Science.gov

Sample records for proliferation-seeking radiotracer technetium-99m-labelled

  1. Placental localization in abdominal pregnancy using technetium-99m-labeled red blood cells

    SciTech Connect

    Martin, B.; Payan, J.M.; Jones, J.S.; Buse, M.G. )

    1990-06-01

    In a patient with third trimester abdominal pregnancy with fetal demise, technetium-99m-labeled erythrocytes ({sup 99m}Tc-RBCs) localized the placenta preoperatively, after nonvisualization by ultrasonography and arteriography. Extrauterine placental localization by blood-pool imaging may be useful when ultrasound fails.

  2. Technetium-99m-labeled monoclonal antibody with preserved immunoreactivity and high in vivo stability

    SciTech Connect

    Arano, Y.; Yokoyama, A.; Furukawa, T.; Horiuchi, K.; Yahata, T.; Saji, H.; Sakahara, H.; Nakashima, T.; Koizumi, M.; Endo, K.

    1987-06-01

    Recent availability of monoclonal antibodies (MoAb) and their radiolabeling through the use of the bifunctional chelating agents (BCA) have become an alternative procedure for in vivo radioimmunodetection. Using a newly synthesized BCA, a p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), the coupling and technetium-99m (/sup 99m/Tc) labeling of monoclonal IgG against hCG were carried out. In the system presented, factors affecting stability and immunoreactivity were examined. Immunoreactivity of the original IgG (56C) was preserved by conjugating one CE-DTS molecule per molecule of IgG (56C) using the phosphorylazide method, however, /sup 99m/Tc labeling pH affected the immunoreactivity and limited the /sup 99m/Tc labeling reaction between pH 4.5 and 6.2. A screening of labeling conditions, such as pH, reaction time, and reducing agent system were then carried out. Technetium-99m-labeled IgG (56C), (/sup 99m/Tc)CE-DTS-IgG (56C), showed good stability upon incubation with mice sera and comparable mice biodistribution to that of indium-111 (/sup 111/In) DTPA-IgG (56C). Thus, these results indicate the excellent potential of CE-DTS as a BCA for labeling MoAb with /sup 99m/Tc.

  3. Technetium-99m-labeled red blood cells in the evaluation of hemangiomas of the liver in infants and children

    SciTech Connect

    Miller, J.H.

    1987-09-01

    The vascular origin lesions of the liver (capillary hemangioma/infantile hemangioendothelioma) that present in infancy or early childhood often have a typical clinical picture of hepatomegaly and congestive heart failure. These lesions rarely present as asymptomatic hepatomegaly, simulating a primary hepatic malignancy. These lesions may also simulate a primary or secondary hepatic malignancy on cross-sectional imaging or angiography. Scintigraphic evaluations with technetium-99m-labeled red blood cells offers an accurate method of identification of these lesions, and allows differentiation from other common primary or secondary hepatic masses in infancy or childhood. This scintigraphic method may also be used to follow these patients after medical, radiation, or embolization therapy. Experience with seven patients with these tumors is reported and compared with eight children with other primary or secondary liver tumors also evaluated by this method.

  4. Technetium-99m labelled macroaggregated albumin arterial catheter perfusion scintigraphy: prediction of gastrointestinal toxicity in hepatic arterial chemotherapy.

    PubMed

    Pelosi, E; Masaneo, I; Clara, R; Valetto, M R; Bellò, M; Zanon, C; Chiappino, I; Grosso, M; Mussa, A; Bisi, G

    2000-06-01

    Gastrointestinal toxicity from hepatic arterial infusion (HAI) of floxuridine in patients with liver metastases is probably due to extrahepatic perfusion or to partial escape of the drug from first-pass liver extraction. The aim of this study was to verify the role of technetium-99m-labelled macroaggregated albumin (99mTc-MAA) arterial catheter perfusion scintigraphy at the beginning of each chemotherapy cycle in decreasing or preventing gastrointestinal toxicity. We studied 167 consecutive patients. On the basis of the scintigraphic follow-up and the presence or absence of an intrahepatic arteriovenous shunt (IHAVS), we classified our patients into the following groups: (1) FU+ hepatic distribution pattern (DP), comprising 29 patients with regular scintigraphic follow-up who showed the expected distribution pattern at each control or a distribution pattern with transient alterations (extrahepatic escape) promptly reversed by the replacement of the catheter. Among these 29 patients there was one case of gastrointestinal toxicity. (2) FU- hepatic DP, comprising 128 patients who were evaluated with 99mTc-MAA only at the beginning of the first chemotherapy cycle, showed the expected distribution pattern and underwent HAI with no further scintigraphic evaluation. Among these 128 patients there were 28 cases of gastrointestinal toxicity. (3) FU+ pulmonary DP, comprising three patients with abnormally elevated pulmonary uptake (higher than 5%) and with regular scintigraphic follow-up. There were two cases of gastrointestinal toxicity among these three patients. (4) FU- pulmonary DP, comprising seven patients with abnormally elevated pulmonary uptake and without regular scintigraphic follow-up. There were four cases of gastrointestinal toxicity among these seven patients. The incidence of toxicity was significantly higher in group FU- hepatic DP than in group FU+ hepatic DP (21.9% vs 3.4%, P<0.05). In both the FU+ pulmonary DP and FU- pulmonary DP groups, the incidence of

  5. Biodistribution and kinetic studies of technetium-99m labeled Naja naja karachiensis venom via gamma scintigraphic and SPECT images.

    PubMed

    Bin-Asad, Muhammad Hassham-Hassan; e-Sabih, Durr; Ahmad, Israr; Choudhry, Bashir Ahmad; Murtaza, Ghulam; Hussain, Izhar

    2015-07-01

    Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio distribution and blood kinetics, venom was labeled with the radiotracer (technetium-99m) by following the method of direct labeling technique. Its maximum labeling percentage was 97.7% (pH 6, 100 µg stannous chloride dihydrate) which was higher than some other reported venom. Radio labeled venom was stable for more than 4 hours both in vivo (96%) and in vitro (serum 94.1%, saline 94.3%) experimentations. Intravenous doses of venom (250 µg, 0.5 mCi) were found to be evenly distributed (having R/L ratio=1.0) in all parts of sacrificed rabbits. Kidneys (53.75% activity/g) and urinary bladder (23.70% activity/g) were found with the copious quantity of injected dose of venom. Rest of all other organs was found with subsequent remaining dose of venom. Among them, lungs (14.2% activity/g), liver (4.32% activity/g), bones (1.38% activity/g), heart (0.8% activity/g), blood (0.56% activity/g), skin (0.45% activity/g), intestines (0.35% activity/g), skeleton muscles (0.3% activity/g), brain (0.14% activity/g) and stomach (0.05% activity/g) are included. After 24 hours of injection, poisoned blood of rabbits was almost cleared from venom. Gamma scintigraphic images (up to 2 hours) along with bio distribution suggest that kidneys are main organs of excretion in rabbits. Elimination started immediately after administration of venom however, possible sites for metabolism of venom are liver and lungs. More accumulation of venom in heart compared to brain suggests its higher affinity (thus possible higher toxicity) to cardiac muscles as compared to brain tissues. PMID:26142502

  6. Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy. II. In vivo validation, LDL receptor-dependent and unspecific hepatic uptake and scintigraphic results.

    PubMed

    Leitha, T; Staudenherz, A; Gmeiner, B; Hermann, M; Hüttinger, M; Dudczak, R

    1993-08-01

    The purpose of this study was to determine whether the hepatic uptake of dialysed technetium-99m labelled low-density lipoprotein (99mTc-LDL) reflects the hepatic LDL receptor activity and to what extent the non-LDL receptor-dependent 99mTc-LDL uptake by non-parenchymal cells relates to the diagnostic utility of quantitative 99mTc-LDL scintigraphy of the liver. New Zealand White rabbits and Watanabe Heritable Hyperlipidaemic rabbits, which were sacrificed 24 h after simultaneous injection of 99mTc-LDL and iodine-125 labelled LDL, were clearly discriminated by their hepatic 99mTc-LDL uptake according to their genetically different hepatic LDL receptor activity. Yet the hepatic 99mTc-LDL uptake exceeded the 125I-LDL uptake in all animals. The different hepatic uptake of the tracers was elucidated in the isolated perfused rat liver and was due to rapid intracellular degradation and the release of low molecular catabolites of 125I-LDL. In contrast, 99mTc activity was trapped in the liver. Analysis of biliary 99mTc activity provided evidence for the excretion of 99mTc-labelled apolipoprotein B. The amount of biliary excreted protein-bound 99mTc was linked to total hepatic 99mTc-LDL uptake and presumably reflected LDL receptor-mediated apolipoprotein excretion. Collagenase liver perfusion in Sprague-Dawley rats 90 min following simultaneous injection of 99mTc- and 125I-LDL and subsequent cell separation by gradient centrifugation revealed that 99mTc-LDL and 125I-LDL had a comparably low uptake into non-parenchymal cells; thus its contribution can be neglected for scintigraphic purposes. Planar scintigraphy was performed in New Zealand White and Watanabe Heritable Hyperlipidaemic rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8404953

  7. Uptake and clearance analysis of Technetium99m labelled iron oxide nanoparticles in a rabbit brain.

    PubMed

    Nadeem, Muhammad; Ahmad, Munir; Saeed, M A; Shaari, Amiruddin; Riaz, Saira; Naseem, Shahzad; Rashid, Khalid

    2015-06-01

    Nanoparticles as solid colloidal particles are extensively studied and used as anticancer drug delivery agents because of their physical properties. This current research aims to prepare water base suspension of uncoated iron oxide nanoparticles and their biodistribution study to different organs, especially the brain, by using a single photon emission computed tomography gamma camera. The water-based suspension of iron oxide nanoparticles was synthesised by a reformed version of the co-precipitation method and labelled with Tc99m for intravenous injection. The nanoparticles were injected without surface modification. X-ray diffraction (XRD), energy dispersive spectrometry (EDS) and transmission electron microscope (TEM) techniques were used for characterisation. Peaks of XRD and EDS indicate that the particles are magnetite and exist in aqueous suspension. The average diameter of iron oxide nanoparticles without any surface coating determined by TEM is 10 nm. These particles are capable of evading the reticuloendothelial system and can cross the blood-brain barrier in the rabbit. The labelling efficiency of iron oxide nanoparticles labelled with Tc99m is 85%, which is good for the biodistribution study. The sufficient amount of iron oxide nanoparticles concentration in the brain as compared with the surrounding soft tissues and their long blood retention time indicates that the water-based suspension of iron oxide nanoparticles may be an option for drug delivery into the brain. PMID:26023157

  8. Technetium-99m labeled RBC imaging in gastrointestinal bleeding from gastric leiomyoma

    SciTech Connect

    Joseph, U.A.; Jhingran, S.G.

    1988-01-01

    Tc-99m labeled RBC imaging is becoming increasingly useful in detecting gastrointestinal (GI) bleeding sites. A patient is presented who had massive GI bleeding from an unsuspected gastric leiomyoma in whom a Tc-99m sulfur colloid GI bleed image was negative. The Tc-99m labeled RBC imaging done on the day after sulfur colloid imaging revealed increased gastric activity due to active bleeding from an intragastric leiomyoma. Tc-99m labeled RBC imaging helped in early detection of the bleeding site resulting in its successful treatment. This experience also reinforces the assertion that Tc-99m labeled RBC imaging may be more helpful than Tc-99m sulfur colloid imaging in patients with upper GI or intermittent bleeding.

  9. Gallbladder visualization during technetium-99m-labeled red cell scintigraphy for gastrointestinal bleeding

    SciTech Connect

    Brill, D.R.

    1985-12-01

    Localization of radionuclide activity in the gallbladder was seen on delayed views following injection of 99mTc-labeled red blood cells for gastrointestinal bleeding in five patients. The mechanism for this unusual finding probably relates to labeling of heme, the biochemical precursor of bilirubin. All patients had had prior transfusions. All but one had severe renal impairment, probably an important predisposing factor.

  10. Protein binding studies of technetium-99m-labeled phosphine and isocyanide cationic complexes

    SciTech Connect

    Zanelli, G.D.; Cook, N.; Lahiri, A.; Ellison, D.; Webbon, P.; Woolley, G.

    1988-01-01

    Most /sup 99m/Tc/phosphine/isocyanide complexes synthesized to date show preferential uptake by the myocardium of many animal species but not in man. A new complex has been synthesized, (/sup 99m/Tc(DEPE)2(CNR)2), +(DEPIC), where R = t - butyl isocyanide, which in three animal species images the myocardium very well, but in humans it remains primarily in the blood pool. One reason for the difference in the behavior of these complexes in different species could be the characteristics of their binding to plasma proteins. The protein binding characteristics of DEPIC and two other well-known complexes have therefore been studied. Whereas the other complexes bind nonspecifically to many proteins both in animal and human plasma, DEPIC binds almost exclusively to prealbumin in humans but nonspecifically to other proteins in the rabbit. The binding sites in human plasma appear to be those normally occupied by thyroxine on the prealbumin tetramer and these can be blocked by sodium salicylate.

  11. Adrenal imaging with technetium-99m-labelled low density lipoproteins

    SciTech Connect

    Isaacsohn, J.L.; Lees, A.M.; Lees, R.S.; Strauss, H.W.; Barlai-Kovach, M.; Moore, T.J.

    1986-04-01

    Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of /sup 99m/Tc-labelled LDL injected into rabbits to obtain external images of the adrenal glands. Adrenal images of all nine rabbits tested were obtained within 18 to 21 hours after injection of /sup 99m/Tc-LDL. Seven of the rabbits were subjected to adrenal cortical suppression with dexamethasone and then all nine rabbits were imaged a second time. In the untreated animals, visualization of the adrenal glands was accompanied by normal serum cortisol concentrations and accumulation of radiolabel in the adrenals, whereas in the dexamethasone-treated animals, lack of visualization of the adrenal glands was correlated with low serum cortisols, and greatly decreased accumulation of the radionuclide in the adrenals. These findings demonstrate for the first time that LDL, when labelled with /sup 99m/Tc, can be used to evaluate adrenal cortical function by external imaging.

  12. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    NASA Astrophysics Data System (ADS)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

    2016-08-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  13. Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.

    2016-06-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  14. Imaging of inflammatory arthritis with technetium-99m-labeled IgG

    SciTech Connect

    Breedveld, F.C.; van Kroonenburgh, M.J.; Camps, J.A.; Feitsma, H.I.; Markusse, H.M.; Pauwels, E.K. )

    1989-12-01

    The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of (99mTc)albumin and (99mTc)nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with (99mTc)IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG.

  15. Pulmonary clearance of radiotracers after positive end-expiratory pressure or acute lung injury

    SciTech Connect

    Barrowcliffe, M.P.; Zanelli, G.D.; Jones, J.G.

    1989-01-01

    In anesthetized rabbits we measured clearance from lung to blood of eight aerosolized technetium-99m-labeled compounds: diethylenetriaminepentaacetate (99mTc-DTPA); cytochrome c; myoglobin; a myoglobin polymer; albumin; and anionic, cationic, and neutral dextrans of equivalent molecular size. We investigated the effect of applying positive end-expiratory pressure (PEEP) and, on a subsequent occasion, of injecting oleic acid intravenously to produce acute lung injury on the pulmonary clearance rate. Base-line clearance rates were monoexponential and varied with the molecular weights of the radiotracers. For each tracer the rate of clearance was increased a similar degree by either PEEP or oleic acid. However, with PEEP, clearance remained monoexponential, whereas after oleic acid, smaller molecular-weight radiotracers had multiexponential clearance curves. This suggests that after oleic acid the alveolar epithelium breaks down in a nonuniform fashion. We conclude that differentiation of the effect of PEEP from that of severe lung injury caused by oleic acid is not readily accomplished by either increasing the size of the tracer molecule or by varying the molecular charge.

  16. Diagnosis of sclerosing cholangitis with technetium 99m-labeled iminodiacetic acid planar and single photon emission computed tomographic scintigraphy

    SciTech Connect

    Rodman, C.A.; Keeffe, E.B.; Lieberman, D.A.; Krishnamurthy, S.; Krishnamurthy, G.T.; Gilbert, S.; Eklem, M.J.

    1987-03-01

    The purpose of this study was to determine whether /sup 99m/Tc-iminodiacetic acid planar biliary scintigraphy combined with single photon emission computed tomography could detect sclerosing cholangitis and provide additional information regarding the extent and severity of disease. Thirteen patients with sclerosing cholangitis and 13 normal control subjects were studied. Scintigraphic results were also compared with previously reported studies of patients with isolated common bile duct obstruction and with primary biliary cirrhosis. The planar scintigraphy in patients with sclerosing cholangitis showed beading or bandlike constrictions of the biliary tract corresponding to lesions seen on cholangiography, and the image pattern was distinctly different from images obtained from patients with isolated common bile duct obstruction or primary biliary cirrhosis. The single photon emission computed tomography images of the liver in patients with sclerosing cholangitis demonstrated multiple focal areas of /sup 99m/Tc-iminodiacetic acid retention, representing bile stasis in intrahepatic bile ducts. Compared to controls, the mean hepatic clearance half-time of /sup 99m/Tc-iminodiacetic acid was markedly delayed in patients with sclerosing cholangitis (6-10 times normal). Individual patients with sclerosing cholangitis had wider variation in isotope clearance half-time from three regions of the liver than patients with isolated common bile duct obstruction, consistent with regional difference in disease severity and variable impairment of bile flow. In 4 patients with sclerosing cholangitis with incomplete filling of the right and left hepatic ducts at cholangiography, planar and single photon emission computed tomographic scintigraphy provided evidence of significant intrahepatic sclerosing cholangitis.

  17. Preparation and Biodistribution of Technetium-99m-Labeled Bis- Misonidazole (MISO) as an Imaging Agent for Tumour Hypoxia.

    PubMed

    Wang, Feng; Fan, Di; Qian, Jun; Zhang, Zhe; Zhu, Jianhua; Chen, Jian

    2015-01-01

    Diagnosis of tumour hypoxia is an important aspect in determining the course of tumour therapy. In this study, we developed a novel imaging agent, (99m)Tc-ethylenedicysteine-bis-misonidazole ((99m)Tc-EC-MISO), for diagnosing tumour hypoxia. We used 2-nitroimidazole as a reactant to synthesize the amino derivative of misonidazole (MISO) in the first step and then conjugated the di-amino derivative of MISO to the chelating agent ethylenedicysteine (EC) for labelling (99m)Tc in the second step. (99m)Tc-pertechnetate ((99m)TcO4-) was reduced by tin chloride (SnCl2) for radiolabeling. The radiochemical purity was up to 94%. Tissue biodistribution and SPECT/CT imaging studies were conducted on subcutaneous gliomal tumour-bearing mice. The tumour-to-muscle ratio in the (99m)Tc-EC-MISO group increased with time, up to 4.6 at 4 h after injection. SPECT/CT imaging confirmed that the tumours could be visualized clearly with (99m)Tc-EC-MISO at 2 h. By introducing a second 2-nitroimidazole redox centre, an apparent hypoxic accumulation of this novel (99m)Tc-labeled imaging agent in the tumour was observed. PMID:25938423

  18. Quantitative conjugate imaging of iodine-123 and technetium-99m labeled brain agents in the basal ganglia

    NASA Astrophysics Data System (ADS)

    Jangha, Desiree N.

    In the research reported in this dissertation, the concept of classic conjugate imaging, a non-tomographic nuclear medicine technique, is modified such that activity of a radiopharmaceutical distribution in the striata can be estimated. A mathematical model is developed that extended the application of classic conjugate imaging to estimation of two distinct and aligned activity distributions. Error analysis of the mathematical model is performed to characterize the accuracy of the model and to benchmark the limitations of the model. Phantom experiments are performed to demonstrate the practical application of the model and to evaluate its' accuracy. A Monte Carlo simulation model of conjugate imaging of activity uptake in the striata of a primate is developed to evaluate the accuracy of the modified conjugate imaging technique as applied in the use of a dedicate conjugate imaging system. In addition, the simulation model is used to determine and characterize the shielding design of the small field of view gamma cameras comprising the dedicated conjugate imaging system. The application of scatter correction is investigated to address the downscatter of high-energy photon emissions into the photopeak window and the inclusion of scattered primary photons in the photopeak window. In this dissertation, it is shown that the modified conjugate imaging technique developed can be used to estimate accurately activity uptake in each of two distinct and aligned activity distributions. The accuracy of the technique was shown to be comparable to that of clinical quantitative SPECT. The modified conjugate imaging technique used with the dedicated conjugate imaging system may, therefore, be a viable quantitative nuclear medicine technique for activity estimation of radiopharmaceutical uptake in the striata of Parkinsonian and schizophrenic patients. The portability and low cost relative to SPECT systems make the dedicated conjugate imaging system advantageous for clinics with Parkinsonian and schizophrenic patients, who are unable to travel due to physical or mental limitation.

  19. Technetium-99m labeled red blood cells for the detection and localization of cavernous hemangiomas of the bone

    SciTech Connect

    Lenane, P.

    1986-09-01

    Labeled red blood cells (RBCs) have already been proven useful in the detection and localization of many vascular abnormalities. One such abnormality is that of a cavernous hemangioma. Cavernous hemangiomas have a distinct circulation and have been found in many areas of the body. The ability to utilize this unique circulation is important to consider when choosing a diagnostic exam. This paper reports a case demonstrating the usefulness of labeled red blood cells for the detection and localization of cavernous hemangioma of the bone. A 31-yr-old female present with a history of persistent generalized headaches for many years. About 1 yr prior to the exam, she noticed that her headaches had become more localized to the right side of her head. Physical examination revealed a palpable lump developing on the right side of her head which was sensitive to the touch. The patient was then scheduled for a CT scan to be followed by both a bone scan and a /sup 99m/Tc blood-pool scan. A flow study using 15 mCi /sup 99m/Tc labeled RBCs was performed in the right lateral position at 1.5 sec/frame for 32 frames. Immediate blood-pool images 30-min, and 1-hr delayed images were recorded.

  20. Distribution of injected technetium(99m)-labeled mesenchymal stem cells in horses with naturally occurring tendinopathy.

    PubMed

    Becerra, Patricia; Valdés Vázquez, Miguel A; Dudhia, Jayesh; Fiske-Jackson, Andrew R; Neves, Francisco; Hartman, Neil G; Smith, Roger K W

    2013-07-01

    This study aimed to investigate immediate cell survival and distribution following different administration routes of mesenchymal stem cells (MSCs) into naturally occurring tendon injuries. Ten million MSCs, labeled with technetium-99m hexamethylpropyleneamine oxime, were implanted into 13 horses with naturally occurring tendon or ligament injuries intra-lesionally, intravenously and by regional perfusion, and traced for up to 48 h using planar gamma scintigraphy. Labeling efficiencies varied between 1.8% and 18.5% (mean 9.3%). Cells were retained in the damaged area after intra-lesional administration but only 24% of cells were still present within the tendon after 24 h. After intravenous injection, cells largely distributed to the lung fields, with no detectable cells in the tendon lesions. Significant labeling of the tendon lesions was observed in 11/12 horses following regional perfusion but at a lower level to intra-lesional injection. The highest cell numbers were retained after intra-lesional injection, although with considerable cell loss, while regional perfusion may be a viable alternative for MSC delivery. Cells did not "home" to damaged tendon in large numbers after intravenous administration. Cells were detected in the lungs most frequently after intravascular administration, although with no adverse effects. Low cell retention has important implications for designing effective clinical therapies for human clinical use. PMID:23508674

  1. Radioactive technetium-99m labelling of Salmonella abortusovis for the assessment of bacterial dissemination in sheep by in vivo imaging.

    PubMed

    Perin, F; Laurence, D; Savary, I; Bernard, S; Le Pape, A

    1997-09-01

    We report the development and validation of a 99mTc-labelling technique of bacteria, applied to Salmonella abortusovis. The radioactive labelling is obtained using a pre-tinning step of the cells followed by direct incubation of S. abortusovis suspension with 99mTc-pertechnetate. Several procedures with different amounts of stannous tin (SnF2 or SnCl2) were evaluated. The selected method, respectful of bacterial viability, provided a 30% labelling yield. Viability of 99mTc-labelled bacteria was assessed by flow cytometry using rhodamine 123 and was demonstrated to be unchanged, turbidimetric measurements showing only a slight increase in the growth rate for radiolabelled cells. Incubation of 99mTc-labelled S. abortusovis with pronase, saponine and urea demonstrated labelling stability and suggested an intra-cellular localization for 99mTc. A preliminary study was also conducted in sheep to evaluate the value of the imaging of radiolabelled S. abortusovis. Spatial and temporal patterns of their in vivo dissemination in the lymphatic system after a sub-cutaneous injection were compared with control lymphoscintigraphic agents. These imaging data supported the assumption that the radioactivity detected in vivo was proportional to the number of 99mTc-labelled bacteria. PMID:9355252

  2. Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

    PubMed

    Gulec, S A; Serafini, A N; Moffat, F L; Vargas-Cuba, R D; Sfakianakis, G N; Franceschi, D; Crichton, V Z; Subramanian, R; Klein, J L; De Jager, R L

    1995-12-01

    Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response. PMID:7493345

  3. Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: Comparison with gallium-67 citrate and technetium-99m-labeled albumin

    SciTech Connect

    Rubin, R.H.; Fischman, A.J.; Needleman, M.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Hansen, W.P.; Kramer, P.B.; Strauss, H.W.

    1989-03-01

    The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with /sup 125/I or /sup 111/In was compared to that of (/sup 67/Ga)citrate and (/sup 99m/Tc)albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, (/sup 111/In)IgG showed greater accumulation at the lesion than (/sup 99m/Tc)HSA (p less than 0.01). Both (/sup 125/I)IgG and (/sup 111/In)IgG showed greater accumulation than (/sup 67/Ga)citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of (/sup 67/Ga)citrate or (/sup 99m/Tc)HSA (p less than 0.01). At all imaging times, (/sup 67/Ga)citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, (/sup 111/In)IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.

  4. Anti-CEA monoclonal antibody: technetium-99m labeling and the validation process of a scintigraphic animal model with a non-cellular antigenic implant.

    PubMed

    Sapienza, Marcelo Tatit; Marques, Fabio Luiz Navarro; Okamoto, Miriam Roseli Yoshie; Hironaka, Fausto Haruki; Buchpiguel, Carlos Alberto

    2002-07-01

    Animal models are currently used to verify the biodistribution of different radiopharmaceuticals before its clinical application in Nuclear Medicine; however, there may be some limitations. The utilization of labelled anti-tumor monoclonal antibodies (MoAb) in experimental models often requires implant of human antigens (usually a cellular implant), which cannot be achieved in immunocompetent animals. Our purpose was to label an anti-CEA MoAb with technetium-99m (99Tc) and to validate a simplified animal model using a noncellular antigenic implant. MoAb was directly labelled with 99mTc, after reduction with 2-mercaptoethanol. Labeling efficiency was checked by ascending chromatography and immunoreactive fraction was measured in plastic wells sensitized with the antigen. Radiopharmaceutical biodistribution was evaluated by dissection and scintigraphy in 5 mice groups; following the subcutaneous administration of Al(OH)3, CEA adsorbed Al(OH)2 and a control group evaluation. Labeling efficiency was 94+/-3%, which showed to be stable for 24 hr, with immunoreactive fraction above 50%. Invasive biodistribution evaluation showed prolonged blood retention, hepatic and renal uptake. A significant increase in uptake was observed in scintigraphic studies of animals with CEA-adsorbed Al(OH)3 implants compared with the other groups (p<0.05). The non-cellular antigenic implant model simplifies the pre-clinical evaluation of labelled MoAb. PMID:12146705

  5. The heritage of radiotracers for PET

    SciTech Connect

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

    1988-05-01

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

  6. The Heritage of Radiotracers for PET

    DOE R&D Accomplishments Database

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

    1988-05-01

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

  7. Principle component analysis for radiotracer signal separation.

    PubMed

    Kasban, H; Arafa, H; Elaraby, S M S

    2016-06-01

    Radiotracers can be used in several industrial applications by injecting the radiotracer into the industrial system and monitoring the radiation using radiation detectors for obtaining signals. These signals are analyzed to obtain indications about what is happening within the system or to determine the problems that may be present in the system. For multi-phase system analysis, more than one radiotracer is used and the result is a mixture of radiotracers signals. The problem is in such cases is how to separate these signals from each other. The paper presents a proposed method based on Principle Component Analysis (PCA) for separating mixed two radiotracer signals from each other. Two different radiotracers (Technetium-99m (Tc(99m)) and Barium-137m (Ba(137m))) were injected into a physical model for simulation of chemical reactor (PMSCR-MK2) for obtaining the radiotracer signals using radiation detectors and Data Acquisition System (DAS). The radiotracer signals are mixed and signal processing steps are performed include background correction and signal de-noising, then applying the signal separation algorithms. Three separation algorithms have been carried out; time domain based separation algorithm, Independent Component Analysis (ICA) based separation algorithm, and Principal Components Analysis (PCA) based separation algorithm. The results proved the superiority of the PCA based separation algorithm to the other based separation algorithm, and PCA based separation algorithm and the signal processing steps gives a considerable improvement of the separation process. PMID:26974488

  8. A Philosophy for CNS Radiotracer Design

    PubMed Central

    2015-01-01

    Conspectus Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test–retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods

  9. Monoamine oxidase: Radiotracer chemistry and human studies

    DOE PAGESBeta

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

    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

  10. Monoamine oxidase: Radiotracer chemistry and human studies

    SciTech Connect

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

    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 variables 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.

  11. Radiotracer investigation in a glass production unit.

    PubMed

    Pant, H J; Goswami, Sunil; Biswal, Jayashree; Samantaray, J S; Sharma, V K; Singhal, Sorabh

    2016-10-01

    A radiotracer investigation was carried out in a glass production unit in a glass industry. Lanthanum-140 as lanthanium oxide mixed with silica was used as a radiotracer to trace the molten glass in various sections of the unit. Residence time distributions of molten glass were measured and analyzed to identify the flow abnormities. The flow parameters such as breakthrough time, mean residence time, homogenization time, dead volume and flow patterns in different sections of the unit were obtained from the measured RTD data. The results of the investigation were used to improve and optimize the operation of the glass production unit. PMID:27474905

  12. Production of gaseous radiotracers for industrial applications.

    PubMed

    Sharma, V K; Pant, H J; Goswami, Sunil; Jagadeesan, K C; Anand, S; Chitra, S; Rana, Y S; Sharma, Archana; Singh, Tej; Gujar, H G; Dash, Ashutosh

    2016-10-01

    This paper describes prerequisite tests, analysis and the procedure for irradiation of gaseous targets and production of gaseous radioisotopes i.e. argon-41 ((41)Ar) and krypton-79 ((79)Kr) in a 100MWTh DHRUVA reactor located at Bhabha Atomic Research Center (BARC), Trombay, Mumbai, India. The produced radioisotopes will be used as radiotracers for tracing gas phase in industrial process systems. Various details and prequalification tests required for irradiation of gaseous targets are discussed. The procedure for regular production of (41)Ar and (79)Kr, and assay of their activity were standardized. Theoretically estimated and experimentally produced amounts of activities of the two radioisotopes, irradiated at identical conditions, were compared and found to be in good agreement. Based on the various tests, radiological safety analysis and standardization of the irradiation procedure, necessary approval was obtained from the competent reactor operating and safety authorities for regular production of gaseous radiotracers in DHRUVA reactor. PMID:27518216

  13. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  14. Radiotracers for PETT: new developments and perspectives

    SciTech Connect

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

    1983-01-01

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

  15. Radiotracer Technology in Mixing Processes for Industrial Applications

    PubMed Central

    Othman, N.; Kamarudin, S. K.

    2014-01-01

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

  16. Exploring the transport of plant metabolites using positron emitting radiotracers

    PubMed Central

    Kiser, Matthew R.; Reid, Chantal D.; Crowell, Alexander S.; Phillips, Richard P.; Howell, Calvin R.

    2008-01-01

    Short-lived positron-emitting radiotracer techniques provide time-dependent data that are critical for developing models of metabolite transport and resource distribution in plants and their microenvironments. Until recently these techniques were applied to measure radiotracer accumulation in coarse regions along transport pathways. The recent application of positron emission tomography (PET) techniques to plant research allows for detailed quantification of real-time metabolite dynamics on previously unexplored spatial scales. PET provides dynamic information with millimeter-scale resolution on labeled carbon, nitrogen, and water transport over a small plant-size field of view. Because details at the millimeter scale may not be required for all regions of interest, hybrid detection systems that combine high-resolution imaging with other radiotracer counting technologies offer the versatility needed to pursue wide-ranging plant physiological and ecological research. In this perspective we describe a recently developed hybrid detection system at Duke University that provides researchers with the flexibility required to carry out measurements of the dynamic responses of whole plants to environmental change using short-lived radiotracers. Following a brief historical development of radiotracer applications to plant research, the role of radiotracers is presented in the context of various applications at the leaf to the whole-plant level that integrates cellular and subcellular signals and∕or controls. PMID:19404430

  17. Radiotracers Used for the Scintigraphic Detection of Infection and Inflammation

    PubMed Central

    Tsopelas, Chris

    2015-01-01

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

  18. Vivid tumor imaging utilizing liposome-carried bimodal radiotracer.

    PubMed

    Kim, Jonghee; Pandya, Darpan N; Lee, Woonghee; Park, Jang Woo; Kim, Youn Ji; Kwak, Wonjung; Ha, Yeong Su; Chang, Yongmin; An, Gwang Il; Yoo, Jeongsoo

    2014-04-10

    By developing a new bimodal radioactive tracer that emits both luminescence and nuclear signals, a trimodal liposome for optical, nuclear, and magnetic resonance imaging is efficiently prepared. Fast clearance of the radiotracer from reticuloendothelial systems enables vivid tumor imaging with minimum background. PMID:24900846

  19. Optimization of integrated impeller mixer via radiotracer experiments.

    PubMed

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

    2014-01-01

    Radiotracer experiments are carried out in order to determine the mean residence time (MRT) as well as percentage of dead zone, V dead (%), in an integrated mixer consisting of Rushton and pitched blade turbine (PBT). Conventionally, optimization was performed by varying one parameter and others were held constant (OFAT) which lead to enormous number of experiments. Thus, in this study, a 4-factor 3-level Taguchi L9 orthogonal array was introduced to obtain an accurate optimization of mixing efficiency with minimal number of experiments. This paper describes the optimal conditions of four process parameters, namely, impeller speed, impeller clearance, type of impeller, and sampling time, in obtaining MRT and V dead (%) using radiotracer experiments. The optimum conditions for the experiments were 100 rpm impeller speed, 50 mm impeller clearance, Type A mixer, and 900 s sampling time to reach optimization. PMID:24741344

  20. Optimization of Integrated Impeller Mixer via Radiotracer Experiments

    PubMed Central

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

    2014-01-01

    Radiotracer experiments are carried out in order to determine the mean residence time (MRT) as well as percentage of dead zone, Vdead (%), in an integrated mixer consisting of Rushton and pitched blade turbine (PBT). Conventionally, optimization was performed by varying one parameter and others were held constant (OFAT) which lead to enormous number of experiments. Thus, in this study, a 4-factor 3-level Taguchi L9 orthogonal array was introduced to obtain an accurate optimization of mixing efficiency with minimal number of experiments. This paper describes the optimal conditions of four process parameters, namely, impeller speed, impeller clearance, type of impeller, and sampling time, in obtaining MRT and Vdead (%) using radiotracer experiments. The optimum conditions for the experiments were 100 rpm impeller speed, 50 mm impeller clearance, Type A mixer, and 900 s sampling time to reach optimization. PMID:24741344

  1. Microbially mediated cobalt oxidation in seawater revealed by radiotracer experiments

    SciTech Connect

    Lee, B.G.; Fisher, N.S. )

    1993-12-01

    The influence of microbial activity on Co and Mn oxidation in decomposing diatom cultures was determined with radiotracer techniques. Adding a consortium of microorganisms collected from coastal seawater (0.2-3-[mu]m size fraction) to the cultures increased particulate Co formation rates at 18[degrees]C by an order of magnitude (to 3.8% d[sup [minus]1]) and particulate Mn formation rates 3-fold (to 7.9% d[sup [minus

  2. Radiotracers for PET and SPECT studies of neurotransmitter systems

    SciTech Connect

    Fowler, J.S.

