutionize discovery and manufacturing processes.

21 CFR 315.1 - Scope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account each intended use. ...

21 CFR 315.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account each intended use. ...

21 CFR 315.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account each intended use. ...

21 CFR 315.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account each intended use. ...

21 CFR 315.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account each intended use. ...

Review of nuclear pharmacy practice in hospitals

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

Kawada, T.K.; Tubis, M.; Ebenkamp, T.

1982-02-01

An operational profile for nuclear pharmacy practice is presented, and the technical and professional role of nuclear pharmacists is reviewed. Key aspects of nuclear pharmacy practice in hospitals discussed are the basic facilities and equipment for the preparation, quality control, and distribution of radioactive drug products. Standards for receiving, storing, and processing radioactive material are described. The elements of a radiopharmaceutical quality assurance program, including the working procedures, documentation systems, data analysis, and specific control tests, are presented. Details of dose preparation and administration and systems of inventory control for radioactive products are outlined.

[Human positron emission tomography with oral 11C-vinpocetine].

PubMed

Vas, Adám; Christer, Halldin; Sóvágó, Judit; Johan, Sandell; Cselényi, Zsolt; Kiss, Béla; Kárpáti, Egon; Lars, Farde; Gulyás, Balázs

2003-11-16

Positron emission tomography (PET) is a useful tool for the investigation of certain physiological changes and for the evaluation of the distribution, and receptor binding of drugs labelled with positron emitting isotopes. Vinpocetine (ethyl-apovincaminate) is a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases. In the clinical practice vinpocetine is usually administered to the patients in intravenous infusion followed by long-term oral treatment. Until presently human data describing vinpocetine's kinetics and brain distribution came from ex vivo (blood, plasma, liquor) and post mortem (brain autoradiography) measurements. The authors wished to investigate the kinetics and distribution of vinpocetine in the brain and body after oral administration with PET in order to prove, that PET is useful in the non-invasive in vivo determination of these parameters. Vinpocetine was labelled with carbon-11 and the radioactivity was measured by PET in the stomach, liver, brain, colon and kidneys in healthy male volunteers. The radioactivity in the blood and urine was also determined. After oral administration, [11C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the oral administration of the labelled drug (average maximum uptake: 0.7% of the administered total dose). Brain distribution was heterogeneous (with preferences in the thalamus, basal ganglia and occipital cortex), similar to the distribution previously reported by the authors after intravenous administration. Vinpocetine, administered orally to human volunteers, readily entered the bloodstream from the stomach and the gastrointestinal tract and thereafter passed the blood-brain barrier and entered the brain. Radioactivity from [11C]vinpocetine was also demonstrated in the kidneys and in urine. The study demonstrates that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally administered labelled drugs active in the central nervous system in the living human body.

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.

Single photon emission computed tomography and positron emission tomography imaging of multi-drug resistant P-glycoprotein--monitoring a transport activity important in cancer, blood-brain barrier function and Alzheimer's disease.

PubMed

Piwnica-Worms, David; Kesarwala, Aparna H; Pichler, Andrea; Prior, Julie L; Sharma, Vijay

2006-11-01

Overexpression of multi-drug resistant P-glycoprotein (Pgp) remains an important barrier to successful chemotherapy in cancer patients and impacts the pharmacokinetics of many important drugs. Pgp is also expressed on the luminal surface of brain capillary endothelial cells wherein Pgp functionally comprises a major component of the blood-brain barrier by limiting central nervous system penetration of various therapeutic agents. In addition, Pgp in brain capillary endothelial cells removes amyloid-beta from the brain. Several single photon emission computed tomography and positron emission tomography radiopharmaceutical have been shown to be transported by Pgp, thereby enabling the noninvasive interrogation of Pgp-mediated transport activity in vivo. Therefore, molecular imaging of Pgp activity may enable noninvasive dynamic monitoring of multi-drug resistance in cancer, guide therapeutic choices in cancer chemotherapy, and identify transporter deficiencies of the blood-brain barrier in Alzheimer's disease.

Liposomal 64Cu-PET Imaging of Anti-VEGF Drug Effects on Liposomal Delivery to Colon Cancer Xenografts.

PubMed

Blocker, Stephanie J; Douglas, Kirk A; Polin, Lisa Anne; Lee, Helen; Hendriks, Bart S; Lalo, Enxhi; Chen, Wei; Shields, Anthony F

