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

  1. Technetium-99m labelling of glycosylated somatostatin-14.

    PubMed

    Du, J; Hiltunen, J; Marquez, M; Nilsson, S; Holmberg, A R

    2001-08-01

    This study presents a technetium-99m labelling method based on organometallic chemistry. It describes the simple mixing of a 99mTc(I)-carbonyl compound [99mTc(OH2)3(CO)3]+ with a histidine-tagged somatostatin-dextran (SMS-Dx-His) conjugate. Somatostatin and histidine was coupled to periodate activated dextran. The linkage was stabilised by reductive amination. The conjugate was then radiolabelled with 99mTc by using the 99mTc(CO)3 core. The labelling efficiency was 65-80% and the radiochemical purity > 95%. In the in vitro cysteine challenge, the result showed that 25% of the radiolabel was released after 1 h incubation at 37 degrees C (cysteine-conjugate at 1000:1 molar ratio). The radiolabelled SMS-Dx-His showed similar HPLC profile as the unlabelled conjugate. This labelling method, employing non reducing conditions, is useful for the labelling of peptides containing disulphide bonds. It should be possible to be used also for labelling with rhenium-188 for therapeutic applications.

  2. 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.

  3. Evaluation of hemangiomas with technetium 99m-labeled RBCs: the perfusion-blood pool mismatch

    SciTech Connect

    Front, D.; Israel, O.; Joachims, H.; Brown, Y.; Eliachar, I.

    1983-03-18

    A case report is presented of a woman with a tumor mass in the nasopharynx. Early and delayed scintigraphy with Technetium 99m-labeled RBCs showed a large area of increased uptake which was later shown to be a hemangioma by contrast angiography. The perfusion-blood pool mismatch observed in hemangiomas is characteristic of these lesions and has not been described in any other abnormalities. The Tc-RBC using both early and delayed scintigraphy is a simple, noninvasive method for assessing the vascular characteristics of these tumors. (JMT)

  4. Technetium-99m-labeled annexin V imaging for detecting prosthetic joint infection in a rabbit model.

    PubMed

    Tang, Cheng; Wang, Feng; Hou, Yanjie; Lu, Shanshan; Tian, Wei; Xu, Yan; Jin, Chengzhe; Wang, Liming

    2015-05-01

    Accurate and timely diagnosis of prosthetic joint infection is essential to initiate early treatment and achieve a favorable outcome. In this study, we used a rabbit model to assess the feasibility of technetium-99m-labeled annexin V for detecting prosthetic joint infection. Right knee arthroplasty was performed on 24 New Zealand rabbits. After surgery, methicillin-susceptible Staphylococcus aureus was intra-articularly injected to create a model of prosthetic joint infection (the infected group, n = 12). Rabbits in the control group were injected with sterile saline (n = 12). Seven and 21 days after surgery, technetium-99m-labeled annexin V imaging was performed in 6 rabbits of each group. Images were acquired 1 and 4 hours after injection of technetium-99m-labeled annexin V (150 MBq). The operated-to-normal-knee activity ratios were calculated for quantitative analysis. Seven days after surgery, increased technetium-99m-labeled annexin V uptake was observed in all cases. However, at 21 days a notable decrease was found in the control group, but not in the infected group. The operated-to-normal-knee activity ratios of the infected group were 1.84 ± 0.29 in the early phase and 2.19 ± 0.34 in the delay phase, both of which were significantly higher than those of the control group (P = 0.03 and P = 0.02). The receiver operator characteristic curve analysis showed that the operated-to-normal-knee activity ratios of the delay phase at 21 days was the best indicator, with an accuracy of 80%. In conclusion, technetium-99m-labeled annexin V imaging could effectively distinguish an infected prosthetic joint from an uninfected prosthetic joint in a rabbit model.

  5. Technetium-99m-labeled nanofibrillar cellulose hydrogel for in vivo drug release.

    PubMed

    Laurén, Patrick; Lou, Yan-Ru; Raki, Mari; Urtti, Arto; Bergström, Kim; Yliperttula, Marjo

    2014-12-18

    Nanoscale celluloses have recently gained an increasing interest in modern medicine. In this study, we investigated the properties of plant derived nanofibrillar cellulose (NFC) as an injectable drug releasing hydrogel in vivo. We demonstrated a reliable and efficient method of technetium-99m-NFC labeling, which enables us to trace the in vivo localization of the hydrogel. The release and distribution of study compounds from the NFC hydrogel after subcutaneous injection in the pelvic region of BALB/c mice were examined with a multimodality imaging device SPECT/CT. The drug release profiles were simulated by 1-compartmental models of Phoenix® WinNonlin®. The NFC hydrogel remained intact at the injection site during the study. The study compounds are more concentrated at the injection site when administered with the NFC hydrogel compared with saline solutions. In addition, the NFC hydrogel reduced the elimination rate of a large compound, technetium-99m-labeled human serum albumin by 2 folds, but did not alter the release rate of a small compound (123)I-β-CIT (a cocaine analogue). In conclusion, the NFC hydrogels is easily prepared and readily injected, and it has potential use as a matrix for controlled release or local delivery of large compounds. The interactions between NFC and specific therapeutic compounds are possible and should be investigated further.

  6. On-site preparation of technetium-99m labeled human serum albumin for clinical application.

    PubMed

    Wang, Yuh-Feng; Chuang, Mei-Hua; Chiu, Jainn-Shiun; Cham, Thau-Ming; Chung, Mei-Ing

    2007-04-01

    Technetium-99m labeled human serum albumin (Tc-99m HSA) is an important radiopharmaceutical for clinical applications, such as cardiac function tests or protein-losing gastroenteropathy assessment. However, because of transfusion-induced infectious diseases, the safety of serum products is a serious concern. In this context, serum products acquired from patients themselves are the most ideal tracer. However, the development of rapid separation and easy clinical labeling methods is not yet well established. Under such situation, products from the same ethnic group or country are now recommended by the World Health Organization as an alternative preparation. This article describes the on-site preparation of Tc-99m HSA from locally supplied serum products. Different formulations were prepared and the labeling efficiency and stability were examined. Radio-labeling efficiencies were more than 90% in all preparation protocols, except for one that omitted the stannous solution. The most cost-effective protocol contained HSA 0.1 mg, treated with stannous fluoride 0.2 mg, and mixed with Tc-99m pertechnetate 30 mCi. A biodistribution study was performed in rats using a gamma camera immediately after intravenous administration of radiolabeled HSA. Tissue/organ uptake was obtained by measuring the radioactivity in organs after sacrificing the rats at timed intervals. The biologic half-life was about 32 min, determined from sequential venous blood collections. These data indicate that our preparation of Tc-99m HSA is useful and potentially applicable clinically. In addition, this on-site preparation provides the possibility of labeling a patient's own serum for subsequent clinical application.