    1991-01-01

    The study of neurotransmitter systems is one of the major thrusts in emission tomography today. The current generation of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) radiotracers examines neurotransmitter properties from a number of different perspectives including their pre and post synaptic sites and the activity of the enzymes which regulate their concentration. Although the dopamine system has been the most extensively investigated, other neurotransmitter systems including the acetylcholine muscarine, serotonin, benzodiazepine, opiate, NMDA and others are also under intensive development. Enzymes involved in the synthesis and regulation of neurotransmitter concentration, for example monoamine oxidase and amino acid decarboxylase has also been probed in vivo. Medical applications range from the study of normal function and the characterization of neurotransmitter activity in neurological and psychiatric diseases and in heart disease and cancer to the study of the binding of therapeutic drugs and substances of abuse. This chapter will provide an overview of the current generation of radiotracers for PET and SPECT studies of neurotransmitter systems including radiotracer design, synthesis localization mechanisms and applications in emission tomography. 60 refs., 1 tab.

  3. PET Radiotracers: crossing the blood-brain barrier and surviving metabolism

    PubMed Central

    Pike, Victor W.

    2009-01-01

    Radiotracers for imaging protein targets in living human brain with positron emission tomography (PET) are increasingly useful in clinical research and in drug development. Such radiotracers must fulfill many criteria, among which an ability to enter brain adequately and reversibly without contamination by troublesome radiometabolites is desirable for accurate measurement of the density of a target protein (e.g., neuroreceptor, transporter, enzyme or plaque). Candidate radiotracers may fail as a result of poor passive brain entry, rejection from brain by efflux transporters or undesirable metabolism. These issues are reviewed. Emerging PET radiotracers for measuring efflux transporter function, and new strategies for ameliorating radiotracer metabolism are discussed. A growing understanding of the molecular features affecting the brain penetration, metabolism and efflux transporter sensitivity of prospective radiotracers should ultimately lead to their more rational and efficient design, and also to their greater efficacy. PMID:19616318

  4. Discharge rate measurements in a canal using radiotracer methods.

    PubMed

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

    2016-06-01

    Discharge rates of water were measured in a canal using radiotracer methods with an objective to validate the efficacy of Concrete Volute Pumps (CVPs) installed at various pumping stations along the canal. Pulse velocity and dilution methods were applied to measure the discharge rates using Iodine-131 as a radiotracer. The discharge rate measured in one of the sections of the canal using the pulse velocity method was found to be 22.5m(3)/s, whereas the discharge rates measured using the dilution method in four different sections of the canal varied from 20.27 to 20.62m(3)/s with single CVP in operation. The standard error in discharge rate measurements using dilution method ranged from ±1.1 to ±1.8%. The experimentally measured values of the discharge rate were in good agreement with the design value of the discharge rate (20m(3)/s) thus validating the performance of the CVPs used in the canal. PMID:27016711

  5. Synthesis, characterization and application of Au-198 nanoparticles as radiotracer for industrial applications.

    PubMed

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

    2016-05-01

    This paper describes synthesis and characterization of radioactive gold nanoparticles ((198)Au-NPs), and explores their utility as a radiotracer for tracing an aqueous phase in a continuous laboratory-scale bubble column at ambient conditions. The performance of the (198)Au-NPs as a radiotracer was compared with the results obtained with a conventional radiotracer i.e. bromine-82 ((82)Br) as ammonium bromide and found to be identical. A tank-in-series with backmixing model (TISBM) was used to simulate the RTDs of the aqueous phase and characterize flow in the bubble column. PMID:26897465

  6. Diffusion of radiotracers in normal and ischemic brain slices.

    PubMed

    Patlak, C S; Hospod, F E; Trowbridge, S D; Newman, G C

    1998-07-01

    Diffusion in the extracellular space (ECS) is important in physiologic and pathologic brain processes but remains poorly understood. To learn more about factors influencing tissue diffusion and the role of diffusion in solute-tissue interactions, particularly during cerebral ischemia, we have studied the kinetics of several radiotracers in control and hypoxic 450-microm hippocampal slices and in 1,050-microm thick slices that model the ischemic penumbra. Kinetics were analyzed by nonlinear least squares methods using models that combine extracellular diffusion with tissue compartments in series or in parallel. Studies with 14C-polyethylene glycol confirmed prior measurements of extracellular volume and that ECS shrinks during ischemia. Separating diffusion from transport also revealed large amounts of 45Ca that bind to or enter brain as well as demonstrating a small, irreversibly bound compartment during ischemia. The rapidity of 3H2O entry into cells made it impossible for us to distinguish intracellular from extracellular diffusion. The diffusion-compartment analysis of 3-O-methylglucose data appears to indicate that 5 mmol/L glucose is inadequate to support glycolysis fully in thick slices. Unexpectedly, the diffusion coefficient for all four tracers rose in thick slices compared with thin slices, suggesting that ECS becomes less tortuous in the penumbra. PMID:9663508

  7. The uses of radiotracers in the life sciences

    NASA Astrophysics Data System (ADS)

    Ruth, Thomas J.

    2009-01-01

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

  8. Cyclotron production of ``very high specific activity'' platinum radiotracers in No Carrier Added form

    NASA Astrophysics Data System (ADS)

    Birattari, C.; Bonardi, M.; Groppi, F.; Gini, L.; Gallorini, M.; Sabbioni, E.; Stroosnijder, M. F.

    2001-12-01

    At the "Radiochemistry Laboratory" of Accelerators and Applied Superconductivity Laboratory, LASA, several production and quality assurance methods for short-lived and high specific activity radionuclides, have been developed. Presently, the irradiations are carried out at the Scanditronix MC40 cyclotron (K=38; p, d, He-4 and He-3) of JRC-Ispra, Italy, of the European Community, while both chemical purity and specific activity determination are carried out at the TRIGA MARK II research reactor of University of Pavia and at LASA itself. In order to optimize the irradiation conditions for platinum radiotracer production, both thin- and thick-target excitation function of natOs(α,xn) nuclear reactions were measured. A very selective radiochemical separation to obtain Pt radiotracers in No Carrier Added form, has been developed. Both real specific activity and chemical purity of radiotracer, have been determined by neutron activation analysis and atomic absorption spectrometry. An Isotopic Dilution Factor (IDF) of the order of 50 is achieved.

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

    DOE R&D Accomplishments Database

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

    1984-09-01

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

  10. Measurement of leaching from simulated nuclear-waste glass using radiotracers

    SciTech Connect

    Bates, J.K.; Jardine, L.J.; Steindler, M.J.

    1982-09-01

    The use of radiotracer spiking as a method of measuring the leaching from simulated nuclear-waste glass is shown to give results comparable with other analytical detection methods. The leaching behavior of /sup 85/Sr, /sup 106/Ru, /sup 133/Ba, /sup 137/Cs, /sup 141/Ce, /sup 152/Eu, and other isotopes is measured for several defense waste glasses. These tests show that radiotracer spiking is a sensitive, multielement technique that can provide leaching data, for actual waste elements, that are difficult to obtain by other methods. Additionally, a detailed procedure is described that allows spiked glass to be prepared with a suitable distribution of radionuclides.

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

    ERIC Educational Resources Information Center

    Hurlburt, Evelyn McClelland

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

  12. [(18)F]-Group 13 fluoride derivatives as radiotracers for positron emission tomography.

    PubMed

    Chansaenpak, Kantapat; Vabre, Boris; Gabbaï, François P

    2016-02-21

    The field of (18)F chemistry is rapidly expanding because of the use of this radionuclide in radiotracers for positron emission tomography (PET). Until recently, most [(18)F]-radiotracers were generated by the direct attachment of (18)F to a carbon in the organic backbone of the radiotracer. The past decade has witnessed the emergence of a new strategy based on the formation of an (18)F-group 13 element bond. This approach, which is rooted in the field of fluoride anion complexation/coordination chemistry, has led to the development of a remarkable family of boron, aluminium and gallium [(18)F]-fluoride anion complexing agents which can be conjugated with peptides and small molecules to generate disease specific PET radiotracers. This review is dedicated to the chemistry of these group 13 [(18)F]-fluorides anion complexing agents and their use in PET. Some of the key fluoride-binding motifs covered in this review include the trifluoroborate unit bound to neutral or cationic electron deficient backbones, the BF2 unit of BODIPY dyes, and AlF or GaF3 units coordinated to multidentate Lewis basic ligands. In addition to describing how these moieties can be converted into their [(18)F]-analogs, this review also dicusses their incorporation into bioconjugates for application in PET. PMID:26548467

  13. Use of supercritical carbon dioxide fluid as a solvent for the purification of pet radiotracers

    SciTech Connect

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

    1993-12-31

    We have identified superfluid chromatography (SFC) as a promising method which could offer advantages in radiotracer purification through rapid separation, as well as, improved recovery and purity of labeled product. Using SF CO{sub 2} as the mobile phase for chromatographic separation of labeled product would eliminate the need for solvent removal from product prior to delivery.

  14. Impact of expression system on the function of the C6.5 diabody PET radiotracer.

    PubMed

    Miller, Joshua; Doss, Mohan; McQuillen, Ryan; Shaller, Calvin C; Tolner, Berend; Yu, Jian Q; Chester, Kerry; Robinson, Matthew K

    2012-06-01

    The ability of engineered antibodies to rapidly and selectively target tumors that express their target antigen makes them well suited for use as radioimaging tracers. The combination of molecular size and bivalent nature makes diabody molecules a particularly promising structure for use as radiotracers for diagnostic imaging. Previous data have demonstrated that the anti-HER2 C6.5 diabody (C6.5db) is an effective radiotracer in preclinical models of HER2-positive cancer. The aim of this study was to evaluate the impact on radiotracer performance, associated with expressing the C6.5db in the Pichia pastoris (P-C6.5db) system as compared to Escherichia coli (E. C6.5db). Glycosylation of P-C6.5db led to faster blood clearance and lower overall tumor uptake than seen with E. coli-produced C6.5db. However, P-C6.5db achieved high tumor/background ratios that are critical for effective imaging. Dosimetry measurements determined in this study for both (124)I-P-C6.5db and (124)I-E-C6.5db suggest that they are equivalent to other radiotracers currently being administered to patients. PMID:22383295

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

    PubMed

    Kuchar, Manuela; Mamat, Constantin

    2015-01-01

    The majority of pharmaceuticals and other organic compounds incorporating radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Metabolic degradation of these drugs is commonly caused by a system of enzymes of low substrate specificity requirement, which is present mainly in the liver, but drug metabolism may also take place in the kidneys or other organs. Thus, radiotracers and all other pharmaceuticals are faced with enormous challenges to maintain their stability in vivo highlighting the importance of their structure. Often in practice, such biologically active molecules exhibit these properties in vitro, but fail during in vivo studies due to obtaining an increased metabolism within minutes. Many pharmacologically and biologically interesting compounds never see application due to their lack of stability. One of the most important issues of radiotracers development based on fluorine-18 is the stability in vitro and in vivo. Sometimes, the metabolism of (18)F-radiotracers goes along with the cleavage of the C-F bond and with the rejection of [(18)F]fluoride mostly combined with high background and accumulation in the skeleton. This review deals with the impact of radiodefluorination and with approaches to stabilize the C-F bond to avoid the cleavage between fluorine and carbon. PMID:26404227

  16. Radiolabeled multimeric cyclic RGD peptides as integrin alphavbeta3 targeted radiotracers for tumor imaging.

    PubMed

    Liu, Shuang

    2006-01-01

    Integrin alphavbeta3 plays a significant role in tumor angiogenesis and is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic (RGD) tripeptide sequence. These include vitronectin, fibronectin, fibrinogen, lamin, collagen, Von Willibrand's factor, osteoponin, and adenovirus particles. Integrin alphavbeta3 is expressed at low levels on epithelial cells and mature endothelial cells, but it is overexpressed on the activated endothelial cells of tumor neovasculature and some tumor cells. The highly restricted expression of integrin alphavbeta3 during tumor growth, invasion, and metastasis presents an interesting molecular target for both early detection and treatment of rapidly growing solid tumors. In the past decade, many radiolabeled linear and cyclic RGD peptide antagonists have been evaluated as the integrin alphavbeta3 targeted radiotracers. Significant progress has been made on their use for imaging tumors of different origin by single photon emission computed tomography (SPECT) or positron emission tomography (PET) in several tumor-bearing animal models. [18F]Galacto-RGD is under clinical investigation as the first integrin alphavbeta3 targeted radiotracer for noninvasive visualization of the activated integrin alphavbeta3 in cancer patients. This review will focus on the radiolabeled multimeric cyclic RGD peptides (dimers and tetramers) useful as radiotracers to image the tumor integrin alphavbeta3 expression by SPECT and PET, and some fundamental aspects for the development of integrin alphavbeta3 targeted radiotracers. These include the choice of radionuclide and bifunctional chelators, selection of targeting biomolecules, and factors influencing the integrin alphavbeta3 binding affinity and tumor uptake, as well as different approaches for modification of radiotracer pharmacokinetics. PMID:17009846

  17. In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use.

    PubMed

    Eriksson, Olof; Laughlin, Maren; Brom, Maarten; Nuutila, Pirjo; Roden, Michael; Hwa, Albert; Bonadonna, Riccardo; Gotthardt, Martin

    2016-07-01

    Radiotracer imaging is characterised by high in vivo sensitivity, with a detection limit in the lower picomolar range. Therefore, radiotracers represent a valuable tool for imaging pancreatic beta cells. High demands are made of radiotracers for in vivo imaging of beta cells. Beta cells represent only a small fraction of the volume of the pancreas (usually 1-3%) and are scattered in the tiny islets of Langerhans throughout the organ. In order to be able to measure a beta cell-specific signal, one has to rely on highly specific tracer molecules because current in vivo imaging technologies do not allow the resolution of single islets in humans non-invasively. Currently, a considerable amount of preclinical data are available for several radiotracers and three are under clinical evaluation. We summarise the current status of the evaluation of these tracer molecules and put forward recommendations for their further evaluation. PMID:27094935

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

    SciTech Connect

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

    1981-01-01

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

  19. Development of a Fluorinated Class-I HDAC Radiotracer Reveals Key Chemical Determinants of Brain Penetrance.

    PubMed

    Strebl, Martin G; Wang, Changning; Schroeder, Frederick A; Placzek, Michael S; Wey, Hsiao-Ying; Van de Bittner, Genevieve C; Neelamegam, Ramesh; Hooker, Jacob M

    2016-05-18

    Despite major efforts, our knowledge about many brain diseases remains remarkably limited. Epigenetic dysregulation has been one of the few leads toward identifying the causes and potential treatments of psychiatric disease over the past decade. A new positron emission tomography radiotracer, [(11)C]Martinostat, has enabled the study of histone deacetylase in living human subjects. A unique property of [(11)C]Martinostat is its profound brain penetrance, a feature that is challenging to engineer intentionally. In order to understand determining factors for the high brain-uptake of Martinostat, a series of compounds was evaluated in rodents and nonhuman primates. The study revealed the major structural contributors to brain uptake, as well as a more clinically relevant fluorinated HDAC radiotracer with comparable behavior to Martinostat, yet longer half-life. PMID:26675505

  20. (68) Ga-labeled Ciprofloxacin Conjugates as Radiotracers for Targeting Bacterial Infection.

    PubMed

    Satpati, Drishty; Arjun, Chanda; Krishnamohan, Repaka; Samuel, Grace; Banerjee, Sharmila

    2016-05-01

    With an aim of developing a bacteria-specific molecular imaging agent, ciprofloxacin has been modified with a propylamine spacer and linked to two common bifunctional chelators, p-SCN-Bz-DOTA and p-SCN-Bz-NOTA. The two ciprofloxacin conjugates, CP-PA-SCN-Bz-DOTA (1) and CP-PA-SCN-Bz-NOTA (2), were radiolabeled with (68)Ga in >90% radiochemical yield and were moderately stable in vitro for 4 h. The efficacy of (68)Ga-1 and (68)Ga-2 has been investigated in vitro in Staphylococcus aureus cells where bacterial binding of the radiotracers (0.9-1.0% for (68)Ga-1 and 1.6-2.3% for (68)Ga-2) could not be blocked in the presence of excess amount of unlabeled ciprofloxacin. However, uptake of radiotracers in live bacterial cells was significantly higher (p < 0.01) than that in non-viable bacterial cells. Bacterial infection targeting efficacy of (68)Ga-1 and (68)Ga-2 was tested in vivo in rats where the infected muscle-to-inflamed muscle ((68)Ga-1: 2 ± 0.2, (68)Ga-2: 3 ± 0.5) and infected muscle-to-normal muscle ratios ((68)Ga-1: 3 ± 0.4, (68)Ga-2: 6.6 ± 0.8) were found to improve at 120 min p.i. Fast blood clearance and renal excretion was observed for both the radiotracers. The two (68)Ga-labeled infection targeting radiotracers could discriminate between bacterial infection and inflammation in vivo and are worthy of further detailed investigation as infection imaging agents at the clinical level. PMID:26647765

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

    PubMed

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

    2015-09-01

    Various types of systems are used to control the reactivity and shutting down of a nuclear reactor during emergency and routine shutdown operations. Injection of boron solution (borated water) into the core of a reactor is one of the commonly used methods during emergency operation. A pilot-scale poison tank was designed and fabricated to simulate injection of boron poison into the core of a reactor along with coolant water. In order to design a full-scale poison tank, it was desired to characterize flow of liquid from the tank. Residence time distribution (RTD) measurement and analysis was adopted to characterize the flow dynamics. Radiotracer technique was applied to measure RTD of aqueous phase in the tank using Bromine-82 as a radiotracer. RTD measurements were carried out with two different modes of operation of the tank and at different flow rates. In Mode-1, the radiotracer was instantaneously injected at the inlet and monitored at the outlet, whereas in Mode-2, the tank was filled with radiotracer and its concentration was measured at the outlet. From the measured RTD curves, mean residence times (MRTs), dead volume and fraction of liquid pumped in with time were determined. The treated RTD curves were modeled using suitable mathematical models. An axial dispersion model with high degree of backmixing was found suitable to describe flow when operated in Mode-1, whereas a tanks-in-series model with backmixing was found suitable to describe flow of the poison in the tank when operated in Mode-2. The results were utilized to scale-up and design a full-scale poison tank for a nuclear reactor. PMID:26057343

  2. Cerenkov Luminescence Endoscopy: Improved Molecular Sensitivity with β−-Emitting Radiotracers

    PubMed Central

    Carpenter, Colin M.; Ma, Xiaowei; Liu, Hongguang; Sun, Conroy; Pratx, Guillem; Wang, Jing; Gambhir, Sanjiv S.; Xing, Lei; Cheng, Zhen

    2015-01-01

    Cerenkov luminescence endoscopy (CLE) is an optical technique that captures the Cerenkov photons emitted from highly energetic moving charged particles (β+ or β−) and can be used to monitor the distribution of many clinically available radioactive probes. A main limitation of CLE is its limited sensitivity to small concentrations of radiotracer, especially when used with a light guide. We investigated the improvement in the sensitivity of CLE brought about by using a β− radiotracer that improved Cerenkov signal due to both higher β-particle energy and lower γ noise in the imaging optics because of the lack of positron annihilation. Methods The signal-to-noise ratio (SNR) of 90Y was compared with that of 18F in both phantoms and small-animal tumor models. Sensitivity and noise characteristics were demonstrated using vials of activity both at the surface and beneath 1 cm of tissue. Rodent U87MG glioma xenograft models were imaged with radiotracers bound to arginine-glycine-aspartate (RGD) peptides to determine the SNR. Results γ noise from 18F was demonstrated by both an observed blurring across the field of view and a more pronounced fall-off with distance. A decreased γ background and increased energy of the β particles resulted in a 207-fold improvement in the sensitivity of 90Y compared with 18F in phantoms. 90Y-bound RGD peptide produced a higher tumor-to-background SNR than 18F in a mouse model. Conclusion The use of 90Y for Cerenkov endoscopic imaging enabled superior results compared with an 18F radiotracer. PMID:25300598

  3. Positron detection in silica monoliths for miniaturised quality control of PET radiotracers.

    PubMed

    Tarn, Mark D; Maneuski, Dzmitry; Alexander, Richard; Brown, Nathaniel J; O'Shea, Val; Pimlott, Sally L; Pamme, Nicole; Archibald, Stephen J

    2016-06-01

    We demonstrate the use of the miniaturised Medipix positron sensor for detection of the clinical PET radiotracer, [(68)Ga]gallium-citrate, on a silica-based monolith, towards microfluidic quality control. The system achieved a far superior signal-to-noise ratio compared to conventional sodium iodide-based radio-HPLC detection and allowed real-time visualisation of positrons in the monolith. PMID:27029282

  4. Investigation of liquid phase axial dispersion in Taylor bubble flow by radiotracer residence time distribution analysis

    NASA Astrophysics Data System (ADS)

    Chughtai, I. R.; Iqbal, W.; Din, G. U.; Mehdi, S.; Khan, I. H.; Inayat, M. H.; Jin, J. H.

    2013-05-01

    A gas-liquid Taylor bubble flow occurs in small diameter channels in which gas bubbles are separated by slugs of pure liquid. This type of flow regime is well suited for solid catalyzed gas-liquid reactors in which the reaction efficiency is a strong function of axial dispersion in the regions of pure liquid. This paper presents an experimental study of liquid phase axial dispersion in a Taylor bubble flow developed in a horizontal tube using high speed photography and radiotracer residence time distribution (RTD) analysis. A parametric dependence of axial dispersion on average volume fraction of gas phase was also investigated by varying the relative volumetric flow rates of the two phases. 137mBa produced from a 137Cs/137mBa radionuclide generator was used as radiotracer and measurements were made using the NaI(Tl) scintillation detectors. Validation of 137mBa in the form of barium chloride as aqueous phase radiotracer was also carried out. Axial Dispersion Model (ADM) was used to simulate the hydrodynamics of the system and the results of the experiment are presented. It was observed that the system is characterized by very high values of Peclet Number (Pe˜102) which reveals an approaching plug type flow. The experimental and model estimated values of mean residence times were observed in agreement with each other.

  5. Carbon-11 labeling of CP-126,998*: A radiotracer for in vivo studies of acetylcholinesterase

    SciTech Connect

    Musachio, J.L.; Flesher, J.E.; Scheffel, U.

    1996-05-01

    The study of acetylcholinesterase (AChE) via PET is of interest as reduced activity of this enzyme has been observed in Alzheimer`s disease. Our efforts to develop a radiotracer for mapping of AChE have focused on the N-benzylpiperidine benzisoxazole, CP-126,998, a highly potent (IC{sub 50}=0.48 nm) and selective inhibitor of AChE. High specific activity [C-11] CP-126,998 was synthesized (14 - 24% radiochemical yield, non-decay corrected) by treatment of the desmethyl precursor, CP-118,954, with [C-11] methyl iodide and tetrabutylammonium hydroxide in DMF. In vivo studies with [C-11] CP-126,998 in mice show that this radiotracer displays highest uptake in striatum (6.2 %ID/g), a brain region known to be rich in AChE. The (striatum-cerebellum)/cerebellar radioactivity ratio reached a maximum of 4.3 at 30 min postinjection, and this ratio decreased to 2.4 at 120 min. .Radiotracer binding was saturable in vivo by pretreatment with CP-118,954. Pretreatment of mice with diisopropylfluorophosphate (4 mg/kg i.p.), a known AChE inhibitor, significantly inhibited binding in striatum in a dose-dependent manner. Initial results suggest that [C-11] CP-126,998 may prove useful as a marker for the study of AChE in humans via PET.

  6. SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for β-cell mass assessments

    PubMed Central

    Eter, Wael A.; Parween, Saba; Joosten, Lieke; Frielink, Cathelijne; Eriksson, Maria; Brom, Maarten; Ahlgren, Ulf; Gotthardt, Martin

    2016-01-01

    Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, 111In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of 111In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers. PMID:27080529

  7. A system to obtain radiotracer uptake data simultaneously with NMR spectra in a high field magnet

    SciTech Connect

    Buchanan, M.; Marsden, P.K.; Garlick, P.B.; Mielke, C.H.

    1996-06-01

    Radiotracer techniques and nuclear magnetic resonance (NMR) spectroscopy are two complementary methods that are widely used to investigate cardiac metabolism. The authors have now developed a novel gamma photon detector system that will operate within a wide-bore, 9.4 T magnet. With this detector in position, it is possible to acquire radiotracer uptake data while simultaneously collecting NMR spectra. The advantages of this new system are firstly, that it enables correlations between radiotracer and NMR data to be made on individual rat hearts, and secondly that it allows the number of experiments required to obtain results of statistical significance to be greatly decreased. The extension of the system, to one in which positron emission tomography (PET) and magnetic resonance imaging (MRI) data are acquired simultaneously, clearly has enormous clinical potential. The detector consists of a NaI(Tl) scintillation crystal coupled to a magnetic field-insensitive photomultiplier tube by a 72.5 cm long, acrylic light pipe. This detector configuration satisfies the two, conflicting requirements of the crystal being near the sample, and thus in a high magnetic field, and the PMT being in a low magnetic field and thus far from the sample. In this paper the authors present the technical specifications of their new system together with what they believe are the first examples of simultaneously acquired NMR spectra and {sup 18}F-fluorodeoxyglucose ({sup 18}FDG) uptake data, obtained from isolated, perfused rat hearts.

  8. SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for β-cell mass assessments.

    PubMed

    Eter, Wael A; Parween, Saba; Joosten, Lieke; Frielink, Cathelijne; Eriksson, Maria; Brom, Maarten; Ahlgren, Ulf; Gotthardt, Martin

    2016-01-01

    Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, (111)In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of (111)In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers. PMID:27080529

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

    PubMed

    Zhou, Yang; Chakraborty, Sudipta; Liu, Shuang

    2011-01-01

    The integrin family is a group of transmembrane glycoprotein comprised of 19 α- and 8 β-subunits that are expressed in 25 different α/β heterodimeric combinations on the cell surface. Integrins play critical roles in many physiological processes, including cell attachment, proliferation, bone remodeling, and wound healing. Integrins also contribute to pathological events such as thrombosis, atherosclerosis, tumor invasion, angiogenesis and metastasis, infection by pathogenic microorganisms, and immune dysfunction. Among 25 members of the integrin family, the α(v)β(3) is studied most extensively for its role of tumor growth, progression and angiogenesis. In contrast, the α(IIb)β(3 )is expressed exclusively on platelets, facilitates the intercellular bidirectional signaling ("inside-out" and "outside-in") and allows the aggregation of platelets during vascular injury. The α(IIb)β(3) plays an important role in thrombosis by its activation and binding to fibrinogen especially in arterial thrombosis due to the high blood flow rate. In the resting state, the α(IIb)β(3) on platelets does not bind to fibrinogen; on activation, the conformation of platelet is altered and the binding sites of α(IIb)β(3 )are exposed for fibrinogen to crosslink platelets. Over the last two decades, integrins have been proposed as the molecular targets for diagnosis and therapy of cancer, thrombosis and other diseases. Several excellent review articles have appeared recently to cover a broad range of topics related to the integrin-targeted radiotracers and their nuclear medicine applications in tumor imaging by single photon emission computed tomography (SPECT) or a positron-emitting radionuclide for positron emission tomography (PET). This review will focus on recent developments of α(v)β(3)-targeted radiotracers for imaging tumors and the use of α(IIb)β(3)-targeted radiotracers for thrombosis imaging, and discuss different approaches to maximize the targeting capability of

  10. The Expanding Reach of Environmental Radiotracers - New Chronometers And More Sensitive Measurements

    NASA Astrophysics Data System (ADS)

    Aalseth, C.

    2015-12-01

    Radiotracers in the environment provide powerful tools for understanding environmental processes. Viewed as an age continuum, methods using shorter-lived radionuclides (<100 y) like 3H, 7Be, 85Kr, 134Cs, and 137Cs generally rely on measurements of radioactive decay in samples. Methods using longer-lived radionuclides (>1,000 y) like 10Be, 14C, 36Cl, and 81Kr generally rely on atom-counting measurements such as accelerator mass spectrometry. Significant challenges exist in the age range between 100 and 1,000 years where useful radiotracers are difficult to measure by either method and can have very low abundance. These challenges are being addressed with more sensitive measurements using both atom counting and radioactive decay, extending the reach of established radiotracers as well as adding new chronometers. Improvements in atom-counting methods will be reviewed; the practicality of using 81Kr (abundance ~5×10-13 in atmospheric krypton) for age-dating old aquifers has been established and current work focuses on improving sample utilization efficiency to allow smaller samples to be measured. Better efficiency also brings lower-abundance isotopes within reach, for example 39Ar. Improvements in radioactive decay counting will be reviewed; these take advantage of ultra-pure materials to achieve lower backgrounds and are adding new age-dating reach to the environmental science tool-set with intermediate half-life radionuclides, for example 32Si for sediment cores. These methods also improve sensitivity for established radiotracers like 3H and will allow smaller samples to be measured, allowing specific processes to be traced. For example, using 3H as an indicator of carbon cycling through organic compounds in soil systems. Progress in both atom counting and decay counting is expanding the use of 39Ar for age-dating aquifers, measuring ocean mixing, and age-dating younger glacial ice. Argon-39 is a challenging intermediate-age radiotracer (269-year half-life) with

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

    PubMed

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

    2015-06-01

    Inflammatory and infectious diseases are one of the most common causes of mortality and morbidity. This paper aimed to prepare and to evaluate the ability of long-circulating and pH-sensitive liposomes, trapping a radiotracer, to identify inflamed focus. The physicochemical characterization of freeze-dried liposomes, using glucose as cryoprotectant, showed 80% of the vesicles with adequate mean diameter and good vesicle size homogeneity. Radiotracer encapsulation percentage in liposomes was 10.65%, of which 4.88% was adsorbed on the surface of the vesicles. Furthermore, liposomes presented positive zeta potential. Freeze-dried liposomes, stored for 180 days at 4 degrees C, did not show significant changes in the mean diameter, indicating good stability. Free radiotracer and radiolabeled liposomes were injected into inflammation focus-bearing rats, and ex-vivo biodistribution studies and scintigraphic images were performed. Results showed that radiopharmaceutical, free and encapsulated into liposomes, were able to identify the inflamed site. Target/non-target ratios, obtained by scintigraphic images, were greater than 1.5 at all investigated times. Data did not show significant differences between the free radiotracer and radiolabeled liposomes. Results suggest that this liposomal preparation could be employed as an alternative procedure for inflamed site detection by means of scintigraphic images. However, as the radiotracer is adsorbed onto the liposome surface by electrostatic forces, it is suggested that a neutral radiopharmaceutical be used to confirm the potential of this formulation as a scintigraphic probe for inflammation/infection detection. PMID:26369024

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

    NASA Astrophysics Data System (ADS)

    Dooraghi, Alex Abreu

    Positron Emission Tomography (PET) is a noninvasive molecular imaging tool that requires the use of a radioactive compound or radiotracer which targets a molecular pathway of interest. We have developed and employed three beta particle radiation detection systems to advance PET. Specifically, the goals of these systems are to: 1. Automate dispensing of solutions containing a positron emitting isotope. 2. Monitor radioactivity on-chip during synthesis of a positron emitting radiotracer. 3. Assay cellular uptake on-chip of a positron emitting radiotracer. Automated protocols for measuring and dispensing solutions containing radioisotopes are essential not only for providing an optimum environment for radiation workers, but also to ensure a quantitatively accurate workflow. For the first project, we describe the development and performance of a system for automated radioactivity distribution of beta particle emitting radioisotopes such as fluorine-18 (F-18). Key to the system is a radiation detector in-line with a peristaltic pump. The system demonstrates volume accuracy within 5 % for volumes of 20 muL or greater. When considering volumes of 20 muL or greater, delivered radioactivity is in agreement with the requested radioactivity as measured with the dose calibrator. The integration of the detector and pump leads to a flexible system that can accurately dispense solutions containing F-18 in radioactivity concentrations directly produced from a cyclotron (~ 0.1-1 mCi/muL), to low activity concentrations intended for preclinical mouse scans (~ 1-10 muCi/muL), and anywhere in between. Electrowetting on dielectric (EWOD) is an attractive microfluidic platform for batch synthesis of PET radiotracers. Visualization of radioisotopes on-chip is critical for synthesis optimization and technological development. For the second project, we describe the development and performance of a Cerenkov/real-time imaging system for PET radiotracer synthesis on EWOD. We also investigate

  13. Prediction of water vapor transport rates across polyvinylchloride packaging systems using a novel radiotracer method

    SciTech Connect

    Wood, R.W.; Mulski, M.J.; Kuu, W.Y. )

    1990-09-01

    A radiotracer method is used to study the transport properties of water vapor in polyvinylchloride (PVC), a plastic commonly used in the packaging of parenteral solutions. Water vapor transport across a PVC film appears to be Fickian in nature. Using the steady-state solution of Fick's second law and the permeability coefficient of water vapor across the PVC film obtained using the described method, the predicted water vapor transport rate (WVTR) for a parenteral solution packaged in PVC is in reasonable agreement with actual WVTR as determined by weight loss under precisely controlled conditions.

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

    SciTech Connect

    Hooker, J.M.; Hooker, J.M.; Kim, S.W.; Reibel, A.T.; Alexoff, D.; Xu, Y.; Shea, C.

    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.

  15. Combination of sealed source and radiotracer technique to understand malfunctioning in a chemical plant.

    PubMed

    Yelgaonkar, V N; Jayakumar, T K; Singh, Sudhir; Sharma, M K

    2009-01-01

    Pure terphthalic acid (PTA) is produced by the oxidation of paraxylene in an oxidation reactor of a PTA plant. Since the reaction is exothermic, the temperature rises above 210 degrees C. Vapours formed in the reactor are passed through a series of heat exchangers and the cooled liquid is fed back to the reactor, which flows to the reactor by gravity. In one of the heat exchangers, improper flow distribution in the inlet and outlet pipelines was suspected. Maldistribution of flow in the heat exchanger was also suspected. Gamma scanning of the pipelines and a radiotracer experiment were carried out in the heat exchanger to study the malfunctioning. A specially fabricated pipe scanner was used to scan both 24in diameter and 16in diameter pipelines. From gamma scanning of the pipelines mostly on the bends, absence of the full bore flow of the liquid was observed. Presence of vapours along with the liquid could be obstructing the liquid flow, thereby causing the malfunctioning. A radiotracer experiment was also carried out to study the flow pattern in the heat exchanger. From the experiment, mean residence time of the heat exchanger was estimated as 470s, which theoretically should be about 102s. It indicated that the flow is decelerated in the heat exchanger because of the presence of vapour lock in the tube side. PMID:19318264

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

    DOEpatents

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

    1998-09-15

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

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

    DOEpatents

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

    1998-09-15

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

  18. Effect of Cyclosporin A on the Uptake of D3-Selective PET Radiotracers in Rat Brain

    PubMed Central

    Tu, Zhude; Li, Shihong; Xu, Jinbin; Chu, Wenhua; Jones, Lynne A.; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    Introduction Four benzamide analogs having a high affinity and selectivity for D3 versus D2 receptors were radiolabeled with 11C or 18F for in vivo evaluation. Methods Precursors were synthesized and the four D3 selective benzamide analogs were radiolabeled. The tissue distribution and brain uptake of the four compounds were evaluated in control rats and rats pretreated with cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux transporters that contribute to the blood brain barrier. MicroPET imaging was carried out for [11C]6 in a control and a cyclosporin A pre-treated rat. Results All four compounds showed low brain uptake in control rats at 5 and 30 min post-injection; despite recently reported rat behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following administration of cyclosporin A, increased brain uptake was observed with all four PET radiotracers at both 5 and 30 min post-i.v. injection. An increase in brain uptake following modulation/inhibition of the ABC transporters was also observed in the microPET study. Conclusions These data suggest that D3 selective conformationally-flexible benzamide analogs which contain a N-2-methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other ABC transporters expressed at the blood-brain barrier, and that PET radiotracers containing this pharmacophore may display low brain uptake in rodents due to the action of these efflux transporters. PMID:21718948

  19. Improving the stability of peptidic radiotracers by the introduction of artificial scaffolds: which structure element is most useful?