2017-01-01

Liposomes (LP) deliver drug to tumors due to enhanced permeability and retention (EPR). LP were labeled with 64 Cu for positron emission tomography (PET) to image tumor localization. Bevacizumab (bev), a VEGF targeted antibody, may modify LP delivery by altering tumor EPR and this change can also be imaged. Objective : Assess the utility of 64 Cu-labeled LP for PET in measuring altered LP delivery early after treatment with bev. Methods: HT-29 human colorectal adenocarcinoma tumors were grown subcutaneously in SCID mice. Empty LP MM-DX-929 (Merrimack Pharmaceuticals, Inc. Cambridge, MA) were labeled with 64 CuCl 2 chelated with 4-DEAP-ATSC. Tumor-bearing mice received ~200-300 μCi of 64 Cu-MM-DX-929 and imaged with microPET. All mice were scanned before and after the treatment period, in which half of the mice received bev for one week. Scans were compared for changes in LP accumulation during this time. Initially, tissues were collected after the second PET for biodistribution measurements and histological analysis. Subsequent groups were divided for further treatment. Tumor growth following bev treatment, with or without LP-I, was assessed compared to untreated controls. Results : PET scans of untreated mice showed increased uptake of 64 Cu-MM-DX-929, with a mean change in tumor SUV max of 43.9%±6.6% (n=10) after 7 days. Conversely, images of treated mice showed that liposome delivery did not increase, with changes in SUV max of 7.6%±4.8% (n=12). Changes in tumor SUV max were significantly different between both groups (p=0.0003). Histology of tumor tissues indicated that short-term bev was able to alter vessel size. Therapeutically, while bev monotherapy, LP-I monotherapy, and treatment with bev followed by LP-I all slowed HT-29 tumor growth compared to controls, combination provided no therapeutic benefit. Conclusions: PET with tracer LP 64 Cu-MM-DX-929 can detect significant differences in LP delivery to colon tumors treated with bev when compared to untreated controls. Imaging with 64 Cu-MM-DX-929 is sensitive enough to measure drug-induced changes in LP localization which can have an effect on outcomes of treatment with LP.

In vitro and in vivo studies of an aqueous extract of Matricaria recutita (German chamomile) on the radiolabeling of blood constituents, on the morphology of red blood cells and on the biodistribution of the radiopharmaceutical sodium pertechnetate

PubMed Central

Garcia-Pinto, Angélica B.; Santos-Filho, Sebastião D.; Carvalho, Jorge J.; Pereira, Mário J. S.; Fonseca, Adenilson S.; Bernardo-Filho, Mário

2013-01-01

Background: Natural products might alter the labeling of blood constituents with technetium-99m (99mTc) and these results may be correlated with modifications of the shape of the red blood cells (RBC). The biodistribution of radiopharmaceuticals can be also altered. Objective: This investigation aimed to determine biological effects of an aqueous extract of chamomile (CE). Materials and Methods: To study the effect of the CE on the labeling of blood constituents with 99mTc, in vitro and in vivo assays were performed. The effect of the CE on the morphology of RBC was observed under light microscope. The images were acquired, processed, and the perimeter/area ratio of the RBC determined. To analyze the effect of the CE on biodistribution of the sodium pertechnetate (Na99mTcO4) in Wistar rats, these animals were treated or not with a CE. Na99mTcO4 was injected, the rats were sacrificed, the organs were removed, weighted and percentage of radioactivity/gram calculated. Result: In the in vitro experiment, the radioactivity on blood cells compartment and on insoluble fractions of plasma was diminished. The shape and the perimeter/area ratio of the RBC were altered in in vitro assays. An increase of the percentage of radioactivity of Na99mTcO4 was observed in stomach after in vivo treatment. Conclusion: These results could be due to substances of the CE or by the products of the metabolism of this extract in the animal organism. These findings are examples of drug interaction with a radiopharmaceutical, which could lead to misdiagnosis in clinical practice with unexpected consequences. PMID:24143045

188Re radiopharmaceuticals for radiosynovectomy: evaluation and comparison of tin colloid, hydroxyapatite and tin-ferric hydroxide macroaggregates

PubMed Central

Savio, Eduardo; Ures, María Cristina; Zeledón, Patricia; Trindade, Victoria; Paolino, Andrea; Mockford, Virginia; Malanga, Antonio; Fernández, Marcelo; Gaudiano, Javier

2004-01-01

Background Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and related diseases. In this study three 188Re particulate compounds were characterized according to their physico-chemical properties and their biological behavior in rabbits. The results were compared in order to establish which was the radiopharmaceutical that better fits the requirements of this kind of radiotherapy. Methods Three radiopharmaceutical formulations, tin colloid, hydroxyapatite particles (HA) and ferric hydroxide macroaggregates coated with tin colloid (FHMA), were physically characterized (number, volume and surface of the particles). For this purpose laser diffraction methodology was used. To evaluate cavity leakage of activity the following studies in New Zealand rabbits were performed: scintigraphic images for 48 hr after intraarticular injection of each radiopharmaceutical, biodistribution at 48 hr and urine samples collection during the first 24 hr post-radiopharmaceutical administration. Results Labeling procedures for 188Re-HA and 188Re-Sn-FHMA were labour intensive while 188Re-Sn was easily prepared. Furthermore, 188Re-Sn colloid offered the greatest surface area in the 2–10 microm range and was obtained with a radiochemical purity over 95%, while percentage of bound activity for 188Re-HA and 188Re-Sn-FHMA were 55% and 92% respectively. Stability was verified for the three radiopharmaceuticals for 24 hr. Scintigraphic studies and biodistribution in rabbits after intraarticular administration of the radiopharmaceuticals showed relevant activity only in the knee, this being over 90% of the residual activity in the whole body at 48 hr in every case. Renal elimination of 188Re-Sn colloid and 188Re-Sn-FHMA was detected by activity measurements in urine samples, during the first 12 hr post-radiopharmaceutical injection. The percentage of activity retained in the knee was 69.1% for 188Re-Sn colloid, 55.1% for 188Re-Sn-FHMA and 33.6% for 188Re-HA. Conclusion The 188Re-Sn colloid was easy to prepare, minimum facilities were required, was stable for 24 hr and showed minimal leakage from the joint after intraarticular injection into the rabbit's knee. Furthermore, 188Re-Sn colloid has greater retention in the knee when it is compared with the other radiopharmaceuticals, so it could provide the best therapeutic effect/absorbed dose ratio for the patient. PMID:15040807

Sorption of99mTc radiopharmaceutical compounds by soils

USGS Publications Warehouse

Jurisson, S.; Gawenis, J.; Landa, E.R.