  7. Localization of obscure gastrointestinal bleeding by technetium 99m-labeled red blood cell scintigraphy.

    PubMed

    Wang, C S; Tzen, K Y; Huang, M J; Wang, J Y; Chen, M F

    1992-01-01

    When a bleeding source from the gastrointestinal (GI) tract cannot be identified with conventional diagnostic studies, it is known as GI bleeding of an obscure origin. In the past three years, in vivo Technetium 99m-labeled red blood cell scintigraphy (RBC scan) has been added to our armamentarium for the diagnosis of obscure GI bleeding. Out of a total of 26 cases, the bleeders could be detected in 12 or 46.2% by RBC scan. The time required ranged from 15 minutes to 24 hours (median, one hour). In 14 patients with active bleeding during the scan period, 11 had positive scans (sensitivity, 78.6%). In 12 patients with inactive bleeding, 11 had negative scans (specificity, 91.7%). Angiography was conducted in nine cases, with all showing negative findings; however, six of them had a positive focus by RBC scan. Laparotomy was performed in seven scan-positive patients, and in three scan-negative patients because of a positive Meckel's scan (two cases) or recurrent bleeding (one case). Of the 12 scan-positive patients, incorrect localization was noted in two patients due to rapid transit of the labeled RBC in the small bowel. False localization could be prevented by shortening the sequential imaging interval. It is concluded that an RBC scan is a very sensitive and safe tool for detection of GI bleeding of an intermittent nature, because the bleeder can be monitored for 24 hours after a single injection. It can be used as a preangiographic screening test and to guide the surgeon in surgical planning or decision-making.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1352337

  8. Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin.

    PubMed

    Svensson, W; Glass, D M; Bradley, D; Peters, A M

    1999-05-01

    A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m-labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with 99mTc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of 99mTc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of 99mTc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after 99mTc-HIG compared with 99mTc-HSA, although ultimately, the blood recovery of 99mTc-HIG was significantly higher (P < 0.05) than that of 99mTc-HSA. Clearance rates of radioactivity from the injection site were not significantly different, however, between the two agents. In patients with PMO, web space injection of 99mTc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per

  9. Radiotherapy and technetium-99m-labeled red blood cell scintigraphy for hemoptysis from chronic MRSA infection

    PubMed Central

    Lapuz, Carminia; Gupta, Sandeep K.; Bennett, Elizabeth A.; Tang, Colin I.

    2013-01-01

    Aim To discuss the application of external beam radiotherapy (EBRT) and technetium-99m-labeled red blood cell scintigraphy (LRBCS) in life-threatening hemoptysis from a non-malignant condition. Materials and methods This case report presents a patient with persistent hemoptysis secondary to chronic Methicillin-resistant Staphylococcus aureus (MRSA) infection in whom conventional management failed to localize the site of pulmonary bleeding or to provide effective therapy. Results EBRT was successfully given for life-threatening hemoptysis with improvement in quality of life for nearly 1 year. LRBCS was used to localize the source of further bleeding and facilitate targeted therapy. Conclusion EBRT can be an effective and well-tolerated modality in treating life-threatening hemoptysis refractory to conventional methods. LRBCS is a non-invasive diagnostic tool that can be used to detect the source of pulmonary bleeding. PMID:24416570

  10. 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.

  11. Synthesis and biodistribution studies of technetium-99m-labeled aminopeptidase N inhibitor conjugates.

    PubMed

    Pathuri, Gopal; Hedrick, Andria F; Disch, Bryan C; Ihnat, Michael A; Awasthi, Vibhudutta; Gali, Hariprasad

    2012-07-15

    Probestin is a potent aminopeptidase N (APN) inhibitor. Four probestin conjugates containing a tripeptide chelator (N(3)S) and a PEG(2) linker were synthesized and radiolabeled with Tc-99m. The number of -COOH groups on the chelator was altered to increase the excretion of the radiotracer from blood stream via the renal-urinary pathway and to decrease its hepatobiliary uptake. Biodistribution of the radiolabeled conjugates was evaluated in healthy CF-1™ mice at 1h post-injection. The results revealed that the Tc-99m labeled probestin conjugate preferentially (>85% injected dose) excreted via the renal route when an aspartic acid residue was added to the linker (conjugate 4). These results suggest that the pharmacokinetic properties of probestin-based APN-targeted agents could be optimized by adding an appropriate amino acid residue in between the linker and the payload.

  12. Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201

    SciTech Connect

    Sinusas, A.J.; Watson, D.D.; Cannon, J.M. Jr.; Beller, G.A. )

    1989-12-01

    The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two-dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations.

  13. 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.

  14. Technetium-99m-labeled red blood cell imaging

    SciTech Connect

    Front, D.; Israel, O.; Groshar, D.; Weininger, J.

    1984-07-01

    Red blood cells labeled with 99mTc constitute a suitable intravascular agent for imaging of vascular abnormalities. Hemangiomas are characterized by low perfusion and a high blood pool. This ''perfusion blood-pool mismatch,'' not encountered in other lesions, may help in the specific diagnosis of this tumor. This is particularly so in cavernous hemangiomas of the liver where three-phase 99mTc-labeled red blood cell scintigraphy should precede liver biopsy. Red cell scintigraphy also is useful for establishing the vascular nature of hemangiomas of the head and neck and the skin and for diagnosis of venous occlusion. Heat-damaged red blood cells provide a specific spleen imaging agent. This should be used when patients with suspected splenic pathology have equivocal colloid scintigraphy.