    PubMed

    Bacher, Lisa; Fischer, Gabriel; Litau, Shanna; Schirrmacher, Ralf; Wängler, Björn; Baller, Marko; Wängler, Carmen

    2015-08-01

    Peptidic radiotracers are highly potent substances for the specific in vivo imaging of various biological targets with Single Photon Emission Computed Tomography and Positron Emission Tomography. However, some radiolabeled peptides such as bombesin analogs were shown to exhibit only a limited stability, hampering a successful target visualization. One option to positively influence the stability of radiolabeled peptides is the introduction of certain artificial molecular scaffolds. In order to comparatively assess the influence of different structure elements on the stability of radiolabeled peptides and to identify those structure elements being most useful for peptide radiotracer stabilization, several monomeric and dimeric bombesin derivatives were synthesized, exhibiting differing molecular designs and the chelator NODAGA for (68) Ga-labeling. The radiolabeled peptides were evaluated regarding their in vitro stability in human serum to determine the influence of the introduced molecular scaffolds on the peptides' serum stabilities. The results of the evaluations showed that the introduction of scaffold structures and the overall molecular design have a substantial impact on the stabilities of the resulting peptidic radiotracers. But besides some general trends found using certain scaffold structures, the obtained results point to the necessity to empirically assess their influence on stability for each susceptible peptidic radiotracer individually. PMID:26219022

  20. Experimental observation of silver and gold penetration into dental ceramic by means of a radiotracer technique

    SciTech Connect

    Moya, F.; Payan, J.; Bernardini, J.; Moya, E.G.

    1987-12-01

    A radiotracer technique was used to study silver and gold diffusion into dental porcelain under experimental conditions close to the real conditions in prosthetic laboratories for porcelain bakes. It was clearly shown that these non-oxidizable elements were able to diffuse into the ceramic as well as oxidizable ones. The penetration depth varied widely according to the element. The ratio DAg/DAu was about 10(3) around 850 degrees C. In contrast to gold, the silver diffusion rate was high enough to allow silver, from the metallic alloy, to be present at the external ceramic surface after diffusion into the ceramic. Hence, the greening of dental porcelains baked on silver-rich alloys could be explained mainly by a solid-state diffusion mechanism.

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

    PubMed

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

    2015-04-13

    With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to favour brain penetration, and which demonstrated specific binding to the target of interest. Adding additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific binding, we were able to design a radioiodinated compound [(125)I]14. This compound exhibited a binding affinity value of 0.094 nM toward human 5-HT4R and a high selectivity over other serotonin receptor subtypes (5-HTR). In vivo SPECT imaging studies and competition experiments demonstrated that the decreased lipophilicity (in comparison with our previously reported compounds 4 and 5) allowed a more specific labelling of the 5-HT4R brain-containing regions. PMID:25778994

  2. Working against time: Rapid radiotracer synthesis and imaging the human brain

    SciTech Connect

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

    1997-04-01

    In this Account, the authors describe some advances in radiotracer chemistry which have made it possible to probe the chemical anatomy of the human brain while working within a very restricted time scale. Though we highlight research from our laboratory, it is important to emphasize that advances in PET brain imaging have come from many laboratories throughout the world. Thus, for a more comprehensive treatment of PET technology the reader is referred to textbooks and review articles cited in this Account. Since many of the milestones in delineating biochemical transformations and the movement of drugs in the human brain have involved radiosynthesis with carbon-11 and fluorine-18, we focus on these two isotopes. 50 refs., 6 figs., 1 tab.

  3. Distribution of nickel hydroxide in sintered nickel plaques measured by radiotracer method during electroimpregnation

    SciTech Connect

    Ng, P.K.; Schneider, E.W.

    1986-01-01

    Sintered nickel positive electrodes were prepared by electroimpregnating nickel hydroxide inside a porous nickel plaque in a nickel nitrate solution. The distribution of nickel hydroxide inside the plaque was measured using a radio-tracer method with /sup 63/Ni as the radioactivity source. Autoradiography and ..beta.. counting were used to follow qualitative and quantitative distributions, respectively, of the pore filling process. Relatively uniform distribution was observed at low current density, and the precipitation of Ni(OH)/sub 2/ extends to the center of the plaque. At high current density, most of the Ni(OH)/sub 2/ aggregated in the region just underneath the plaque surface, causing a somewhat nonuniform distribution. Nickel hydroxide also precipitates heavily on the surface of the plaque at high current density, reducing the penetration of electrolyte to the inside of the plaque.

  4. In vivo distribution of liposome encapsulated hemoglobin studied with imaging radiotracers. Progress report

    SciTech Connect

    Phillips, W.T.

    1992-12-01

    This project has as its objective the development of radiotracer imaging technology to follow the in vivo circulation and organ deposition of liposome encapsulated hemoglobin (LEH). LEH will be labeled with technetium-99m or indium-111 and infused into small animals to monitor any in vivo differences between different LEH formulations. These studies will be correlated with any hematological and pathological changes associated with LEH treatment. Development of such non-invasive monitoring techniques may lead to significant cost effective manufacturing and formulation improvements, and ultimately a more efficacious LEH product. The development of this elegant labeling technique should make it possible to study the effect of various LEH modifications on biodistribution non-invasively in primates and humans.

  5. Radiotracers for Cardiac Sympathetic Innervation: Transport Kinetics and Binding Affinities for the Human Norepinephrine Transporter

    PubMed Central

    Raffel, David M.; Chen, Wei; Jung, Yong-Woon; Jang, Keun Sam; Gu, Guie; Cozzi, Nicholas V.

    2013-01-01

    Introduction Most radiotracers for imaging of cardiac sympathetic innervation are substrates of the norepinephrine transporter (NET). The goal of this study was to characterize the NET transport kinetics and binding affinities of several sympathetic nerve radiotracers, including [11C]-(−)-meta-hydroxyephedrine, [11C]-(−)-epinephrine, and a series of [11C]-labeled phenethylguanidines under development in our laboratory. For comparison, the NET transport kinetics and binding affinities of some [3H]-labeled biogenic amines were also determined. Methods Transport kinetics studies were performed using rat C6 glioma cells stably transfected with the human norepinephrine transporter (C6-hNET cells). For each radiolabeled NET substrate, saturation transport assays with C6-hNET cells measured the Michaelis-Menten transport constants Km and Vmax for NET transport. Competitive inhibition binding assays with homogenized C6-hNET cells and [3H]mazindol provided estimates of binding affinities (KI) for NET. Results Km, Vmax and KI values were determined for each NET substrate with a high degree of reproducibility. Interestingly, C6-hNET transport rates for ‘tracer concentrations’ of substrate, given by the ratio Vmax/Km, were found to be highly correlated with neuronal transport rates measured previously in isolated rat hearts (r2 = 0.96). This suggests that the transport constants Km and Vmax measured using the C6-hNET cells accurately reflect in vivo transport kinetics. Conclusion The results of these studies show how structural changes in NET substrates influence NET binding and transport constants, providing valuable insights that can be used in the design of new tracers with more optimal kinetics for quantifying regional sympathetic nerve density. PMID:23306137

  6. Process for preparing radiopharmaceuticals

    DOEpatents

    Barak, Morton; Winchell, Harry S.

    1977-01-04

    A process for the preparation of technetium-99m labeled pharmaceuticals is disclosed. The process comprises initially isolating technetium-99m pertechnetate by adsorption upon an adsorbent packing in a chromatographic column. The technetium-99m is then eluted from the packing with a biological compound to form a radiopharmaceutical.

  7. Evaluation of LeVeen-shunt patency using Tc-99m labelled macroaggregated albumin.

    PubMed

    Adil, Allah Rakha; Waqar, Amin

    2005-12-01

    A LeVeen peritoneo-venous shunt is placed for intractable ascites. Determination of obstruction site in the shunt tube is a difficult problem. We describe a simple nuclear medicine method using 111MBq (3mCi) of Technetium-99m labeled macro-aggregated albumin injected intraperitoneally. PMID:16398982

  8. Development of gamma emitting receptor binding radiotracers for imaging the brain and pancreas. Final technical progress report, March 1, 1988--May 31, 1993

    SciTech Connect

    1996-01-01

    This document give paragraph synopses of results in research on brain and pancreas imaging, using radiotracers. General catagories of research included chemistry, pharmacology, imaging physics, and kinetic modeling. A list of publications is included

  9. Measurement of residence time distribution of liquid phase in an industrial-scale continuous pulp digester using radiotracer technique.

    PubMed

    Sheoran, Meenakshi; Goswami, Sunil; Pant, Harish J; Biswal, Jayashree; Sharma, Vijay K; Chandra, Avinash; Bhunia, Haripada; Bajpai, Pramod K; Rao, S Madhukar; Dash, A

    2016-05-01

    A series of radiotracer experiments was carried out to measure residence time distribution (RTD) of liquid phase (alkali) in an industrial-scale continuous pulp digester in a paper industry in India. Bromine-82 as ammonium bromide was used as a radiotracer. Experiments were carried out at different biomass and white liquor flow rates. The measured RTD data were treated and mean residence times in individual digester tubes as well in the whole digester were determined. The RTD was also analyzed to identify flow abnormalities and investigate flow dynamics of the liquid phase in the pulp digester. Flow channeling was observed in the first section (tube 1) of the digester. Both axial dispersion and tanks-in-series with backmixing models preceded with a plug flow component were used to simulate the measured RTD and quantify the degree of axial mixing. Based on the study, optimum conditions for operating the digester were proposed. PMID:26896681

  10. Chemistry and biology of radiotracers that target changes in sympathetic and parasympathetic nervous systems in heart disease.

    PubMed

    Eckelman, William C; Dilsizian, Vasken

    2015-06-01

    Following the discovery of the sympathetic and parasympathetic nervous system, numerous adrenoceptor drugs were radiolabeled and potent radioligands were prepared in order to image the β-adrenergic and the muscarinic systems. But the greatest effort has been in preparing noradrenaline analogs, such as norepinephrine, (11)C-metahydroxyephedrine, and (123)I-metaiodobenzylguanidine that measure cardiac sympathetic nerve varicosities. Given the technical and clinical challenges in designing and validating targeted adrenoceptor-binding radiotracers, namely the heavily weighted flow dependence and relatively low target-to-background ratio, both requiring complicated mathematic analysis, and the inability of targeted adrenoceptor radioligands to have an impact on clinical care of heart disease, the emphasis has been on radioligands monitoring the norepinephrine pathway. The chemistry and biology of such radiotracers, and the clinical and prognostic impact of these innervation imaging studies in patients with heart disease, are examined. PMID:26033907

  11. Establishment of a trimodality analytical platform for tracing, imaging and quantification of gold nanoparticles in animals by radiotracer techniques.

    PubMed

    Chen, Chien-Hung; Lin, Fong-Sian; Liao, Wei-Neng; Liang, Sanching L; Chen, Min-Hua; Chen, Yo-Wen; Lin, Wan-Yu; Hsu, Ming-Hua; Wang, Mei-Ya; Peir, Jinn-Jer; Chou, Fong-In; Chen, Ching-Ya; Chen, Sih-Yu; Huang, Su-Chin; Yang, Mo-Hsiung; Hueng, Dueng-Yuan; Hwu, Yeukuang; Yang, Chung-Shi; Chen, Jen-Kun

    2015-01-01

    This study aims to establish a (198)Au-radiotracer technique for in vivo tracing, rapid quantification, and ex vivo visualization of PEGylated gold nanoparticles (GNPs) in animals, organs and tissue dissections. The advantages of GNPs lie in its superior optical property, biocompatibility and versatile conjugation chemistry, which are promising to develop diagnostic probes and drug delivery systems. (198)Au is used as a radiotracer because it simultaneously emits beta and gamma radiations with proper energy and half-life; therefore, (198)Au can be used for bioanalytical purposes. The (198)Au-tagged radioactive gold nanoparticles ((198)Au-GNPs) were prepared simply by irradiating the GNPs in a nuclear reactor through the (197)Au(n,γ)(198)Au reaction and subsequently the (198)Au-GNPs were subjected to surface modification with polyethylene glycol to form PEGylated (198)Au-GNPs. The (198)Au-GNPs retained physicochemical properties that were the same as those of GNP before neutron irradiation. Pharmacokinetic and biodisposition studies were performed by intravenously injecting three types of (198)Au-GNPs with or without PEGylation into mice; the γ radiation in blood specimens and dissected organs was then measured. The (198)Au-radiotracer technique enables rapid quantification freed from tedious sample preparation and shows more than 95% recovery of injected GNPs. Clinical gamma scintigraphy was proved feasible to explore spatial- and temporal-resolved biodisposition of (198)Au-GNPs in living animals. Moreover, autoradiography, which recorded beta particles from (198)Au, enabled visualizing the heterogeneous biodisposition of (198)Au-GNPs in different microenvironments and tissues. In this study, the (198)Au-radiotracer technique facilitated creating a trimodality analytical platform for tracing, quantifying and imaging GNPs in animals. PMID:25424326

  12. Semi-automated lab-on-a-chip for dispensing GA-68 radiotracers

    SciTech Connect

    Weinberg, Irving

    2014-03-12

    We solved a technical problem that is hindering American progress in molecular medicine, and restricting US citizens from receiving optimal diagnostic care. Specifically, the project deals with a mother/daughter generator of positron-emitting radiotracers (Ge-68/Ga-68). These generator systems are approved in Europe but cannot be used in the USA, because of safety issues related to possible breakthrough of long-lived Ge-68 (mother) atoms. Europeans have demonstrated abilities of Ga-68-labeled radiotracers to image cancer foci with high sensitivity and specificity, and to use such methods to effectively plan therapy.The USA Food and Drug Administration (FDA) and Nuclear Regulatory Commission (NRC) have taken the position that every patient administration of Ga-68 should be preceded by an assay demonstrated that Ge-68 breakthrough is within acceptable limits. Breakthrough of parent elements is a sensitive subject at the FDA, as evidenced by the recent recall of Rb-82 generators due to inadvertent administrations of Sr-82. Commercially, there is no acceptable rapid method for assaying breakthrough of Ge-68 prior to each human administration. The gamma emissions of daughter Ga-68 have higher energies than the parent Ge-68, so that the shielding assays typically employed for Mo-99/Tc-99m generators cannot be applied to Ga-68 generators. The half-life of Ga-68 is 68 minutes, so that the standard 10-half-life delay (used to assess breakthrough in Sr-82/Rb-82 generators) cannot be applied to Ga-68 generators. As a result of the aforementioned regulatory requirements, Ga-68 generators are sold in the USA for animal use only.The American clinical community’s inability to utilize Ga-68 generators impairs abilities to treat patients domestically, and puts the USA at a disadvantage in developing exportable products. The proposed DOE project aimed to take advantage of recent technological advances developed for lab-on-a-chip (LOC) applications. Based on our experiences

  13. Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.

    PubMed

    Mossine, Andrew V; Brooks, Allen F; Jackson, Isaac M; Quesada, Carole A; Sherman, Phillip; Cole, Erin L; Donnelly, David J; Scott, Peter J H; Shao, Xia

    2016-05-18

    Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [(11)C]CO2 followed by an intermolecular cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported. PMID:27043721

  14. Development of indazolylpyrimidine derivatives as high-affine EphB4 receptor ligands and potential PET radiotracers.

    PubMed

    Ebert, Kristin; Wiemer, Jens; Caballero, Julio; Köckerling, Martin; Steinbach, Jörg; Pietzsch, Jens; Mamat, Constantin

    2015-09-01

    Due to their essential role in the pathogenesis of cancer, members of the Eph (erythropoietin-producing hepatoma cell line-A2) receptor tyrosine kinase family represent promising candidates for molecular imaging. Thus, the development and preparation of novel radiotracers for the noninvasive imaging of the EphB4 receptor via positron emission tomography (PET) is described. First in silico investigations with the indazolylpyrimidine lead compound which is known to be highly affine to EphB4 were executed to identify favorable labeling positions for an introduction of fluorine-18 to retain the affinity. Based on this, reference compounds as well as precursors were developed and labeled with carbon-11 and fluorine-18, respectively. For this purpose, a protecting group strategy essentially had to be generated to prevent unwanted methylation and to enable the introduction of fluorine-18. Further, a convenient radiolabeling strategy using [(11)C]methyl iodide was established which afforded the isotopically labeled radiotracer in 30-35% RCY (d.c.) which is identical with the original inhibitor molecule. A spiro ammonium precursor was prepared for radiolabeling with fluorine-18. Unfortunately, the labeling did not lead to the desired (18)F-radiotracer under the chosen conditions. PMID:26189032

  15. Production of 191Pt radiotracer with high specific activity for the development of preconcentration procedures

    NASA Astrophysics Data System (ADS)

    Parent, M.; Strijckmans, K.; Cornelis, R.; Dewaele, J.; Dams, R.

    1994-04-01

    A radiotracer of Pt with suitable nuclear characteristics and high specific activity (i.e. activity to mass ratio) is a powerful tool when developing preconcentration methods for the determination of base-line levels of Pt in e.g. environmental and biological samples. Two methods were developed for the production of 191Pt with high specific activity and radionuclidic purity: (1) via the 190Pt(n, γ) 191Pt reaction by neutron irradiation of enriched Pt in a nuclear reactor at high neutron fluence rate and (2) via the 191Ir(p, n) 191Pt reaction by proton irradiation of natural Ir with a cyclotron, at an experimentally optimized proton energy. For the latter method it was necessary to separate Pt from the Ir matrix. For that reason either liquid-liquid extraction with dithizone or adsorption chromatography were used. The yields, the specific activities and the radionuclidic purities were experimentally determined as a function of the proton energy and compared to the former method. The half-life of 191Pt was accurately determined to be 2.802 ± 0.025 d.

  16. Fluorinated quinazolinones as potential radiotracers for imaging kinesin spindle protein expression.

    PubMed

    Holland, Jason P; Jones, Michael W; Cohrs, Susan; Schibli, Roger; Fischer, Eliane

    2013-01-15

    Anti-mitotic anti-cancer drugs offer a potential platform for developing new radiotracers for imaging proliferation markers associated with the mitosis-phase of the cell-cycle. One interesting target is kinesin spindle protein (KSP)-an ATP-dependent motor protein that plays a vital role in bipolar spindle formation. In this work we synthesised a range of new fluorinated-quinazolinone compounds based on the structure of the clinical candidate KSP inhibitor, ispinesib, and investigated their properties in vitro as potential anti-mitotic agents targeting KSP expression. Anti-proliferation (MTT and BrdU) assays combined with additional studies including fluorescence-assisted cell sorting (FACS) analysis of cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Additional studies using confocal fluorescence microscopy showed that these compounds induce M-phase arrest via monoaster spindle formation. Structural studies revealed that compound 20-(R) is the most potent fluorinated-quinazolinone inhibitor of KSP and represents a suitable lead candidate for further studies on designing (18)F-radiolabelled agents for positron-emission tomography (PET). PMID:23245569

  17. Calcium carbonate scaling kinetics determined from radiotracer experiments with calcium-47

    SciTech Connect

    Turner, C.W.; Smith, D.W.

    1998-02-01

    The deposition of calcium carbonate is one of the principal modes of fouling of the heat-transfer surface of a fresh-water-cooled heat exchanger. The deposition rate of calcium carbonate on a heat-transfer surface has been measured using a calcium-47 radiotracer and compared to the measured rate of thermal fouling. The crystalline phase of calcium carbonate that precipitates depends on the degree of supersaturation at the heat-transfer surface, with aragonite precipitating at higher supersaturations and calcite precipitating at lower supersaturations. Whereas the mass deposition rates were constant with time, the thermal fouling rates decreased throughout the course of each experiment as a result of densification of the deposit. It is proposed that the densification was driven by the temperature gradient across the deposit together with the retrograde solubility of calcium carbonate. The temperature dependence of the deposition rate yielded an activation energy of 79 {+-} 4 kJ/mol for the precipitation of calcium carbonate on a heat-transfer surface.

  18. Investigating phosphorus uptake in anoxic and sulfidic surface sediments with 33P radiotracer experiments

    NASA Astrophysics Data System (ADS)

    Dijkstra, Nikki; Kraal, Peter; Gonzalez, Santiago; Slomp, Caroline

    2016-04-01

    Phosphorus (P) is a key nutrient for marine organisms. Enhanced P availability in the water column can fuel algal blooms and the development of bottom water anoxia. Recently, it was suggested that micro-organisms in sediments overlain by anoxic and sulfidic bottom waters might take up dissolved P and form Fe(II)-P minerals, thereby enhancing P removal. In this study, we investigated the uptake of P in surface sediments with 33P radiotracer experiments. The sediments were recovered from the anoxic and sulfidic deep basin of the Black Sea and, for comparison, from the adjacent oxic shelf. Results suggest a very fast sedimentary uptake of 33P at all sites but in particular for sediments from the oxic shelf. At all sites, most 33P was sequestered in the citrate-dithionite-bicarbonate-(CDB)-extractable sediment P fraction. No significant differences with abiotic controls were observed, implying that micro-organisms were not directly involved in the P uptake. Whereas 33P uptake by the oxic shelf sediment was likely controlled by sorption of 33P to iron(Fe)-(oxyhydr)oxides, the nature of the CDB-extractable P fraction in the deep basin sediments remains unclear. We discuss whether authigenic formation of Fe(II)-P minerals or fast adsorption of P to calcites may explain our findings.

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

    SciTech Connect

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

    1982-01-01

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

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

    PubMed

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

    2016-08-01

    Development of nickel mining activities along the New Caledonia coasts threatens the biodiversity of coral reefs. Although the validation of tropical marine organisms as bioindicators of metal mining contamination has received much attention in the literature over the last decade, few studies have examined the potential of corals, the fundamental organisms of coral reefs, to monitor nickel (Ni) contamination in tropical marine ecosystems. In an effort to bridge this gap, the present work investigated the bioaccumulation of (63)Ni in the scleractinian coral Stylophora pistillata and in its isolated zooxanthellae Symbiodinium, using radiotracer techniques. Results highlight the high capacities of coral tissues (zooxanthellae and host tissues) to efficiently bioconcentrate (63)Ni compared to skeleton (Concentration Factors CF at 14 days of exposure are 3 orders of magnitude higher in tissues than in skeleton). When non-contaminated conditions were restored, (63)Ni was more efficiently retained in skeleton than in coral tissues, with biological half-lives (Tb½) of 44.3 and 6.5 days, respectively. In addition, our work showed that Symbiodinium bioconcentrated (63)Ni exponentially, with a vol/vol concentration factor at steady state (VCFSS) reaching 14,056. However, compilation of our results highlighted that despite efficient bioconcentration of (63)Ni in Symbiodinium, their contribution to the whole (63)Ni accumulation in coral nubbins represents less than 7%, suggesting that other biologically controlled processes occur in coral host allowing such efficient bioconcentration in coral tissues. PMID:27192479

  1. Biochemical quantification of sympathetic nervous activity in humans using radiotracer methodology: fallibility of plasma noradrenaline measurements

    SciTech Connect

    Esler, M.; Leonard, P.; O'Dea, K.; Jackman, G.; Jennings, G.; Korner, P.

    1982-01-01

    We have developed radiotracer techniques for studying noradrenaline kinetics, to assess better sympathetic nervous system function in humans. Tritiated l-noradrenaline was infused intravenously (0.35 microCi/m2/min) to plateau plasma concentration. Noradrenaline plasma clearance was calculated from plasma tritiated noradrenaline concentration at steady state, and the rate of spillover of noradrenaline to plasma derived from plasma noradrenaline specific radioactivity. Mean noradrenaline spillover at rest in 34 normal subjects was 0.33 micrograms/m2/min (range 0.17-0.61 micrograms/m2/min). Predictably, noradrenaline spillover was reduced in patients with subnormal sympathetic nervous system activity, 0.16 +/- 0.09 micrograms/m2/min in eight patients with idiopathic peripheral autonomic insufficiency, and 0.11 +/- 0.07 micrograms/m2/min (mean +/- SD) in six patients with essential hypertension treated with clonidine (0.45 mg daily). Noradrenaline line plasma clearance in normal subjects was 1.32 +/- 0.28 L/m2/min. Clearance fell with age, causing the previously described rise in plasma noradrenaline concentration with aging. Unexpected effects of drugs were encountered, for example chronic beta-adrenergic blockade in patients with essential hypertension reduced noradrenaline clearance. Plasma noradrenaline concentration measurements were not in agreement with noradrenaline release rate values, and do not reliably indicate sympathetic nervous system activity, in instances such as these where noradrenaline clearance is abnormal.

  2. Characterization of fast-decaying PET radiotracers solely through LC-MS/MS of constituent radioactive and carrier isotopologues

    PubMed Central

    2013-01-01

    Background The characterization of fast-decaying radiotracers that are labeled with carbon-11 (t1/2 = 20.38 min), including critical measurement of specific radioactivity (activity per mole at a specific time) before release for use in positron-emission tomography (PET), has relied heavily on chromatographic plus radiometric measurements, each of which may be vulnerable to significant errors. Thus, we aimed to develop a mass-specific detection method using sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) for identifying 11C-labeled tracers and for verifying their specific radioactivities. Methods The LC-MS/MS was tuned and set up with methods to generate and measure the product ions specific for carbon-11 species and M + 1 carrier (predominantly the carbon-13 isotopologue) in four 11C-labeled tracers. These radiotracers were synthesized and then analyzed before extensive carbon-11 decay. The peak areas of carbon-11 species and M + 1 carrier from the LC-MS/MS measurement and the calculated abundances of carbon-12 carrier and M + 1 radioactive species gave the mole fraction of carbon-11 species in each sample. This value upon multiplication with the theoretical specific radioactivity of carbon-11 gave the specific radioactivity of the radiotracer. Results LC-MS/MS of each 11C-labeled tracer generated the product ion peaks for carbon-11 species and M + 1 carrier at the expected LC retention time. The intensity of the radioactive peak diminished as time elapsed and was undetectable after six half-lives of carbon-11. Measurements of radiotracer-specific radioactivity determined solely by LC-MS/MS at timed intervals gave a half-life for carbon-11 (20.43 min) in excellent agreement with the value obtained radiometrically. Additionally, the LC-MS/MS measurement gave specific radioactivity values (83 to 505 GBq/μmol) in good agreement with those from conventional radiometric methods. Conclusions 11C-Labeled tracers were

  3. Evaluation of 64Cu-Labeled Acridinium Cation: A PET Radiotracer Targeting Tumor Mitochondria

    PubMed Central

    Zhou, Yang; Kim, Young-Seung; Shi, Jiyun; Jacobson, Orit; Chen, Xiaoyuan; Liu, Shuang

    2011-01-01

    This report presents the synthesis and evaluations of 64Cu(DO3A-xy-ACR) (DO3A-xy-ACR = 2,6-bis(dimethylamino)-10-(4-((4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)methyl)benzyl)acridin-10-ium) as a radiotracer for imaging tumors in athymic nude mice bearing U87MG glioma xenografts by PET (positron emission tomography). The biodistribution data suggested that 64Cu(DO3A-xy-ACR) was excreted mainly through the renal system with >65% of injected radioactivity being recovered from urine samples at 1 h post-injection (p.i.). The tumor uptake of 64Cu(DO3A-xy-ACR) was 1.07 ± 0.23, 1.58 ± 0.55, 2.71 ± 0.66, 3.47 ± 1.19, and 3.52 ± 1.72 %ID/g at 0.5, 1, 2, 4 and 24 h p.i., respectively. 64Cu(DO3A-xy-ACR) had very high liver uptake (31.90 ± 3.98, 24.95 ± 5.64, 15.20 ± 4.29, 14.09 ± 6.82, and 8.18 ± 1.27 %ID/g at 0.5, 1, 2, 4 and 24 h p.i., respectively) with low tumor/liver ratios. MicroPET studies showed that the tumors were clearly visualized as early as 30 min p.i. in the glioma-bearing mouse administered with 64Cu(DO3A-xy-ACR). The high liver radioactivity accumulation was also seen. 64Cu(DO3A-xy-ACR) had a relatively high metabolic stability during excretion via both renal and hepatobiliary routes; but it was completely decomposed in the liver homogenate. We explored the localization mechanism of Cu(DO3A-xy-ACR) using both U87MG human glioma and the cultured primary U87MG glioma cells. The results from the cellular staining assays showed that 64Cu(DO3A-xy-ACR) is able to localize in the mitochondria of living U87MG glioma cells due to the enhanced negative mitochondrial potential as compared to normal cells. Although 64Cu(DO3A-xy-ACR) is not an ideal PET radiotracer for tumor imaging due to its high liver uptake, the results from this study strongly suggest that 64Cu-labeled acridinium cations are indeed able to localize in the energized mitochondria of tumor cells. PMID:21413736

  4. A radiotracer study of cerium and manganese uptake onto suspended particles in Chesapeake Bay

    SciTech Connect

    Moffett, J.W. )

    1994-01-01

    The oxidation kinetics of Ce(III) and Mn(II) were studied in Chesapeake Bay in March and July 1990 to establish the role of water column redox processes in contributing to Ce anomalies observed in this estuary (SHOLKOVITZ and ELDERFIELD, 1988; SHOLKOVITZ et al., 1992). Oxidation was measured by adding Mn(II) and Ce(III) to freshly collected water samples as radiotracers and measuring their uptake onto the ambient suspended particle assemblage. Mn(II) oxidation was measured by following the uptake of [sup 54]Mn(II) onto suspended particles and utilizing protocols established by other workers to distinguish oxidation from Mn(II) adsorption. The same protocols were applicable to Ce(III), using [sup 139]Ce(III), and were supported by the use of [sup 152]Eu(III) as a nonredox reactive control. Specific rates of Ce(III) and MN(II) oxidation measured at a station in the North Bay (depth = 4 m) in July were 2016% per day and 4032% per day, respectively. In March, at the same station, the specific rate of Mn(II) of oxidation was only 1-% per day, and Ce(III) oxidation was undetectable. Both Ce(III) and Mn(II) oxidation processes were inhibited by azide, indicating that they were microbially mediated. The seasonal differences probably reflect strong seasonal variation in the abundance of Mn oxidizing bacteria. No Ce(III) oxidation occured in samples collected below the oxic/anoxic interface in July. The specific rates of oxidation for both elements were over 1000 times higher than those measured in the Sargasso Sea. However, the specific rates for Ce(III) and Mn(II) were very similar to each other. This fact, coupled with similar spatial and temporal trends for specific oxidation rates, suggests a common mechanism of oxidation of both elements which may be significant in a wide range of marine environments.

  5. SU-E-I-80: Beta-Minus Emitting Radiotracers Improves Molecular Endoscopy

    SciTech Connect

    Carpenter, C; Ma, X; Sun, C; Pratx, G; Cheng, Z; Xing, L

    2014-06-01

    Purpose: Molecular Endoscopy using Cerenkov Luminescence can be used to monitor the distribution of many clinically-available PET and SPECT probes for endoscopic applications. A main limitation of Cerenkov is its limited sensitivity to small concentrations of radiotracer when using light guides s. Herein we demonstrate that the use of a high energy beta emitting radioisotope, exemplified here with 90Y provides superior sensitivity to 18F because of its higher light output and its lack of corresponding gamma emission. Methods: A series of phantom experiments were performed to compare the sensitivity and noise of the CLE system for imaging 90Y and 18F. Three vials of known concentrations of 90Y (0.008 μCi, 0.08 μCi, 1 μCi) were placed in centrifuge tubes and isolated from each other. One vial of 18F (100 μCi) was placed in the imaging chamber and imaged over the course of decay (19 hours, 43 minutes, or ∼10 half-lives). Image time-points were formed from 5-minute integrations. Results: Using an SNR of 10 to define the noise-floor, the 90Y minimum detectable activity was 0.056 μCi. To the contrast, the minimum detectable activity for 18F was 11.63 μCi. These data demonstrate a 207-fold improvement in SNR of 90Y compared to 18F, when controlled for activity. Conclusion: This study demonstrated that a pure β- radionuclide such as 90Y be used is superior to 18F for Cerenkov Endoscopy. Further study is needed to demonstrate its utility in preclinical studies, endoscopic applications, intraoperative, and radiotherapy applications.

  6. Improving AMS Detection of the Biomedical Radiotracer 41Ca with Segmented Radio-Frequency Quadrupoles

    NASA Astrophysics Data System (ADS)

    Alary, Jean-Francois; Javahery, Gholamreza; Kieser, William E.; Litherland, Albert E.; Cousins, Lisa M.

    41Ca is an important biomedical radiotracer finding many applications in biological, nutritional and medical studies. The detection of 41Ca by AMS is however limited by an important background signal of 41K originating from biological samples and from contaminated cesium in the source. An approach consisting of using PbF2-assisted in-source fluorination in combination with an Isobar Separator for Anions (ISA), a device incorporating a low energy radio frequency quadrupole (RFQ) gas cell, promises to push down the limit of detection of 41Ca attainable on small (<3 MV) accelerator mass spectrometry (AMS) systems by several orders of magnitude. Such on-line reduction of 41K should also result in a simplification of biological sample preparation and less concern about variable 41K contamination of the cesium beam. The selective collision-induced fragmentation of KF3- versus CaF3-, occurring in the gas cell of an ISA equipped with a double segment RFQ, have been reported earlier1), leading to K being suppressed by a factor of 1e4 over Ca. We present here the future configuration of the ISA, redesigned using multi-segmented RFQ to enhance further this effect and improve transmission through the gas cell. A segmented RFQ is an appropriate tool to finely control ion energy down to the few eV's separating the fragmentation energies of the two fluoride species. This pre-commercial ISA destined to be used at the newly established A. E. Lalonde AMS laboratory at University of Ottawa (Canada) will be presented. Some practicalities of integrating a low energy RFQ-based device in a high energy AMS system will also be discussed.

  7. [18F]Fluoromethyl-[1,2-2H4]-choline: A novel radiotracer for imaging choline metabolism in tumors by positron emission tomography

    PubMed Central

    Leyton, Julius; Smith, Graham; Zhao, Yongjun; Perumal, Meg; Nguyen, Quang-De; Robins, Edward; Årstad, Erik; Aboagye, Eric O.

    2009-01-01

    Current radiotracers for positron emission tomography (PET) imaging of choline metabolism have poor systemic metabolic stability in vivo. We describe a novel radiotracer, [18F]fluoromethyl-[1,2-2H4]-choline (D4-FCH), that employs deuterium isotope effect to improve metabolic stability. D4-FCH proved more resistant to oxidation than its non-deuterated analog, [18F]fluoromethylcholine (FCH), in plasma, kidneys, liver and tumor, while retaining phosphorylation potential. Tumor radiotracer levels, a determinant of sensitivity in imaging studies, was improved by deuterium substitution; tumor uptake values expressed as %injected dose/voxel at 60 min were 7.43 ± 0.47 and 5.50 ± 0.49 for D4-FCH and FCH, respectively, (P = 0.04). D4-FCH was also found to be a useful response biomarker. Treatment with the mitogenic extracellular kinase inhibitor, PD0325901, resulted in a reduction in tumor radiotracer uptake that occurred in parallel with reductions in choline kinase A expression. In conclusion, D4-FCH is a very promising metabolically stable radiotracer for imaging choline metabolism in tumors. PMID:19773436

  8. Diffuse pulmonary uptake of bone-seeking radiotracer in bone scintigraphy of a rare case of pulmonary alveolar microlithiasis

    PubMed Central

    Fallahi, Babak; Ghafary, Bahar Moasses; Fard-Esfahani, Armaghan; Eftekhari, Mohammad

    2015-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare diffuse pulmonary disease representing microliths formed by deposition of calcium phosphonate in the alveolar airspaces. PAM is often diagnosed incidentally during chest X-ray imaging. Most of them are asymptomatic. We present a 39-year-old man referring for a bone scan due to a complaint of right leg pain. Bone scan showed diffuse uptake of bone-seeking radiotracer on both lung fields predominantly in basal regions. The bronchoalveolar lavage test confirmed the diagnosis of PAM. PMID:26170578

  9. Synthesis and Biological Evaluation of Thiophene-Based Cannabinoid Receptor Type 2 Radiotracers for PET Imaging

    PubMed Central

    Haider, Ahmed; Müller Herde, Adrienne; Slavik, Roger; Weber, Markus; Mugnaini, Claudia; Ligresti, Alessia; Schibli, Roger; Mu, Linjing; Mensah Ametamey, Simon

    2016-01-01

    . Evaluation of the CB2-positive spleen, however, showed no accumulation of the radiotracer. Despite the promising in vitro binding affinities, specific binding of [11C]AAT-015, and [11C]AAT-778 could not be demonstrated. PMID:27512365

  10. Batch-reactor microfluidic device: first human use of a microfluidically produced PET radiotracer.

    PubMed

    Lebedev, Artem; Miraghaie, Reza; Kotta, Kishore; Ball, Carroll E; Zhang, Jianzhong; Buchsbaum, Monte S; Kolb, Hartmuth C; Elizarov, Arkadij

    2013-01-01

    The very first microfluidic device used for the production of (18)F-labeled tracers for clinical research is reported along with the first human Positron Emission Tomography scan obtained with a microfluidically produced radiotracer. The system integrates all operations necessary for the transformation of [(18)F]fluoride in irradiated cyclotron target water to a dose of radiopharmaceutical suitable for use in clinical research. The key microfluidic technologies developed for the device are a fluoride concentration system and a microfluidic batch reactor assembly. Concentration of fluoride was achieved by means of absorption of the fluoride anion on a micro ion-exchange column (5 μL of resin) followed by release of the radioactivity with 45 μL of the release solution (95 ± 3% overall efficiency). The reactor assembly includes an injection-molded reactor chip and a transparent machined lid press-fitted together. The resulting 50 μL cavity has a unique shape designed to minimize losses of liquid during reactor filling and liquid evaporation. The cavity has 8 ports for gases and liquids, each equipped with a 2-way on-chip mechanical valve rated for pressure up to 20.68 bar (300 psi). The temperature is controlled by a thermoelectric heater capable of heating the reactor up to 180 °C from RT in 150 s. A camera captures live video of the processes in the reactor. HPLC-based purification and reformulation units are also integrated in the device. The system is based on "split-box architecture", with reagents loaded from outside of the radiation shielding. It can be installed either in a standard hot cell, or as a self-shielded unit. Along with a high level of integration and automation, split-box architecture allowed for multiple production runs without the user being exposed to radiation fields. The system was used to support clinical trials of [(18)F]fallypride, a neuroimaging radiopharmaceutical under IND Application #109,880. PMID:23135409

  11. Novel Histone Deacetylase Class IIa Selective Substrate Radiotracers for PET Imaging of Epigenetic Regulation in the Brain

    PubMed Central

    Bonomi, Robin; Mukhopadhyay, Uday; Shavrin, Aleksandr; Yeh, Hsien-Hsien; Majhi, Anjoy; Dewage, Sajeewa W.; Najjar, Amer; Lu, Xin; Cisneros, G. Andrés; Tong, William P.; Alauddin, Mian M.; Liu, Ren-Shuan; Mangner, Thomas J.; Turkman, Nashaat; Gelovani, Juri G.