2004-01-01

Study of the sorption of 99mTc radiopharmaceutical compounds by soils has assessed the fate of these compounds in the event of a surface spill and examined the potential of these compounds as hydrologic tracers. Sorption from deionized water, filtered Missouri River water, and artificial seawater by five surface soils was investigated. For all water types, the Tc radiopharmaceutical compounds showed greater sorption than the uncomplexed pertechnetate. The most lipophilic complexes showed the highest sorption on soils.

[Shielding effect of clinical X-ray protector and lead glass against annihilation radiation and gamma rays of 99mTc].

PubMed

Fukuda, Atsushi; Koshida, Kichiro; Yamaguchi, Ichiro; Takahashi, Masaaki; Kitabayashi, Keitarou; Matsubara, Kousuke; Noto, Kimiya; Kawabata, Chikako; Nakagawa, Hiroto

2004-12-01

Various pharmaceutical companies in Japan are making radioactive drugs available for positron emission tomography (PET) in hospitals without a cyclotron. With the distribution of these drugs to hospitals, medical check-ups and examinations using PET are expected to increase. However, the safety guidelines for radiation in the new deployment of PET have not been adequately improved. Therefore, we measured the shielding effect of a clinical X-ray protector and lead glass against annihilation radiation and gamma rays of (99m)Tc. We then calculated the shielding effect of a 0.25 mm lead protector, 1 mm lead, and lead glass using the EGS4 (Electron Gamma Shower Version 4) code. The shielding effects of 22-mm lead glass against annihilation radiation and gamma rays of (99m)Tc were approximately 31.5% and 93.3%, respectively. The clinical X-ray protector against annihilation radiation approximately doubled the skin-absorbed dose.

Simultaneous acquisition of magnetic resonance spectroscopy (MRS) data and positron emission tomography (PET) images with a prototype MR-compatible, small animal PET imager

NASA Astrophysics Data System (ADS)

Raylman, Raymond R.; Majewski, Stan; Velan, S. Sendhil; Lemieux, Susan; Kross, Brian; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.

2007-06-01

Multi-modality imaging (such as PET-CT) is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET, fused with anatomical images created by MRI, allow the correlation of form with function. Perhaps more exciting than the combination of anatomical MRI with PET, is the melding of PET with MR spectroscopy (MRS). Thus, two aspects of physiology could be combined in novel ways to produce new insights into the physiology of normal and pathological processes. Our team is developing a system to acquire MRI images and MRS spectra, and PET images contemporaneously. The prototype MR-compatible PET system consists of two opposed detector heads (appropriate in size for small animal imaging), operating in coincidence mode with an active field-of-view of ˜14 cm in diameter. Each detector consists of an array of LSO detector elements coupled through a 2-m long fiber optic light guide to a single position-sensitive photomultiplier tube. The use of light guides allows these magnetic field-sensitive elements of the PET imager to be positioned outside the strong magnetic field of our 3T MRI scanner. The PET scanner imager was integrated with a 12-cm diameter, 12-leg custom, birdcage coil. Simultaneous MRS spectra and PET images were successfully acquired from a multi-modality phantom consisting of a sphere filled with 17 brain relevant substances and a positron-emitting radionuclide. There were no significant changes in MRI or PET scanner performance when both were present in the MRI magnet bore. This successful initial test demonstrates the potential for using such a multi-modality to obtain complementary MRS and PET data.

Laser transmission welding of poly(ethylene terephthalate) and biodegradable poly(ethylene terephthalate) - Based blends

NASA Astrophysics Data System (ADS)

Gisario, Annamaria; Veniali, Francesco; Barletta, Massimiliano; Tagliaferri, Vincenzo; Vesco, Silvia

2017-03-01

Joining of Poly(Ethylene Terephthalate) PET and its biodegradable derivatives is of high relevance to ensure good productive rate, low cost and operational safety for fabrication of medical and electronic devices, sport equipments as well as for manufacturing of food and drug packaging solutions. In the present investigation, granules of PET and PETs modified by organic additives, which promote biodegradation of the polymeric chains, were prepared by extrusion compounding. The achieved granules were subsequently re-extruded to shape thin (330 μm) flat sheets. Substrates cut from these sheets were joined by Laser Transmission Welding (LTW) with a continuous wave High Power Diode Laser (cw-HPDL). First, based on a qualitative evaluation of the welded joints, the most suitable operational windows for PETs laser joining were identified. Second, characterization of the mechanical properties of the welded joints was performed by tensile tests. Accordingly, Young's modulus of PET and biodegradable PET blends was studied by Takayanagi's model and, based on the experimental results, a novel predicting analytical model derived from the mixture rule was developed. Lastly, material degradation of the polymeric joints was evaluated by FT-IR analysis, thus allowing to identify the main routes to thermal degradation of PET and, especially, of biodegradable PET blends during laser processing.

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

PubMed

Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally administered labelled CNS drugs in the living human body.