  15. Evaluation of a technetium-99m labeled bombesin homodimer for GRPR imaging in prostate cancer.

    PubMed

    Yu, Zilin; Carlucci, Giuseppe; Ananias, Hildo J K; Dierckx, Rudi A J O; Liu, Shuang; Helfrich, Wijnand; Wang, Fan; de Jong, Igle J; Elsinga, Philip H

    2013-02-01

    Multimerization of peptides can improve the binding characteristics of the tracer by increasing local ligand concentration and decreasing dissociation kinetics. In this study, a new bombesin homodimer was developed based on an ε-aminocaproic acid-bombesin(7-14) (Aca-bombesin(7-14)) fragment, which has been studied for targeting the gastrin-releasing peptide receptor (GRPR) in prostate cancer. The bombesin homodimer was conjugated to 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and labeled with (99m)Tc for SPECT imaging. The in vitro binding affinity to GRPR, cell uptake, internalization and efflux kinetics of the radiolabeled bombesin dimer were investigated in the GRPR-expressing human prostate cancer cell line PC-3. Biodistribution and the GRPR-targeting potential were evaluated in PC-3 tumor-bearing athymic nude mice. When compared with the bombesin monomer, the binding affinity of the bombesin dimer is about ten times lower. However, the (99m)Tc labeled bombesin dimer showed a three times higher cellular uptake at 4 h after incubation, but similar internalization and efflux characters in vitro. Tumor uptake and in vivo pharmacokinetics in PC-3 tumor-bearing mice were comparable. The tumor was visible on the dynamic images in the first hour and could be clearly distinguished from non-targeted tissues on the static images after 4 h. The GRPR-targeting ability of the (99m)Tc labeled bombesin dimer was proven in vitro and in vivo. This bombesin homodimer provides a good starting point for further studies on enhancing the tumor targeting activity of bombesin multimers.

  16. Technetium-99m labeled monoclonal antibodies in the detection of metastatic melanoma

    SciTech Connect

    Serafini, A.N.; Kotler, J.; Feun, L.; Dewanjee, M.; Robinson, D.; Salk, D.; Sfakianakis, G.; Abrams, P.; Savaraj, N.; Goodwin, D.; )

    1989-08-01

    Twenty-six stage II/III malignant melanoma patients with 321 measurable metastatic lesions were imaged using Fab fragments of an IgG murine monoclonal antibody labeled specifically with 10-30 mCi Tc-99m with a bi-functional chelating method (NeoRx, Seattle, WA). There were no side effects or adverse reactions. Immunoscintigraphy demonstrated 66.6% of lesions larger than 1 cm and 92.5% of lesions larger than 3 cm. Most frequently detected metastases were in lymph nodes, subcutaneous areas, and bone. Of lesions less than 1 cm, 23.6% were detected if superficial cutaneous lesions were excluded. The smallest detectable lesion was 4 mm. Twenty-one additional clinically unsuspected sites were visualized in 12 of the 26 patients studied. Of these, 56% were confirmed as metastasis by other tests. There were apparent nonspecific localizations owing to other causes, including fracture, varicosities, skin abscess and pneumonitis. Increased experience in image analysis facilitates correct interpretation of these localizations. This study demonstrates that imaging with Tc-99m labeled antibody fragments detects melanoma lesions in organs routinely surveyed and in other areas not routinely assessed by other imaging techniques. The procedure is readily performed and safe. The principal advantage of the test is its ability to survey the entire body and all organs with a single test. Its principal limitation, in common with other diagnostic imaging procedures, is its poor sensitivity for detecting lesions less than 1 cm.

  17. 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.

  18. 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.

  19. 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.

  20. Technetium-99m labelling of the anti-tumour antibody PR1A3 by photoactivation.

    PubMed

    Stalteri, M A; Mather, S J

    1996-02-01

    Irradiation of antibody with ultraviolet light leads to reduction of disulphide bonds. Thus irradiation can be used to generate free thiols prior to direct labelling of antibody with technetium-99m, and has a potential advantage over methods using chemical reducing agents such as mercaptoethanol or tin, in that no purification step is needed to remove excess reducing agent. We have used the photoactivation method developed by Sykes et al. to label the anti-tumour antibody PR1A3 with 99mTc. The antibody was irradiated at 300 nm using a Rayonet photochemical reactor with eight RMR3000 lamps. In a typical experiment, the antibody solution was injected into a nitrogen-filled borosilicate glass vial and purged with nitrogen. A degassed solution containing stannous fluoride and methylene diphosphonate was then added to the antibody and the vial was irradiated. Following the irradiation, [99mTc]pertechnetate was injected into the vial and the reaction mixture was incubated for 30 min at room temperature before being analysed by size-exclusion high-pressure liquid chromatography and instant thin-layer chromatography. Labelling yields greater than 95% were obtained using antibody concentrations ranging from 0.5mg/ml to 5mg/ml. Irradiation times as short as 5 min and tin to antibody ratios in the range between 11 and 32 microg tin per mg antibody gave high labelling yields. Labelling yields greater than 95% were obtained after storage of the photoactivated antibody at -70 degrees C for several weeks. The stability of the 99mTc-labelled photoactivated PR1A3 was similar to that of 99mTc-labelled mercaptoethanol-reduced PR1A3. The mean immunoreactive fraction was 77% for the photoactivation-labelled PR1A3, compared to 93% for PR1A3 labelled by mercaptoethanol reduction. Biodistribution studies were carried out using 99mTc-photoactivation-labelled PR1A3 or PR1A3 labelled by mercaptoethanol reduction in Balb/c mice and in nude mice with MKN-45 human tumour xenografts. There was no significant difference in tumour uptake between the mice that received photoactivated PR1A3 and those that received mercaptoethanol-reduced PR1A3. There was also no significant difference in uptake in most organs in Balb/c mice; however, the photoactivated antibody cleared more rapidly from the blood, and whole-body clearance was also faster for the photoactivated PR1A3. In conclusion, the photoactivation technique provides a very convenient "one-pot" method for labelling antibodies with 99mTc.

  1. 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.

  2. 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.

  3. 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.

  4. Detection of a local staphylococcal infection in mice with technetium-99m-labeled polyclonal human immunoglobulin

    SciTech Connect

    Calame, W.; Feitsma, H.I.; Ensing, G.J.; Goedemans, W.T.; Camps, J.A.; van Furth, R.; Pauwels, E.K. )

    1991-03-01

    The purpose of this study was to investigate both the ability of 99mTc-labeled polyclonal human immunoglobulin (HIG) to localize an infection and the modes of action involved in this process. Mice, infected with Staphylococcus aureus ATCC 25923 in a thigh muscle, received HIG intravenously. Scintigrams were made 1, 4, and 24 hr later; subsequently the mice were killed and the activity in several organs and thighs was determined. The radiopharmaceutical demonstrated a time-dependent accumulation at the site of infection. It was found that vascular permeability or Fc binding alone could not account for the mode of action of HIG. Neither the origin of Ig (human versus murine) nor the total amount of protein (0.01-1.0 mg Ig per mouse) affected the target-to-background (T/B) ratios. Ratios were not different for leukocytopenic animals. A correlation (p less than 0.001) was demonstrated between the number of bacteria at the site of infection and the T/B ratio. This was also found after antibiotic treatment (p less than 0.02).

  5. 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.