    2015-01-01

    Histone deacetylases (HDAC’s) became increasingly important targets for therapy of various diseases, resulting in a pressing need to develop HDAC class- and isoform-selective inhibitors. Class IIa deacetylases possess only minimal deacetylase activity against acetylated histones, but have several other client proteins as substrates through which they participate in epigenetic regulation. Herein, we report the radiosyntheses of the second generation of HDAC class IIa–specific radiotracers: 6-(di-fluoroacetamido)-1-hexanoicanilide (DFAHA) and 6-(tri-fluoroacetamido)-1-hexanoicanilide ([18F]-TFAHA). The selectivity of these radiotracer substrates to HDAC class IIa enzymes was assessed in vitro, in a panel of recombinant HDACs, and in vivo using PET/CT imaging in rats. [18F]TFAHA showed significantly higher selectivity for HDAC class IIa enzymes, as compared to [18F]DFAHA and previously reported [18F]FAHA. PET imaging with [18F]TFAHA can be used to visualize and quantify spatial distribution and magnitude of HDAC class IIa expression-activity in different organs and tissues in vivo. Furthermore, PET imaging with [18F]TFAHA may advance the understanding of HDACs class IIa mediated epigenetic regulation of normal and pathophysiological processes, and facilitate the development of novel HDAC class IIa-specific inhibitors for therapy of different diseases. PMID:26244761

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

    PubMed

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

    2015-03-01

    An alkaline based continuous leaching process is commonly used for extraction of uranium from uranium ore. The reactor in which the leaching process is carried out is called a continuous leaching reactor (CLR) and is expected to behave as a continuously stirred tank reactor (CSTR) for the liquid phase. A pilot-scale CLR used in a Technology Demonstration Pilot Plant (TDPP) was designed, installed and operated; and thus needed to be tested for its hydrodynamic behavior. A radiotracer investigation was carried out in the CLR for measurement of residence time distribution (RTD) of liquid phase with specific objectives to characterize the flow behavior of the reactor and validate its design. Bromine-82 as ammonium bromide was used as a radiotracer and about 40-60MBq activity was used in each run. The measured RTD curves were treated and mean residence times were determined and simulated using a tanks-in-series model. The result of simulation indicated no flow abnormality and the reactor behaved as an ideal CSTR for the range of the operating conditions used in the investigation. PMID:25528019

  13. A Radiotracer Strategy to Quantify PARP-1 Expression In Vivo Provides a Biomarker That Can Enable Patient Selection for PARP Inhibitor Therapy.

    PubMed

    Makvandi, Mehran; Xu, Kuiying; Lieberman, Brian P; Anderson, Redmond-Craig; Effron, Samuel Sander; Winters, Harrison D; Zeng, Chenbo; McDonald, Elizabeth S; Pryma, Daniel A; Greenberg, Roger A; Mach, Robert H

    2016-08-01

    Despite the availability of PARP inhibitors for cancer therapy, a biomarker to clearly stratify patients for selection of this treatment remains lacking. Here we describe a radiotracer-based method that addresses this issue, using the novel compound [(125)I] KX1: as a PARP-1-selective radiotracer that can accurately measure PARP-1 expression in vitro and in vivo The pharmacologic properties of the PARP radiotracer [(125)I] KX1: was characterized in multiple cell lines where single-agent sensitivity was correlated with [(125)I] KX1: binding to PARP-1. In vivo evaluation of [(125)I] KX1: verified in vitro results, validating PARP radiotracers to define PARP-1 enzyme expression as an in vivo biomarker. Notably, PARP-1 expression as quantified by [(125)I] KX1: correlated positively with the cytotoxic sensitivity of cell lines evaluated with PARP inhibitors. Overall, our results defined a novel technology with the potential to serve as a companion diagnostic to identify patients most likely to respond therapeutically to a PARP inhibitor. Cancer Res; 76(15); 4516-24. ©2016 AACR. PMID:27261505

  14. Radiotracer measurements as a sensitive tool for the detection of metal penetration in molecular-based organic electronics

    SciTech Connect

    Scharnberg, M.; Hu, J.; Kanzow, J.; Raetzke, K.; Adelung, R.; Faupel, F.; Pannemann, C.; Hilleringmann, U.; Meyer, S.; Pflaum, J.

    2005-01-10

    The metallization of organic thin films is a crucial point in the development of molecular electronics. However, there is no method established yet to detect trace amounts of metal atoms in those thin films. Radiotracer measurements can quantify even very small amounts of material penetrating into the bulk, in our case less than 0.01% of a monolayer. Here, the application of this technique on two different well-characterized organic thin film systems (diindenoperylene and pentacene) is demonstrated. The results show that Ag is mainly adsorbed on the surface, but indicate that already at moderate deposition temperatures Ag can penetrate into the organic thin films and agglomerate at the film/substrate interface.

  15. Diffusion Experiment in Lithium Ionic Conductors with the Radiotracer of {sup 8}Li: from Micro- to Nano-diffusion

    SciTech Connect

    Jeong, Sun-Chan; Katayama, Ichiro; Kawakami, Hirokane; Watanabe, Yutaka; Ishiyama, Hironobu; Imai, Nobuaki; Hirayama, Yoshikazu; Miyatake, Hiroari; Sataka, Masao; Sugai, Hiroyuki; Okayasu, Satoru; Ichikawa, Shin-Ichi; Nishio, Katsuhisa; Mitsuoka, Shinichi; Nakanoya, Takamitsu; Hashimoto, Takashi; Hashimoto, Takanori; Yahagi, Masahito

    2009-05-04

    We have developed a radiotracer method for diffusion studies in lithium ionic conductors, by using, as the tracer, the short-lived {alpha}-emitting radioisotope of {sup 8}Li from TRIAC (Tokai Radioactive Ion Accelerator Complex). In the method, we measured {alpha}-particles coming out of the sample of interest and have found that the time-dependent yields of {alpha}-particle from the diffusing {sup 8}Li primarily implanted is a good measure of the Li diffusion in the sample. The method has been successfully applied to measure the lithium diffusion coefficients in a typical defect-mediated lithium ionic conductor of LiGa, well demonstrating that the method is very efficient to measure the diffusion in the micro-meter regime per second. Further development, as an extension of the present method, was proposed to measure the diffusion on the nanoscale in lithium ionic conductors.

  16. The role of electromagnetic separators in the production of radiotracers for bio-medical research and nuclear medical application

    NASA Astrophysics Data System (ADS)

    Beyer, Gerd J.; Ruth, Thomas J.

    2003-05-01

    With the growing complexity of positron emission tomography/single photon emission computed tomography imaging and the new developments in systemic radionuclide therapy there is a growing need for radioisotope preparations with higher radiochemical and radionuclidic purity that has not been achievable before. Especially important for the new applications is the specific activity of the radiotracer. Conventional methods in medical isotope production have reached their technical limitations. The role of isotope separators is discussed with examples of typical production and characterization experiments conducted at the ISOLDE and TRIUMF facilities. These preliminary experiments indicate that isotope separators have a definite role to play in the future for the production of radioisotopes for biomedical research and medical application.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-15

    (68)Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: (68)Ga-1, using DOTA-monoamide as the chelating agent; (68)Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and (68)Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). (68)Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to (68)Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. (68)Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation (68)Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging. PMID:27076393

  19. 124I-Epidepride: A PET Radiotracer for Extended Imaging of Dopamine D2/D3 Receptors

    PubMed Central

    Pandey, Suresh; Venugopal, Archana; Kant, Ritu; Coleman, Robert; Mukherjee, Jogeshwar

    2014-01-01

    Objectives A new radiotracer, 124I-epidepride, has been developed for the imaging of dopamine D2/3 receptors (D2/3Rs). 124I-epidepride (half-life of 124I = 4.2days) allows imaging over extended periods compared to 18F-fallypride (half-life of 18F = 0.076days) and may maximize visualization of D2/3Rs in the brain and pancreas (allowing clearance from adjacent organs). D2/3Rs are also present in pancreatic islets where they co-localize with insulin to produce granules and may serve as a surrogate marker for imaging diabetes. Methods 124I-Epidepride was synthesized using N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-tributyltin-2,3-dimethoxybenzamide and 124I-iodide under no carrier added condition. Rats were used for in vitro and in vivo imaging. Brain slices were incubated with 124I-epidepride (0.75μCi/cc) and nonspecific binding measured with 10 μM haloperidol. Autoradiograms were analyzed by OptiQuant. 124I-Epidepride (0.2 to 0.3 mCi, iv) was administered to rats and brain uptake at 3 hours, 24 hours, and 48 hours post injection was evaluated. Results 124I-Epidepride was synthesized with 50% radiochemical yield and high radiochemical purity (>95%). 124I-Epidepride localized in the striatum with a striatum to cerebellum ratio of 10. Binding was displaced by dopamine and haloperidol. Brain slices demonstrated localization of 124I-epidepride up until 48 hr in the striatum. However, the extent of binding was reduced significantly. Conclusions 124I-Epidepride is a new radiotracer suitable for extended imaging of dopamine D2/3 receptors and may have applications in imaging of receptors in the brain and monitoring pancreatic islet cell grafting. PMID:24602412

  20. Aqueous and dietary copper uptake and elimination in Daphnia magna determined by the ⁶⁷cu radiotracer.

    PubMed

    Zhao, Chun-Mei; Fan, Wen-Hong; Wang, Wen-Xiong

    2009-11-01

    Among the many toxic metals, the biokinetics of copper (Cu) in the freshwater cladoceran Daphnia magna have not been studied due to the lack of an ideal radiotracer. In the present study, a gamma radiotracer, ⁶⁷Cu (half-life = 61.9 h), was used to study the uptake of copper from the dissolved and dietary phase and efflux in D. magna, an important toxicity testing species. The influx rate of Cu from the dissolved phase increased with dissolved Cu concentration, with a calculated uptake rate constant of 0.055 L/g/h. The assimilation efficiency (AE) of Cu decreased significantly (from 92 to 16%) as the available food concentration increased, and the AE differed among the food types. As low as 1% of Cu AE was found in daphnids fed high concentrations (1.54 mg/L) of the green algae Chlorella pyrenoidosa. The AE decreased linearly as the ingestion rate of the daphnids increased. The efflux rate constant was 0.20/d at high food concentrations. Excretion accounted for 82 to 94% of total Cu loss from the animals, although Cu also was transferred maternally from female adults to their offspring. Under conditions of high food concentrations, approximately 6.5% of the mother's Cu was transferred to the offspring over 7 d. It was concluded that Cu accumulation is dominated by uptake from dietary sources, and there is a substantial need to understand the dietary toxicity of Cu to daphnids. The present study has implications for the choice of food particles in conducting the Cu toxicity testing in cladocerans. PMID:19839654

  1. A one-step microwave-assisted synthetic method for an O/S-chemoselective route to derivatives of the first adenosine A3 PET radiotracer.

    PubMed

    Shanab, Karem; Neudorfer, Catharina; Holzer, Wolfgang; Mitterhauser, Markus; Wadsak, Wolfgang; Spreitzer, Helmut

    2014-01-01

    The synthesis of reference standards and expected in vivo metabolites of the first adenosine A3 PET radiotracer [18F]FE@SUPPY ([18F]fluoroethyl 4,6-diethyl-5-[(ethyl-sulfanyl)carbonyl]-2-phenylpyridine-3-carboxylate) was achieved by using a straightforward microwave assisted alkylation method, which allowed O/S-chemoselective alkylation of the starting material 1 to give each target compound 2-8 in a single step. PMID:24699149

  2. Improving the In Vivo Profile of Minigastrin Radiotracers: A Comparative Study Involving the Neutral Endopeptidase Inhibitor Phosphoramidon.

    PubMed

    Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

    2016-02-01

    Minigastrin radiotracers, such as [(111)In-DOTA]MG0 ([(111)In-DOTA-DGlu(1)]minigastrin), have been considered for diagnostic imaging and radionuclide therapy of CCK2R-positive human tumors, such as medullary thyroid carcinoma. However, the high kidney retention assigned to the pentaGlu(2-6) repeat in the peptide sequence has compromised their clinical applicability. On the other hand, truncated des(Glu)(2-6)-analogs, such as [(111)In-DOTA]MG11 ([(111)In-DOTA-DGlu(10),desGlu(2-6)]minigastrin), despite their low renal uptake, show poor bioavailability and tumor targeting. [(111)In]CP04 ([(111)In-DOTA-DGlu(1-6)]minigastrin) acquired by Glu(2-6)/DGlu(2-6) substitution showed promising tumor-to-kidney ratios in rodents. In the present study, we compare the biological profiles of [(111)In]CP04, [(111)In-DOTA]MG11, and [(111)In-DOTA]MG0 during in situ neutral endopeptidase (NEP) inhibition, recently shown to improve the bioavailability of several peptide radiotracers. After coinjection of the NEP inhibitor, phosphoramidon (PA), the stability of [(111)In]CP04 and [(111)In-DOTA]MG0 in peripheral mouse blood increased, with an exceptional >14-fold improvement monitored for [(111)In-DOTA]MG11. In line with these findings, PA treatment increased the uptake of [(111)In]CP04 (8.5 ± 0.4%ID/g to 16.0 ± 2.3%ID/g) and [(111)In-DOTA]MG0 (11.9 ± 2.2%ID/g to 17.2 ± 0.9%ID/g) in A431-CCK2R(+) tumors at 4 hours postinjection, whereas the respective increase for [(111)In-DOTA]MG11 was >6-fold (2.5 ± 0.9%ID/g to 15.1 ± 1.7%ID/g). Interestingly, kidney uptake remained lowest for [(111)In-DOTA]MG11, but unfavorably increased by PA treatment for [(111)In-DOTA]MG0. Thus, overall, the most favorable in vivo profile was displayed by [(111)In-DOTA]MG11 during NEP inhibition, highlighting the need to validate this promising concept in the clinic. PMID:26844849

  3. Synthesis and Evaluation of [N-methyl-11C]N-Desmethyl-loperamide as a New and Improved PET Radiotracer for Imaging P-gp Function

    PubMed Central

    Lazarova, Neva; Zoghbi, Sami S.; Hong, Jinsoo; Seneca, Nicholas; Tuan, Ed; Gladding, Robert L.; Liow, Jeih-San; Taku, Andrew; Innis, Robert B.; Pike, Victor W.

    2009-01-01

    [11C]Loperamide has been proposed for imaging P-glycoprotein (P-gp) function with positron emission tomography (PET), but its metabolism to [N-methyl-11C]N-desmethyl-loperamide ([11C]dLop; [11C]3) precludes quantification. We considered that [11C]3 might itself be a superior radiotracer for imaging brain P-gp function and therefore aimed to prepare [11C]3 and characterize its efficacy. An amide precursor (2) was synthesized and methylated with [11C]iodomethane to give [11C]3. After administration of [11C]3 to wild type mice, brain radioactivity uptake was very low. In P-gp (mdr-1a (−/−)) knockout mice, brain uptake of radioactivity at 30 min increased about 3.5 fold by PET measures, and over seven-fold by ex vivo measures. In knockout mice, brain radioactivity was predominantly (90%) unchanged radiotracer. In monkey PET experiments, brain radioactivity uptake was also very low, but after P-gp blockade increased more than seven-fold. [11C]3 is an effective new radiotracer for imaging brain P-gp function and, in favor of future successful quantification, appears free of extensive brain-penetrant radiometabolites. PMID:18783208

  4. The Synthesis and Evaluations of the 68Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography

    PubMed Central

    Li, Xuena; Yin, Yafu; Du, Bulin; Li, Na; Li, Yaming

    2016-01-01

    Purpose. The aim of this study is to synthesize and evaluate 68Ga-labeled Lissamine Rhodamine B (LRB) as a new radiotracer for imaging MDA-MB-231 and MCF-7 cells induced tumor mice by positron emission tomography (PET). Methods. Firstly, we performed the radio synthesis and microPET imaging of 68Ga(DOTA-LRB) in athymic nude mice bearing MDA-MB-231 and MCF-7 human breast cancer xenografts. Additionally, the evaluations of 18F-fluorodeoxyglucose (FDG), as a glucose metabolism radiotracer for imaging tumors in the same xenografts, have been conducted as a comparison. Results. The radiochemical purity of 68Ga(DOTA-LRB) was >95%. MicroPET dynamic imaging revealed that the uptake of 68Ga(DOTA-LRB) was mainly in normal organs, such as kidney, heart, liver, and brain and mainly excreted from kidney. The MDA-MB-231 and MCF-7 tumors were not clearly visible in PET images at 5, 15, 30, 40, 50, and 60 min after injection of 68Ga(DOTA-LRB). The tumor uptake values of 18F-FDG were 3.79 ± 0.57 and 1.93 ± 0.48%ID/g in MDA-MB-231 and MCF-7 tumor xenografts, respectively. Conclusions. 68Ga(DOTA-LRB) can be easily synthesized with high radiochemical purity and stability; however, it may be not an ideal PET radiotracer for imaging of MDR-positive tumors. PMID:26949707

  5. Estimating Endogenous Dopamine Levels at D2 and D3 Receptors in Humans using the Agonist Radiotracer [11C]-(+)-PHNO

    PubMed Central

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-01-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [11C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [11C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [11C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [11C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [11C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations. PMID:24874713

  6. Development of a system for real-time measurements of metabolite transport in plants using short-lived positron-emitting radiotracers

    NASA Astrophysics Data System (ADS)

    Kiser, Matthew R.

    Over the past 200 years, the Earth's atmospheric carbon dioxide (CO 2) concentration has increased by more than 35%, and climate experts predict that CO2 levels may double by the end of this century. Understanding the mechanisms of resource management in plants is fundamental for predicting how plants will respond to the increase in atmospheric CO 2. Plant productivity sustains life on Earth and is a principal component of the planet's system that regulates atmospheric CO2 concentration. As such, one of the central goals of plant science is to understand the regulatory mechanisms of plant growth in a changing environment. Short-lived positron-emitting radiotracer techniques provide time-dependent data that are critical for developing models of metabolite transport and resource distribution in plants and their microenvironments. To better understand the effects of environmental changes on resource transport and allocation in plants, we have developed a system for real-time measurements of rnetabolite transport in plants using short-lived positron-emitting radio-tracers. This thesis project includes the design, construction, and demonstration of the capabilities of this system for performing real-time measurements of metabolite transport in plants. The short-lived radiotracer system described in this dissertation takes advantage of the combined capabilities and close proximity of two research facilities at. Duke University: the Triangle Universities Nuclear Laboratory (TUNL) and the Duke University Phytotron, which are separated by approximately 100 meters. The short-lived positron-emitting radioisotopes are generated using the 10-MV tandem Van de Graaff accelerator located in the main TUNL building, which provides the capability of producing short-lived positron-emitting isotopes such as carbon-11 (11C: 20 minute half-life), nitrogen-13 (13N; 10 minute half-life), fluorine-18 (18F; 110 minute half-life), and oxygen-15 (15O; 2 minute half-life). The radioisotopes may

  7. Design, Synthesis, and Evaluation of an (18)F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2).

    PubMed

    Kaur, Jatinder; Tietz, Ole; Bhardwaj, Atul; Marshall, Alison; Way, Jenilee; Wuest, Melinda; Wuest, Frank

    2015-10-01

    A series of novel fluorine-containing cyclooxygenase-2 (COX-2) inhibitors was designed and synthesized based on the previously reported fluorescent COX-2 imaging agent celecoxib-NBD (3; NBD=7-nitrobenzofurazan). In vitro COX-1/COX-2 inhibitory data show that N-(4-fluorobenzyl)-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (5; IC50 =0.36 μM, SI>277) and N-fluoromethyl-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (6; IC50 =0.24 μM, SI>416) are potent and selective COX-2 inhibitors. Compound 5 was selected for radiolabeling with the short-lived positron emitter fluorine-18 ((18) F) and evaluated as a positron emission tomography (PET) imaging agent. Radiotracer [(18) F]5 was analyzed in vitro and in vivo using human colorectal cancer model HCA-7. Although radiotracer uptake into COX-2-expressing HCA-7 cells was high, no evidence for COX-2-specific binding was found. Radiotracer uptake into HCA-7 tumors in vivo was low and similar to that of muscle, used as reference tissue. PMID:26287271

  8. Optimizing tumor targeting of the lipophilic EGFR-binding radiotracer SKI243 using a liposomal nanoparticle delivery system

    PubMed Central

    Pillarsetty, Nagavarakishore; Glekas, Athanasios; Punzalan, Blesida; Longo, Valerie; Gönen, Mithat; Zanzonico, Pat; Smith-Jones, Peter

    2015-01-01

    Positron emission tomography (PET) of epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide a means for non-invasively characterizing EGFR expression and signaling activity in patients' tumors before, during, and after therapy with EGFR inhibitors. Towards this goal, our group has developed PET tracers which irreversibly bind to EGFR. However, tumor uptake is relatively low because of both the lipophilicity of such tracers (e.g. the morpholino-[124I]-IPQA [SKI212243]), with octanol-to-water partition coefficients of up to 4, and a short dwell time in the blood and significant hepatobiliary clearance and intestinal reuptake. Liposomal nanoparticle delivery systems may favorably alter the pharmacokinetic profile and improve tumor targeting of highly lipophilic but otherwise promising cancer imaging tracers, such as the EGFR inhibitor SKI243. SKI243 is therefore an interesting model molecule for incorporation into lipid-based nanoparticles, as it would not only improve their solubility but also increase the circulation time, availability and, potentially, targeting of tumors. In the current study, we compared the pharmacokinetics and tumor targeting of the bare EGFR kinase-targeting radiotracer SKI212243 (SKI243) with that of the same tracer embedded in liposomes. SKI243 and liposomal SKI243 are both taken up by tumor xenografts but liposomal SKI243 remained in the blood longer and consequently exhibited a 3- to 6-fold increase in uptake in the tumor among several other organs. PMID:21047536

  9. Radiotracer computer modeling evidence that phospho-base methylation is the main route of choline synthesis in tobacco

    SciTech Connect

    McNeil, S.D.; Nuccio, M.L.; Rhodes, D.; Shachar-Hill, Y.; Hanson, A.D.

    2000-05-01

    Among flowering plants, the synthesis of choline (Cho) from ethanolamine (EA) can potentially occur via three parallel, interconnected pathways involving methylation of free bases, phospho-bases, or phosphatidyl-bases. The authors investigated which pathways operate in tobacco (Nicotiana tabacum L.) because previous work has shown that the endogenous Cho supply limits accumulation of glycine betaine in transgenic tobacco plants engineered to convert Cho to glycine betaine. The kinetics of metabolite labeling were monitored in leaf discs supplied with [{sup 33}P]phospho-EA,[{sup 33}P]phospho-monomethylethanolamine, or [{sup 14}C]formate, and the data were subjected to computer modeling. Because partial hydrolysis of phospho-bases occurred in the apoplast, modeling of phospho-base metabolism required consideration of the re-entry of [{sup 33}P]phosphate into the network. Modeling of [{sup 14}C]formate metabolism required consideration of the labeling of the EA and methyl moieties of Cho. Results supported the following conclusions: (a) The first methylation step occurs solely at the phospho-base level; (b) the second and third methylations occur mainly (83%--92% and 65%--85%, respectively) at the phospho-base level, with the remainder occurring at the phosphatidyl-base level; and (c) free Cho originates predominantly from phosphatidylcholine rather than from phospho-Cho. This study illustrates how computer modeling of radiotracer data, in conjunction with information on chemical pool sizes, can provide a coherent, quantitative picture of fluxes within a complex metabolic network.

  10. Optimizing tumor targeting of the lipophilic EGFR-binding radiotracer SKI 243 using a liposomal nanoparticle delivery system.

    PubMed

    Medina, Oula Penate; Pillarsetty, Nagavarakishore; Glekas, Athanasios; Punzalan, Blesida; Longo, Valerie; Gönen, Mithat; Zanzonico, Pat; Smith-Jones, Peter; Larson, Steven M

    2011-02-10

    Positron emission tomography (PET) of epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide a means for non-invasively characterizing EGFR expression and signaling activity in patients' tumors before, during, and after therapy with EGFR inhibitors. Towards this goal, our group has developed PET tracers which irreversibly bind to EGFR. However, tumor uptake is relatively low because of both the lipophilicity of such tracers (e.g. the morpholino-[124I]-IPQA [SKI 212243]), with octanol-to-water partition coefficients of up to 4, and a short dwell time in the blood and significant hepatobiliary clearance and intestinal reuptake. Liposomal nanoparticle delivery systems may favorably alter the pharmacokinetic profile and improve tumor targeting of highly lipophilic but otherwise promising cancer imaging tracers, such as the EGFR inhibitor SKI 243. SKI 243 is therefore an interesting model molecule for incorporation into lipid-based nanoparticles, as it would not only improve their solubility but also increase the circulation time, availability and, potentially, targeting of tumors. In the current study, we compared the pharmacokinetics and tumor targeting of the bare EGFR kinase-targeting radiotracer SKI 212243 (SKI 243) with that of the same tracer embedded in liposomes. SKI 243 and liposomal SKI 243 are both taken up by tumor xenografts but liposomal SKI 243 remained in the blood longer and consequently exhibited a 3- to 6-fold increase in uptake in the tumor among several other organs. PMID:21047536

  11. Investigating the pharmacokinetics and biological distribution of silver-loaded polyphosphoester-based nanoparticles using (111) Ag as a radiotracer.

    PubMed

    Aweda, Tolulope A; Zhang, Shiyi; Mupanomunda, Chiedza; Burkemper, Jennifer; Heo, Gyu Seong; Bandara, Nilantha; Lin, Mai; Cutler, Cathy S; Cannon, Carolyn L; Youngs, Wiley J; Wooley, Karen L; Lapi, Suzanne E

    2015-05-30

    Purified (111) Ag was used as a radiotracer to investigate silver loading and release, pharmacokinetics, and biodistribution of polyphosphoester-based degradable shell crosslinked knedel-like (SCK) nanoparticles as a comparison to the previously reported small molecule, N-heterocyclic silver carbene complex analog (SCC1) for the delivery of therapeutic silver ions in mouse models. Biodistribution studies were conducted by aerosol administration of (111) Ag acetate, [(111) Ag]SCC1, and [(111) Ag]SCK doses directly into the lungs of C57BL/6 mice. Nebulization of the (111) Ag antimicrobials resulted in an average uptake of 1.07 ± 0.12% of the total aerosolized dose given per mouse. The average dose taken into the lungs of mice was estimated to be 2.6 ± 0.3% of the dose inhaled per mouse for [(111) Ag]SCC1 and twice as much dose was observed for the [(111) Ag]SCKs (5.0 ± 0.3% and 5.9 ± 0.8% for [(111) Ag]aSCK and [(111) Ag]zSCK, respectively) at 1 h post administration (p.a.). [(111) Ag]SCKs also exhibited higher dose retention in the lungs; 62-68% for [(111) Ag]SCKs and 43% for [(111) Ag]SCC1 of the initial 1 h dose were observed in the lungs at 24 h p.a.. This study demonstrates the utility of (111) Ag as a useful tool for monitoring the pharmacokinetics of silver-loaded antimicrobials in vivo. PMID:25952472

  12. 2'[(18)F]-fluoroethylrhodamine B is a promising radiotracer to measure P-glycoprotein function.

    PubMed

    Trencsényi, György; Kertész, István; Krasznai, Zoárd T; Máté, Gábor; Szalóki, Gábor; Szabó Judit, P; Kárpáti, Levente; Krasznai, Zoltán; Márián, Teréz; Goda, Katalin

    2015-07-10

    In vivo detection of the emergence of P-glycoprotein (Pgp) mediated multidrug resistance in tumors could be beneficial for patients treated with anticancer drugs. PET technique in combination with appropriate radiotracers could be the most convenient method for detection of Pgp function. Rhodamine derivatives are validated fluorescent probes for measurement of mitochondrial membrane potential and also Pgp function. The aim of this study was to investigate whether 2'[(18)F]-fluoroethylrhodamine B ((18)FRB) a halogenated rhodamine derivative previously synthesized for PET assessment of myocardial perfusion preserved its Pgp substrate character. ATPase assay as well as accumulation experiments carried out using Pgp(+) and Pgp(-) human gynecologic (A2780/A2780(AD) and KB-3-1/KB-V1) and a mouse fibroblast cell pairs (NIH 3T3 and NIH 3T3 MDR1) were applied to study the interaction of (18)FRB with Pgp. ATPase assay proved that (18)FRB is a high affinity substrate of Pgp. Pgp(-) cells accumulated the (18)FRB rapidly in accordance with its lipophilic character. Dissipation of the mitochondrial proton gradient by a proton ionophore CCCP decreased the accumulation of rhodamine 123 (R123) and (18)FRB into Pgp(-) cells. Pgp(+) cells exhibited very low R123 and (18)FRB accumulation (around 1-8% of the Pgp(-) cell lines) which was not sensitive to the mitochondrial proton gradient; rather it was increased by the Pgp inhibitor cyclosporine A (CsA). Based on the above data we conclude that (18)FRB is a high affinity Pgp substrate and consequently a potential PET tracer to detect multidrug resistant tumors as well as the function of physiological barriers expressing Pgp. PMID:25857708

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

    PubMed

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

    2014-07-01

    The objective of this study was to develop a kit formulation for [(99m) TcN(mpo)(PNP5)](+) (MPO = 2-mercaptopyridine oxide), ((99m) TcN-MPO) to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two-vial formulation and single-vial formulations with/without SnCl2 ) to explore the factors influencing radiochemical purity (RCP) of (99m) TcN-MPO. We found that the most important factor affecting the RCP of (99m) TcN-MPO was the purity of PNP5. (99m) TcN-MPO was prepared >98% RCP (n = 20) using the two-vial formulation. For single-vial formulations with/without SnCl2 , β-cyclodextrin (β-CD) is particularly useful as a stabilizer for PNP5. The RCP of (99m) TcN-MPO was 95-98% using β-CD, but its RCP was only 90-93% with γ-cyclodextrin (γ-CD). It seems that PNP5 fits better into the inner cavity of β-CD, which forms more stable inclusion complex than γ-CD in the single-vial formulations. The results from biodistribution and imaging studies in Sprague-Dawley rats clearly demonstrated biological equivalence of three different formulations. Single photon-emission computed tomography data suggested that high quality images could be obtained at 0-30-min post-injection without significant interference from the liver radioactivity. Considering the ease for (99m) Tc-labeling and high RCP of (99m) TcN-MPO, the non-SnCl2 single-vial formulation is an attractive choice for future clinical studies. PMID:25070025

  14. Investigating the pharmacokinetics and biological distribution of silver-loaded polyphosphoester-based nanoparticles using 111Ag as a radiotracer

    PubMed Central

    Aweda, Tolulope A.; Zhang, Shiyi; Mupanomunda, Chiedza; Burkemper, Jennifer; Heo, Gyu Seong; Bandara, Nilantha; Lin, Mai; Cutler, Cathy S.; Cannon, Carolyn L.; Youngs, Wiley; Wooley, Karen L.; Lapi, Suzanne E.

    2015-01-01

    Purified 111Ag was used as a radiotracer to investigate silver loading and release, pharmacokinetics and biodistribution of polyphosphoester-based degradable shell crosslinked knedel-like (SCK) nanoparticles as a comparison to the previously reported small molecule, N-heterocyclic silver carbene complex analogue (SCC1) for the delivery of therapeutic silver ions in mouse models. Biodistribution studies were conducted by aerosol administration of 111Ag acetate, [111Ag]SCC1 and [111Ag]SCK doses directly into the lungs of C57BL/6 mice. Nebulization of the 111Ag antimicrobials resulted in an average uptake of 1.07 ± 0.12% of the total aerosolized dose given per mouse. The average dose taken into the lungs of mice was estimated to be 2.6 ± 0.3% of the dose inhaled per mouse for [111Ag]SCC1 and twice as much dose was observed for the [111Ag]SCKs (5.0 ± 0.3% and 5.9 ± 0.8% for [111Ag]aSCK and [111Ag]zSCK, respectively) at 1 h post administration (p.a.). [111Ag]SCKs also exhibited higher dose retention in the lungs; 62 – 68% for [111Ag]SCKs and 43% for [111Ag]SCC1 of the initial 1 h dose was observed in the lungs at 24 h post administration (p.a.). This study demonstrates the utility of 111Ag as a useful tool for monitoring the pharmacokinetics of silver loaded antimicrobials in vivo. PMID:25952472

  15. Study of ⁷Be and ²¹⁰Pb as radiotracers of African intrusions in Malaga (Spain).

    PubMed

    Gordo, E; Liger, E; Dueñas, C; Fernández, M C; Cañete, S; Pérez, M

    2015-10-01

    The relationship between the particulate matter in the atmosphere of Malaga and the origin of air masses with special attention to African intrusions was analyzed. The concentrations of PM10 and the activities of some radionuclides ((7)Be and (210)Pb) as tracers of these intrusions are discussed. The origin of these radiotracers is completely different. (210)Pb is a good tracer of air masses traveling close to the ground and come from inland areas. On the other hand, the production of (7)Be is very low in the vicinity of the Earth's surface, and increases with altitude, making it a great tracer of stratospheric air masses in the troposphere. Studies of radionuclide activities in aerosol particles provide a means for evaluating the integrated effects of transport and meteorology on the atmospheric loadings of substances with different sources. Measurements of aerosol mass concentration and specific activities of (7)Be and (210)Pb in aerosols at Malaga (36° 43' 40″ N; 4° 28' 8″ W) for the period 2009-2011 were used to obtain the relationships between radionuclide activities and airflow patterns by comparing the data grouped by air mass trajectory. The average concentration values of (7)Be and (210)Pb over the 3-year period have been found to be 5.05 and 0.55 mBq m(-3), respectively, with mean aerosol mass concentration of 53.6 μg m(-3). Taking into account the outbreaks of the daily values limits of PM10 in the study period (2009-2011), the origin of air masses is studied to explain three different situations of both radionuclides (7)Be and (210)Pb: 1) high concentrations of (7)Be and low concentrations of (210)Pb; 2) high concentrations of (210)Pb and low concentrations of (7)Be and 3) high concentrations of (7)Be and (210)Pb. PMID:26164283

  16. Improved Most-Probable-Number Method To Detect Sulfate-Reducing Bacteria with Natural Media and a Radiotracer

    PubMed Central

    Vester, Flemming; Ingvorsen, Kjeld

    1998-01-01

    A greatly improved most-probable-number (MPN) method for selective enumeration of sulfate-reducing bacteria (SRB) is described. The method is based on the use of natural media and radiolabeled sulfate (35SO42−). The natural media used consisted of anaerobically prepared sterilized sludge or sediment slurries obtained from sampling sites. The densities of SRB in sediment samples from Kysing Fjord (Denmark) and activated sludge were determined by using a normal MPN (N-MPN) method with synthetic cultivation media and a tracer MPN (T-MPN) method with natural media. The T-MPN method with natural media always yielded significantly higher (100- to 1,000-fold-higher) MPN values than the N-MPN method with synthetic media. The recovery of SRB from environmental samples was investigated by simultaneously measuring sulfate reduction rates (by a 35S-radiotracer method) and bacterial counts by using the T-MPN and N-MPN methods, respectively. When bacterial numbers estimated by the T-MPN method with natural media were used, specific sulfate reduction rates (qSO42−) of 10−14 to 10−13 mol of SO42− cell−1 day−1 were calculated, which is within the range of qSO42− values previously reported for pure cultures of SRB (10−15 to 10−14 mol of SO42− cell−1 day−1). qSO42− values calculated from N-MPN values obtained with synthetic media were several orders of magnitude higher (2 × 10−10 to 7 × 10−10 mol of SO42− cell−1 day−1), showing that viable counts of SRB were seriously underestimated when standard enumeration media were used. Our results demonstrate that the use of natural media results in significant improvements in estimates of the true numbers of SRB in environmental samples. PMID:9572939

  17. Radiation Dosimetry and Biodistribution of the Translocator Protein Radiotracer [11C]DAA1106 Determined with PET/CT in Healthy Human Volunteers

    PubMed Central

    Brody, Arthur L.; Okita, Kyoji; Shieh, Jennifer; Liang, Lidia; Hubert, Robert; Mamoun, Michael; Farahi, Judah; Mandelkern, Mark A.