Nuclear Medicine | RadTown USA | US EPA

EPA Pesticide Factsheets

2018-05-01

>Nuclear medicine procedures can help detect and treat disease by using a small amount of radioactive material, called a radiopharmaceutical. Some radiopharmaceuticals are used with imaging equipment to detect diseases.

'Naked' radiopharmaceuticals

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

Wallner, Paul E.

The term 'naked' radiopharmaceuticals, more appropriately, 'unbound' radiopharmaceuticals, refers to any radioisotope used for clinical research or clinical purposes that is not attached to a chemical or biological carrier, and that localizes in various tissues because of a physiologic or chemical propensity/affinity, or secondary to focal anatomic placement. Although they remain useful in selected clinical circumstances, the available agents (except for Iodine-131) have been relegated to an unfortunate and somewhat secondary role. The agents remain useful and worthy of consideration for new clinical investigation and clinical use.

Simultaneous MRI and PET imaging of a rat brain

NASA Astrophysics Data System (ADS)

Raylman, Raymond R.; Majewski, Stan; Lemieux, Susan K.; Sendhil Velan, S.; Kross, Brian; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.; Zorn, Carl; Marano, Gary D.

2006-12-01

Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

Synthesis of C-functionalized TE1PA and comparison with its analogues. An example of bioconjugation on 9E7.4 mAb for multiple myeloma 64Cu-PET imaging.

PubMed

Le Bihan, Thomas; Navarro, Anne-Sophie; Le Bris, Nathalie; Le Saëc, Patricia; Gouard, Sébastien; Haddad, Ferid; Gestin, Jean-François; Chérel, Michel; Faivre-Chauvet, Alain; Tripier, Raphaël

2018-04-27

In view of the excellent copper(ii) and 64-copper(ii) complexation of a TE1PA ligand, a monopicolinate cyclam, in both aqueous medium and in vivo, we looked for a way to make it bifunctional, while maintaining its chelating properties. Overcoming the already known drawback of grafting via its carboxyl group, which is essential to the overall properties of the ligand, a TE1PA bifunctional derivative bearing an additional isothiocyanate coupling function on a carbon atom of the macrocyclic ring was synthesized. This led to an architecture that is comparable to that of other commercially available bifunctional copper(ii) chelators such as p-SCN-Bn-DOTA already used in clinical trials for 64Cu-immuno-PET imaging. The C-functionalization of TE1PA on one carbon atom in the β-N position of the cyclam backbone was successfully achieved by adapting our patented methodology to the huge challenge, allowing the regiospecific mono-N-functionalization of the unsymmetrical ligand. The obtained ligand p-SCN-Bn-TE1PA was coupled to a 9E7.4 murine antibody (mAb), an IgG2a anti CD-138 for multiple myeloma (MM) targeting. The conjugation efficiency was assessed by looking at the 64Cu radiolabeling and the radiopharmaceutical 64Cu-9E7.4-p-SCN-Bn-TE1PA immunoreactivity, and in particular by comparing with 9E7.4-p-SCN-Bn-NOTA and 9E7.4-p-SCN-Bn-DOTA obtained from commercial and presumably highly efficient chelators NOTA and DOTA, respectively. The results are quite clear, showing that p-SCN-Bn-TE1PA has a coupling rate 5 times higher and an immunoreactivity 1.5 to 2 times greater than those of its two competitors. p-SCN-Bn-TE1PA also outperforms TE1PA conjugated via its carboxylic function on the same antibody. The first 64Cu-immuno-PET preclinical study in a syngeneic model of MM was performed, confirming the good in vivo properties of 64Cu-9E7.4-p-SCN-Bn-TE1PA for PET imaging, considering the high clearance even after 24 h and the particularly important tumor-to-liver ratio that was increasing at 48 h.

Drugs in breast milk.

PubMed

Hervada, A R; Feit, E; Sagraves, R

1978-09-01

The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

‘Double cortex’ sign on FDG-PET/CT in diffuse band heterotopia

PubMed Central

Tripathi, Madhavi; Tripathi, Manjari; Kumar, Ganesh; Malhotra, Arun; Bal, Chandra Sekhar

2013-01-01

F-18 Fluorodeoxyglucose (FDG) Positron emission tomography/Computed Tomography (PET/CT) has come to play an increasingly important role for the pre-surgical evaluation of drug resistant epilepsy and complements Magnetic Resonance Imaging (MRI) in the evaluation of grey matter heterotopias. This case illustrates the characteristic pattern of metabolic abnormality in diffuse band heterotopia (DBH) which is otherwise called double cortex syndrome. The presence of metabolic activity in the heterotopic inner cortical band and in the overlying true cortex gives rise to the ‘double cortex’ sign on FDG-PET, concurrent CT provides a good anato-metabolic coregistration. PMID:24379541

Medicare and Amyloid PET Imaging: The Battle Over Evidence.

PubMed

Maschke, Karen J; Gusmano, Michael K

2017-01-01

We examine a recent dispute regarding the Centers for Medicare and Medicaid Services' (CMS) refusal to unconditionally pay for amyloid positron emission tomography (PET) imaging for Medicare beneficiaries being assessed for Alzheimer's disease. CMS will only pay for amyloid PET imaging when patients are enrolled in clinical trials that meet certain criteria. The dispute reflects CMS's willingness in certain circumstances to require effectiveness evidence that differs from the Food and Drug Administration's standard for pre-market approval of a medical intervention and reveals how stakeholders with differing perspectives about evidentiary standards have played a role in attempting to shape the Medicare program's coverage policies.