  6. Technetium 99m-labeled VQ peptide: a new imaging agent for the early detection of tumors or premalignancies.

    PubMed

    Shi, Jiyun; Cui, Liyang; Jia, Bing; Liu, Zhaofei; He, Peng; Dong, Chengyan; Jin, Xiaona; Zhao, Huiyun; Li, Fang; Wang, Fan

    2013-01-01

    There is a critical need to develop diagnostic procedures enabling early detection of tumors while at a curable stage. Technetium 99m (99mTc)-labeled VQ peptide (99mTc-HYNIC-VQ) identified through screening phage display peptide libraries against fresh human colonic adenomas was prepared and evaluated for tumor detection. 99mTc-HYNIC-VQ was prepared by a non-SnCl2 method with more than 99% radiochemical purity. The biodistribution in the HT-29 tumor model showed that although the absolute tumor uptake values were relatively low (0.60 ± 0.09, 0.41 ± 0.09, 0.36 ± 0.18, and 0.19 ± 0.08 %ID/g at 0.5, 1, 2, and 4 hours postinjection, respectively), the tumor uptake was higher than that of any of the other organs except for the kidneys at any time point examined, which led to the high tumor to nontarget ratios. The tumors and inflammation were clearly visualized with high contrast. Although the mechanism of accumulation of radiolabeled VQ peptide in tumors and inflammation needs to be further investigated, 99mTc-HYNIC-VQ is a promising imaging agent for the early detection of tumors or premalignancies, at least for screening patients with a high risk of developing cancers.

  7. Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung.

    PubMed

    Loutsios, Chrystalla; Farahi, Neda; Simmonds, Rosalind; Cullum, Ian; Gillett, Daniel; Solanki, Chandra; Solanki, Kishor; Buscombe, John; Condliffe, Alison M; Peters, A Mike; Chilvers, Edwin R

    2015-11-01

    The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated.

  8. 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.

  9. 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.

  10. Analysis of binding of a technetium-99m-labeled monoclonal antibody to lentivirus-infected cells

    SciTech Connect

    Papageorges, M.; Gavin, P.R.; Adams, D.S.; Cheevers, W.P.; Barbee, D.D.; Sande, R.D. )

    1990-11-01

    Caprine arthritis-encephalitis (CAE) is a model for the study of lentiviral infections. The authors' hypothesis is that radioimmunodetection has the potential to detect lentiviral proteins at the surface of infected cells. A monoclonal antibody (CAEV92A1) specific for a CAE virus (CAEV)-associated glycoprotein and a control antibody were radiolabeled with technetium-99m ({sup 99m}Tc) using the pretinning method. Cell binding assays were used to evaluate immunoreactivity and binding properties of {sup 99m}Tc-labeled antibodies to CAEV-infected cells. {sup 99m}Tc-CAEV92A1 bound preferentially to paraformaldehyde-fixed and live CAEV-infected cells. {sup 99m}Tc-CAEV92A1 did not appear to be shed rapidly from its binding site.

  11. 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.

  12. Conversion to Paradoxical Finding on Technetium-99m-labeled RBC Scintigraphy after Treatment for Secondary Raynaud's Phenomenon.

    PubMed

    Chong, Ari; Ha, Jung-Min; Song, Ho-Chun; Kim, Jahae; Choi, Soo Jin Na

    2013-12-01

    An 18-year-old woman reported that after exposure to cold temperatures her fingers appeared blue and her hands and feet felt cold. Secondary Raynaud's phenomenon (RP) associated with peripheral vascular disease was suspected. Technetium (Tc)-99m-labeled RBC hand scintigraphy after cold change showed decreased blood pool activity in her fingers. The patient's symptoms improved after she received sarpogrelate HCL (200 mg/day) and nifedifine (40 mg/day). Follow-up scintigraphy performed 7 months after the patient started treatment showed paradoxically increased blood pool activity in her fingers after cold challenge. To the best of our knowledge, this is the first case report of a patient with secondary RP showing paradoxical change on scintigraphy after she received medication that improved her symptoms.

  13. 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.

  14. 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

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

    PubMed Central

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

    2016-01-01

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

  16. Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

    PubMed

    Papantoniou, Vassilios; Valsamaki, Pipitsa; Sotiropoulou, Evangelia; Tsaroucha, Angeliki; Tsiouris, Spyridon; Sotiropoulou, Maria; Marinopoulos, Spyridon; Kounadi, Evangelia; Karianos, Theodore; Fothiadaki, Athina; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Ptohis, Nikolaos; Makris, Nikolaos; Limouris, Georgios; Antsaklis, Aris

    2011-10-01

    The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

  17. Linker modification reduced the renal uptake of technetium-99m-labeled Arg-Ala-Asp-conjugated alpha-melanocyte stimulating hormone peptide.

    PubMed

    Yang, Jianquan; Flook, Adam M; Feng, Changjian; Miao, Yubin

    2014-01-01

    The purpose of this study was to examine the biodistribution of (99m)Tc-RAD-Arg-(Arg(11))CCMSH in B16/F1 melanoma-bearing C57 mice to determine whether the replacement of the Lys linker with an Arg linker could decrease the renal uptake of (99m)Tc-RAD-Arg-(Arg(11))CCMSH. (99m)Tc-RAD-Arg-(Arg(11))CCMSH exhibited rapid and high tumor uptake (17.98±4.96% ID/g at 2h post-injection) in B16/F1 melanoma-bearing C57 mice. As compared to (99m)Tc-RAD-Lys-(Arg(11))CCMSH, the replacement of the Lys linker with an Arg linker dramatically decreased the renal uptake of (99m)Tc-RAD-Arg-(Arg(11))CCMSH by 68%, 62%, 73% and 64% at 0.5, 2, 4 and 24h post-injection, respectively. Flank B16/F1 melanoma lesions were clearly imaged at 2h post-injection using (99m)Tc-RAD-Arg-(Arg(11))CCMSH as an imaging probe.

  18. Synthesis, characterization and bioevaluation of technetium-99m labeled N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose as a tumor imaging agent.

    PubMed

    Nadeem, Qaisar; Khan, Irfanullah; Javed, Muhammad; Mahmood, Zaid; Dar, Ume-Kalsoom; Ali, Muhammad; Hyder, Syed Waqar; Murad, Sohail

    2013-03-01

    N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose (NHADG) was synthesized by conjugation of salicylaldehyde to glucosamine. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m ((99m)Tc) in pertechnetate form ((99m)Tc O4-) was carried out via chelation reaction in the presence of stannous chloride dihydrate. Maximum radiochemical yield of (99m)Tc-NHADG complex (99%) was obtained by using 1 mg NHADG, 200 μg SnCl2.2H2O, at pH 9.5 and reaction time of 15 min. The radiochemical purity of the (99m)Tc-NHADG complex was measured by instant thin layer chromatography (ITLC) and paper chromatography (PC), without any notable decomposition at room temperature over a period of 4h. The biological evaluation results show that the (99m)Tc labeled NHADG conjugate is able to specifically target mammary carcinoma in mice models, thus highlighting its potential as an effective (99m)Tc labeled glucose-derived agent for tumor imaging.