    2014-01-01

    Introduction When microglia become activated (an integral part of neuroinflammation), cellular morphology changes and expression of translocator protein (TSPO) 18 kDa is increased. Over the past several years, [11C]DAA1106 has emerged as a reliable radiotracer for labeling TSPO with high affinity during positron emission tomography (PET) scanning. While [11C]DAA1106 PET scanning has been used in several research studies, a radiation dosimetry study of this radiotracer in humans has not yet been published. Methods Twelve healthy participants underwent full body dynamic [11C]DAA1106 PET scanning, with 8 sequential whole body scans (approximately 12 bed positions each), following a single injection. Regions of interest were drawn manually and time activity curves (TACs) were obtained for 15 organs. OLINDA/EXM 1.1 was used to compute radiation absorbed doses to the target organs, as well as effective dose (ED) and effective dose equivalent (EDE). Results The ED and EDE were 4.06 ± 0.58 μSv/MBq and 5.89 ± 0.83 μSv/MBq, respectively. The highest absorbed doses were to the heart wall, kidney, liver, pancreas, and spleen. TACs revealed that peak dose rates are during the first scan (at 6 min) for all organs other than the urinary bladder wall, which had its peak dose rate during the fourth scan (at 30 min). Conclusions The recently developed radiotracer [11C]DAA1106 has its EDE and target-organ absorbed dose such that, for a single administration, its radiation dosimetry is well within the U.S. FDA guidelines for basic research studies in adults. This dose level implies that the dosimetry for multiple [11C]DAA1106 scans within a given year also falls within FDA guidelines, and this favorable property makes this radiotracer suitable for examining microglial activation repeatedly over time, which may in the future be useful for longitudinal tracking of disease progression and monitoring of therapy response in conditions marked by neuroinflammation (e.g., head trauma and

  18. [{sup 11}C]d-threo-Methylphenidate, a new radiotracer for the dopamine transporter. Characterization in baboon and human brain

    SciTech Connect

    Ding, Y.S.; Volkow, N.D.; Fowler, J.S.

    1995-05-01

    dl-threo Methylphenidate (MP, Ritalin) is a psychostimulant drug which binds to the dopamine transporter (DAT). We evaluated [{sup 11}C]d-threo-methylphenidate ([{sup 11}C]d-MP), the more active enantiomer, as a radiotracer for the DAT in baboons and human brain. Stereoselectivity, saturability and pharmacological specificity and reproducibility were examined. Stereoselectivity was examined in baboons by comparing [{sup 11C}]d-MP,[{sup 11}C]l-MP and [{sup 11}C]dl-MP. Unlabeled MP was used to assess the reversibility and saturability of the binding. GBR 12909,{beta}-(4-iodophenyl)tropane-2-carboxylic acid methyl ester ({beta}-CIT), tomoxetine and citalopram were used to assess the specificity of the binding. The ratios between the radioactivity in the striatum to that in cerebellum (ST/CB) were 3.3,2.2 and 1.1 for [{sup 11}C]d-MP,[{sup 11}C]dl-MP and [{sup 11}C]l-MP respectively. Most of the striatal binding of [{sup 11}C]d-threo-MP was displaced by injection of nonradioactive MP demonstrating reversibility. Pretreatment with MP (0.5 mg/kg), GBR12909 (1.5 mg/kg) or {beta}-CIT (0.3 mg/kg) reduced ST/CB by about 60% and the ratios of distribution volumes at the steady-state for the triatum to cerebellum (DV{sub st/}DV{sub cb}) by about 50%. Pretreatment with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg), inhibitors of the norepinephrine and serotonin transporter, had no effect. Studies of [{sup 11}C]d-MP in the human brain showed highest uptake in basal ganglia with a half clearance time of about 60 minutes. Repeated studies in 6 normal human subjects showed differences in DV{sub st/}DV{sub cb} between -7% and 8%. MP pretreatment decreased BG but no cortical or cerebellar binding and reduced Bmax/Kd by 91%.

  19. Identification of ABC Transporter Interaction of a Novel Cyanoquinoline Radiotracer and Implications for Tumour Imaging by Positron Emission Tomography

    PubMed Central

    Slade, Rozanna L.; Pisaneschi, Federica; Nguyen, Quang-De; Smith, Graham; Carroll, Laurence; Beckley, Alice; Kaliszczak, Maciej A.; Aboagye, Eric O.

    2016-01-01

    Background The epidermal growth factor receptor (EGFR) is overexpressed in many cancers including lung, ovarian, breast, head and neck and brain. Mutation of this receptor has been shown to play a crucial role in the response of non-small cell lung carcinoma (NSCLC) to EGFR-targeted therapies. It is envisaged that imaging of EGFR using positron emission tomography (PET) could aid in selection of patients for treatment with novel inhibitors. We recognised multi-drug resistant phenotype as a threat to development of successful imaging agents. In this report, we describe discovery of a novel cyanoquinoline radiotracer that lacks ABC transporter activity. Methods Cellular retention of the prototype cyanoquinoline [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxyquinolin-6-yl}-4-({[1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl]methyl}amino)-but-2-enamide ([18F]FED6) and [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxyquinolin-6-yl}-4-[({1-[(2R,5S)-3-fluoro-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]-1H-1,2,3-triazol-4-yl}methyl)amino]but-2-enamide ([18F]FED20) were evaluated to establish potential for imaging specificity. The substrate specificity of a number of cyanoquinolines towards ABC transporters was investigated in cell lines proficient or deficient in ABCB1 or ABCG2. Results FED6 demonstrated substrate specificity for both ABCG2 and ABCB1, a property that was not observed for all cyanoquinolines tested, suggesting scope for designing novel probes. ABC transporter activity was confirmed by attenuating the activity of transporters with drug inhibitors or siRNA. We synthesized a more hydrophilic compound [18F]FED20 to overcome ABC transporter activity. FED20 lacked substrate specificity for both ABCB1 and ABCG2, and maintained a strong affinity for EGFR. Furthermore, FED20 showed higher inhibitory affinity for active mutant EGFR versus wild-type or resistant mutant EGFR; this property resulted in higher [18F]FED20 cellular retention in active

  20. Synthesis and Evaluation of [11C]LY2795050 as a Novel Kappa Opioid Receptor Antagonist Radiotracer for PET Imaging

    PubMed Central

    Zheng, Ming-Qiang; Nabulsi, Nabeel; Kim, Su Jin; Tomasi, Giampaolo; Lin, Shu-fei; Mitch, Charles; Quimby, Steven; Barth, Vanessa; Rash, Karen; Masters, John; Navarro, Antonio; Seest, Eric; Morris, Evan E.; Carson, Richard E.; Huang, Yiyun

    2013-01-01

    is a suitable ligand for imaging the KOR in primates. This newly developed KOR antagonist tracer has since been advanced to PET imaging of KOR in humans and constitutes the first successful KOR antagonist radiotracer. PMID:23353688

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

    PubMed

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

    2014-12-01

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

  2. Design, synthesis and evaluation of [(3)H]PF-7191, a highly specific nociceptin opioid peptide (NOP) receptor radiotracer for in vivo receptor occupancy (RO) studies.

    PubMed

    Zhang, Lei; Drummond, Elena; Brodney, Michael A; Cianfrogna, Julie; Drozda, Susan E; Grimwood, Sarah; Vanase-Frawley, Michelle A; Villalobos, Anabella

    2014-11-15

    Herein we report the identification of (+)-N-(2-((1H-pyrazol-1-yl)methyl)-3-((1R,3r,5S)-6'-fluoro-8-azaspiro[bicyclo[3.2.1]octane-3,1'-isochroman]-8-yl)propyl)-N-[(3)H]-methylacetamide {[(3)H]PF-7191 [(+)-11]} as a promising radiotracer for the nociceptin opioid peptide (NOP) receptor. (+)-11 demonstrated high NOP binding affinity (Ki = 0.1 nM), excellent selectivity over other opioid receptors (>1000×) and good brain permeability in rats (C(b,u)/C(p,u) = 0.29). Subsequent characterization of [(3)H](+)-11 showed a high level of specific binding and a brain bio-distribution pattern consistent with known NOP receptor expression. Furthermore, the in vivo brain binding of [(3)H](+)-11 in rats was inhibited by a selective NOP receptor antagonist in a dose-responsive manner. This overall favorable profile indicated that [(3)H](+)-11 is a robust radiotracer for pre-clinical in vivo receptor occupancy (RO) measurements and a possible substrate for carbon-11 labeling for positron emission tomography (PET) imaging in higher species. PMID:25442316

  3. Development of a system for real-time measurements of metabolite transport in plants using short-lived positron-emitting radiotracers

    NASA Astrophysics Data System (ADS)

    Kiser, Matthew R.

    Over the past 200 years, the Earth's atmospheric carbon dioxide (CO 2) concentration has increased by more than 35%, and climate experts predict that CO2 levels may double by the end of this century. Understanding the mechanisms of resource management in plants is fundamental for predicting how plants will respond to the increase in atmospheric CO 2. Plant productivity sustains life on Earth and is a principal component of the planet's system that regulates atmospheric CO2 concentration. As such, one of the central goals of plant science is to understand the regulatory mechanisms of plant growth in a changing environment. Short-lived positron-emitting radiotracer techniques provide time-dependent data that are critical for developing models of metabolite transport and resource distribution in plants and their microenvironments. To better understand the effects of environmental changes on resource transport and allocation in plants, we have developed a system for real-time measurements of rnetabolite transport in plants using short-lived positron-emitting radio-tracers. This thesis project includes the design, construction, and demonstration of the capabilities of this system for performing real-time measurements of metabolite transport in plants. The short-lived radiotracer system described in this dissertation takes advantage of the combined capabilities and close proximity of two research facilities at. Duke University: the Triangle Universities Nuclear Laboratory (TUNL) and the Duke University Phytotron, which are separated by approximately 100 meters. The short-lived positron-emitting radioisotopes are generated using the 10-MV tandem Van de Graaff accelerator located in the main TUNL building, which provides the capability of producing short-lived positron-emitting isotopes such as carbon-11 (11C: 20 minute half-life), nitrogen-13 (13N; 10 minute half-life), fluorine-18 (18F; 110 minute half-life), and oxygen-15 (15O; 2 minute half-life). The radioisotopes may

  4. Model studies using supercritical carbon dioxide fluid (SF CO{sub 2}) as a reaction medium for radiotracer synthesis and purification

    SciTech Connect

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

    1994-05-01

    Supercritical fluids (SFs) have found widespread use in the analytical field as solvents for compound purification, and initial results on their use for radiotracer synthesis have been reported. SF`s possess the unique feature that their solvating strength can be altered drastically through small changes in pressure and temperature of the fluid within the supercritical regime. We have modified a SF chromatograph to allow us to investigate its use in radiotracer synthesis and purification. The solubility of several PET radiotracers was measured in SF CO{sub 2} at 5000 psi and 55{degrees}C and showed the following: raclopride, 68 {mu}g/mL{sup 2}; (L)-deprenyl, 85 {mu}g/mL; flumazenil, 61 {mu}g/mL; (-)cocaine, 108 {mu}g/mL; ritalin, 45 {mu}g/Ml; and cogentin, 250 {mu}g/mL. Analytical separations were achieved on 30 to 50 {mu}g amounts of (L)-deprenyl (3.9 min RT) and nor-deprenyl (4.7 min RT), as well as raclopride (10.8 min RT) and nor-raclopride (10.3 min RT) using 250 mm x 4.5 mm i.d. Ultracarb 5 ODS (30), and 75 mm x 4.5 mm i.d. silica columns, respectively, and pure SF CO{sub 2} as the mobile phase. Model studies on simple N-alkylation reactions were also carried out using pur SF CO{sub 2} as the reaction medium on a modified alumina support. (L)-Deprenyl was synthesized from only 100 {mu}g of the starting labelling substrate using 500 mg of alumina impregnated with triphenylphosphine diiodide (20% by wt.) and maintained at 170{degrees}C. The methylating agent, methyl iodide, was generated in situ from methanol, but was always present in excess of the substrate. Studies are in progress to reduce methanol amounts. Pressure studies of SF CO{sub 2} ranging from 3000 to 6000 psi showed an 80% increase in the methylation reaction relative to the amount of starting substrate suggesting an effect of the fluid density. Temperature was also a critical parameter here as the reaction did not proceed at 80{degrees}C for similiar pressures.

  5. 111In- and 203Pb-Labeled Cyclic RGD Peptide Conjugate as an αvβ3 Integrin-Binding Radiotracer

    PubMed Central

    Nwe, Kido; Kim, Young-Seung; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2012-01-01

    Methodology for site-specific modification and chelate conjugation of a cyclic RGD (cRGD) peptide for the preparation of a radiotracer molecular imaging agent suitable for detecting αvβ3 integrin is described. The method involves functionalizing the peptide with an aldehyde moiety and conjugation to a 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) derivative that possesses an aldehyde reactive aminooxy group. The binding assay of the 111In-labeled peptide conjugate with αvβ3 integrin showed 60% bound when four equivalents of the integrin was added, a reasonable binding affinity for a mono-valent modified RGD peptide. PMID:23162207

  6. Inappropriate Intra-cervical Injection of Radiotracer for Sentinel Lymph Node Mapping in a Uterine Cervix Cancer Patient: Importance of Lymphoscintigraphy and Blue Dye Injection

    PubMed Central

    Kadkhodayan, Sima; Farahabadi, Elham Hosseini; Yousefi, Zohreh; Hasanzadeh, Malihe; Sadeghi, Ramin

    2014-01-01

    Herein, we report a case of sentinel lymph node mapping in a uterine cervix cancer patient, referring to the nuclear medicine department of our institute. Lymphoscintigraphy images showed inappropriate intra-cervical injection of radiotracer. Blue dye technique was applied for sentinel lymph node mapping, using intra-cervical injection of methylene blue. Two blue/cold sentinel lymph nodes, with no pathological involvement, were intra-operatively identified, and the patient was spared pelvic lymph node dissection. The present case underscores the importance of lymphoscintigraphy imaging in sentinel lymph node mapping and demonstrates the added value of blue dye injection in selected patients. It is suggested that pre-operative lymphoscintigraphy imaging be considered as an integral part of sentinel lymph node mapping in surgical oncology. Detailed results of lymphoscintigraphy images should be provided for surgeons prior to surgery, and in case the sentinel lymph nodes are not visualized, use of blue dye for sentinel node mapping should be encouraged.

  7. Inappropriate Intra-cervical Injection of Radiotracer for Sentinel Lymph Node Mapping in a Uterine Cervix Cancer Patient: Importance of Lymphoscintigraphy and Blue Dye Injection.

    PubMed

    Kadkhodayan, Sima; Farahabadi, Elham Hosseini; Yousefi, Zohreh; Hasanzadeh, Malihe; Sadeghi, Ramin

    2014-01-01

    Herein, we report a case of sentinel lymph node mapping in a uterine cervix cancer patient, referring to the nuclear medicine department of our institute. Lymphoscintigraphy images showed inappropriate intra-cervical injection of radiotracer. Blue dye technique was applied for sentinel lymph node mapping, using intra-cervical injection of methylene blue. Two blue/cold sentinel lymph nodes, with no pathological involvement, were intra-operatively identified, and the patient was spared pelvic lymph node dissection. The present case underscores the importance of lymphoscintigraphy imaging in sentinel lymph node mapping and demonstrates the added value of blue dye injection in selected patients. It is suggested that pre-operative lymphoscintigraphy imaging be considered as an integral part of sentinel lymph node mapping in surgical oncology. Detailed results of lymphoscintigraphy images should be provided for surgeons prior to surgery, and in case the sentinel lymph nodes are not visualized, use of blue dye for sentinel node mapping should be encouraged. PMID:27408871

  8. Synthesis and biological evaluation of positron emission tomography radiotracers targeting serotonin 4 receptors in brain: [18F]MNI-698 and [18F]MNI-699.

    PubMed

    Caillé, Fabien; Morley, Thomas J; Tavares, Adriana Alexandre S; Papin, Caroline; Twardy, Nicole M; Alagille, David; Lee, H Sharon; Baldwin, Ronald M; Seibyl, John P; Barret, Olivier; Tamagnan, Gilles D

    2013-12-01

    Two new benzodioxane derivatives were synthesized as candidates to image the serotonin 4 receptors by positron emission tomography (PET) and radiolabeled with fluorine-18 via a two-step procedure. Competition binding assays demonstrated that MNI-698 and MNI-699 had sub-nanomolar binding affinities against rat striatal 5-HT4 receptors (Ki of 0.20 and 0.07 nM, respectively). PET imaging in rhesus monkey showed that the regional brain distribution of [(18)F]MNI-698 and [(18)F]MNI-699 were consistent with the known densities of 5-HT4 in brain. [(18)F]MNI-698 and [(18)F]MNI-699 are among the first fluorine-18 radiotracers developed for imaging the 5-HT4 receptors in vivo and are currently under preclinical investigation in primates for future human use. PMID:24157369

  9. Synthesis and characterization of (68)Ga-labeled curcumin and curcuminoid complexes as potential radiotracers for imaging of cancer and Alzheimer's disease.

    PubMed

    Asti, Mattia; Ferrari, Erika; Croci, Stefania; Atti, Giulia; Rubagotti, Sara; Iori, Michele; Capponi, Pier C; Zerbini, Alessandro; Saladini, Monica; Versari, Annibale

    2014-05-19

    Curcumin (CUR) and curcuminoids complexes labeled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer's disease. Gallium-68 is a positron-emitting, generator-produced radionuclide, and its properties can be exploited in situ in medical facilities without a cyclotron. Moreover, CUR showed a higher uptake in tumor cells compared to normal cells, suggesting potential diagnostic applications in this field. In spite of this, no studies using labeled CUR have been performed in this direction, so far. Herein, (68)Ga-labeled complexes with CUR and two curcuminoids, namely diacetyl-curcumin (DAC) and bis(dehydroxy)curcumin (bDHC), were synthesized and characterized by means of experimental and theoretical approaches. Moreover, a first evaluation of their affinity to synthetic β-amyloid fibrils and uptake by A549 lung cancer cells was performed to show the potential application of these new labeled curcuminoids in these diagnostic fields. The radiotracers were prepared by reacting (68)Ga(3+) obtained from a (68)Ge/(68)Ga generator with 1 mg/mL curcuminoids solutions. Reaction parameters (precursor amount, reaction temperature, and pH) were optimized to obtain high and reproducible radiochemical yield and purity. Stoichiometry and formation of the curcuminoid complexes were investigated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, NMR, ultraviolet-visible, and fluorescence spectroscopy on the equivalent (nat)Ga-curcuminoids (nat = natural) complexes, and their structure was computed by theoretical density functional theory calculations. The analyses evidenced that CUR, DAC, and bDHC were predominantly in the keto-enol form and attested to Ga(L)2(+) species formation. Identity of the (68)Ga(L)2(+) complexes was confirmed by coelution with the equivalent (nat)Ga(L)2(+) complexes in ultrahigh-performance liquid chromatography analyses.(68)Ga(CUR)2(+), (68)Ga(DAC)2(+), and (68)Ga(bDHC)2

  10. Evaluation of the anti-HER2 C6.5 diabody as a PET radiotracer to monitor HER2 status and predict response to trastuzumab treatment

    PubMed Central

    Reddy, Smitha; Shaller, Calvin C.; Doss, Mohan; Shchaveleva, Irina; Marks, James D.; Yu, Jian Q.; Robinson, Matthew K.

    2011-01-01

    Purpose The rapid tumor targeting and pharmacokinetic properties of engineered antibodies make them potentially suitable for use in imaging strategies to predict and monitor response to targeted therapies. This study aims to evaluate C6.5 diabody (C6.5db), a non-covalent anti-HER2 single chain-Fv dimer, as a radiotracer for predicting response to HER2-targeted therapies such as trastuzumab. Experimental Design Immunodeficient mice bearing established HER2-positive tumor xenografts were injected with radioiodinated C6.5db and imaged using PET/CT. Radiotracer biodistribution was quantified using biopsied tumor and normal tissues. Potential competition between trastuzumab and C6.5db was examined in vitro by flow cytometry and co-immunoprecipitations. Results Biodistribution analysis of mice bearing xenografts with varying HER2 density revealed that the tumor uptake of 125I-C6.5db correlates with HER2 tumor density. In vitro competition experiments suggest that the C6.5db targets an epitope on HER2 that is distinct from that bound by trastuzumab. Treatment of SK-OV-3-tumored mice with trastuzumab for 3 d caused a 42% (P=0.002) decrease in tumor uptake of 125I-C6.5db. This is consistent with a dramatic decrease in the tumor PET signal of 124I-C6.5db after trastuzumab treatment. Furthermore, BT-474-tumored mice showed a ∼60% decrease (P=0.0026) in C6.5db uptake after 6 d of trastuzumab treatment. Immunohistochemistry of excised xenograft sections and in vitro flow cytometry revealed that the decreased C6.5db uptake upon trastuzumab treatment is not associated with HER2 downregulation. Conclusions These studies suggest that 124I-C6.5db-based imaging can be used to evaluate HER2 levels as a predictor of respone to HER2-directed therapies. PMID:21177408

  11. Measurement of Bmax and Kd with the glycine transporter 1 radiotracer ¹⁸F-MK6577 using a novel multi-infusion paradigm.

    PubMed

    Xia, Yan; Zheng, Ming-Qiang; Holden, Daniel; Lin, Shu-fei; Kapinos, Michael; Ropchan, Jim; Gallezot, Jean-Dominique; Huang, Yiyun; Carson, Richard E

    2015-12-01

    Glycine is a co-agonist of glutamate at the NMDA receptor. Glycine transporter 1 (GlyT1) inhibitors are reported to be potential therapeutic agents for schizophrenia. (18)F-MK6577 is a new positron emission tomography (PET) radiotracer useful for imaging brain GlyT1 and its occupancy in humans. We devised a novel multi-infusion paradigm of radiolabeled and unlabeled compound and an iterative linear/nonlinear alternating fitting method to allow for the determination of in vivo affinity (Kd) and target concentration (Bmax) images, constraining Kd to be uniform across the brain. This paradigm was tested with (18)F-MK6577 in baboons. Voxel-based analysis produced high quality Bmax images and reliable Kd estimates, and also suggested that the nondisplaceable distribution volume (VND) is not uniform throughout the brain. In vivo GlyT1 Kd was estimated to be 1.87 nmol/L for (18)F-MK6577, and the rank order of GlyT1 distribution measured in the baboon brain was: high in the brainstem (133 nmol/L), medium in the cerebellum (83 nmol/L), and low in the cortex (30 nmol/L). These in vivo Kd and Bmax values agreed well with those determined in vitro, thus validating our novel multi-infusion approach. PMID:26198176

  12. Methodological considerations regarding the use of inorganic 197Hg(II) radiotracer to assess mercury methylation potential rates in lake sediment

    USGS Publications Warehouse

    Perez, Catan S.; Guevara, S.R.; Marvin-DiPasquale, M.; Magnavacca, C.; Cohen, I.M.; Arribere, M.

    2007-01-01

    Methodological considerations on the determination of benthic methyl-mercury (CH3Hg) production potentials were investigated on lake sediment, using 197Hg radiotracer. Three methods to arrest bacterial activity were compared: flash freezing, thermal sterilization, and ??-irradiation. Flash freezing showed similar CH3Hg recoveries as thermal sterilization, which was both 50% higher than the recoveries obtained with ??-ray irradiation. No additional radiolabel was recovered in kill-control samples after an additional 24 or 65 h of incubation, suggesting that all treatments were effective at arresting Hg(II)-methylating bacterial activity, and that the initial recoveries are likely due to non-methylated 197Hg(II) carry-over in the organic extraction and/or [197Hg]CH3Hg produced via abiotic reactions. Two CH3Hg extraction methods from sediment were compared: (a) direct extraction into toluene after sediment leaching with CuSO4 and HCl and (b) the same extraction with an additional back-extraction step to thiosulphate. Similar information was obtained with both methods, but the low efficiency observed and the extra work associated with the back-extraction procedure represent significant disadvantages, even tough the direct extraction involves higher Hg(II) carry over. ?? 2007 Elsevier Ltd. All rights reserved.

  13. Radiosynthesis of a dopamine receptor-binding radiotracer for positron emission tomography: 3-N-(C-11-methyl)-methyl-spiperone

    SciTech Connect

    Ravert, H.T.; Burns, H.D.; Dannals, R.F.; Langstrom, B.; Duelfer, T.; Wilson, A.A.; Zemyan, S.E.; Wagner, H.N. Jr.

    1984-01-01

    Dopamine receptors appear to be involved with abnormalities related to disorders such as Parkinson's disease and schizophrenia. Spiperone is an extremely potent neuroleptic which binds with high affinity to dopamine receptors. Based on in vitro binding studies, the authors selected 3-N-methylspiperone, a derivative of spiperone which has similar binding characteristics, for radiolabeling. C-11 Methyl iodide was prepared from C-11 carbon dioxide and bubbled through a methylene chloride solution of spiperone. Aqueous tetrabutylammonium hydroxide was added with mixing by sonication. The product was isolated by preparative reverse phase high performance liquid chromatography (HPLC) and analyzed for radiochemical purity by analytical C-18 HPLC. Further refinement of the radiochemical synthesis has reduced the time of preparation from an average of 80 minutes to approximately 30 minutes. As many as 5 production runs have been carried out per day. Three are performed routinely due to the shortened synthesis time and the judicious use of remote handling. Automation of the process is now in progress. In 108 consecutive production runs of this radiotracer, the average radiochemical yield has been 35% with an average synthesis time of 36 minutes and the average specific activity of 294 mCi/..mu..mole E.O.S.

  14. Depuration and uptake kinetics of I, Cs, Mn, Zn and Cd by the earthworm (Lumbricus terrestris) in radiotracer-spiked litter

    SciTech Connect

    Sheppard, S.C.; Evenden, W.G.; Cornwell, T.C.

    1997-10-01

    The relative depuration and uptake kinetics of contaminants should be known to interpret appropriately the use of organisms such as earthworms in environmental bioassays and monitoring. For example, 14-d earthworm bioassays should be interpreted with the knowledge that some contaminants will continue to accumulate in tissues for months. The radiotracers {sup 125}I, {sup 134}Cs, {sup 54}Mn, {sup 65}Zn, and {sup 109}Cd were applied to deciduous litter and specimens of Lumbricus terrestris were exposed, either to litter alone or to litter on the top of soil columns. Depuration was monitored for 120 d and uptake, in a separate experiment, for 20 d. Both depuration and uptake were described using two-phase, first-order statistical models. Cut clearance had a mean half-time of 1.4 d. The mean half-time for physiological depuration decreased from I (210 d) > Cd (150 d) > Zn (69 d) > Mn (40 d) > Cs (24 d). Both the depuration and the uptake experiments were necessary to resolve even partially the multiphase processes. Earthworm/soil dry weight concentration ratios decreased from Cd > Zn > I {ge} Cs {ge} Mn. The very slow kinetics indicate that tissue concentrations will increase continuously for a long time, with important implications for subsequent food-chain transfers.

  15. Radiotracers binding to estrogen receptors: I: tissue distribution of 17 alpha-ethynylestradiol and moxestrol in normal and tumor-bearing rats

    SciTech Connect

    Feenstra, A.; Nolten, G.M.; Vaalburg, W.; Reiffers, S.; Woldring, M.G.

    1982-07-01

    Ethynylestradiol and moxestrol can be labeled with /sup 11/C by introducing this positron emitter in the 17 alpha-ethynyl group. To investigate their potential as radiotracers binding to estrogen receptors, researchers studied the tissue distribution of tritiated ethynylestradiol and moxestrol, with specific activities of 57 Ci/mmol and 77-90 Ci/mmol, respectively, in the adult female rat. At 30 min after injection, both compounds showed specific uptake in the uterus (% dose/g): 2.52 for ethynylestradiol and of 2.43 for moxestrol. A decrease of the specific activity to 6-9 Ci/mmol resulted in uterine uptakes of 1.60 and 2.10 respectively, for ethynylestradiol and moxestrol, at 30 min. In the female rat bearing DMBA-induced mammary tumors, specific uptake was also measured in the tumors, although the values were only 25-30% of the uterine uptake. Moxestrol showed a greater uptake selectivity in the tumors compared with ethynylestradiol. From this study researchers conclude that ethynylestradiol and moxestrol have good potential as tracers binding to mammary tumors that contain estrogen receptors.

  16. A Mn-54 Radiotracer Study of Mn Isotope Solid-Liquid Exchange during Reductive Transformation of Vernadite (δ-MnO₂) by Aqueous Mn(II)

    SciTech Connect

    Elzinga, Evert J.; Kustka, Adam B.

    2015-04-09

    We employed Mn-54 radiotracers to characterize the extent and dynamics of Mn atom exchange between aqueous Mn(II) and vernadite (δ-Mn(IV)O2) at pH 7.5 under anoxic conditions. Exchange of Mn atoms between the solid and liquid phase is rapid, reaching dynamic equilibrium in 2–4 days. We propose that during the initial stages of reaction, Mn atom exchange occurs through consecutive comproportionation-disproportionation reactions where interfacial electron transfer from adsorbed Mn(II) to lattice Mn(IV) generates labile Mn(III) cations that rapidly disproportionate to reform aqueous Mn(II) and solid-phase Mn(IV). Following nucleation of Mn(III)OOH phases, additional exchange likely occurs through electron transfer from aqueous Mn(II) to solid-phase Mn(III). Our results provide evidence for the fast and extensive production of transient Mn(III) species at the vernadite surface upon contact of this substrate with dissolved Mn(II). We further show that HEPES buffer is a reductant of lattice Mn(IV) in the vernadite structure in our experiments. The methods and results presented here introduce application of Mn-54 tracers as a facile tool to further investigate the formation kinetics of labile Mn(III) surface species and their impacts on Mn-oxide structure and reactivity over a range of environmentally relevant geochemical conditions.

  17. Affinity of (nat/68)Ga-Labelled Curcumin and Curcuminoid Complexes for β-Amyloid Plaques: Towards the Development of New Metal-Curcumin Based Radiotracers.

    PubMed

    Rubagotti, Sara; Croci, Stefania; Ferrari, Erika; Iori, Michele; Capponi, Pier C; Lorenzini, Luca; Calzà, Laura; Versari, Annibale; Asti, Mattia

    2016-01-01

    Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer's disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide). Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of three (nat/68)Ga-labelled curcumin analogues, namely curcumin curcumin (CUR), bis-dehydroxy-curcumin (bDHC) and diacetyl-curcumin (DAC), was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of (68)Ga(CUR)₂⁺, (68)Ga(DAC)₂⁺, and (68)Ga(bDHC)₂⁺ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood-brain barrier. Like curcumin, all (nat/68)Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo. PMID:27608011

  18. Bioconcentration of Ag, Cd, Co, Mn and Zn in the Mangrove Oyster (Crassostrea gasar) and Preliminary Human Health Risk Assessment: A Radiotracer Study.

    PubMed

    Kuranchie-Mensah, Harriet; Teyssié, Jean-Louis; Oberhänsli, François; Tumnoi, Yutthana; Pouil, Simon; Warnau, Michel; Metian, Marc

    2016-09-01

    Bioaccumulation kinetics of five dissolved metals were determined in the mangrove oyster Crassostrea gasar, using corresponding radiotracers ((54)Mn, (57)Co, (65)Zn, (109)Cd and (110m)Ag). Additionally, their bioaccessibility to human consumers was estimated. Results indicated that over a 14-day exposure (54)Mn and (57)Co were linearly concentrated in oysters whereas (109)Cd, (65)Zn and (110m)Ag were starting to saturate (steady-state not reached). Whole-body concentration factors at 14 days (CF14d in toto) ranged from 187 ± 65 to 629 ± 179 with the lowest bioconcentration capacity for Co and the highest for Ag. Depuration kinetics were best described by a double-exponential model with associated biological half-lives ranging from 26 days (Ag) to almost 8 months (Zn and Cd). Bioaccessible fraction of the studied elements was estimated using in vitro digestions, which suggested that oysters consumed seasoned with lemon enhanced the accessibility of Cd, Mn and Zn to human consumers, but not Ag and Co. PMID:27194421

  19. Technetium-99m-HIDA visualization of an obstructed gallbladder via an accessory hepatic duct

    SciTech Connect

    Reimer, D.E.; Donald, J.W.

    1981-09-01

    Technetium-99m-labeled iminodiacetic acid (HIDA) and paraisopropyliminodiacetic acid (PIPIDA) scintigraphy after sonographic evaluation of the gallbladder have been advocated recently for the diagnosis of acute obstructive cholecystitis and cholelithiasis. Several authors have stated or inferred that gallbladder visualization with /sup 99m/Tc-HIDA excludes acute cholecystitis and cystic duct obstruction. We describe a patient with surgically proven cystic duct obstruction whose gallbladder visualized on a /sup 99m/Tc-HIDA scan via an accessory hepatic duct which directly entered the gallbladder.

  20. Delayed positive gastrointestinal bleeding studies with technetium-99m-red blood cells: Utility of a second injection

    SciTech Connect

    Jacobson, A.F. )

    1991-02-01

    Two patients studied with technetium-99m-labeled red blood cells (RBCs) for gastrointestinal bleeding had positive findings only on 24-hr delayed images, at which time the site of bleeding could not be ascertained. In each instance, when additional delayed images suggested that active bleeding was occurring, a second aliquot of RBCs was labeled and injected. Sites of active hemorrhage were identified following further imaging in both patients. When delayed GI bleeding images are positive, further views should be obtained to ascertain if the pattern of intraluminal activity changes. If renewed active hemorrhage is suspected, reinjection with a second dose of labeled RBCs may identify the bleeding site.

  1. Creatine kinase MB isoenzyme in dermatomyositis: a noncardiac source

    SciTech Connect

    Larca, L.J.; Coppola, J.T.; Honig, S.

    1981-03-01

    Three patients with polymyositis had elevated serum levels of creatine kinase MB isoenzyme. The presence of this isoenzyme is used extensively to diagnose myocardial infarction, but the isoenzyme is also found in sera of patients with primary muscular and neuromuscular disorders. Researchers studied cardiac function in two of our patients with electrocardiograms, technetium stannous pyrophosphate scanning, and technetium 99m-labeled erythrocyte gated blood pool imaging and in the third patient by postmortem examination. There was no evidence of myocardial involvement to account for the high serum levels of isoenzyme. Creatine kinase MB in the sera of patients with polymyositis does not necessarily indicate myocardial necrosis.