1-11C-acetate as a PET radiopharmaceutical for imaging fatty acid synthase expression in prostate cancer.

PubMed

Vāvere, Amy L; Kridel, Steven J; Wheeler, Frances B; Lewis, Jason S

2008-02-01

Although it is accepted that the metabolic fate of 1-(11)C-acetate is different in tumors than in myocardial tissue because of different clearance patterns, the exact pathway has not been fully elucidated. For decades, fatty acid synthesis has been quantified in vitro by the incubation of cells with (14)C-acetate. Fatty acid synthase (FAS) has been found to be overexpressed in prostate carcinomas, as well as other cancers, and it is possible that imaging with 1-(11)C-acetate could be a marker for its expression. In vitro and in vivo uptake experiments in prostate tumor models with 1-(11)C-acetate were performed both with and without blocking of fatty acid synthesis with either C75, an inhibitor of FAS, or 5-(tetradecyloxy)-2-furoic acid (TOFA), an inhibitor of acetyl-CoA carboxylase (ACC). FAS levels were measured by Western blot and immunohistochemical techniques for comparison. In vitro studies in 3 different prostate tumor models (PC-3, LNCaP, and 22Rv1) demonstrated blocking of 1-(11)C-acetate accumulation after treatment with both C75 and TOFA. This was further shown in vivo in PC-3 and LNCaP tumor-bearing mice after a single treatment with C75. A positive correlation between 1-(11)C-acetate uptake into the solid tumors and FAS expression levels was found. Extensive involvement of the fatty acid synthesis pathway in 1-(11)C-acetate uptake in prostate tumors was confirmed, leading to a possible marker for FAS expression in vivo by noninvasive PET.

Experience with a small animal hyperthermia ultrasound system (SAHUS): report on 83 tumours

NASA Astrophysics Data System (ADS)

Novák, P.; Moros, E. G.; Parry, J. J.; Rogers, B. E.; Myerson, R. J.; Zeug, A.; Locke, J. E.; Rossin, R.; Straube, W. L.; Singh, A. K.

2005-11-01

An external local ultrasound (US) system was developed to induce controlled hyperthermia of subcutaneously implanted tumours in small animals (e.g., mice and rats). It was designed to be compatible with a small animal positron emission tomography scanner (microPET) to facilitate studies of hyperthermia-induced tumour re-oxygenation using a PET radiopharmaceutical, but it is applicable for any small animal study requiring controlled heating. The system consists of an acrylic applicator bed with up to four independent 5 MHz planar disc US transducers of 1 cm in diameter, a four-channel radiofrequency (RF) generator, a multiple thermocouple thermometry unit, and a personal computer with custom monitoring and controlling software. Although the system presented here was developed to target tumours of up to 1 cm in diameter, the applicator design allows for different piezoelectric transducers to be exchanged and operated within the 3.5-6.5 MHz band to target different tumour sizes. Temperature feedback control software was developed on the basis of a proportional-integral-derivative (PID) approach when the measured temperatures were within a selectable temperature band about the target temperature. Outside this band, an on/off control action was applied. Perfused tissue-mimicking phantom experiments were performed to determine optimum controller gain constants, which were later employed successfully in animal experiments. The performance of the SAHUS (small animal hyperthermia ultrasound system) was tested using several tumour types grown in thighs of female nude (nu/nu) mice. To date, the system has successfully treated 83 tumours to target temperatures in the range of 41-43 °C for periods of 65 min on average.

The strange case of the [13N]NH3: validation of the production process for human use.

PubMed

Statuto, Massimo; Galli, Elisa; Bertagna, Francesco; Migliorati, Elena; Zanella, Isabella; Di Lorenzo, Diego; De Agostini, Antonio; Rodella, Carlo; Apostoli, Pietro; Caimi, Luigi; Giubbini, Raffaele; Biasiotto, Giorgio

2016-04-01

PET radiopharmaceuticals are often injected in patients before all quality controls are performed and before sterility results are available. We propose a process validation to produce very safe and pure [N]NH3 for human use. [N]NH3 was produced in the cyclotron target. Online purification was performed by anionic exchange resin. All the production steps were subjected to a sterility test. Some additional controls were added to those required by the monograph. The radiochemical yield of the syntheses was 26.3 and 61.5% corrected for decay, with a radiochemical purity of 100%. In addition to quality controls requested by the European Pharmacopeia monograph, we carefully analyzed the product for the presence of possible contaminants. Some elements, mainly metals, were found in very low amounts at concentrations in the range of ppb. The radionuclidic purity was verified. The achievement of the parameters of osmolality, by addition of saline solution to the preparation, made the analysis of chemical purity difficult and worsened the measurement of radiochemical purity by high performance liquid chromatography. Only pH control is necessary before administration to patients and therefore a safe production process was set up to prevent microbiological contamination. All phases were carefully standardized, starting from in-target production of [N]NH3, to final splitting in the syringes. Sterility tests showed no bacterial growth, indicating the safety of the production process. All our syntheses followed the monograph indications and were optimal to obtain PET imaging of a patient's myocardium.

21 CFR 570.13 - Indirect food additives resulting from packaging materials prior sanctioned for animal feed and...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food. 570.13 Section 570.13 Food and Drugs FOOD AND DRUG... FOOD ADDITIVES General Provisions § 570.13 Indirect food additives resulting from packaging materials...