  19. Formulation and evaluation of a single vial lyophilized preparation of technetium-99m labeled ethylene dicysteine as a renal scintigraphic agent.

    PubMed

    Sohaib, Muhammad; Afshan, Anjum; Saeed, Shabana; Khalid, Mujahid Ali; Yousuf, Mohammad

    2014-09-01

    (99m)Tc labeled N-N-ethylene-L, L-dicysteine (EC) was introduced in form of multiple-step kit as an alternate renal imaging radiopharmaceutical for commonly used (99m)Tc-MAG3. We developed a single component lyophilized kit of EC ready to be labeled with (99m)Tc. We present the optimization of the components of our formulation, its evaluation in animal models, normal human volunteers and patients of various renal diseases, in comparison with (99m)Tc-MAG3. Efficient labeling of EC was achieved with our preparation at pH 7 to 12. The formulation at pH 8 was used further for bio distribution studies in organs of sacrificed Sprague Dawley rats and a live rhesus monkey using scintigraphy. After satisfactory bio-distribution results, the kit was then evaluated in normal human volunteers through renography. But the renogram parameters of (99m)Tc-EC (pH 8) were statistically inferior to (99m)Tc-MAG3. Surrogate kit at pH 10 was therefore developed and re-evaluated in rats for organ bio distribution. After favorable results the kit was then assessed further in normal volunteers and a group of patients with various renal disorders via scintigraphy. The EC kit developed at pH 10 gave images better than and scintigraphic parameters comparable to (99m)Tc-MAG3. It was concluded that single vial kit we formulated easy to prepare than three-vial kit and can be used as an alternate to (99m)Tc-MAG3.

  20. Comparative properties of a technetium-99m-labeled single-stranded natural DNA and a phosphorothioate derivative in vitro and in mice.

    PubMed

    Hnatowich, D J; Mardirossian, G; Fogarasi, M; Sano, T; Smith, C L; Cantor, C R; Rusckowski, M; Winnard, P

    1996-01-01

    Oligonucleotides, particularly single stranded, may ultimately be of considerable use as radiopharmaceuticals. We have compared a synthetic 22-base single-stranded phosphodiester DNA with its phosphorothioate analog after both were radiolabeled with 99mTc via the hydrazino nicotinamide chelator. Whole body clearance of the label in mice was much slower when introduced on the phosphorothioate (30% vs. 75% clearance at 6 hr) because of immediate and persistent accumulation in liver (47% vs. 2% injected dose/g at 4 hr). The label in both cases was present in urine primarily on low molecular weight catabolites. High-performance liquid chromatography analysis of 37 degrees C serum incubates showed serum protein binding of 99mTc in both cases (about 100% bound at 24 hr) but to different proteins. Different behavior with respect to protein binding was also observed in the analysis of liver and kidney homogenates: the phosphodiester label was almost quantitatively converted to lower molecular weight catabolites after only 15 min, whereas the phosphorothioate label was primarily on proteins. The rapid digestion of the phosphodiester by nucleases was not observed, probably because protein binding of the labeled oligonucleotides stabilized against degradation. Thus the phosphodiester DNA may be the preferred 99mTc-labeled oligonucleotide in certain circumstances to avoid the high and persistent liver uptake observed with the phosphorothioate DNA. PMID:8558450

  1. 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.

  2. Biological and imaging characteristics and radiation dose rates associated with the use of technetium-99m-labelled imidodiphosphate in the horse.

    PubMed

    Riddolls, L J; Byford, G G; McKee, S L

    1996-04-01

    The biological and imaging characteristics of technetium-99m imidodiphosphate (Tc99m-IDP) were measured in 4 horses once and in 1 horse twice. All computational results are expressed with 95.5% (mean +/- 2 SD) confidence limits. The clearance half-time of the radiopharmaceutical from the blood was 29.6 +/- 2.3 min. The percentage of the administered dose circulating in the whole-blood volume at 4 h was 3.9 +/- 0.8%. The Tc99m-IDP radioactivity confined at the plasma fraction of the whole blood at 4 h was 85.3 +/- 1.6%. At 8 h, approximately 45 +/- 16% of the dose administered had been excreted via the urine. The mean effective half-time of the urine activity concentration was 1.1 +/- 0.3 h. The ratios of bone-to-soft tissue activities increased with time postinjection. Urinary radioactivity concentration measurements and radiation dose rate measurements immediately behind the elbows were analysed and it was determined that 24 h is an appropriate radioisolation time for mature horses administered 3.7 GBq (100 mCi) Tc99m-IDP.

  3. 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.

  4. Pulmonary, hepatic and splenic sequestration of technetium-99m labelled autologous rabbit granulocytes: scintigraphic cell distributions after intravenous and intraarterial injections, exsanguination and intraarterial injection of cells passed through an intermediary host.

    PubMed

    Farstad, B S; Sundrehagen, E; Opdahl, H; Benestad, H B

    1991-10-01

    In man, about half the intravascular granulocytes are not freely circulating, but temporarily sequestered ('marginated'), so that they cannot be retrieved by bleeding. Where and how the sequestration occurs is not settled and is the subject of the present report. Isolated autologous rabbit granulocytes, labelled with two different 99mTc methods, were reinjected and followed with external scintigraphy. Intraarterial as well as intravenous injection led to rapid accumulation of radioactivity over the lungs. This finding was corroborated and extended by similar experiments, where the labelled cells had firstly been passed through an intermediary rabbit host to remove altered cells, i.e. cells damaged, 'primed' (pre-activated), or activated. In the final autologous host about two thirds of the label rapidly localized to the lungs and liver, and a few per cent to the spleen (which is very small in the rabbit). Even though more than half of the intermediary rabbit's calculated blood volume was removed, the blood sample contained only a few per cent of the rabbit's radioactivity; consequently, many of the labelled leucocytes had marginated during the bleeding. The proportional distribution of radioactivity over lungs, spleen, kidneys, and the rest of the intermediary animal was not markedly changed by this exsanguination, but there was a 4-20% decrease over the liver. Taken together, our findings indicate that normal granulocytes marginate in lungs, liver, and spleen--apparently explicable by the effects of cell size, vessel diameter, cell stiffness (visco-elastic properties) and size of the arterio-venous hydrostatic pressure difference. The liver and spleen seemed to play additional roles, since radioactivity over these organs decreased much slower than expected from reported blood half-times of intact and slightly damaged rabbit granulocytes. This led to a suggestion that macrophages exposed to blood normally phagocytose apoptotically dying granulocytes.