  2. (54)Mn Radiotracers Demonstrate Continuous Dissolution and Reprecipitation of Vernadite (δ-MnO2) during Interaction with Aqueous Mn(II).

    PubMed

    Elzinga, Evert J

    2016-08-16

    (54)Mn radiotracers were used to assess Mn atom exchange between aqueous Mn(II) and vernadite (δ-MnO2) at pH 5.0. Continuous solid-liquid redistribution of (54)Mn atoms occurred, and systems are near isotopic equilibrium after reaction for 3 months. Despite this extensive exchange, X-ray diffraction and X-ray absorption spectroscopy data showed no major changes in vernadite bulk mineralogy. These results demonstrate that the vernadite-Mn(II) interface is dynamic, with the substrate undergoing continuous dissolution and reprecipitation mediated by aqueous Mn(II) without observable impacts on its mineralogy. Interfacial redox reactions between adsorbed Mn(II) and solid-phase Mn(IV) and Mn(III) are proposed as the main drivers of this process. Interaction between aqueous Mn(II) and structural Mn(III) likely involves interfacial electron transfer coupled with Mn atom exchange. The exchange of aqueous Mn(II) and solid-phase Mn(IV) is more complex and is proposed to result from coupled interfacial comproportionation-disproportionation reactions, where electron transfer from adsorbed Mn(II) to lattice Mn(IV) produces transient Mn(III) species that disproportionate to regenerate aqueous Mn(II) and structural Mn(IV). These findings provide further evidence of the importance of Mn(II)(aq)-MnO2(s) interactions and the attendant production of transient Mn(III) intermediates to the geochemical functioning of phyllomanganates in environments undergoing Mn redox cycling. PMID:27403960

  3. Further evaluation of the carbon11-labelled D2/3 agonist PET radiotracer PHNO: reproducibility in tracer characteristics and characterization of extrastriatal binding

    PubMed Central

    Egerton, Alice; Hirani, Ella; Ahmad, Rabia; Turton, David R; Brickute, Diana; Rosso, Lula; Howes, Oliver D; Luthra, Sajinder K; Grasby, Paul M

    2014-01-01

    [11C]-(+)-PHNO is a new dopamine D2/3 receptor agonist radiotracer which has been successfully used to measure D2/3 receptor availability in experimental animals and man. Here we report in vivo evaluation in the rat of the biodistribution, metabolism, specificity, selectivity and dopamine sensitivity of carbon-11 labeled PHNO ([11C]-3-PHNO) produced by an alternative radiochemical synthesis method. [11C]-3-PHNO showed rapid metabolism and clearance from most peripheral organs and tissues. [11C]-3-PHNO, but not its polar metabolite, readily crossed the blood-brain barrier and showed high levels of uptake in the D2/3 -rich striatum. Pre-treatment with unlabelled PHNO and the D2/3 receptor antagonist raclopride indicated that binding in the striatum was specific and selective to D2/3 receptors. PET studies in anaesthetized rats revealed significant reductions in [11C]-3-PHNO binding in the striatum following amphetamine administration, indicating sensitivity to increases in endogenous dopamine concentrations. D2/3 antagonist pre-treatment additionally indicated moderate levels of [11C]-3-PHNO specific binding in several extrastriatal brain areas – most notably the olfactory bulbs and tubercles, thalamus and hypothalamus. Of particular interest, approximately 30% of [11C]-3-PHNO signal in the cerebellum – a region often used as a ‘low-binding’ reference region for PET quantification - was attributable to specific signal. These data demonstrate that [11C]-3-PHNO shows similar tracer characteristics to [11C]-(+)-PHNO, but additionally indicate that radiolabeled PHNO may be used to estimate D2/3 receptor availability in select extrastriatal brain regions with PET. PMID:19957364

  4. Imaging glutamate homeostasis in cocaine addiction with the mGluR5 PET radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy

    PubMed Central

    Martinez, Diana; Slifstein, Mark; Nabulsi, Nabeel; Grassetti, Alexander; Urban, Nina; Perez, Audrey; Liu, Fei; Lin, Shu-fei; Ropchan, Jim; Mao, Xiangling; Kegeles, Lawrence S.; Shungu, Dikoma C.; Carson, Richard E.; Huang, Yiyun

    2014-01-01

    Background Preclinical studies demonstrate that glutamate homeostasis in the striatum is disrupted following cocaine exposure, including a decrease in metabotropic glutamate receptor type 5 (mGluR5) expression and reduced glutamate turnover. The goal of this study was to use imaging of the human brain to investigate alterations in the glutamate signaling in cocaine addiction. Methods Positron Emission tomography (PET) imaging with the radiotracer [11C]ABP688 was used to measure mGluR5 binding and magnetic resonance spectroscopy (MRS) was used to measure glutamate-glutamine levels in the striatum of cocaine addicted participants (n=15) compared to healthy controls (n=15). Following the scans, the cocaine addicted volunteers performed cocaine self-administration sessions in order to investigate the correlation between cocaine seeking behavior and mGluR5 receptor binding. Results The results of the study showed that cocaine addiction was associated with a 20–22% reduction in [11C]ABP688 binding in the striatum. A secondary analysis of cortical and subcortical regions other than the striatum showed a similar reduction in [11C]ABP688 binding, suggesting that the decrease is widespread. No between-group differences were seen in the MRS measures of glutamate-glutamine in the left striatum. In addition, no correlation was seen between [11C]ABP688 binding in the striatum and the choice to self-administer cocaine. Conclusions Overall, these results show that long-term cocaine use is associated with a decrease in mGluR5 availability compared to matched healthy controls and suggests that this receptor may serve as a viable target for treatment development for this disorder. PMID:24035345

  5. Test-retest reproducibility of binding parameters in humans with 11C-LY2795050, an antagonist PET radiotracer for the kappa opioid receptor

    PubMed Central

    Naganawa, Mika; Zheng, Ming-Qiang; Henry, Shannan; Nabulsi, Nabeel; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Najafzadeh, Soheila; Kapinos, Michael; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E.; Huang, Yiyun

    2015-01-01

    11C-LY2795050 is a new antagonist PET radioligand for the kappa opioid receptor (KOR). In this study, we assessed the reproducibility of the binding parameters of 11C-LY2795050 in healthy human subjects. Methods Sixteen healthy subjects (11 men, 5 women) underwent two separate 90-min PET scans with arterial input function and plasma free fraction measurements. The two-tissue compartment model and multilinear analysis-1 were applied to calculate five outcome measures in 14 brain regions: distribution volume (VT), distribution volume normalized by plasma free fraction (VT/fP), and three binding potentials (BPND, BPP, BPF). Since KOR is distributed ubiquitously throughout the brain, there are no suitable reference regions. We used a fixed fraction of individual cerebellum VT value as the non-displaceable distribution volume VND (= VT CER/1.17). The relative and absolute test-retest variability and intra-class correlation coefficient were evaluated for the outcome measures of 11C-LY2795050. Results The test-retest variability of 11C-LY2795050 for VT was ≤ 10% in all regions, and 12% in the amygdala. For binding potentials (BPND and BPP), the test-retest variability was good in regions of moderate and high KOR density (BPND > 0.4) and poor in regions of low density. Correction by fP (VT/fP or BPF) did not improve the test-retest performance. Conclusion Our results suggest that quantification of 11C-LY2795050 imaging is reproducible and reliable in the regions with moderate and high KOR density. Therefore we conclude that this first antagonist radiotracer is highly useful for PET studies of KOR. PMID:25593119

  6. Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin αvβ3-targeting Radiotracer.

    PubMed

    Yu, Xinhe; Wu, Yue; Liu, Hao; Gao, Liquan; Sun, Xianlei; Zhang, Chenran; Shi, Jiyun; Zhao, Huiyun; Jia, Bing; Liu, Zhaofei; Wang, Fan

    2016-05-01

    Purpose To assess the potential utility of an integrin αvβ3-targeting radiotracer, technetium 99m-PEG4-E[PEG4-cyclo(arginine-glycine-aspartic acid-D-phenylalanine-lysine)]2 ((99m)Tc-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model. Materials and Methods All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. (99m)Tc-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5). Results Accumulation of (99m)Tc-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 ± 3.39 vs 19.01 ± 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin αvβ3 on the activated hepatic stellate cells, and the integrin αvβ3 levels in the liver corresponded to the results of SPECT/CT (R(2) = 0.75, P < .0001). (99m)Tc-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon α2b compared with that in the control group (relative liver-to-background ratio: 0.45 ± 0.05 vs 1.01 ± 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 ± 0.06 vs 1.01 ± 0.05; P < .0001). Conclusion (99m)Tc-3PRGD2 SPECT/CT was successfully

  7. Radiotracer Imaging of Sediment Columns

    NASA Astrophysics Data System (ADS)

    Moses, W. W.; O'Neil, J. P.; Boutchko, R.; Nico, P. S.; Druhan, J. L.; Vandehey, N. T.

    2010-12-01

    Nuclear medical PET and SPECT cameras routinely image radioactivity concentration of gamma ray emitting isotopes (PET - 511 keV; SPECT - 75-300 keV). We have used nuclear medical imaging technology to study contaminant transport in sediment columns. Specifically, we use Tc-99m (T1/2 = 6 h, Eγ = 140 keV) and a SPECT camera to image the bacteria mediated reduction of pertechnetate, [Tc(VII)O4]- + Fe(II) → Tc(IV)O2 + Fe(III). A 45 mL bolus of Tc-99m (32 mCi) labeled sodium pertechnetate was infused into a column (35cm x 10cm Ø) containing uranium-contaminated subsurface sediment from the Rifle, CO site. A flow rate of 1.25 ml/min of artificial groundwater was maintained in the column. Using a GE Millennium VG camera, we imaged the column for 12 hours, acquiring 44 frames. As the microbes in the sediment were inactive, we expected most of the iron to be Fe(III). The images were consistent with this hypothesis, and the Tc-99m pertechnetate acted like a conservative tracer. Virtually no binding of the Tc-99m was observed, and while the bolus of activity propagated fairly uniformly through the column, some inhomogeneity attributed to sediment packing was observed. We expect that after augmentation by acetate, the bacteria will metabolically reduce Fe(III) to Fe(II), leading to significant Tc-99m binding. Imaging sediment columns using nuclear medicine techniques has many attractive features. Trace quantities of the radiolabeled compounds are used (micro- to nano- molar) and the half-lives of many of these tracers are short (<1 day). This allows multiple measurements to be made on the same column and thus the sediment biology to be monitored non-invasively over time (i.e. after an augmentation has been introduced) and minimizes long-lived radioactive waste. Different parameters can be measured, depending on the tracer type and delivery. A constant infusion of a conservative tracer, such as the positron emitter Br-76 (T1/2= 16.2 hr), measures the exclusion fraction (as a function of position in the column), while a bolus maps the flow velocity as a function of position. A tracer that interacts chemically with the contents of the column (e.g., [99m-Tc(VII)O4]- reduced to 99m-TcO2 by Fe(II) ) yields a map of the chemical environment (e.g., the distribution of Fe(II)). Image of Tc-99m distribution in a column containing Rifle sediment at four times.

  8. Synthesis and in vivo Evaluation of Fluorine-18 and Iodine-123 Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives as PET and SPECT Radiotracers for Mapping A2A Receptors.

    PubMed

    Vala, Christine; Morley, Thomas J; Zhang, Xuechun; Papin, Caroline; Tavares, Adriana Alexandre S; Lee, H Sharon; Constantinescu, Cristian; Barret, Olivier; Carroll, Vincent M; Baldwin, Ronald M; Tamagnan, Gilles D; Alagille, David

    2016-09-01

    Imaging agents that target adenosine type 2A (A2A ) receptors play an important role in evaluating new pharmaceuticals targeting these receptors, such as those currently being developed for the treatment of movement disorders like Parkinson's disease. They are also useful for monitoring progression and treatment efficacy by providing a noninvasive tool to map changes in A2A receptor density and function in neurodegenerative diseases. We previously described the successful evaluation of two A2A -specific radiotracers in both nonhuman primates and in subsequent human clinical trials: [(123) I]MNI-420 and [(18) F]MNI-444. Herein we describe the development of both of these radiotracers by selection from a series of A2A ligands, based on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine core of preladenant. Each of this series of 16 ligands was found to bind to recombinant human A2A receptor in the low nanomolar range, and of these 16, six were radiolabeled with either fluorine-18 or iodine-123 and evaluated in nonhuman primates. These initial in vivo results resulted in the identification of 7-(2-(4-(4-(2-[(18) F]fluoroethoxy)phenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine ([(18) F]MNI-444) and 7-(2-(4-(2-fluoro-4-[(123) I]iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-amine ([(123) I]MNI-420) as PET and SPECT radiopharmaceuticals for mapping A2A receptors in brain. PMID:27407017

  9. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment.

    PubMed

    Krause, B J; Baum, R P; Staib-Sebler, E; Lorenz, M; Niesen, A; Hör, G

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%. PMID:9044881

  10. Prediction of acute cardiac rejection by changes in left ventricular volumes

    SciTech Connect

    Novitzky, D.; Cooper, D.K.; Boniaszczuk, J.

    1988-11-01

    Sixteen patients underwent heart transplantation (11 orthotopic, five heterotopic). Monitoring for acute rejection was by both endomyocardial biopsy (EMB) and multigated equilibrium blood pool scanning with technetium 99m-labelled red blood cells. From the scans information was obtained on left ventricular volumes (stroke, end-diastolic, and end-systolic), ejection fraction, and heart rate. Studies (208) were made in the 16 patients. There was a highly significant correlation between the reduction in stroke volume and end-diastolic volume (and a less significant correlation in end-systolic volume) and increasing acute rejection seen on EMB. Heart rate and ejection fraction did not correlate with the development of acute rejection. Correlation of a combination of changes in stroke volume and end-diastolic volume with EMB showed a sensitivity of 85% and a specificity of 96%. Radionuclide scanning is therefore a useful noninvasive tool for monitoring acute rejection.

  11. Contrast venography vs radionuclide venography: a study of discrepancies and their possible significance

    SciTech Connect

    Gomes, A.S.; Webber, M.M.; Buffkin, D.

    1982-03-01

    In 51 instances, patients underwent radionuclide venography with technetium 99m-labeled macroaggregated albumin followed by contrast venography. The criteria used for diagnosis of a positive radionuclide venogram (flow pattern and retention of radionuclide) were evaluated. Cases in which there were discrepancies between the two studies were analyzed. Multiple factors were found to result in a lack of correlation between the two studies. These are: failure to recognize nonfilling of the deep venous system on the radionuclide venogram, disparate distribution of the venographic imaging agents, presence of varicose veins, large venous valves, previous femoral venipuncture, postsurgical narrowing with obstruction, age of the thrombus, and other factors. These factors and their implications with respect to venographic technique are discussed.

  12. Preparation and characterization of two complexes of technetium with 2-mercaptocarboxylic acids.

    PubMed

    Livni, E; Davis, M A; Warner, V D

    1981-06-01

    We have synthesized the tetraphenylarsonium salts of oxotechnetium(V)bis-(2-mercaptopropionate) and oxotechnetium(V)bis-(2-mercaptohexadecanoate) containing macromolar quantities of the long-lived isotope technetium-99. The compounds were investigated by elemental analysis, paper electrophoresis, and infrared and ultraviolet-visual spectroscopy, proton nuclear magnetic resonance, and field-desorption mass spectrometry. The findings suggest that the technetium atom is coordinated by two sulfur and three oxygen atoms in a square pyramid, the two sulfur atoms and two of the oxygen atoms forming the base and the third oxygen atom the apex. The carboxyl oxygen coordinated to technetium will not be available for binding in vivo. This factor should be considered in the design of technetium 99m-labeled radiopharmaceuticals containing a mercapto group alpha to a carboxyl group. PMID:7229724

  13. Iliopelvic radionuclide lymphoscintigraphy in patients with testicular cancer

    SciTech Connect

    Kaplan, W.D.; Garnick, M.B.; Richie, J.P.

    1983-04-01

    The utility of iliopelvic lymphoscintigraphy was assessed in 21 patients with testicular cancer (six seminoma patients, 15 nonseminoma patients). Normal lymphoscintiscans demonstrated symmetric uptake of technetium-99m-labeled radiocolloid throughout the lymphatic chain, from the internal iliac nodes to the level of the renal hilum. Signs of abnormality included decreased or no uptake of radionuclide in consecutive nodes of a lymphatic chain or in an entire lymphatic chain, and diminished uptake at the level of the renal hilum. In the 15 patients with nonseminomatous germ cell cancer, correlation of the results of scanning with pathologic specimens obtained upon dissection of retroperitoneal lymph nodes revealed a sensitivity of 0.89 an a specificity of 0.83. In the six patients with seminoma, there was good correlaton between scan findings and results of other radiologic tests. This study suggests that iliopelvic lymphoscintigraphy is a sensitive means of determining whether lymph node metastases are present in patients with testicular cancer.

  14. Effect of time of dosing relative to a meal on the raft formation of an anti-reflux agent.

    PubMed

    Washington, N; Greaves, J L; Wilson, C G

    1990-01-01

    Gamma scintigraphy was used in twelve healthy volunteers to establish whether the time of dosing of Liquid Gaviscon relative to a meal influenced its therapeutic action. Indium-113m labelled Liquid Gaviscon was administered to fasted subjects, 30 min after a technetium-99m labelled meal or immediately before ingestion of the meal. The time for 50% of the Gaviscon to empty from the stomach was 0.36 +/- 0.13 h, 3.10 +/- 0.31 h and 0.68 +/- 0.04 h (s.e.m.), respectively. The preparation was found to empty rapidly from the fasted stomach and could not be floated on a meal consumed subsequently. For raft formation to occur, Liquid Gaviscon should be taken 30 min after a meal. PMID:1969950

  15. Acute Hydrothorax Complicating continuous Ambulatory Peritoneal Dialysis: A Case Report and Review of Literature.

    PubMed

    Kechrid, M C; Malik, G H; Shaikh, J F; Al-Mohaya, S; Al-Wakeel, J S; El Gamal, H

    1999-01-01

    We describe here hydrothorax that occurred in a patient on continuous ambulatory peritoneal dialysis (CAPD) and highlight the problems of diagnosis and management. A 48 years-old man with history of obstructive uropathy secondary to urolithiasis was stared on CAPD when he reached end-stage renal failure. Two months later, he was admitted with two days history of shortness of breath on exertion and dry cough increasing in supine position. Chest examination was suggestive of right sided pleural effusion confusion confirmed by chest X-ray. Radioisotope Technetium 99m labeled albumin instilled through the peritoneal catheter was detected in the right pleural fluid confirming the peritoneo-pleural leak. The peritoneal dialysis (PD) was discontinued and the patient was switched to hemodialysis. The pleural effusion subsided and has not recurred for the following three years. PMID:18212427

  16. Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution.

    PubMed Central

    Zainudin, B M; Biddiscombe, M; Tolfree, S E; Short, M; Spiro, S G

    1990-01-01

    The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution. Images PMID:2392793

  17. California Alliance For Radiotracer Education, CARE

    SciTech Connect

    Sutcliffe, Julie

    2015-02-19

    The report contains a summary of the accomplishments made during the CARE proposal. The overall goal of this proposal was to train graduate students and postdoctoral fellows in the field of radiochemistry. The goal was to expose trainees to the fundamentals of radioisotope production, radiochemistry synthesis, synthetic organic chemistry as well as applications and hands on experience in small animal imaging. In summary approximately 30 trainees were involved including trainees both at the graduate and postdoctoral levels. This funding has to date resulted in publications in high impact journals such as Med Chem Comm, Journal of Nuclear Medicine and Molecular Imaging and Biology. Trainees have gone on to further their careers in both academia, industry and the private sector. The funding will result in seven Master’s and six Ph.D dissertations. Without the DOE funding it simply would not have been possible to continue to train the next generation of radiochemists needed to assure a future US-based Nuclear and Radiochemistry Expertise.

  18. MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.

    SciTech Connect

    FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

    2000-09-28

    PET is uniquely capable of providing information on biochemical transformations in the living human body. Although most of the studies of monoamine oxidase (MAO) have focused on measurements in the brain, the role of peripheral MAO as a phase 1 enzyme for the metabolism of drugs and xenobiotics is gaining attention (Strolin Benedetti and Tipton, 1998; Castagnoli et al., 1997.). MAO is well suited for this role because its concentration in organs such as kidneys, liver and digestive organs is high sometimes exceeding that in the brain. Knowledge of the distribution of the MAO subtypes within different organs and different cells is important in determining which substrates (and which drugs and xenobiotics) have access to which MAO subtypes. The highly variable subtype distribution with different species makes human studies even more important. In addition, the deleterious side effects of combining MAO inhibitors with other drugs and with foodstuffs makes it important to know the MAO inhibitory potency of different drugs both in the brain and in peripheral organs (Ulus et al., 2000). Clearly PET can play a role in answering these questions, in drug research and development and in discovering some of the factors which contribute to the highly variable MAO levels in different individuals.

  19. Radiotracers based on technetium-94m.

    PubMed

    Gagnon, Katherine; McQuarrie, Steve; Abrams, Doug; McEwan, Alexander J; Wuest, Frank

    2011-04-01

    This review gives a survey on the use and applications of technetium-94m ((94m)Tc) as a non-conventional positron emission tomography (PET) radionuclide for molecular imaging. The first part of this review describes the production and processing of (94m)Tc. The second part covers basic concepts of technetium coordination chemistry with a special focus on the synthesis of (94m)Tc-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the prospects of using (94m)Tc in the field of PET chemistry and molecular imaging. PMID:22191648

  20. In situ anion diffusion experiments using radiotracers

    NASA Astrophysics Data System (ADS)

    Jansson, Mats; Eriksen, Trygve E.

    2004-02-01

    Diffusion experiments in compacted bentonite have been carried out in situ using the borehole laboratory CHEMLAB. The "ordinary" anion iodide and the redox-sensitive pertechnetate ion have been investigated. In spite of strongly reducing groundwater conditions, technetium was found to diffuse mostly unreduced as TcO 4-, although in some spots in the compacted clay, the activity was significantly higher, which may be explained by reduction of some TcO 4- by iron-containing minerals in the bentonite. The measured concentration profiles in the clay cannot be accommodated by assuming one single diffusion process. The experimental data are modeled assuming two diffusion paths, intralamellar diffusion and diffusion in external water. The apparent diffusivity for the intralamellar diffusion was found to be 8.6×10 -11 m 2 s -1 for iodide with a capacity factor of 0.1, while the apparent diffusivity for the diffusion in external water was found to be 5×10 -14 m 2 s -1 with α=2.26. The corresponding values for Tc were found to be Da=6×10 -11 m 2 s -1, α=0.1 and Da=1×10 -13 m 2 s -1, α=0.46, respectively. The diffusion constants and capacity factors obtained in this study are in accordance with data from laboratory experiments.

  1. Radiotracers application to determine laminar flow at a pipe

    SciTech Connect

    Ramirez-Garcia, F.P.; Cortes-Islas, E. )

    1988-06-01

    To measure gas flow in a gas venting line in an Oil Refinery the method of two points and iodine-131 labelled methyl iodide molecule was used. Forty-four complete sets of data were obtained corresponding to measurements performed in the gas venting line. Conditions of laminar and semi-turbulent flow were found. In the case of laminar flow measurement it was necessary to construct an injection equipment, consisting of a tubing with five slits to simultaneously inject the tracer into the gas stream at different points. For the laminar flow is obtained the transversal distribution of fluid velocities. The mean flow of the gas transported by the line under study was determined, and its standard deviation was calculated.

  2. Free Radical Polymerization of Styrene: A Radiotracer Experiment

    ERIC Educational Resources Information Center

    Mazza, R. J.

    1975-01-01

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

  3. Short-lived positron emitter labeled radiotracers - present status

    SciTech Connect

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

    1982-01-01

    The preparation of labelled compounds is important for the application of positron emission transaxial tomography (PETT) in biomedical sciences. This paper describes problems and progress in the synthesis of short-lived positron emitter (/sup 11/C, /sup 18/F, /sup 13/N) labelled tracers for PETT. Synthesis of labelled sugars, amino acids, and neurotransmitter receptors (pimozide and spiroperidol tagged with /sup 11/C) is discussed in particular. (DLC)

  4. Novel, convenient, and nonpersistent radiotracer for environmental and energy applications

    SciTech Connect

    Grant, P.M.

    1984-03-12

    A newly-available radioisotopic system, /sup 172/Hf-/sup 172/Lu, has excellent potential for tracer applications in which nuclear data acquisition must be accomplished in real time. The 6.7-day half-life of /sup 172/Lu is sufficient for a large fraction of tracer experiments, and should allow the direct incorporation of /sup 172/Lu into tests that have traditionally utilized much longer-lived radionuclides. Since /sup 172/Lu is the daughter component of a radioisotope generator, however, its effective shelf-life is determined by the half-life of its 1.9-year /sup 172/Hf parent. Consequently, the frequency of isotope procurement need not be any more extensive than investigators would normally be accustomed to. Discussion relevant to isotope production, generator operation, and nuclide acquisition is presented in this paper.

  5. Development of radiotracers for oncology – the interface with pharmacology

    PubMed Central

    Sharma, Rohini; Aboagye, Eric

    2011-01-01

    There is an increasing role for positron emission tomography (PET) in oncology, particularly as a component of early phase clinical trials. As a non-invasive functional imaging modality, PET can be used to assess both pharmacokinetics and pharmacodynamics of novel therapeutics by utilizing radiolabelled compounds. These studies can provide crucial information early in the drug development process that may influence the further development of novel therapeutics. PET imaging probes can also be used as early biomarkers of clinical response and to predict clinical outcome prior to the administration of therapeutic agents. We discuss the role of PET imaging particularly as applied to phase 0 studies and discuss the regulations involved in the development and synthesis of novel radioligands. The review also discusses currently available tracers and their role in the assessment of pharmacokinetics and pharmacodynamics as applied to oncology. 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:21175573

  6. RADIOTRACER STUDIES OF INTERACTIONS BETWEEN SEDIMENTS AND FRESHWATER MACROBENTHOS

    EPA Science Inventory

    Gamma-emitting radioiosotopes were used to study the effect of five species of benthic macrofauna, common to the North American Great Lakes, on the movement of solutes and particles in sediments. In a special control cell with worm tubes but no live worms, there was no enhancemen...

  7. Training requirements for chemists in radiotracer development for nuclear medicine

    SciTech Connect

    Finn, R.; Fowler, J.

    1988-01-01

    This panel was organized to address the current and anticipated future shortage of chemists with advanced training to fill positions in the nuclear medicine field. Although hard data and statistics are difficult to acquire, we will attempt to highlight the impact of chemistry on nuclear medicine and to describe the growth of the field which has led to an increasing need for chemists resulting in the current manpower shortage. We also will make recommendations for attracting Ph.D. chemists to careers in nuclear medicine research and possible mechanisms for postgraduate training. Solving this problem and establishing a long term committment and mechanism for advanced training is critically important to meet the current needs of the profession and to assure future growth and innovation. 3 tabs.

  8. Regional respiratory clearance of aerosolized /sup 99m/Tc-DTPA: posture and smoking effects

    SciTech Connect

    Dusser, D.J.; Minty, B.D.; Collignon, M.A.; Hinge, D.; Barritault, L.G.; Huchon, G.J.

    1986-06-01

    We studied 10 healthy nonsmokers and 8 healthy smokers, in both the upright and supine position, to investigate whether regional differences in respiratory clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid /sup 99m/Tc-DTPA (RC-DTPA) existed and to assess the influence of posture and smoking on the regional RC-DTPA. RC-DTPA was assessed by the lung clearance rates (%/min) of aerosolized /sup 99m/Tc-DTPA (0.8 micron MMD; 2.4 GSD), using data corrected for recirculating radioactivity, in the upper (zone 1), middle (zone 2), and lower (zone 3) posterior lung fields. In nonsmokers, RC-DTPA in zone 1 was faster than in zone 2 or 3 in both the upright (P less than 0.001) and supine positions (P less than 0.0). No effect was produced by changes in posture on the regional RC-DTPA. In smokers, RC-DTPA was increased in all zones compared with the nonsmokers (P = 0.004), with a further increase in RC-DTP in zone 1 in the upright posture compared with the other regions (P less than 0.001). We conclude that in nonsmokers regional RC-DTPA is faster in zone 1 than in other zones, and this is not related to recirculation of radioactivity; posture does not modify the regional RC-DTPA of nonsmokers; smoking increases RC-DTPA in all zones and more in zone 1 in the upright posture.

  9. Impairment of nasal mucociliary clearance in woodworkers in the furniture industry

    PubMed Central

    Black, A.; Evans, J. C.; Hadfield, Esme H.; Macbeth, R. G.; Morgan, A.; Walsh, M.

    1974-01-01

    Black, A., Evans, J. C., Hadfield, Esme H., Macbeth, R. G., Morgan, A., and Walsh, M. (1974).British Journal of Industrial Medicine,31, 10-17. Impairment of nasal mucociliary clearance in woodworkers in the furniture industry. Measurements of mucociliary clearance from the anterior end of the middle turbinate were made using technetium-99m-labelled particles in nine woodworkers from the furniture industry and in 12 controls, none of whom had been occupationally exposed to wood dust. Clearance rates in the controls ranged from 1·9 to 18·5 mm min-1 with a mean of 6·8. These values are in good agreement with measurements reported elsewhere for normal subjects. Only one of the woodworkers had a clearance rate which fell within the normal range and he had been occupationally exposed for the shortest period (6 years). In four woodworkers clearance was very slow (< 1 mm min-1) and in three there was almost complete stasis. The results of this preliminary investigation suggest that nasal mucociliary function is significantly impaired in workers who have been exposed to wood dust in the furniture industry for more than 10 years. PMID:4821406

  10. Significance of left ventricular volume measurement after heart transplantation using radionuclide techniques

    SciTech Connect

    Novitzky, D.; Cooper, D.; Boniaszczuk, J.; Isaacs, S.; Fraser, R.C.; Commerford, P.J.; Uys, C.J.; Rose, A.G.; Smith, J.A.; Barnard, C.N.

    1985-02-01

    Multigated equilibrium blood pool scanning using Technetium 99m labeled red blood cells was used to measure left ventricular volumes in three heterotopic and one orthotopic heart transplant recipient(s). Simultaneously, an endomyocardial biopsy was performed and the degree of acute rejection was assessed by a histological scoring system. The scores were correlated to changes in ejection fraction and heart rate. Technetium 99m scanning data were pooled according to the endomyocardial biopsy score: no rejection; mild rejection; moderate rejection, and severe rejection. In each group, the median of the left ventricular volume parameters was calculated and correlated with the endomyocardial biopsy score, using a non-parametric one-way analysis of variance. A decrease in stroke volume correlated best with the endomyocardial biopsy score during acute rejection. A decrease in end-diastolic left ventricular volumes did not correlate as well. Changes in the end-systolic left ventricular volumes were not statistically significant, but using a simple correlation between end-systolic left ventricular volumes and endomyocardial biopsy the correlation reached significance. Changes in left ventricular volumes measured by Technetium 99m scanning may be useful to confirm the presence or absence of acute rejection in patients with heart grafts.

  11. Relationship of end-expiratory pressure, lung volume, and /sup 99m/Tc-DTPA clearance

    SciTech Connect

    Cooper, J.A.; van der Zee, H.; Line, B.R.; Malik, A.B.

    1987-10-01

    We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH/sub 2/O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH/sub 2/O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH/sub 2/O PEEP. At 2.5 cmH/sub 2/O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH/sub 2/O (P less than 0.05). Between 15 and 20 cmH/sub 2/O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized /sup 99m/Tc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.

  12. Alveolar albumin leakage during large tidal volume ventilation and surfactant dysfunction.

    PubMed

    Liu, J M; Evander, E; Zhao, J; Wollmer, P; Jonson, B

    2001-07-01

    Detergent given as an aerosol and large tidal volume ventilation (LTVV) have been observed, by us, to promote lung injury by an additive effect on alveolocapillary barrier function. The surfactant system may be further damaged if protein leakage occurs into the alveoli. The aim was to study the effect of detergent and LTVV on the alveolar leakage of albumin and also the effect of detergent on surface activity of lung washings and lung tissue extracts. Technetium-99m-labelled human serum albumin was given intravenously. The alveolar leakage of albumin was measured after perturbing the surfactant system with the detergent dioctyl sodium sulfosuccinate either singly or in combination with LTVV. Four groups of rabbits were studied after 3 h of experimental ventilation. Surface tension measurements of tissue extracts, lung mechanics and gas exchange did not show any differences between groups. Wet lung weight and albumin leakage were significantly increased in the two groups subjected to LTVV compared with groups given normal tidal volume ventilation. Low doses of detergent did not affect surface activity of lung tissue extracts or alveolar leakage of albumin. LTVV increased alveolar leakage of albumin and produced oedema. No additive effect was seen when detergent and LTVV were combined. PMID:11442575

  13. Prognosis of parathyroid function after minimally invasive radioguided parathyroidectomy (MIRP) and percutaneous ethanol injection therapy (PEIT) for primary hyperparathyroidism.

    PubMed

    Kakuta, Takatoshi; Suzuki, Yutaka; Tadaki, Futoshi; Uemura, Katsuya; Tanaka, Reika; Tanaka, Shinichi; Kubota, Mitsuhiro; Sakai, Hideto; Kurokawa, Kiyoshi; Saito, Akira

    2002-01-01

    During parathyroidectomy (PTx) for primary hyperparathyroidism (PHP), we surgically explored the contralateral parathyroid glands as well as those whose localization was clarified by ultrasonography and parathyroid scintigraphy. Although it is important to explore the contralateral side and other glands, we frequently treat only the gland whose localization is confirmed. Recently, we have performed minimally invasive radioguided parathyroidectomy (MIRP) that resects only one gland observed on the imaging under technetium 99m-labeled sestamibi (MIBI) scanning guidance after obtaining prior informed consent. In this surgery, even if recurrence is observed contralaterally, it is possible to apply a similar procedure to the contralateral side again. We examined six PHP patients who underwent MIRP and two PHP patients treated with percutaneous ethanol injection therapy (PEIT). The follow-up period was 2 years. PEIT was selected as a treatment method for two patients based on the patients' characteristics. When only one gland is treated, the efficacy of PEIT was considered to be similar to that of MIRP. PMID:12487250

  14. An unusual white blood cell scan in a child with inflammatory bowel disease: a case report.

    PubMed

    Porn, U; Howman-Giles, R; O'Loughlin, E; Uren, R; Chaitow, J

    2000-10-01

    Technetium-99m-labeled leukocyte (WBC) imaging is a valuable screening method for inflammatory bowel disease, especially in children, because of its high rate of sensitivity, low cost, and ease of preparation. A 14-year-old girl is described who had juvenile arthritis and iritis complicated by inflammatory bowel disease. She was examined for recurrent abdominal pain. A Tc-99m stannous colloid WBC scan was performed, and tracer accumulation was seen in the small bowel in the region of the distal ileum on the initial 1-hour image. Delayed imaging at 3 hours also revealed tracer accumulation in the cecum and ascending colon, which was not seen on the early image. A biopsy of the colon during endoscopy showed no evidence of active inflammation in the colon. The small bowel was not seen. Computed tomography revealed changes suggestive of inflammatory bowel disease in the distal ileum. The appearance on the WBC study was most likely a result of inflammatory bowel disease involving the distal ileum, with transit of luminal activity into the large bowel. PMID:11043720

  15. Platelet thrombosis in cardiac-valve prostheses

    SciTech Connect

    Dewanjee, M.K.

    1989-01-01

    The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs.

  16. Assessment of soft tissue hemangiomas in children utilizing Tc-99m labelled red blood cells

    SciTech Connect

    Miller, J.H.

    1984-01-01

    Hemangiomas may present in infancy as soft tissue masses. Occasionally these lesions may be extensive or may not be clinically recognized as a hemangioma, often causing concern for the presence of a malignant lesion. In later childhood these lesions, which may be occult, may cause overgrowth of an extremity. Evaluation of soft tissue masses suspected of being a hemangioma utilizing Technetium 99m labelled red blood cells has been very valuable. This method allows a dynamic evaluation of first pass blood flow. Subsequent static scintiphotos allow an assessment of the lesion itself. These scintiphotos may be obtained sequentially to evaluate therapy. Twenty patients were evaluated by this method ranging in age from two months to eleven years. There were 13 females and seven males. Lesions evaluated by this method include six hemangiomas of the head and neck: parotic region (2), facial (3), and tongue (1). Extremity lesions were evaluated in six children including both upper extremity (1) and lower extremity (5). Torso lesions evaluated include chest wall (2), abdominal wall (2), and one hemangioma of the gut. This procedure is quickly performed on an outpatient basis, has high anatomic resolution, provides and assessment of these lesions in a manner not available by any other imaging procedure and usually requires no sedation. The radiation exposure for this procedure is low (approximately, a 400mR total body dose) and has been well tolerated by both patients and their parents. Scintigraphic evaluation should be the first diagnostic method utilized in the evaluation of these lesions.