21 CFR 570.13 - Indirect food additives resulting from packaging materials prior sanctioned for animal feed and...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food. 570.13 Section 570.13 Food and Drugs FOOD AND DRUG... FOOD ADDITIVES General Provisions § 570.13 Indirect food additives resulting from packaging materials...

21 CFR 570.13 - Indirect food additives resulting from packaging materials prior sanctioned for animal feed and...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food. 570.13 Section 570.13 Food and Drugs FOOD AND DRUG... FOOD ADDITIVES General Provisions § 570.13 Indirect food additives resulting from packaging materials...

21 CFR 570.13 - Indirect food additives resulting from packaging materials prior sanctioned for animal feed and...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food. 570.13 Section 570.13 Food and Drugs FOOD AND DRUG... FOOD ADDITIVES General Provisions § 570.13 Indirect food additives resulting from packaging materials...

21 CFR 570.13 - Indirect food additives resulting from packaging materials prior sanctioned for animal feed and...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Indirect food additives resulting from packaging materials prior sanctioned for animal feed and pet food. 570.13 Section 570.13 Food and Drugs FOOD AND DRUG... FOOD ADDITIVES General Provisions § 570.13 Indirect food additives resulting from packaging materials...

Neurochemical mechanisms underlying responses to psychostimulants

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

Volkow, N.D.; Fowler, J.S.; Hitzemann, R.

1994-11-01

This study employed positron emission tomography (PET) to investigate biochemical and metabolic characteristics of the brain of individuals which could put them at risk for drug addiction. It takes advantage of the normal variability between individuals in response to psychoactive drugs to investigate relation between mental state, brain neurochemistry and metabolism and the behavioral response to drugs. We discuss its use to assess if there is an association between mental state and dompaminergic reactivity in response to the psychostimulant drug methylphenidate (MP). Changes in synaptic dopamine induced by MP were evaluated with PET and [11C]raclopride, a D{sub 2} receptor radioligandmore » that is sensitive to endogenous dopamine. Methylpphenidate significantly decreased striatal [11C]raclopride binding. The study showed a correlation between the magnitude of the dopamine-induced changes by methylphenidate, and the mental state of the subjects. Subjects reporting high levels of anxiety and restlessness at baseline had larger changes in MP-induced dopamine changes than those that did not. Further investigations on the relation between an individual`s response to a drug and his/her mental state and personality as well as his neurochemical brain composition may enable to understand better differences in drug addiction vulnerability.« less

Development of Purine-Derived 18F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET

PubMed Central

2014-01-01

Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluorinated side chains have been synthesized and evaluated as putative pro-drug tracers. The tracers were designed to undergo conjugation with glutathione within the brain and hence form the corresponding MRP1 substrate tracers in situ. 6-Bromo-7-(2-[18F]fluoroethyl)purine showed good brain uptake and rapid metabolic conversion. Dynamic PET imaging demonstrated a marked difference in brain clearance rates between wild-type and mrp1 knockout mice, suggesting that the tracer can allow noninvasive assessment of MRP1 activity in vivo. PMID:24456310

PET Studies in Nonhuman Primate Models of Cocaine Abuse: Translational Research Related to Vulnerability and Neuroadaptations

PubMed Central

Gould, Robert W.; Duke, Angela N.; Nader, Michael A.

2013-01-01

The current review highlights the utility of positron emission tomography (PET) imaging to study the neurobiological substrates underlying vulnerability to cocaine addiction and subsequent adaptations following chronic cocaine self-administration in nonhuman primate models of cocaine abuse. Environmental (e.g., social rank) and sex-specific influences on dopaminergic function and sensitivity to the reinforcing effects of cocaine are discussed. Cocaine-related cognitive deficits have been hypothesized to contribute to high rates of relapse and are described in nonhuman primate models. Lastly, the long-term consequences of cocaine on neurobiology are discussed. PET imaging and longitudinal, within-subject behavioral studies in nonhuman primates have provided a strong framework for designing pharmacological and behavioral treatment strategies to aid drug-dependent treatment seekers. Non-invasive PET imaging will allow for individualized treatment strategies. Recent advances in radiochemistry of novel PET ligands and other imaging modalities can further advance our understanding of stimulant use on the brain. PMID:23458573

Prototype design of singles processing unit for the small animal PET

NASA Astrophysics Data System (ADS)

Deng, P.; Zhao, L.; Lu, J.; Li, B.; Dong, R.; Liu, S.; An, Q.

2018-05-01

Position Emission Tomography (PET) is an advanced clinical diagnostic imaging technique for nuclear medicine. Small animal PET is increasingly used for studying the animal model of disease, new drugs and new therapies. A prototype of Singles Processing Unit (SPU) for a small animal PET system was designed to obtain the time, energy, and position information. The energy and position is actually calculated through high precison charge measurement, which is based on amplification, shaping, A/D conversion and area calculation in digital signal processing domian. Analysis and simulations were also conducted to optimize the key parameters in system design. Initial tests indicate that the charge and time precision is better than 3‰ FWHM and 350 ps FWHM respectively, while the position resolution is better than 3.5‰ FWHM. Commination tests of the SPU prototype with the PET detector indicate that the system time precision is better than 2.5 ns, while the flood map and energy spectra concored well with the expected.

Safety assessment of modified terephthalate polymers as used in cosmetics.