  5. 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.

  6. 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.

  7. A philosophy for CNS radiotracer design.

    PubMed

    Van de Bittner, Genevieve C; Ricq, Emily L; Hooker, Jacob M

    2014-10-21

    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 are available

  8. Monoamine oxidase: radiotracer chemistry and human studies.

    PubMed

    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 serotonin, 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 years since the first radiotracers were developed and the first positron emission tomography (PET) images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables that 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 the following: (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological, and psychiatric disorders; and (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers that are currently used and possible new applications.

  9. Monoamine oxidase: Radiotracer chemistry and human studies

    DOE PAGES

    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. Radiotracer investigation in an industrial-scale oxidizer.

    PubMed

    Pant, H J; Sharma, V K

    2015-05-01

    A radiotracer investigation was carried out in an industrial-scale oxidizer. The main objectives of the investigation were to measure residence time distribution (RTD) of organic process fluid, determine the mean residence time (MRT) and investigate the degree of axial mixing. Bromine-82 as p-dibromo biphenyl was used as a radiotracer for measuring RTD of the organic process fluid. The MRT of the fluid in the oxidizer was determined to be 390min. An ideal stirred tank model with a plug flow reactor in recirculation stream was used to simulate the measured RTD data and was found suitable for describing flow in the system. Based on the model simulation the mean residence times in oxidizer and recycle stream were estimated. The results of the investigation showed that the oxidizer behaved as a well-mixed reactor whereas the recycle stream behaved as a plug flow reactor. PMID:25766114

  19. 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

  20. 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

  1. Radiotracer Dilution Method for Mercury Inventory Study in Electrolytic Cells

    SciTech Connect

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

    2010-06-22

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

  2. Radionuclides, radiotracers and radiopharmaceuticals for in vivo diagnosis

    NASA Astrophysics Data System (ADS)

    Wiebe, Leonard I.

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

  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. 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.

  6. PET-Specific Parameters and Radiotracers in Theoretical Tumour Modelling

    PubMed Central

    Marcu, Loredana G.; Bezak, Eva

    2015-01-01

    The innovation of computational techniques serves as an important step toward optimized, patient-specific management of cancer. In particular, in silico simulation of tumour growth and treatment response may eventually yield accurate information on disease progression, enhance the quality of cancer treatment, and explain why certain therapies are effective where others are not. In silico modelling is demonstrated to considerably benefit from information obtainable with PET and PET/CT. In particular, models have successfully integrated tumour glucose metabolism, cell proliferation, and cell oxygenation from multiple tracers in order to simulate tumour behaviour. With the development of novel radiotracers to image additional tumour phenomena, such as pH and gene expression, the value of PET and PET/CT data for use in tumour models will continue to grow. In this work, the use of PET and PET/CT information in in silico tumour models is reviewed. The various parameters that can be obtained using PET and PET/CT are detailed, as well as the radiotracers that may be used for this purpose, their utility, and limitations. The biophysical measures used to quantify PET and PET/CT data are also described. Finally, a list of in silico models that incorporate PET and/or PET/CT data is provided and reviewed. PMID:25788973

  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. OpenPET: A Flexible Electronics System for Radiotracer Imaging.

    PubMed

    Moses, W W; Buckley, S; Vu, C; Peng, Q; Pavlov, N; Choong, W-S; Wu, J; Jackson, C

    2009-10-24

    We present the design for OpenPET, an electronics readout system designed for prototype radiotracer imaging instruments. The critical requirements are that it has sufficient performance, channel count, channel density, and power consumption to service a complete camera, and yet be simple, flexible, and customizable enough to be used with almost any detector or camera design. An important feature of this system is that each analog input is processed independently. Each input can be configured to accept signals of either polarity as well as either differential or ground referenced signals. Each signal is digitized by a continuously sampled ADC, which is processed by an FPGA to extract pulse height information. A leading edge discriminator creates a timing edge that is "time stamped" by a TDC implemented inside the FPGA. This digital information from each channel is sent to an FPGA that services 16 analog channels, and information from multiple channels is processed by this FPGA to perform logic for crystal lookup, DOI calculation, calibration, etc. As all of this processing is controlled by firmware and software, it can be modified / customized easily. The system is open source, meaning that all technical data (specifications, schematics and board layout files, source code, and instructions) will be publicly available.

  9. OpenPET: A Flexible Electronics System for Radiotracer Imaging

    PubMed Central

    Moses, W. W.; Buckley, S.; Vu, C.; Peng, Q.; Pavlov, N.; Choong, W.-S.; Wu, J.; Jackson, C.

    2011-01-01

    We present the design for OpenPET, an electronics readout system designed for prototype radiotracer imaging instruments. The critical requirements are that it has sufficient performance, channel count, channel density, and power consumption to service a complete camera, and yet be simple, flexible, and customizable enough to be used with almost any detector or camera design. An important feature of this system is that each analog input is processed independently. Each input can be configured to accept signals of either polarity as well as either differential or ground referenced signals. Each signal is digitized by a continuously sampled ADC, which is processed by an FPGA to extract pulse height information. A leading edge discriminator creates a timing edge that is “time stamped” by a TDC implemented inside the FPGA. This digital information from each channel is sent to an FPGA that services 16 analog channels, and information from multiple channels is processed by this FPGA to perform logic for crystal lookup, DOI calculation, calibration, etc. As all of this processing is controlled by firmware and software, it can be modified / customized easily. The system is open source, meaning that all technical data (specifications, schematics and board layout files, source code, and instructions) will be publicly available. PMID:21297894

  10. 64Cu-labeled phosphonium cations as PET radiotracers for tumor imaging.

    PubMed

    Zhou, Yang; Liu, Shuang

    2011-08-17

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

  11. Cyclotron production and potential clinical application of Iodine-124 labeled radiotracers

    NASA Astrophysics Data System (ADS)

    Finn, R.; Balatoni, J.; Kothari, P.; Pentlow, K.; Sheh, Y.; Lom, C.; Dahl, J.; Eckelman, W.; Plascjak, P.; Adams, H. R.; Larson, S. M.