  17. Estimation of Organ Absorbed Doses in Patients from 99mTc-diphosphonate Using the Data of MIRDose Software

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Cheki, Mohsen; Moslehi, Masoud

    2012-01-01

    The purpose of this study was to compare estimation of radiation absorbed doses to patients following bone scans with technetium-99m-labeled methylene diphosphonate (MDP) with the estimates given in MIRDose software. In this study, each patient was injected 25 mCi of 99mTc-MDP. Whole-body images from thirty patients were acquired by gamma camera at 10, 60, 90, 180 minutes after 99mTc-MDP injection. To determine the amount of activity in each organ, conjugate view method was applied on images. MIRD equation was then used to estimate absorbed doses in different organs of patients. At the end, absorbed dose values obtained in this study were compared with the data of MIRDose software. The absorbed doses per unit of injected activity (mGy/MBq × 10–4) for liver, kidneys, bladder wall and spleen were 3.86 ± 1.1, 38.73 ± 4.7, 4.16 ± 1.8 and 3.91 ± 1.3, respectively. The results of this study may be useful to estimate the amount of activity that can be administered to the patient and also showed that methods used in the study for absorbed dose calculation is in good agreement with the data of MIRDose software and it is possible to use by a clinician. PMID:23724374

  18. Noninvasive evaluation of the swollen extremity: Experiences with 190 lymphoscintigraphic examinations

    SciTech Connect

    Gloviczki, P.; Calcagno, D.; Schirger, A.; Pairolero, P.C.; Cherry, K.J.; Hallett, J.W.; Wahner, H.W.

    1989-05-01

    Lymphoscintigraphy (LS), performed with technetium 99m-labeled antimony trisulfide colloid, was used as a noninvasive diagnostic examination to evaluate the lymphatic circulation in 190 extremities of 115 patients. Forty-six patients had primary lymphedema, 48 had secondary lymphedema, and 21 patients had other causes of limb swelling. To determine the value of LS in surgical decision making, preoperative and postoperative LS of 16 patients who underwent surgical repair of the lymphatic abnormality were studied separately. Semiquantitative evaluation of the lymphatic drainage and visual interpretation of the image patterns were reliable to differentiate lymphedema from edemas of other origin (sensitivity: 92%, specificity: 100%). Although certain image patterns were characteristic of either primary or secondary lymphedema, LS could not consistently differentiate between the two types. Episodes of cellulitis in lymphedema clearly delayed lymph transport. LS was helpful in patient selection and follow-up after lymphatic surgery, but it did not prove patency of lymphovenous anastomoses. It was diagnostic in the evaluation of lymphangiectasia and was used to document successful surgical treatment of reflux of chyle. LS is safe and reliable and has no side effects. It should replace contrast lymphangiography in the routine evaluation of the swollen extremity.

  19. Effect of the timing of tourniquet release on postoperative hematoma formation: an experimental animal study

    SciTech Connect

    Himel, H.N.; Ahmad, M.; Parmett, S.R.; Strauss, H.W.; May, J.W. Jr.

    1989-04-01

    There is a controversy over when to release a pneumatic tourniquet after completing a hand surgical procedure. To study this controversy, we performed a standardized operation with tourniquet inflow occlusion on both lower legs of a series of rabbits. Total tourniquet time and the procedure performed, including intraoperative Bovie electrocautery of actual and potential bleeding points identified with 2.5 X loupe magnification, were identical on the two sides, except for the method of tourniquet release. On one leg, the tourniquet was released and all new bleeding points were controlled prior to wound closure. On the other leg, the tourniquet was released after the wound had been closed and dressed. Animals were injected with technetium-99m-labeled red blood cells and scanned to measure hematoma formation. Qualitatively, we observed more label in the leg whose tourniquet was released after wound closure in 17 of the 20 animals (p less than 0.005). Quantitatively, we also measured more mean label in the leg whose tourniquet was released after the wound was closed (p less than 0.001). Tourniquet release after wound closure was associated with greater hematoma formation.

  20. The effect of omeprazole pre-treatment on rafts formed by reflux suppressant tablets containing alginate.

    PubMed

    Dettmar, P W; Little, S L; Baxter, T

    2005-01-01

    Alginate-based reflux suppressant preparations provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study investigated whether reduced acidity in the stomach brought about by omeprazole pre-treatment affected the formation and gastric residence time of alginate rafts. It was a balanced, cross-over study in 12 healthy non-patient volunteers following a single dose of two indium-111-labelled alginate tablets in the presence or absence of 3 days' pre-treatment with omeprazole. Raft formation and gastric residence, in the presence of a technetium-99m-labelled meal, were assessed by gamma scintigraphy for 3 h after alginate tablet administration. The relative raft-forming ability of alginate tablets after omeprazole compared with alginate tablets alone was 0.950 with 95% confidence intervals of 0.882 and 1.018. Pre-treatment and co-administration with omeprazole has no significant effect on the raft-forming ability of alginate tablets. PMID:15938591

  1. Gastrointestinal symptoms, motility, and transit after the Roux-en-Y operation

    SciTech Connect

    Perino, L.E.; Adcock, K.A.; Goff, J.S.

    1988-04-01

    Roux-en-Y patients have symptoms that vary from almost none to inability to tolerate oral feedings. This study was designed to determine whether there is a relationship between a patient's symptoms and the function of the gastric remnant or the Roux-limb. Gastric remnant and Roux-limb emptying were studied in eight patients with technetium-99m-labeled oatmeal and Roux-limb motor activity was measured with a water-perfused manometry system. We found that gastric emptying was rarely significantly slowed, but emptying of the Roux-limb was delayed in several patients. We also found that there was a rough correlation between the patient's symptoms and the degree of abnormal motility found in the Roux-limb. There is no known reason for these abnormalities in Roux-limb function in some patients after a Roux-en-Y, but our finding of worse abnormalities in those who had multiple previous gastric surgeries suggests that the symptoms and dysfunction may be related to the number of surgeries, as well as to the type of surgery.

  2. Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction

    SciTech Connect

    Lieberman, D.A.; Brown, P.H.; Krishnamurthy, G.T. )

    1990-11-01

    In previous studies, we found that biliary scintigraphy with technetium-99m-labeled iminodiacetic acid (({sup 99m}Tc)IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of ({sup 99m}Tc)IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin greater than or equal to 3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N = 13) had an HEF of 100%. Patients with CBDO (N = 13) had slightly reduced HEF values (92.8 +/- 3.2%) despite profound hyperbilirubinemia (6.1 +/- 1.0 mg/dl). Patients with IHD (N = 23) had a markedly reduced HEF (43.1 +/- 4.1%) which was significantly lower than patients with CBDO and normal subjects (P less than 0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin greater than or equal to 3.0 mg/dl).

  3. Diagnostic value of a new myocardial perfusion agent, teboroxime (SQ 30,217), utilizing a rapid planar imaging protocol: Preliminary results

    SciTech Connect

    Hendel, R.C.; McSherry, B.; Karimeddini, M.; Leppo, J.A. )

    1990-10-01

    Technetium-99m-labeled agents have advantages over thallium-201 in terms of photon statistics, cost and clinical availability. They have been suggested as an alternative to thallium for myocardial perfusion imaging. Teboroxime is a new boronic acid adduct of technetium dioxime (BATO) compound that demonstrates favorable characteristics in preliminary studies. With use of a novel (seated) patient positioning technique and a rapid dynamic acquisition protocol, 30 patients underwent planar imaging with teboroxime while at rest and after maximal treadmill exercise. Postexercise scans were completed in an average time (mean +/- SD) of 4.4 +/- 1.6 min, with 4.8 +/- 1.5 min for the views at rest. These results were compared with coronary arteriography or thallium scintigraphy after treadmill exercise, or both. Diagnostic agreement (abnormal versus normal) was present in 28 of the 30 patients (p less than 0.001). Regarding physiologic assessment as compared with thallium scintigraphy, the finding of infarction and ischemia was concordant in 89% and 86% of patients, respectively. This report describes the initial use of teboroxime with a rapid dynamic planar imaging technique, resulting in a high correlation with exercise thallium scintigraphy. Delayed postexercise images obtained 5 to 10 min after exercise demonstrated rapid disappearance of exercise-induced defects noted on the initial (0 to 5 min) postexercise views. The rapid differential washout with teboroxime has not been previously described and the possible clinical significance is discussed.

  4. Diagnostic value of a new myocardial perfusion agent, teboroxime (SO 30,217), utilizing a rapid planar imaging protocol: Preliminary results

    SciTech Connect

    Hendel, R.C.; McSherry, B.; Karimeddini, M.; Leppo, J.A. )

    1990-11-01

    Technetium-99m-labeled agents have advantages over thallium-201 in terms of photon statistics, cost and clinical availability. They have been suggested as an alternative to thallium for myocardial perfusion imaging. Teboroxime is a new boronic acid adduct of technetium dioxime (BATO) compound that demonstrates favorable characteristics in preliminary studies. With use of a novel (seated) patient positioning technique and a rapid dynamic acquisition protocol, 30 patients underwent planar imaging with teboroxoime while at rest and after maximal treadmill exercise. Postexercise scans were completed in an average time (mean +/- SD) of 4.4 +/- 1.6 min, with 4.8 +/- 1.5 min for the views at rest. These results were compared with coronary arteriography or thallium scintigraphy after treadmill exercise, or both. Diagnostic agreement (abnormal versus normal) was present in 28 of the 30 patients (p less than 0.001). Regarding physiologic assessment as compared with thallium scintigraphy, the finding of infarction and ischemia was concordant in 89% and 86% of patients, respectively. This report describes the initial use of teboroxime with a rapid dynamic planar imaging technique, resulting in a high correlation with exercise thallium scintigraphy. Delayed postexercise images obtained 5 to 10 min after exercise demonstrated rapid disappearance of exercise-induced defects noted on the initial (0 to 5 min) postexercise views. The rapid differential washout with teboroxime has not been previously described and the possible clinical significance is discussed.

  5. Experimental studies of the physiologic properties of technetium-99m agents: Myocardial transport of perfusion imaging agents

    SciTech Connect

    Meerdink, D.J.; Leppo, J.A. )

    1990-10-16

    The physiologic properties of new technetium-99m-labeled myocardial imaging agents (Tc-99m sestamibi, an isonitrile; and Tc-99m teboroxime, a boronic acid adduct of technetium dioxime) are discussed and compared to thallium-201 (Tl-201). Studies with isolated hearts, subcellular fractions and cell cultures indicate that Tc-99m sestamibi, Tc-99m teboroxime and Tl-201 do not share common transport or sequestration mechanisms. Although peak Tc-99m sestamibi myocardial extraction over time is about half that of Tl-201 at equivalent coronary blood flows, the amount of Tc-99m sestamibi that remains in the heart is similar to that of Tl-201 because of its higher retention efficiency. The high retention efficiency for Tc-99m sestamibi also results in minimal redistribution. In contrast, Tc-99m teboroxime myocardial extraction is higher than that of Tl-201, but its retention is less efficient, resulting in relatively rapid washout characteristics which may quickly result in tracer redistribution. During reperfusion after a no-flow period, Tc-99m sestamibi extraction and retention increase, but for Tc-99m teboroxime and Tl-201 these values tend to decrease. All tracers show adequate transport characteristics for perfusion imaging, and differences in transport and retention should lead to the development of new clinical protocols.27 references.

  6. Radioisotope penile plethysmography: A technique for evaluating corpora cavernosal blood flow during early tumescence

    SciTech Connect

    Schwartz, A.N.; Graham, M.M.; Ferency, G.F.; Miura, R.S.

    1989-04-01

    Radioisotope penile plethysmography is a nuclear medicine technique which assists in the evaluation of patients with erectile dysfunction. This technique attempts to noninvasively quantitate penile corpora cavernosal blood flow during early penile tumescence using technetium-99m-labeled red blood cells. Penile images and counts were acquired in a steady-state blood-pool phase prior to and after the administration of intracorporal papaverine. Penile counts, images, and time-activity curves were computer analyzed in order to determine peak corporal flow and volume changes. Peak corporal flow rates were compared to arterial integrity (determined by angiography) and venosinusoidal corporal leak (determined by cavernosometry). Peak corporal flow correlated well with arterial integrity (r = 0.91) but did not correlate with venosinusoidal leak parameters (r = 0.01). This report focuses on the methodology and the assumptions which form the foundation of this technique. The strong correlation of peak corporal flow and angiography suggests that radioisotope penile plethysmography could prove useful in the evaluation of arterial inflow disorders in patients with erectile dysfunction.

  7. Use of technetium-99m sulfur colloid to evaluate changes in reticuloendothelial function in dogs with experimentally induced chronic biliary cirrhosis and portosystemic shunting.

    PubMed

    Koblik, P D; Hornof, W J; Yen, C K; Fisher, P E; Komtebedde, J

    1995-05-01

    Technetium-99m sulfur colloid scintigraphy was used to study alterations of reticuloendothelial function in 7 dogs with experimentally induced biliary cirrhosis and portosystemic shunting. Scintigraphic studies were performed before and 6 weeks after common bile duct ligation. Radiocolloid plasma clearance rate was determined by measuring activity in plasma samples and by analyzing the rate of liver uptake on dynamic scintigraphic image sequences. Percentage of uptake in the liver, spleen, and lungs, as well as the ratio of hepatic-to-extrahepatic uptake, was determined from static equilibrium images. Relative to preoperative values, there were significant decreases in plasma clearance rate, percentage of liver uptake, and ratio of hepatic-to-extrahepatic uptake and significant increases in percentage of spleen and lung uptake on postoperative studies. The mechanism of technetium-99m-labeled sulfur colloid extraction by the liver is different from that of other radiocolloids; it does not require active phagocytosis or pinocytosis. Thus, liver uptake of this tracer principally reflects effective liver blood flow. Portosystemic shunting was documented in these dogs at the time of the postoperative radiocolloid scans, and we believed was responsible for the decrease in liver reticuloendothelial activity. Possible mechanisms for the increased splenic and pulmonary reticuloendothelial activities are discussed. PMID:7661466

  8. Intraarterial versus intravenous adriamycin in the rabbit Vx-2 tumor system

    SciTech Connect

    Swistel, A.J.; Bading, J.R.; Raaf, J.H.

    1984-03-15

    Intraarterial (IA) chemotherapy can theoretically result in a high tissue level of the drug with reduced systemic toxicity compared with intravenous (IV) administration. The authors compared these two modes of therapy using Adriamycin (doxorubicin) in the rabbit Vx-2 tumor system. Vx-2 implanted in hind limb muscle, and silastic catheters were placed in the jugular vein and femoral artery. Nuclear imaging of technetium-99m-labeled autologous erythrocytes in nine animals was used to measure the kinetics of tumor blood flow. Presence of tumor increased flow through the involved limb up to threefold. One minute following injection there was no difference in concentration of /sup 99m/Tc in tumor whether labeled cells were introduced IA or IV. Twelve rabbits received IA or IV Adriamycin (3 mg/kg), while eight animals received normal saline IA or IV as controls. Tumor progressed in all control rabbits, whereas there was an objective or complete response in 83% of animals receiving adriamycin. One hundred percent of those treated IA responded compared with 67% for IV. Median time to initial response in animals treated IA was 7 days versus 21 days for those treated IV. Thus, IA Adriamycin achieves a more complete and more rapid response than the drug given IV. This occurs despite a large tumor blood flow and rapid equilibrium using both methods.

  9. The first experience of using of 99mTc-Al2O3 for detection of sentinel lymph nodes in breast cancer

    NASA Astrophysics Data System (ADS)

    Doroshenko, A.; Chernov, V.; Medvedeva, A.; Zeltchan, R.; Slonimskaya, E.; Varlamova, N.; Skuridin, V.; Dergilev, A.; Sinilkin, I.

    2016-06-01

    Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. Materials and methods. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n=34) were injected with radioactive 99mTc-Al203, and Group II patients (n=30) received 99mTc-labeled phytate colloid. Results. A total of 37 SLNs were detected in Group I patients. The number of identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. At 18 hours after 99mTc-Al203 injection, the percentage of its accumulation in the SLN was 7-11% (of the counts in the injection site) by SPECT and 17-31% by gamma probe detection. In Group II patients, SLNs were detected in 27 patients. At 18 hours after injection of the phytate colloid, the percentage of its accumulation in the SLN was 1.5-2% out of the counts in the injection site by SPECT and 4-7% by gamma probe. Conclusion. The new radiopharmaceutical based on the 99mTc - Al203 demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. Sensitivity and specificity of 99mTc - Al203 were 100% for both SPECT and intraoperative gamma probe identification.

  10. Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes

    SciTech Connect

    Eisen, H.J.; Eisenberg, S.B.; Saffitz, J.E.; Bolman, R.M. 3d.; Sobel, B.E.; Bergmann, S.R.

    1987-04-01

    To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 (/sup 111/In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous /sup 111/In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed. In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures.

  11. Effect of inspiratory resistance and PEEP on /sup 99m/Tc-DTPA clearance

    SciTech Connect

    O'Brodovich, H.; Coates, G.; Marrin, M.

    1986-05-01

    Experiments were performed to determine the effect of markedly negative pleural pressure (Ppl) or positive end-expiratory pressure (PEEP) on the pulmonary clearance (k) of technetium-99m-labeled diethylenetriaminepentaacetic acid (/sup 99m/Tc-DTPA). A submicronic aerosol containing /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized intubated sheep. In six experiments k was 0.44 +/- 0.46% (SD)/min during the initial 30 min and was unchanged during the subsequent 30-min interval (k = 0.21 +/- 12%/min) when there was markedly increased inspiratory resistance. A 3-mm-diam orifice in the inspiratory tubing created the resistance. It resulted on average in a 13-cmH2O decrease in inspiratory Ppl. In eight additional experiments sheep were exposed to 2, 10, and 15 cmH2O PEEP (20 min at each level). During 2 cmH2O PEEP k = 0.47 +/- 0.15%/min, and clearance increased slightly at 10 cmH2O PEEP (0.76 +/- 0.28%/min, P less than 0.01). When PEEP was increased to 15 cmH2O a marked increase in clearance occurred (k = 1.95 +/- 1.08%/min, P less than 0.001). The experiments demonstrate that markedly negative inspiratory pressures do not accelerate the clearance of /sup 99m/Tc-DTPA from normal lungs. The effect of PEEP on k is nonlinear, with large effects being seen only with very large increases in PEEP.

  12. Role of PET/CT in Workup of Fever without a Source.

    PubMed

    Dibble, Elizabeth H; Yoo, Don C; Noto, Richard B

    2016-01-01

    Fever without source is a febrile illness without localizing signs or initial obvious cause. Early workup will often include chest radiography and computed tomography (CT) of the abdomen and pelvis, with or without CT of the chest. To evaluate localizing signs or symptoms or to further evaluate findings from initial studies, targeted imaging according to body part can be performed by using radiography, ultrasonography, CT, or magnetic resonance (MR) imaging. Nuclear medicine studies can provide imaging of the whole body and may be helpful when the clinical and conventional imaging workup findings are negative or equivocal in identifying a source of fever. Nuclear medicine studies can be used to detect pathologic changes early in a disease course, even in the absence of an anatomic abnormality. Gallium 67 scintigraphy, indium 111- and technetium 99m-labeled leukocyte scintigraphy, and fluorine 18 fluorodeoxyglucose positron emission tomography (PET)/CT studies are all useful in the evaluation of fever, but the radiopharmaceutical cost for PET/CT is much lower than that for radiolabeled leukocyte studies. The increased use of bundled payments for inpatient admissions requires updated cost evaluations for the preferred nuclear medicine study. For inpatients in whom the findings from the initial clinical workup and imaging studies are nondiagnostic, PET/CT examination may be preferable to radiolabeled leukocyte studies because of its high sensitivity and lower cost. Negative findings at PET/CT can be helpful in excluding a suspected site of infection, and positive findings at PET/CT can be helpful in confirming a suspected site of infection or in identifying an unexpected cause of fever. (©)RSNA, 2016. PMID:27399241

  13. Bone Scans Are Reliable for the Identification of Lumbar Disk and Facet Pathology

    PubMed Central

    Malham, Gregory M.; Parker, Rhiannon M.; Ballok, Zita E.; Goss, Ben; Diwan, Ashish D.; Uribe, Juan S.

    2014-01-01

    Study Design Surgeon survey. Objective To evaluate the reliability of bone single-photon emission computed tomography (SPECT) versus bone SPECT images co-registered with computed tomography (bone SPECT-CT) by analyzing interobserver agreement for identification of the anatomical location of technetium99m-labeled oxidronate uptake in the lumbar disk and/or facet joint. Methods Seven spine surgeons interpreted 20 bone scans: 10 conventional black-and-white tomograms (bone SPECT) and 10 color-graded bone SPECT-CT scans. Each surgeon was asked to identify the location of any diagnostically relevant uptake in the disk and/or facet joint between L1 and S1. Reliability was evaluated using the free-marginal kappa statistic, and the level of agreement was assessed using the Landis and Koch interpretation. Results Conventional bone SPECT scans and bone SPECT-CT scans were reliable for the identification of diagnostically relevant uptake, with bone SPECT-CT having higher reliability (kappa = 0.72) than bone SPECT alone (0.59). Bone SPECT and bone SPECT-CT were also reliable in identifying disk pathology, with kappa values of 0.72 and 0.81, respectively. However, bone SPECT-CT was more reliable (0.81) than bone SPECT (0.60) when identifying facet disease. Conclusions For the identification of disk pathology, it is reasonable to use either conventional bone SPECT or bone SPECT-CT; however, bone SPECT-CT is more reliable for facet joint pathology. PMID:25648168

  14. Harvard--MIT research program in short-lived radiopharmaceuticals

    SciTech Connect

    Not Available

    1991-03-01

    This report describes progress on five projects. The first project showed a 1000 fold concentration of the cationic complex {sup 99m}Tc (MIBI) in heart cell mitochondria vs heart cell cytoplasm, as determined by high resolution electron probe microanalysis. Additional technetium-99m based complexes are being developed and tested. The second project involves evaluating technetium acetylacteonates as potential indicators of cerebral blood flow. An intermediate in the synthesis of a technetium porphyrin complex has been synthesized; an oxotechnetium(V)-2,4-pentanedione complex has been prepared and is currently being characterized. The third project involves using radio labelled antibodies for diagnosis and treatment of cancer. An early discovery was that chloramine-T based iodination protocols resulted in a reversal of the charge on mouse lgGs. Immunoperoxidase-labelled monoclonal antibody MOv 18 was shown to bind specifically to the most frequent ovarian aderon carcinomas, and not to healthy tissue, making this antibody a good candidate for immunotherapy or immunodetection. Work on a specific immunotherapy protocol suffered a setback when one reagent, a {sup 125}I-biotin complex, proved to be unstable in vivo. The fourth project involves labelling antibodies with positron emitting radionuclides. Radiofluorination was accomplished through reductive alkylation of {sup 18}F-aldehyde, or pentafluorophenyl esters. Radioiodination was accomplished using alkyl-tin derivation exchange. The fifth project examined antibody modification for use in radioimmune imaging. Technetium-99m-labelled lgG was shown to be biologically equivalent to Indium-III-labelled lgG for imaging focal sites of inflamation. Also, Indium III labelling of small bioactive peptides was examined as a means of imaging important physiological processes. 44 refs., 2 figs.

  15. Utility of 99mTc-Hynic-TOC in 131I Whole-Body Scan Negative Thyroid Cancer Patients with Elevated Serum Thyroglobulin Levels

    PubMed Central

    Shinto, Ajit S.; Kamaleshwaran, K. K.; Mallia, Madhav; Korde, Aruna; Samuel, Grace; Banerjee, Sharmila; Velayutham, Pavanasam; Damodharan, Suresh; Sairam, Madhu

    2015-01-01

    Several studies have reported on the expression of somatostatin receptors (SSTRs) in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed Technetium-99m labeled somatostatin analog, 99mTc-Hynic-TOC, in terms of precise localization of the disease. The study population consisted of 28 patients (16 men, 12 women; age range: 39-72 years) with histologically confirmed DTC, who presented with recurrent or persistent disease as indicated by elevated serum thyroglobulin (Tg) levels after initial treatment (serum Tg > 10 ng/ml off T4 suppression for 4-6 weeks). All patients were negative on the Iodine-131 posttherapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed in all patients. SSTR scintigraphy was true positive in 23 cases (82.1%), true negative in two cases (7.1%) and false negative in three cases (10.7%) which resulted in a sensitivity of 88.46%, specificity of 100% and an accuracy of 89.2%. Sensitivity of 99mTc-Hynic-TOC scan was higher (93.7%) for patients with advanced stages, that is stages III and IV. 18F-FDG showed a sensitivity of 93.7%, a specificity of 50% and an accuracy of 89.3%. 18F-FDG PET was found to be more sensitive, with lower specificity due to false positive results in 2 patients. Analysis on a lesion basis demonstrated substantial agreement between the two imaging techniques with a Cohen's kappa of 0.66. Scintigraphy with 99mTc-Hynic-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localization diagnostics in thyroid cancer patients with recurrent or metastatic disease. PMID:26097420

  16. Dual-energy micro-CT imaging of pulmonary airway obstruction: correlation with micro-SPECT

    NASA Astrophysics Data System (ADS)

    Badea, C. T.; Befera, N.; Clark, D.; Qi, Y.; Johnson, G. A.

    2014-03-01

    To match recent clinical dual energy (DE) CT studies focusing on the lung, similar developments for DE micro-CT of the rodent lung are required. Our group has been actively engaged in designing pulmonary gating techniques for micro- CT, and has also introduced the first DE micro-CT imaging method of the rodent lung. The aim of this study was to assess the feasibility of DE micro-CT imaging for the evaluation of airway obstruction in mice, and to compare the method with micro single photon emission computed tomography (micro-SPECT) using technetium-99m labeled macroaggregated albumin (99mTc-MAA). The results suggest that the induced pulmonary airway obstruction causes either atelectasis, or air-trapping similar to asthma or chronic bronchitis. Atelectasis could only be detected at early time points in DE micro-CT images, and is associated with a large increase in blood fraction and decrease in air fraction. Air trapping had an opposite effect with larger air fraction and decreased blood fraction shown by DE micro-CT. The decrease in perfusion to the hypoventilated lung (hypoxic vasoconstriction) is also seen in micro-SPECT. The proposed DE micro-CT technique for imaging localized airway obstruction performed well in our evaluation, and provides a higher resolution compared to micro-SPECT. Both DE micro-CT and micro-SPECT provide critical, quantitative lung biomarkers for image-based anatomical and functional information in the small animal. The methods are readily linked to clinical methods allowing direct comparison of preclinical and clinical results.

  17. Selective Internal Radiotherapy (SIRT) of Hepatic Tumors: How to Deal with the Cystic Artery

    SciTech Connect

    Theysohn, Jens M.; Mueller, Stefan; Schlaak, Joerg F.; Ertle, Judith; Schlosser, Thomas W.; Bockisch, Andreas; Lauenstein, Thomas C.

    2013-08-01

    PurposeSelective internal radiotherapy (SIRT) with the beta emitter yttrium-90 (Y90) is a rapidly developing therapy option for unresectable liver malignancies. Nontarget irradiation of the gallbladder is a complication of SIRT. Thus, we aimed to assess different strategies to avoid infusion of Y90 into the cystic artery (CA).MethodsAfter hepatic digital subtraction angiography and administration of technetium-99m-labeled human serum albumin ({sup 99}mTc-HSA), 295 patients with primary or secondary liver tumors underwent single-photon emission computed tomography/computed tomography (SPECT/CT). Different measures were taken before repeated Y90 mapping and SIRT to avoid unintended influx into the CA where necessary. Clinical symptoms, including pain, fever, or a positive Murphy sign, were assessed during patient follow-up.ResultsA significant {sup 99}mTc-HSA accumulation in the gallbladder wall (higher {sup 99}mTc-HSA uptake than in normal liver tissue) was seen in 20 patients. The following measures were taken to avoid unintended influx into the CA: temporary/permanent occlusion of the CA with gelfoam (n = 5)/microcoil (n = 1), induction of vasospasm with a microwire (n = 4), or altering catheter position (n = 10). Clinical signs of cholecystitis were observed in only one patient after temporary CA occlusion with gelfoam and were successfully treated by antibiotics. Cholecystectomy was not required for any patient.ConclusionIt is important to identify possible nontarget irradiation of the gallbladder. The risk for radiation-induced cholecystitis can be easily minimized by temporary or permanent CA embolization, vasospasm induction, or altering the catheter position.

  18. Imaging human atherosclerosis with /sup 99m/Tc-labeled low density lipoproteins

    SciTech Connect

    Lees, A.M.; Lees, R.S.; Schoen, F.J.; Isaacsohn, J.L.; Fischman, A.J.; McKusick, K.A.; Strauss, H.W.

    1988-09-01

    The feasibility of localizing human atherosclerotic plaques by gamma scintillation camera external imaging with technetium-99m-labeled low density lipoproteins (99mTc-LDL) was tested in 17 patients who had atherosclerosis. Imaging demonstrated focal accumulation of radiolabel consistent with 99mTc-LDL sequestration by plaques in the carotid, iliac, or femoral vessels of four patients 8 to 21 hours after intravenous injection of the radiopharmaceutical. Focal accumulation of 99mTc-LDL also appeared in the location of coronary lesions in four patients, but this accumulation could not be distinguished with certainty from residual blood pool radioactivity. When carotid endarterectomy specimens from six patients who received 99mTc-LDL 1 day before endarterectomy were examined, the specimens had focal accumulations of radiolabel, with two to four times greater radioactivity in some regions of each specimen than in others; this occurred whether or not the lesions were detected on the gamma camera images. Lesion composition may have determined whether accumulation was quantitatively sufficient to produce an external image. Histologically, the imaged carotid specimen had abundant foam cells and macrophages and poorly organized intramural blood consistent with a plaque hemorrhage; in contrast, nonimaged endarterectomy specimens were mature, fibrocalcific plaques. We conclude that: 1) 99mTc-LDL did accumulate in human atherosclerotic plaques; 2) in some patients, the accumulation of 99mTc-LDL was sufficient for detection by gamma camera imaging; 3) the amount of LDL that accumulated appeared to depend on lesion composition; and 4) the design of new radiopharmaceuticals with reduced residual blood pool activity relative to plaque accumulation should lead to improved external imaging of atherosclerosis.

  19. The use of 99mTc-Al2O3 for detection of sentinel lymph nodes in breast cancer

    NASA Astrophysics Data System (ADS)

    Sinilkin, I.; Chernov, V.; Medvedeva, A.; Zeltchan, R.; Slonimskaya, E.; Doroshenko, A.; Varlamova, N.; Skuridin, V.

    2016-08-01

    Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n = 34) were injected with radioactive 99mTc-Al2O3, and Group II patients (n = 30) received 99mTc-labeled phytate colloid. A total of 37 SLNs were detected in Group I patients. The number of identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. 18 hours after 99mTc-Al2O3 injection, the percentage of its accumulation in the SLN was 7-11% (of the counts in the injection site) by SPECT and 17-31% by gamma probe detection. In Group II SLNs were detected in 27 patients. 18 hours after injection of the phytate colloid the percentage of its accumulation in the SLN was 1.5-2% out of the counts in the injection site by SPECT and 4-7% by gamma probe. The new radiopharmaceutical based on the 99mTc-Al2O3 demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. The sensitivity and specificity of 99mTc-Al2O3 were 100% for both SPECT and intraoperative gamma probe identification.

  20. Effects of lidocaine and droxicainide on myocardial necrosis: a comparative study

    SciTech Connect

    Faria, D.B.; Cheung, W.M.; Ribeiro, L.G.; Maroko, P.R.

    1983-06-01

    Lidocaine has been shown to protect ischemic myocardium, but the degree of its effectiveness is not yet well established. Therefore, in this study, the effects of this drug on ultimate infarct size were examined quantitatively. Another member of the same class of drugs, droxicainide (ALS1249), DL-N-(2-hydroxyethyl)-pipecolinyl-2,6-dimethylanilide hydrochloride, is a new antiarrhythmic agent that has shown a good therapeutic index in the initial experimental studies. Accordingly, the effects of this drug on ultimate infarct size were examined and compared with those of lidocaine. Coronary artery occlusion was performed on 29 dogs. One minute later, technetium-99m labeled microspheres were injected into the left atrium for assessment of the hypoperfused zone (the zone at risk of infarction). Fifteen minutes after occlusion, the dogs were randomized into three groups: 9 dogs served as a control group, 10 were given lidocaine and 10 were given the same dosage of droxicainide. Six hours after occlusion, the dogs were sacrificed and the hearts cut into 3 mm thick slices and incubated in triphenyltetrazolium chloride to delineate the area of myocardial damage. Autoradiography of the same slices provided images of the areas of myocardial hypoperfusion. Thereafter, in each dog, the percent of hypoperfused area that evolved to necrosis was calculated. In control dogs, it was 85.6 +/- 2.0%; in lidocaine-treated dogs, 68.1 +/- 4.1% (p less than 0.01), a reduction of 20%; and in droxicainide-treated dogs, 50.1 +/- 5.3%, a reduction of 41% (p less than 0.001 versus control and p less than 0.005 versus lidocaine).

  1. Sentinel Node Biopsy Interpretation: The Milan Experience.

    PubMed

    Galimberti, Viviana; Zurrida, Stefano; Intra, Mattia; Monti, Simonetta; Arnone, Paolo; Pruneri, Giancarlo; De Cicco, Concetta

    2000-10-01

    From March 1996 to December 1999 we performed 1,266 sentinel node biopsies (SNBs) in patients with small breast cancers. The technique is to inject technetium 99m-labeled albumin particles close to the tumor, locate the sentinel node (SN) scintigraphically, and use a handheld gamma-detecting probe to guide its removal via a small incision during breast surgery. Our experience was divided into three phases. In the first phase, complete axillary dissection was performed to assess the accuracy of SNB in predicting axillary status. We also assessed safety, perfected tracer injection technique, determined optimal particle size and radioactivity levels, optimized lymphoscintigraphic scanning, and perfected the surgical technique. The SN was identified and removed in 98.7% of cases. Comparison with complete axillary dissection showed that the SN predicted axillary status in 96.8% of cases. However, use of an intraoperative frozen section method predicted axillary status in only 86.5% of cases. In the second phase we developed a new method for intraoperative histologic analysis. Extensive sampling (up to 60 sections/SN) and an experienced pathologist proved more important than use of antikeratin immunostaining in identifying tumor cells, and the new method has the accuracy of a definitive histologic examination. The third phase, a randomized trial, closed at the end of 1999. Trial objectives were to confirm that the SN predicts axillary status, to determine the number of axillary relapses, and to assess overall and disease-free survival. Patients were randomized in the operating room to complete axillary dissection or SNB. If the SN was positive, complete axillary dissection was performed; if the SN was negative, no further axillary treatment was given. We expect the trial to confirm our clinical experience that SNB is a safe and accurate procedure for staging patients with early breast cancer and a clinically negative axilla. PMID:11348387

  2. Effect of increased surface tension and assisted ventilation on /sup 99m/Tc-DTPA clearance

    SciTech Connect

    Jefferies, A.L.; Kawano, T.; Mori, S.; Burger, R.

    1988-02-01

    Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (/sup 99m/Tc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. /sup 99m/Tc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP (k = 7.57 +/- 0.71%/min (SE)) and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of /sup 99m/Tc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.

  3. Lung deposition of nebulised pentamidine in children.

    PubMed Central

    O'Doherty, M J; Thomas, S H; Gibb, D; Page, C J; Harrington, C; Duggan, C; Nunan, T O; Bateman, N T

    1993-01-01

    BACKGROUND: Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. METHODS: Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. RESULTS: Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. CONCLUSIONS: These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser. PMID:8497819

  4. In vivo distribution and elimination of hemoglobin modified by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate

    SciTech Connect

    Bleeker, W.K.; van der Plas, J.; Feitsma, R.I.; Agterberg, J.; Rigter, G.; de Vries-van Rossen, A.; Pauwels, E.K.; Bakker, J.C.