PubMed

Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2014-01-01

The safety of 6 modified terephthalate polymers as cosmetic ingredients was assessed. These ingredients mostly function as exfoliants, bulking agents, hair fixatives, and viscosity-increasing agents-nonaqueous. Polyethylene terephthalate (PET) is used in leave-on products up to 100% and in rinse-off products up to 2%. The Cosmetic Ingredient Review Expert Panel (Panel) considered that the PET used in cosmetics is chemically equivalent to that used in medical devices. The Panel determined that the Food and Drug Administration's determination of safety of PET in several medical devices, which included human and animal safety data, can be used as the basis for the determination of safety of PET and related polymers used in cosmetics. Use studies of cosmetic eye products that contain PET demonstrated no ocular irritation or dermal sensitization. The Panel concluded that modified terephthalate polymers were safe as cosmetic ingredients in the practices of use and concentration described in this safety assessment. © The Author(s) 2014.

Bid purchasing of radiopharmaceuticals and radiopaque contrast media

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

Swanson, D.P.; Jakubowski, D.L.; Shoup, L.K.

Use of product standardization and competitive-bid purchasing for radiopharmaceuticals and radiopaque contrast media in a 1000-bed teaching hospital is described. The hospital's use of radiopharmaceuticals was reviewed, and all agents were listed with their product specifications and order quantity or frequency. Manufacturers and wholesalers were asked to submit unit prices for each of their products. Similar procedures were followed for radiopaque contrast media; wholesalers and manufacturers were asked to submit unit prices that would be guaranteed for a 12-month contract period. A nuclear pharmacist and radiologists reviewed the submitted bids and awarded contracts, basing their decisions primarily on product acceptabilitymore » and selection criteria and then on relative costs of the agents. Annual costs were reduced 16% ($16,500) for radiopharmaceuticals and 21.3% ($66,500) for radiopaque contrast media. The program also resulted in decreased inventory of radiopaque contrast media and in faster and less expensive acquisition of emergency orders. Working with the radiology department to compile a standard list of radiopharmaceuticals and radiopaque contrast media and soliciting competitive bids by vendors of these products resulted in annual savings of more than $83,000.« less

An improved synthesis and biological evaluation of a new cage-like bifunctional chelator, 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1-ylamino)methyl)benzoic acid, for 64Cu radiopharmaceuticals.

PubMed

Cai, Hancheng; Li, Zibo; Huang, Chiun-Wei; Park, Ryan; Shahinian, Anthony H; Conti, Peter S

2010-01-01

Stable attachment of (64)Cu(2+) to a targeting molecule usually requires the use of a bifunctional chelator (BFC). Sarcophagine (Sar) ligands rapidly coordinate (64)Cu(2+) within the multiple macrocyclic rings comprising the cage structure under mild conditions, providing high stability in vivo. Previously, we have designed a new versatile cage-like BFC Sar ligand, 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1-ylamino)methyl)benzoic acid (AmBaSar), for (64)Cu radiopharmaceuticals. Here we report the improved synthesis of AmBaSar, (64)Cu(2+) labeling conditions and its biological evaluation compared with the known BFC 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The AmBaSar was synthesized in four steps starting from (1,8-diamine-Sar) cobalt(III) pentachloride ([Co(DiAmSar)]Cl(5)) using an improved synthetic method. The AmBaSar was labeled with (64)Cu(2+) in pH 5.0 ammonium acetate buffer solution at room temperature, followed by analysis and purification with HPLC. The in vitro stability of (64)Cu-AmBaSar complex was evaluated in phosphate buffered saline (PBS), fetal bovine serum and mouse blood. The microPET imaging and biodistribution studies of (64)Cu-AmBaSar were performed in Balb/c mice, and the results were compared with (64)Cu-DOTA. The AmBaSar was readily prepared and characterized by MS and (1)H NMR. The radiochemical yield of (64)Cu-AmBaSar was >or=98% after 30 min of incubation at 25 degrees C. The (64)Cu-AmBaSar complex was analyzed and purified by HPLC with a retention time of 17.9 min. The radiochemical purity of (64)Cu-AmBaSar was more than 97% after 26 h of incubation in PBS or serum. The biological evaluation of (64)Cu-AmBaSar in normal mouse demonstrated renal clearance as the primary mode of excretion, with improved stability in vivo compared to (64)Cu-DOTA. The new cage-like BFC AmBaSar was prepared using a simplified synthetic method. The (64)Cu-AmBaSar complex could be obtained rapidly with high radiochemical yield (>/=98%) under mild conditions. In vitro and in vivo evaluation of AmBaSar demonstrated its promising potential for preparation of (64)Cu radiopharmaceuticals. Copyright 2010. Published by Elsevier Inc.

Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

PubMed Central

Upadhyay, Ravi Kant

2014-01-01

Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

21 CFR 1.328 - What definitions apply to this subpart?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Section 1.328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL.... Farm means a facility in one general physical location devoted to the growing and harvesting of crops...; animal feed, including pet food; food and feed ingredients and additives, including substances that...

21 CFR 1.328 - What definitions apply to this subpart?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Section 1.328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL.... Farm means a facility in one general physical location devoted to the growing and harvesting of crops...; animal feed, including pet food; food and feed ingredients and additives, including substances that...