    2001-07-01

    Positron emission tomography (PET) is a dynamic molecular imaging technique applicable to clinical research, drug development as well as clinical diagnoses. The potential for PET is derived from specificity of the radiotracers and radioligands that are synthesized to monitor the biochemical or physiological processes. Further developments will depend on an increasing availability of unique radiotracers. Iodine-124, a radionuclide that has potential for both diagnostic and therapeutic applications, possesses a half-life of 4.18 days and decays by positron emission (23.3%) and electron capture (76.7%). The preparation of this radionuclide via the 124Te(p,n)124I nuclear reaction is described as well as chemistry associated with the preparation of specific radiotracers and radiopharmaceuticals incorporating iodine-124 at Memorial Sloan-Kettering Cancer Center.

  12. 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.

  13. Distributed microprocessor automation network for synthesizing radiotracers used in positron emission tomography

    SciTech Connect

    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. 20 refs. (DT)

  14. 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)

  15. 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.

  16. [(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

  17. Increasing the accuracy of radiotracer monitoring in one-dimensional flow using polynomial deconvolution correction.

    PubMed

    Peyvandi, Reza Gholipour; Taheri, Ali

    2016-01-01

    Factors such as type of fluid movement and gamma-ray scattering may decrease the precision of the radiotracer monitoring as the response to a short tracer injection. Practical experiences using polynomial deconvolution techniques are presented. These techniques were successfully applied for correcting the obtained experimental results and increasing the time resolution of the method. PMID:26609682

  18. 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

  19. 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.

  20. Indium-111-labeled platelet scintigraphy in carotid atherosclerosis

    SciTech Connect

    Minar, E.; Ehringer, H.; Dudczak, R.; Schoefl, R.J.; Jung, M.; Koppensteiner, R.; Ahmadi, R.; Kretschmer, G.

    1989-01-01

    We evaluated platelet accumulation in carotid arteries by means of a dual-radiotracer method, using indium-111-labeled platelets and technetium-99m-labeled human serum albumin, in 123 patients (92 men, 31 women; median age 60 years). Sixty patients had symptoms of transient ischemic carotid artery disease, and 63 patients with peripheral arterial occlusive disease served as controls. Antiplatelet treatment with acetylsalicylic acid was taken by 53 of the 123 patients. In 36 of the 60 symptomatic patients, platelet scintigraphy was repeated 3-4 days after carotid endarterectomy. Comparison of different scintigraphic parameters (platelet accumulation index and percent of the injected dose of labeled platelets at the carotid bifurcation) showed no significant differences between symptomatic and asymptomatic patients, and the severity of stenosis and the presence of plaque ulceration also had no influence on the parameters. There was no difference between patients with a short (less than 4 weeks) or long (greater than 4 weeks) interval from the last transient ischemic attack to scintigraphy and no difference between patients with or without antiplatelet treatment. Classifying the patients according to plaque morphology judged by high-resolution real-time ultrasonography also demonstrated no differences. No significant correlation was found between any scintigraphic parameter and other platelet function parameters such as platelet survival time, platelet turnover rate, and concentration of platelet-specific proteins. Quantification of platelet deposition after carotid endarterectomy in 36 patients demonstrated a significant increase of the median platelet accumulation index and the percent injected dose index.

  1. Synthesis and evaluation of 99mTc-N-sulfanilamide ferrocene carboxamide as bacterial infections detector.

    PubMed

    Essouissi, Imen; Ghali, Wafa; Saied, Nadia Malek; Saidi, Mouldi

    2010-10-01

    A technetium-99m-labeled derivative from sulfanilamide, further referred to as (99m)Tc-N-SFC, targeting infections in experimental animals, has been synthesized. The biological features of this radioactive agent have also been studied. The N-sulfanilamide ferrocene carboxamide (N-SFC) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that it is stable and obtained with radiolabelling yield (>87%). Radiochemical analyses of (99m)Tc-N-SFC revealed that the molecule was labeled rapidly (within 2 min) and effectively with little free pertechnetate in the preparations containing purified compound. Furthermore, in vitro investigations were conducted and the label's stability in serum was observed up to 24 h of testing. Uptake of the tracer with live and heat/killed bacteria was compared in physiological conditions and was about 69% and 61.9% for the Escherichia coli and Staphylococcus aureus strains, respectively. We concluded that synthesis and labeling of Sulfanilamide derivative with (99m-)Tc by this method is rapid, efficient and safe. Biodistribution studies demonstrated that our radiolabeled compound is accumulated rapidly and significantly (P<.05) at infection sites. The comparison of the (99m)Tc-N-SFC accumulation at sites of S. aureus-infected animals, which is expressed as target-to-non-target ratio, (2.88 ± 0.10) with other radiotracers was discussed. PMID:20870157

  2. [(64)Cu]diacetyl-bis(N(4)-methyl-thiosemicarbazone) - a radiotracer for tumor hypoxia.

    PubMed

    Wood, Katie A; Wong, Wai Lup; Saunders, Michele I

    2008-05-01

    Positron emission tomography scanning using the radiotracer-labeled copper (II)-diacetyl-bis(N(4)-methylthiosemicarbazone) has been proposed as a noninvasive method for evaluating tumor hypoxia. Tumor hypoxia results in a more aggressive tumor phenotype together with resistance to both radiotherapy and chemotherapy. A noninvasive technique for evaluation of tumor hypoxia is not currently available. Validation of this technique would provide clinicians with a tool for determining the most appropriate cancer therapy, prognostic information, and subvolume delineation for the radiotherapy dose escalation to the radioresistant hypoxic regions within a tumor. This review article describes the background to the development of this tracer, its proposed retention mechanism, biodistribution dosimetry and the preclinical and clinical studies to date. It outlines the potential use of this radiotracer for imaging in the field of oncology.

  3. 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.

  4. Design, evaluation, and comparison of ghrelin receptor agonists and inverse agonists as suitable radiotracers for PET imaging.

    PubMed

    Chollet, Constance; Bergmann, Ralf; Pietzsch, Jens; Beck-Sickinger, Annette G

    2012-04-18

    Ghrelin agonist and inverse agonist radiotracers, suitable for positron emission tomography (PET), were developed to study the behavior of ghrelin receptor ligands in vivo and for further design of druggable peptides. The target peptides were synthesized on solid support and conjugated to the bifunctional chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), which is known to form a stable complex with Ga(3+). Complexation with (68)Ga could be achieved under mild conditions and led to radiotracers with high radiochemical purity and specific activity. The biological activity of the radiotracers was evaluated in vitro by an inositol phosphate turnover assay. Pharmacokinetic profile and metabolic stability of the (68)Ga-NODAGA-radiotracers were investigated by small animal PET in rodent. Ghrelin derived agonists presented very high kidney accumulation, negligible tissue distribution, fast blood clearance, and poor stability in blood. Contrarily, the inverse agonist radiotracer exhibited very high stability in blood, large diffusion in tissues, reasonable kidney and liver metabolism, and slow blood clearance. This pharmacokinetic profile makes the ghrelin inverse agonist motif KwFwLL-CONH(2) suitable for further development of radiotracers and a promising lead to design peptide-based therapeutics against obesity. PMID:22372770

  5. (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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. In Vivo Metabolic Trapping Radiotracers for Imaging Monoamine Oxidase-A and -B Enzymatic Activity.