    1989-02-01

    Modified hemoglobin solutions have potential application as plasma expanders with oxygen-transporting capacity. In a previous study it was found that modification of hemoglobin by intramolecular cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate (NFPLP) improves the vascular retention time by a factor of three, and it also improves the oxygen-transporting properties. In the present study we investigated in rats how, after exchange transfusion of a clinically relevant dose, the modified hemoglobin (HbNFPLP) was distributed in the body compared with how the unmodified hemoglobin was distributed. By using a new technetium 99m labeling technique, we found in a scintigraphic study that accumulation of hemoglobin in the kidneys was greatly diminished by the intramolecular cross-linking with NFPLP. These findings were confirmed by light-microscopic observations after diaminobenzidine staining. It was concluded that the impairment of kidney function caused by blockade of the tubuli is not to be expected from HbNFPLP. In the liver and spleen, where the free HbNFPLP is possibly eliminated, some accumulation of 99mTc label was observed, but the major part of the extravascular label was diffusely spread throughout the body. This led to the conclusion that important accumulation of undegraded HbNFPLP does not occur in the liver and spleen. Rapid appearance of both hemoglobin and HbNFPLP in the lymph showed that cross-linking with NFPLP does not prevent the distribution of hemoglobin over the interstitial space in the first hours after administration. However, pharmacokinetic analysis demonstrated that transcapillary transfer contributes only to a limited extent to the disappearance from the circulation. During 24-hour infusions of HbNFPLP, a steady state with a constant plasma concentration was easily reached.

  5. Effects of histamine, ethanol, and a detergent on exudation and absorption across guinea pig airway mucosa in vivo.

    PubMed Central

    Greiff, L; Erjefält, I; Wollmer, P; Pipkorn, U; Persson, C G

    1991-01-01

    This study examined effects of three substances that cause mucosal provocation (histamine, ethanol, and the detergent dioctylsodium sulphosuccinate (DOSS] on the flux of solutes across airway vascular mucosal barriers in anaesthetised guinea pigs. The inward flux was assessed as absorption of iodine-131 labelled albumin (MW 69,000) from the tracheobronchial surface into the circulation and the outward flux as the exudation of two intravenously administered plasma tracers--125I albumin (MW 69,000) and fluorescein isothiocyanate conjugated (FITC) dextran (MW 70,000)--into the airway. The absorption of technetium-99m labelled DTPA (MW 492) from the tracheobronchial airways was determined in separate experiments. Histamine (5.0 nmol) dissolved in 40 microliters saline and superfused on the tracheobronchial mucosal surface caused significant and similar entry of 125I albumin and FITC dextran into the airway lumen. This dose of histamine did not, however, alter the absorption of small (99mTc DTPA) or large (131I albumin) solutes across the airway mucosa. Ethanol (0.17 mumol), superfused in the same way, also caused significant exudation of the plasma tracers into the airway lumen. In addition, ethanol increased the absorption of 131I albumin without causing change in the disappearance rate of 99mTc DTPA. The detergent, DOSS (0.28 nmol), dissolved in ethanol (0.17 mumol), caused a pronounced increase in exudation and much increased absorption of small and large tracer solutes. Thus three patterns of change in airway mucosal barriers were found. The agents that are toxic to membranes, ethanol and DOSS, caused a bidirectional increase in permeability across the mucosa, whereas histamine caused only an outward exudative flux. The results obtained with histamine are similar to those seen previously with bradykinin, capsaicin, and allergen, suggesting that endogenous inflammatory mediators have a role in mucosal defence, producing entry of plasma exudates into the airway lumen

  6. In liver transplantation, T tube bile represents total bile flow: physiological and scintigraphic studies on biliary secretion of organic anions.

    PubMed

    Lenzen, R; Bähr, A; Eichstädt, H; Marschall, U; Bechstein, W O; Neuhaus, P

    1999-01-01

    The present study was performed to clarify the recovery of hepatocellular uptake and the biliary secretion of bile acids during the first 14 days after orthotopic liver transplantation (OLT) and to determine the fraction of bile flow appearing outside through the T tube and entering the duodenum. Therefore, we determined primary and secondary bile acids in bile samples obtained from the T tube at day 5 after OLT, while the T tube was permanently open, and at days 10 and 14 after OLT, i.e., 4 and 9 days after closure of the T tube, respectively, thus restoring enterohepatic bile acid circulation. In addition, we performed hepatobiliary scintigraphy using technetium 99m-labeled [2,4,6 trimethyl-3-bromo]imino-diacetic acid (technetium 99m-BRIDA) in 12 patients between days 4 and 17 after OLT. Chromatographic analyses of biliary bile acids showed no secondary bile acids during the first 5 days after OLT, as opposed to 10 and 14 days after OLT when enterohepatic circulation was restored. Eleven patients with an uncomplicated postoperative course after OLT showed a significantly reduced hepatic uptake and biliary secretion of 99mTc-BRIDA during the first days after OLT with progressive recovery. One patient with an acute allograft rejection episode showed almost no uptake and only minimal secretion. The bile fraction appearing outside through the inserted T tube represented 94.6% +/- 6.2% of the injected 99mTc-BRIDA. We conclude that OLT results in markedly impaired hepatocellular uptake and biliary secretion of organic anions. Simultaneously, bile acid synthesis is significantly reduced, which, in addition, diminishes bile secretion of the graft. We show that T tube bile is a valid tool for bile physiological studies in patients in whom transplantation was successfully performed. PMID:9873086

  7. Nuclear medicine program progress report for quarter ending March 31, 1995

    SciTech Connect

    Knapp, F.F. Jr.; Ambrose, K.R.; Beets, A.L.; Luo, H.; McPherson, D.W.; Mirzadeh, S.

    1995-06-01

    In this report the conditions for ``direct`` labeling of the anti-granulocyte (MAb) BW 250/183 monoclonal antibody with rhenium-188 (Re-188) from a generator are described. Re-188-BW 250/183 is of interest for potential use for bone marrow ablation. The labeling time, temperature, pH, and the amount of tin and citric acid were optimized utilizing IgG. Radiolabeling yields of greater than 97% were achieved using 1 mL of a phthalate/tartrate buffer (pH 5.{und M}=?), 250 {micro} g BW 250/183, 1.0 mg citric acid, 400 {micro} g tin (II) chloride, and 1 mL of the tungsten-188/rhenium-188 generator eluent (200--800 {micro} Ci of Re-188). Analysis of the Re-188-labeled IgG and BW 250/183 was performed by Instant Thin Layer Chromatography (ITLC), Sephadex purification and High Performance Liquid Chromatography (HPLC). When the labeling was performed at room temperature or 37 C, in vitro stability studies performed in HSA solution, cysteine solution, 6 {und M} urea solution and a 1% casein solution showed that the Re-188 label demonstrated a similar stability profile in all solutions. Initial studies indicate that Re-188-BW 250/183 retained {approximately} 90% of immunoreactivity when compared to the technetium-99m labeled antibody prepared from the same kit. During this period, several radioisotopes prepared in the ORNL HFIR were also supplied on a cost-recovery basis or provided to collaborators for ongoing collaborative projects. These include tin-117m, processed tungsten-188 and the ORNL alumina-based tungsten-188/rhenium-188 generators.

  8. Influence of endothelial cell seeding on platelet deposition and patency in small-diameter Dacron arterial grafts

    SciTech Connect

    Allen, B.T.; Long, J.A.; Clark, R.E.; Sicard, G.A.; Hopkins, K.T.; Welch, M.J.

    1984-01-01

    Serial platelet deposition, surface topography, and patency were evaluated in control (N . 28) and endothelial cell-seeded (N . 28) small-diameter (4 mm inner diameter) USCI Dacron grafts implanted in the carotid and femoral arteries of dogs. All dogs received aspirin (325 mg) daily for 2 weeks starting 24 hours prior to graft implantation. Endothelial cell seeding was performed by mixing suspensions of autologous endothelial cells that had been enzymatically harvested from segments of external jugular vein with blood that was used to preclot the prostheses. The platelet deposition on each graft was quantitated by means of indium 111-labeled platelets and technetium 99m-labeled red cells in a dual-isotope platelet-imaging technique. Platelet deposition on seeded grafts 24 hours after implantation was significantly higher than on the controls (p less than 0.05). Two weeks after implantation platelet deposition on seeded prostheses had decreased to a level significantly lower than that on the controls and continued to decline on serial studies up to 7 months. In contrast to seeded grafts, platelet accumulation on control grafts dramatically increased after the withdrawal of aspirin therapy and was associated with a sharp rise in control graft thromboses. Cumulative 7-month patency for seeded prostheses was significantly higher than for the controls (96% and 29%, respectively; p less than 0.001). We conclude that endothelial cell seeding in combination with short-term aspirin therapy is a simple, reliable diameter Dacron prostheses. Abrupt withdrawal of aspirin therapy may be contraindicated in nonseeded control grafts because it results in increased platelet deposition and thrombosis.

  9. In vitro evaluation of radioiodinated butyrophenones as radiotracer for dopamine receptor study

    SciTech Connect

    Nakatsuka, I.; Saji, H.; Shiba, K.; Shimizu, H.; Okuno, M.; Yoshitake, A.; Yokoyama, A.

    1987-10-26

    Radioiodinated butyrophenone compounds are attracting the interest of those working on dopamine receptor studies; structure-activity relationship study has revealed the ortho position of the p-fluorobutyrophenone moiety as a very plausible iodination site. Various synthesized butyrophenones iodinated at the ortho position of p-fluorobutyrophenone moiety, 2'-iodohaloperidol (2'-IHP), 2'-iodotrifluperidol (2'-ITP) and 2'-iodospiperone (2'-ISP) were tested for their abilities to inhibit /sup 3/H-spiperone (SP) binding for the dopamine (D-2) receptor, together with reference compounds (SP, haloperidol(HP) and 4-iodospiperone (4-ISP)). The order of binding affinity of the tested compounds was SP > 2'-ISP > HP > 4-ISP > 2'-IHP > 2'-ITP. Whereas, the serotonin (S-2) receptor binding affinity of SP and its iodinated analogues were in the order of SP >> 4-ISP > 2'-ISP. These data indicated the 2'-ISP as holding high affinity for dopamine receptors and a low affinity for serotonin receptors. Thus, the /sup 125/I-2'-ISP was a very potent radioligand for in vitro dopamine (D-2) receptor studies, and /sup 123/I-2'-ISP holds very promising characteristics as for in vivo dopamine receptor studies, as well.

  10. Phase I Report: Technetium Radiotracers for the Dopamine Transporter. [September 1998 - March 1999

    SciTech Connect

    Baldwin, R.N.

    1999-03-17

    This project (a) demonstrated specific dopamine transporter (DAT) uptake in vivo and metabolic stability of a radiolabelled cycloplentadieny rhenium compound in rats and baboons, (b) showed that cyclopentadieny tricarbonyl rhenium and technetium compounds conjugated tropanel could be made by metal transfer with ferrocenes; and (c) explored new methods of synthesizing these compounds under mild conditions.

  11. Toward the Optimization of Bombesin-Based Radiotracers for Tumor Targeting.

    PubMed

    Valverde, Ibai E; Vomstein, Sandra; Mindt, Thomas L

    2016-04-28

    The peptide bombesin (BBN) is a peptide with high affinity for the gastrin-releasing peptide receptor (GRPr), a receptor that is overexpressed by, for example, breast and prostate cancers. Thus, GRPr agonists can be used as cancer-targeting vectors to shuttle diagnostic and therapeutic agents into tumor cells. With the aim of optimizing the tumor targeting properties of a radiolabeled [Nle(14)]BBN(7-14) moiety, novel BBN(7-14)- and BBN(6-14)-based radioconjugates were synthesized, labeled with Lu-177, and fully evaluated in vitro and in vivo. The effect of residue and backbone modification on several parameters such as the internalization of the radiolabeled peptides into PC3 and AR42J tumor cells, their affinity toward the human GRPr, metabolic stability in blood plasma, and biodistribution in mice bearing GRPr-expressing PC3 xenografts was studied. As a result of our investigations, a novel radiolabeled GRPr agonist with a high tumor uptake and a high tumor-to-kidney ratio was identified. PMID:27054526

  12. Training Grant in Radiochemistry and Radiotracer Development. Design and Synthesis of Molecular and Nanoparticulate Probes

    SciTech Connect

    Hanson, Robert N.

    2015-01-15

    Original overall objective was to develop a training program within the Department of Chemistry and Chemical Biology that would provide an experience in radiochemistry. A combination of educational and research experiences would prepare organic chemistry graduate students to enter the field.

  13. Dosimetry of exendin-4 based radiotracer for glucagonlike peptide-1 receptor imaging: an initial report

    NASA Astrophysics Data System (ADS)

    Tomaszuk, M.; Sowa-Staszczak, A.; Lenda-Tracz, W.; Glowa, B.; Pach, D.; Buziak-Bereza, M.; Stefanska, A.; Janota, B.; Pawlak, D.; Mikolajczak, R.; Hubalewska-Dydejczyk, A. B.

    2011-09-01

    Overexpression of glucagonlike peptide-1 (GLP-1) receptors in human tumours is a potential target for future imaging and therapy. The GLP-1 receptor imaging using [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 could be useful in the localization of unknown insulinoma focus. The aim of this study was to present the first experience of our unit with the new radiopharmaceutical and its dose estimates. Imaging studies and dose assessment, according to the MIRD schema and MIRD Pamphlet No.11, were performed for 3 patients (2 with suspicion of insulinoma, 1 with suspected insulinoma recurrence). In the first case suspicion of insulinoma was not confirmed. In the second case localized accumulation of tracer in the pancreas was removed by surgery and the clinical symptoms of insulinoma receded. In the third case, pathological accumulation of tracer was localized and recurrence of insulinoma was confirmed in fusion with CT images. The biological half-time did not exceed 2.7.h. The effective half-time did not exceed 4.8 h. The total-body radiation dose did not exceed 0.0038 mGy/MBq and is comparable with the radiation dose to patient after somatostatin receptor scintigraphy. The highest radiation dose was calculated for kidneys (~ 0.070 mGy/MBq). [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 is a good candidate for clinical GLP-1 receptor imaging studies and appears safe for the patient from radiological safety point of view.

  14. Radio-tracer techniques for the study of flow in saturated porous materials

    USGS Publications Warehouse

    Skibitzke, H.E.; Chapman, H.T.; Robinson, G.M.; McCullough, Richard A.

    1961-01-01

    An experiment was conducted by the U.S. Geological Survey to determine the feasibility of using a radioactive substance as a tracer in the study of microscopic flow in a saturated porous solid. A radioactive tracer was chosen in preference to dye or other chemical in order to eliminate effects of the tracer itself on the flow system such as those relating to density, viscosity and surface tension. The porous solid was artificial "sandstone" composed of uniform fine grains of sand bonded together with an epoxy adhesive. The sides of the block thus made were sealed with an epoxy coating compound to insure water-tightness. Because of the chemical inertness of the block it was possible to use radioactive phosphorus (P32). Ion-exchange equilibrium was created between the block and nonradioactive phosphoric acid. Then a tracer tagged with P32 was injected into the block in the desired geometric configuration, in this case, a line source. After equilibrium in isotopic exchange was reached between the block and the line source, the block was rinsed, drained and sawn into slices. It was found that a quantitative analysis of the flow system may be made by assaying the dissected block. ?? 1961.

  15. Evaluation of the In Vivo and Ex Vivo Binding of Novel BC1 Cannabinoid Receptor Radiotracers

    SciTech Connect

    Miller, A.; Gatley, J.; Gifford, A.

    2002-01-01

    The primary active ingredient of marijuana, 9-tetrahydrocannabinol, exerts its psychoactive effects by binding to cannabinoid CB1 receptors. These receptors are found throughout the brain with high concentrations in the hippocampus and cerebellum. The current study was conducted to evaluate the binding of a newly developed putative cannabinoid antagonist, AM630, and a classical cannabinoid 8-tetrahydrocannabinol as potential PET and/or SPECT imaging agents for brain CB1 receptors. For both of these ligands in vivo and ex vivo studies in mice were conducted. AM630 showed good overall brain uptake (as measure by %IA/g) and a moderately rapid clearance from the brain with a half-clearance time of approximately 30 minutes. However, AM630 did not show selective binding to CB1 cannabinoid receptors. Ex vivo autoradiography supported the lack of selective binding seen in the in vivo study. Similar to AM630, 8-tetrahydrocanibol also failed to show selective binding to CB1 receptor rich brain areas. The 8-tetrahydrocanibol showed moderate overall brain uptake and relatively slow brain clearance as compared to AM630. Further studies were done with AM2233, a cannabinoid ligand with a similar structure as AM630. These studies were done to develop an ex vivo binding assay to quantify the displacement of [131I]AM2233 binding by other ligands in Swiss-Webster and CB1 receptor knockout mice. By developing this assay we hoped to determine the identity of an unknown binding site for AM2233 present in the hippocampus of CB1 knockout mice. Using an approach based on incubation of brain slices prepared from mice given intravenous [131I]AM2233 in either the presence or absence of AM2233 (unlabelled) it was possible to demonstrate a significant AM2233-displacable binding in the Swiss-Webster mice. Future studies will determine if this assay is appropriate for identifying the unknown binding site for AM2233 in the CB1 knockout mice.

  16. Radiotracers in PETT: strategies for in vivo receptor activity, Schizophernia, and Alzheimer's Dementia studies

    SciTech Connect

    Wolf, A.P.

    1984-01-01

    Using /sup 18/F-spiperone, a one compartment system with a driving function as model, blocking agents such as butaclamol and ketanserin, assay of the live adult female baboon striatum over the 8 h period, and assay of the parent compound in plasma, it is apparent that residence times in the living tissue and those estimated from in vitro tritium data are at variance. Occupancy rises to a maximum for /sup 18/F benperidol and /sup 18/F haloperidol after approx. 25 minutes and for /sup 18/F spiperone after approx. 75 minutes, but the striatum concentration of /sup 18/F-spiperone and benperiodol remain nearly constant over an eight hour period whereas /sup 18/F haloperidol concentration starts falling almost immediately to half its maximum value at 8 hrs. The best fit to our current data gives a preliminary off rate constant of 0.0057 min/sup -1/.

  17. Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers

    NASA Astrophysics Data System (ADS)

    Spinelli, Antonello E.; D'Ambrosio, Daniela; Calderan, Laura; Marengo, Mario; Sbarbati, Andrea; Boschi, Federico

    2010-01-01

    In this paper, we showed that Cerenkov radiation (CR) escaping from the surface of small living animals injected with 18F-FDG can be detected with optical imaging techniques. 18F decays by emitting positrons with a maximum energy of 0.635 MeV; such positrons, when travelling into tissues faster than the speed of light in the same medium, are responsible of CR emission. A detailed model of the CR spectrum considering the positron energy spectrum was developed in order to quantify the amount of light emission. The results presented in this work were obtained using a commercial optical imager equipped with charged coupled detectors (CCD). Our data open the door to optical imaging (OI) in vivo of the glucose metabolism, at least in pre-clinical research. We found that the heart and bladder can be clearly identified in the animal body reflecting the accumulation of the 18F-FDG. Moreover, we describe two different methods based on the spectral analysis of the CR that can be used to estimate the depth of the source inside the animal. We conclude that 18F-FDG can be employed as it is as a bimodal tracer for positron emission tomography (PET) and OI techniques. Our results are encouraging, suggesting that it could be possible to apply the proposed approach not only to β+ but also to pure β- emitters.

  18. Comparison of three high affinity SPECT radiotracers for the dopamine D2 receptor.

    PubMed

    al-Tikriti, M S; Baldwin, R M; Zea-Ponce, Y; Sybirska, E; Zoghbi, S S; Laruelle, M; Malison, R T; Kung, H F; Kessler, R M; Charney, D S

    1994-02-01

    The regional brain distribution and pharmacological specificity of three high affinity tracers for the dopamine (DA) D2 receptor: [123I]IBF, [123I]epidepride, and [123I]2'-ISP were assessed by SPECT imaging of non-human primates. The ratios of striatal-to-occipital activities at the time of peak striatal uptake were 2.2, 6.3 and 1.7, respectively. From the peak striatal activities, washout rates were 33, 4 and 16%/h for [123I]IBF, [123I]epidepride and [123I]2'-ISP, respectively. The reversibility of the striatal uptake of all three agents was demonstrated by the rapid displacement induced by the dopamine D2 selective antipsychotic agent raclopride, which increased washout rates to 96, 58 and 43%/h. The administration of d-amphetamine, which induces release of dopamine, had no noticeable effect on [123I]epidepride but increased the washout rate of [123I]IBF. These results suggest that, among these three agents, [123I]epidepride is the superior tracer for in vivo displacement studies because of its slow washout and high target-to-background ratios. However, for tracer kinetic modeling, [123I]IBF may be the superior agent because of its early time of peak uptake and its higher target-to-background ratios than [123I]2'-ISP. PMID:9234281

  19. Impact of D2 Receptor Internalization on Binding Affinity of Neuroimaging Radiotracers

    PubMed Central

    Guo, Ningning; Guo, Wen; Kralikova, Michaela; Jiang, Man; Schieren, Ira; Narendran, Raj; Slifstein, Mark; Abi-Dargham, Anissa; Laruelle, Marc; Javitch, Jonathan A; Rayport, Stephen

    2010-01-01

    Synaptic dopamine (DA) levels seem to affect the in vivo binding of many D2 receptor radioligands. Thus, release of endogenous DA induced by the administration of amphetamine decreases ligand binding, whereas DA depletion increases binding. This is generally thought to be due to competition between endogenous DA and the radioligands for D2 receptors. However, the temporal discrepancy between amphetamine-induced increases in DA as measured by microdialysis, which last on the order of 2 h, and the prolonged decrease in ligand binding, which lasts up to a day, has suggested that agonist-induced D2 receptor internalization may contribute to the sustained decrease in D2 receptor-binding potential seen following a DA surge. To test this hypothesis, we developed an in vitro system showing robust agonist-induced D2 receptor internalization following treatment with the agonist quinpirole. Human embryonic kidney 293 (HEK293) cells were stably co-transfected with human D2 receptor, G-protein-coupled receptor kinase 2 and arrestin 3. Agonist-induced D2 receptor internalization was demonstrated by fluorescence microscopy, flow cytometry, and radioligand competition binding. The binding of seven D2 antagonists and four agonists to the surface and internalized receptors was measured in intact cells. All the imaging ligands bound with high affinity to both surface and internalized D2 receptors. Affinity of most of the ligands to internalized receptors was modestly lower, indicating that internalization would reduce the binding potential measured in imaging studies carried out with these ligands. However, between-ligand differences in the magnitude of the internalization-associated affinity shift only partly accounted for the data obtained in neuroimaging experiments, suggesting the involvement of mechanisms beyond competition and internalization. PMID:19956086

  20. First-pass cerebral extraction of benzamide-derivative radiotracers for SPECT.

    PubMed

    Bottoncetti, A; Pupi, A; Sestini, S; Pecorale, A; Raspanti, S; Meldolesi, U

    1998-04-01

    Central dopaminergic receptors are widely studied for their importance in the pathophysiology of neurological and psychiatric diseases. We have investigated the cerebral delivery kinetics of three dopaminergic ligands in rats through the use of an indicator fractionation method to measure the tracer's regional influx rate constant with respect to regional blood flow. The aim is to collect the in vivo kinetic parameters of the radioligand cerebral distribution, which are necessary if, dealing with SPECT and "trapped" tracers, one wishes to analyse data using a graphical approach. PMID:9620635

  1. Stochastic modelling of physiologic processes with radiotracers and positron emission tomography

    SciTech Connect

    Rescigno, A.; Lambrecht, R.M.; Duncan, C.C.

    1982-01-01

    The compartment model, so often used in nuclear medicine and in pharmacokinetics, is formed by a set of linear differential equations of order one with constant coefficients; its validity depends upon the hypothesis that the system described contains a finite number of components, and that each component is homogeneous. These hypotheses exclude the presence of diffusion and of age-dependent processes, or in general of transport of a non-Markovian nature. The fact that frequently the experimental data agree with this model does not necessarily prove the model is appropriate, but only that it is flexible. In addition to the consistency with the experimental data, an obvious conceptual requirement of the model is that its parameters could be interpreted in terms of perceivable physical properties. All this considered, it will be demonstrated that the experimental data can be examined in terms of a model making a minimum number of assumptions and giving the best physical interpretations to the parameters involved. By way of example, a high resolution positron emission tomograph will be used to determine the successive moments describing the blood circulation through different sections of the brain. Whereever the relative moments form a geometric progression, the circulation in that section follows the rules of a perfect compartment; if this is not the case, the analytical method described can be used to describe the behavior of a tracer particle in the part of the organ. (ERB)

  2. Marine anthropogenic radiotracers in the Southern Hemisphere: New sampling and analytical strategies

    NASA Astrophysics Data System (ADS)

    Levy, I.; Povinec, P. P.; Aoyama, M.; Hirose, K.; Sanchez-Cabeza, J. A.; Comanducci, J.-F.; Gastaud, J.; Eriksson, M.; Hamajima, Y.; Kim, C. S.; Komura, K.; Osvath, I.; Roos, P.; Yim, S. A.

    2011-04-01

    The Japan Agency for Marine Earth Science and Technology conducted in 2003-2004 the Blue Earth Global Expedition (BEAGLE2003) around the Southern Hemisphere Oceans, which was a rare opportunity to collect many seawater samples for anthropogenic radionuclide studies. We describe here sampling and analytical methodologies based on radiochemical separations of Cs and Pu from seawater, as well as radiometric and mass spectrometry measurements. Several laboratories took part in radionuclide analyses using different techniques. The intercomparison exercises and analyses of certified reference materials showed a reasonable agreement between the participating laboratories. The obtained data on the distribution of 137Cs and plutonium isotopes in seawater represent the most comprehensive results available for the Southern Hemisphere Oceans.

  3. A generally adoptable radiotracing method for tracking carbon nanotubes in animals

    NASA Astrophysics Data System (ADS)

    Deng, Xiaoyong; Yang, Shengtao; Nie, Haiyu; Wang, Haifang; Liu, Yuanfang

    2008-02-01

    Carbon nanotube (CNT) mediated drug delivery systems have currently aroused a great deal of interest. Such delivery systems for drugs, proteins and genes have been preliminarily studied using cellular and animal models. For the further study of the pharmacokinetics and related biological behaviours of CNTs in vivo, a fast and convenient tracing method is particularly demanded. In this paper, we developed a generally adoptable tracing method for the biodistribution study of functionalized CNTs in vivo. Taurine covalently functionalized multi-walled carbon nanotubes (tau-MWNTs) and Tween-80 wrapped MWNTs (Tween-MWNTs) were labelled with 125I, and then their distribution in mice was determined. It is interesting that Tween-80 can reduce the RES uptake of MWNTs remarkably. The resulting distribution of 125I-tau-MWNTs was very consistent with that using 14C-taurine-MWNTs as the CNTs tracer, which means the easy 125I labelling method is reliable and effective.

  4. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers

    NASA Astrophysics Data System (ADS)

    Singh, Ravi; Pantarotto, Davide; Lacerda, Lara; Pastorin, Giorgia; Klumpp, Cédric; Prato, Maurizio; Bianco, Alberto; Kostarelos, Kostas

    2006-02-01

    Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium (111In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications. nanomedicine | blood circulation half-life | drug delivery | pharmacokinetics | nanotoxicology

  5. Comparison of intravascular (nondiffusible) and diffusible radiotracers in diagnosis of testicular-scrotal disorders

    SciTech Connect

    Skarzynski, J.J.; Rosenberg, R.J.; Sziklas, J.J.; Walzak, M.P.; Karimeddini, M.K.; Spencer, R.P.

    1985-05-01

    The radionuclide approach to testicular-scrotal lesions has been described in the literature in terms of dynamic and static images. However, there has been little consideration of which radiopharmaceutical to utilize. In essence, the desired procedure is to estimate relative blood flow to each testicular-scrotal area. An intravascular (nondiffusible) radiolabel may therefore be advantageous. We reviewed 18 consecutive radionuclide studies that were performed for suspected testicular-scrotal pathology. Three radiopharmaceuticals were utilized; 7 with Tc-99m-RBC or HSA, 7 with Tc-99m-pertechnetate, and 4 with Tc-99m-DTPA. Studies were read ''blind'' as to the agent employed and rated on a scale of 1+ (least satisfactory) to 4+. Criteria included ability to delineate the testes-scrotum, background activity, and clarity of the dynamic phase. Studies with the intravascular labels (6 with tagged RBC and 1 with labeled HSA) had a mean rating of 3.6 out of 4. Pertechnetate studies had a rating of 3.0. Those performed with DTPA received a rating of 2.0. The major problems with DTPA studies were rapid entry into soft tissue (likely extracellular fluid), which created a high background; in addition, bladder counts detracted from imaging the testicular-scrotal region. Intravascular labels appear to be a distinct improvement over Tc-99m-pertechnetate for testicular-scrotal imaging.

  6. Dual radiotracer measurement of zoobenthos-mediated solute and particle transport in freshwater sediments

    NASA Astrophysics Data System (ADS)

    Krezoski, John R.; Robbins, John A.; White, David S.

    1984-09-01

    Gamma spectroscopy methods have been applied to determine the effects of Stylodrilus heringianus and Pontoporeia hoyi, two freshwater benthic macroinvertebrates, on the reworking of sediments and the transfer of solutes across the sediment-water interface. Natural lake sediments (sieved to remove organisms) and overlying water were contained in temperature-regulated rectangular plastic cells. A submillimeter layer of sediment solids labeled with 137Cs was deposited on the sediment interface while overlying water was spiked with 22Na. After addition of Stylodrilus (oligochaete worms) and Pontoporeia (crustacean amphipods) to these microcosms, the vertical distributions of 137Cs (a tracer of particle transport) and 22Na (a tracer of solute transport) were determined at daily to weekly intervals for 3 months by scanning the length of the cells with a well-collimated NaI detector. In cells with Stylodrilus, the 137Cs layer moved downward at a rate that decreased exponentially with time. The displacement of the layer is the result of the conveyor-belt feeding mode of this organism. The rate of marked layer burial is consistent with that of other freshwater annelids (0.18×10-5 cm d-1 individual-1 m-2; 11.6°C). The exponential decrease in burial rate is ascribed to uniformly distributed feeding of Stylodrilus within the feeding zone of 4.4 cm. In cells with Pontoporeia, 137Cs activity was smeared downward in time owing to eddy diffusive mixing of sediments over a small range (1-2 cm). In cells without worms, the veneer of Cs active material remained at the interface while the penetration of 22Na into sediments was consistent with diffusion in free solution with small corrections for sediment porosity and sorption (KD = 0.17). The effective diffusion coefficient De for 22Na in this cell (8.2×10-6 cm2 s-1) was essentially the same as that for a cell that had been inhabited by worms for 3 weeks and then poisoned with formalin just before addition of 22Na. Thus the presence of biogenically reworked sediments (with pelletized materials and remnant burrow structures) did not affect solute transport. In cells with live Stylodrilus, penetration of 22Na within the feeding zone was considerably more rapid, implying an apparent De twice as high as in cells without worms. Inferences based on the particle reworking results were used to develop an illustrative transport model that includes advective as well as diffusive terms. Advective transport arises from the incorporation of 22Na into pore fluids moved downward as a result of conveyor-belt feeding. The model indicates that within the feeding zone, solute transport is dominated by advection and that the apparent enhancement of De in pure diffusion models is really the result of solute flow induced by particle reworking. In cells with Pontoporeia, De is approximately twice that in control cells. In these cells, 22Na profiles may be treated theoretically without advection.

  7. New Radiotracers for Imaging of Vascular Targets in Angiogenesis-related Diseases

    PubMed Central

    Hong, Hao; Chen, Feng; Zhang, Yin; Cai, Weibo

    2014-01-01

    Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients. PMID:25086372

  8. Dual radiotracer measurement of zoobenthos-mediated solute and particle transport in freshwater sediments

    SciTech Connect

    Krezoski, J.R.; Robbins, J.A.; White, D.S.

    1984-09-01

    ..gamma.. spectroscopy methods have been applied to determine the effects of two freshwater benthic macroinvertebrates, on reworking of sediments and the transfer of solutes across the sediment-water interface. Natural lake sediments and overlying water were contained in temperature-regulated rectangular plastic cells. After addition of Stylodrilus (oligochaete worms) and Pontoporeia (crustacean amphipods) to these microcosms, the vertical distribution of Cs-137 (a tracer of particle transport) and Na-22 (a tracer of solute transport) were determined. In cells with Stylodrilus, the Cs-137 layer moved downward at a rate that decreased exponentially with time. In cells with Pontoporeia, Cs-137 activity was smeared downward in time owing to eddy diffusive mixing of sediments over a small range (1-2 cm). In cells without worms, the veneer of Cs active material remained at the interface while the penetration of Na-22 into sediments was consistent with diffusion in free solution with small corrections for sediment porosity and sorption. In cells with live Stylodrilus, penetration of Na-22 within the feeding zone was considerably more rapid. Advective transport arises from the incorporation of Na-22 into pore fluids moved downward as a result of conveyor-belt feeding. In cells with Pontoporeia, De is approximately twice that in control cells. In these cells, Na-22 profiles may be treated theoretically without advection. 47 references, 6 figures, 2 tables.

  9. Determination of CFTR chloride channel activity and pharmacology using radiotracer flux methods.

    PubMed

    Norez, Caroline; Heda, Ghanshyam D; Jensen, Timothy; Kogan, Ilana; Hughes, Lauren K; Auzanneau, Céline; Dérand, Renaud; Bulteau-Pignoux, Laurence; Li, Canhui; Ramjeesingh, Mohabir; Li, Hongyu; Sheppard, David N; Bear, Christine E; Riordan, John R; Becq, Frédéric

    2004-08-01

    Flux studies using either radioisotopes or ion-selective electrodes are a convenient method to assay the function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Here, we described three different protocols to study the properties, regulation and pharmacology of the CFTR Cl- channel in populations of cells and artificial vesicles. These techniques are widely used to evaluate the function of wild-type and mutant CFTR prior to detailed analyses using the patch-clamp technique. Moreover, they have proved especially valuable in the search for new drugs to treat cystic fibrosis. PMID:15463942

  10. Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for (64)Cu Radiotracers.

    PubMed

    Dale, Ajit V; An, Gwang Il; Pandya, Darpan N; Ha, Yeong Su; Bhatt, Nikunj; Soni, Nisarg; Lee, Hochun; Ahn, Heesu; Sarkar, Swarbhanu; Lee, Woonghee; Huynh, Phuong Tu; Kim, Jung Young; Gwon, Mi-Ri; Kim, Sung Hong; Park, Jae Gyu; Yoon, Young-Ran; Yoo, Jeongsoo

    2015-09-01

    Bifunctional chelators have been successfully used to construct (64)Cu-labeled radiopharmaceuticals. Previously reported chelators with cross-bridged cyclam backbones have various essential features such as high stability of the copper(II) complex, high efficiency of radiolabeling at room temperature, and good biological inertness of the radiolabeled complex, along with rapid body clearance. Here, we report a new generation propylene-cross-bridged chelator with hybrid acetate/phosphonate pendant groups (PCB-TE1A1P) developed with the aim of combining these key properties in a single chelator. The PCB-TE1A1P was synthesized from cyclam with good overall yield. The Cu(II) complex of our chelator showed good robustness in kinetic stability evaluation experiments, such as acidic decomplexation and cyclic voltammetry studies. The Cu(II) complex of PCB-TE1A1P remained intact under highly acidic conditions (12 M HCl, 90 °C) for 8 d and showed quasi-reversible reduction/oxidation peaks at -0.77 V in electrochemical studies. PCB-TE1A1P was successfully radiolabeled with (64)Cu ions in an acetate buffer at 60 °C within 60 min. The electrophoresis study revealed that the (64)Cu-PCB-TE1A1P complex has net negative charge in aqueous solution. The biodistribution and in vivo stability study profiles of (64)Cu-PCB-TE1A1P indicated that the radioactive complex was stable under physiological conditions and cleared rapidly from the body. A whole body positron emission tomography (PET) imaging study further confirmed high in vivo stability and fast clearance of the complex in mouse models. In conclusion, PCB-TE1A1P has good potential as a bifunctional chelator for (64)Cu-based radiopharmaceuticals, especially those involving peptides. PMID:26286436