21 CFR 1.328 - What definitions apply to this subpart?

Code of Federal Regulations, 2014 CFR

2014-04-01

... Section 1.328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL.... Farm means a facility in one general physical location devoted to the growing and harvesting of crops...; animal feed, including pet food; food and feed ingredients and additives, including substances that...

21 CFR 1.328 - What definitions apply to this subpart?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Section 1.328 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL.... Farm means a facility in one general physical location devoted to the growing and harvesting of crops...; animal feed, including pet food; food and feed ingredients and additives, including substances that...

Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM.

PubMed

Yamasaki, Tomoteru; Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Yoshida, Yuichiro; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu; Zhang, Ming-Rong

2012-04-01

In this study, we evaluate the utility of 4-[(18)F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [(18)F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V(T)) was detected in the cerebellum (V(T) = 11.5). [(18)F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [(18)F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.

Imaging of cellular proliferation in liver metastasis by [18F]fluorothymidine positron emission tomography: effect of therapy.

PubMed

Contractor, Kaiyumars; Challapalli, Amarnath; Tomasi, Giampaolo; Rosso, Lula; Wasan, Harpreet; Stebbing, Justin; Kenny, Laura; Mangar, Stephen; Riddle, Pippa; Palmieri, Carlo; Al-Nahhas, Adil; Sharma, Rohini; Turkheimer, Federico; Coombes, R Charles; Aboagye, Eric

2012-06-07

Although [(18)F]fluorothymidine positron emission tomography (FLT-PET) permits estimation of tumor thymidine kinase-1 expression, and thus, cell proliferation, high physiological uptake of tracer in liver tissue can limit its utility. We evaluated FLT-PET combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT-PET(KSF)) for detecting drug response in liver metastases. FLT-PET and computed tomography data were collected from patients with confirmed breast or colorectal liver metastases before, and two weeks after the first cycle of chemotherapy. Changes in tumor FLT-PET and FLT-PET(KSF) variables were determined. Visual distinction between tumor and normal liver was seen in FLT-PET(KSF) images. Of the 33 metastases from 20 patients studied, 26 were visible after kinetic filtering. The net irreversible retention of the tracer (Ki; from unfiltered data) in the tumor, correlated strongly with tracer uptake when the imaging variable was an unfiltered average or maximal standardized uptake value, 60 min post-injection (SUV(60,av): r = 0.9, SUV(60,max): r = 0.7; p < 0.0001 for both) and occurrence of high intensity voxels derived from FLT-PET(KSF) (r = 0.7, p < 0.0001). Overall, a significant reduction in the imaging variables was seen in responders compared to non-responders; however, the two week time point selected for imaging was too early to allow prediction of long term clinical benefit from chemotherapy. FLT-PET and FLT-PET(KSF) detected changes in proliferation in liver metastases.

Patient doses in the healing arts

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

NONE

Determinations of radiation doses to patients from x-ray procedures and radiopharmaceuticals are detailed in this chapter. Instructions are given for estimating doses from x-ray procedures. For selected pediatric procedures, the methodology developed by the Food and Drug Administration is presented. The effect of testicular and ovarian shielding is illustrated in tabular form. Estimates of the Genetically Significant Dose (GSD) and mean annual bone marrow dose from diagnostic x-ray examinations are presented for the US populations (1990). This chapter also provides tables of patient doses from selected nuclear medicine procedures and estimates of fetal doses from {sup 131}I.

Prospective Randomized Trial of Use of In-House Prepared Low-Cost Radiopharmaceutical Versus Commercial Radiopharmaceutical for Sentinel Lymph Node Biopsy in Patients with Early Stage Invasive Breast Cancer.

PubMed

Agarwal, Gaurav; Rajan, Sendhil; Mayilvaganan, Sabaretnam; Mishra, Anjali; Krishnani, Narendra; Gambhir, Sanjay

2018-05-01

The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) early breast cancers is sentinel lymph node biopsy (SLNB), which requires expensive radiopharmaceuticals for efficacious results. In-house produced low-cost radiopharmaceuticals may be the solution and have shown efficacy in earlier observational/pilot studies. We compared SLNB using in-house prepared radiopharmaceutical ( 99m Tc-Antimony-colloid) versus commercially marketed radiopharmaceutical ( 99m Tc-Sulphur-colloid) in this prospective randomized study. 78 clinically N0 early breast cancer patients (T1/2, N0 stages), undergoing primary surgery were prospectively randomized 1:1 into two groups; to receive SLNB using methylene blue, and either 99m Tc-Antimony colloid (Group-1) or   99m Tc-Sulphur colloid (Group-2). Completion axillary dissection was done in all (validation SLNB). SLNB indices were compared between the groups. The groups were comparable with regard to age, stage, tumour size, hormone receptors and HER2neu status. Cost of the in-house prepared 99m Tc-antimony colloid was 16-times lesser compared to 99m Tc-sulphur colloid. SLN identification rates (IR) in Groups 1 and 2 were 100 and 97.4% respectively, (p > 0.05). False negative rates (FNR) in Group 1 and 2 were 6.3% (1/16 patients) and 7.7% (1/13 patients), respectively, (p > 0.05). There were no major allergic reactions in either group. In this prospective randomized trial on early breast cancer patients, accuracy of SLNB was comparable using in-house prepared, 99m Tc-antimony colloid and commercially marketed 99m Tc-sulphur colloid as radiopharmaceutical, while 99m Tc-antimony colloid was much cheaper than 99m Tc-sulphur colloid.