    PubMed

    Brooks, Allen F; Shao, Xia; Quesada, Carole A; Sherman, Phillip; Scott, Peter J H; Kilbourn, Michael R

    2015-12-16

    The isozymes of monoamine oxidase (MAO-A and MAO-B) are important enzymes involved in the metabolism of numerous biogenic amines, including the neurotransmitters serotonin, dopamine, and norepinephrine. Recently, changes in concentrations of MAO-B have been proposed to be an in vivo marker of neuroinflammation associated with Alzheimer's disease. Previous developments of in vivo radiotracers for imaging changes in MAO enzyme expression or activity have utilized the irreversible propargylamine-based suicide inhibitors or high-affinity reversibly binding inhibitors. As an alternative approach, we have investigated 1-[(11)C]methyl-4-aryloxy-1,2,3,6-tetrahydropyridines as metabolic trapping agents for the monoamine oxidases. MAO-mediated oxidation and spontaneous hydrolysis yield 1-[(11)C]methyl-2,3-dihydro-4-pyridinone as a hydrophilic metabolite that is trapped within brain tissues. Radiotracers with phenyl, biphenyl, and 7-coumarinyl ethers were evaluated using microPET imaging in rat and primate brains. No isozyme selectivity for radiotracer trapping was observed in the rat brain for any compound, but in the monkey brain, the phenyl ether demonstrated MAO-A selectivity and the coumarinyl ether showed MAO-B selectivity. These are lead compounds for further development of 1-[(11)C]methyl-4-aryloxy-1,2,3,6-tetrahydropyridines with optimized brain pharmacokinetics and isozyme selectivity.

  11. 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

  12. 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

  13. 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

  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. Radiotracer studies on ion-selective membranes based on poly(vinyl chloride) matrices.

    PubMed

    Jaber, A M; Moody, G J; Thomas, J D; Willcox, A

    1977-10-01

    Radiotracer studies with (45)Ca, (89)Sr and (133)Ba have provided evidence that the permeation of magnesium, strontium and barium ions through PVC membranes containing Orion 92-20-02 liquid ion-exchanger is inhibited by their low affinity for the liquid ion-exchanger sites. Experiments with (7)Be indicate a strong affinity of the membrane for beryllium ions with corresponding inhibition of permeation. When acid is present in the solution on one side of the membrane, preferential permeation by protons may lead to transport of ions against their concentration gradient in order to maintain the balance of charge.

  16. [(18)F]6-fluoro-3,4-dihydroxy-L-phenylalanine--recent modern syntheses for an elusive radiotracer.

    PubMed

    Edwards, Richard; Wirth, Thomas

    2015-05-15

    [(18)F]6-fluoro-3,4-dihydroxy-L-phenylalanine ([(18)F]F-DOPA) has been known to be a useful radiotracer for over 30 years. Its widespread clinical use has been hampered by the lack of a robust, high yielding synthesis. This review summarises new developments in radiochemistry that are providing solutions to long standing problems involved in the synthesis of this important but elusive radiotracer. Considerable advances in nucleophilic synthesis have been achieved by optimising multistep strategies and using both hypervalent iodine chemistry and transition metal-mediated fluorinations allowing for the production of high specific activity [(18)F]F-DOPA. PMID:25882075

  17. [(18)F]6-fluoro-3,4-dihydroxy-L-phenylalanine--recent modern syntheses for an elusive radiotracer.

    PubMed

    Edwards, Richard; Wirth, Thomas

    2015-05-15

    [(18)F]6-fluoro-3,4-dihydroxy-L-phenylalanine ([(18)F]F-DOPA) has been known to be a useful radiotracer for over 30 years. Its widespread clinical use has been hampered by the lack of a robust, high yielding synthesis. This review summarises new developments in radiochemistry that are providing solutions to long standing problems involved in the synthesis of this important but elusive radiotracer. Considerable advances in nucleophilic synthesis have been achieved by optimising multistep strategies and using both hypervalent iodine chemistry and transition metal-mediated fluorinations allowing for the production of high specific activity [(18)F]F-DOPA.

  18. Cross-coupling reactions as valuable tool for the preparation of PET radiotracers.

    PubMed

    Pretze, Marc; Grosse-Gehling, Philipp; Mamat, Constantin

    2011-01-26

    The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of new radiotracers and novel radiolabeling procedures with the most prominent short-lived positron emitters carbon-11 and fluorine-18. Radiolabeling with these radionuclides represents a remarkable challenge. Special attention has to be paid to synthesis time and specific labeling techniques due to the short physical half life of the respective radionuclides ¹¹C (t(½) = 20.4 min) and ¹⁸F (t½) = 109.8 min). In the past, numerous transition metal-catalyzed reactions were employed in organic chemistry, even though only a handful of these coupling reactions were adopted in radiochemical practice. Thus, the implementation of modern synthesis methods like cross-coupling reactions offers the possibility to develop a wide variety of novel radiotracers. The introduction of catalysts based on transition metal complexes bears a high potential for rapid, efficient, highly selective and functional group-tolerating incorporation of carbon-11 and fluorine-18 into target molecules. This review deals with design, application and improvement of transition metal-mediated carbon-carbon as well as carbon-heteroatom cross-coupling reactions as a labeling feature with the focus on the preparation of radiolabeled compounds for molecular imaging.

  19. Development of gamma-emitting, receptor binding radiotracers for imaging the brain and pancreas

    SciTech Connect

    Reba, R.C.

    1990-01-01

    This progress report covers period from Nov. 1, 1989 to Aug. 31, 1990. The long term objective was to develop receptor-binding radiotracers for SPECT or PET imaging of CNS or peripheral nervous system. The specific chemistry aims, as understood on the basis of past findings, were: to synthesize and develop a more polar analogs of 4IQNB, possessing similar binding characteristics but eliminated more rapidly from the surrounding tissues and the target organ, to design a method of introducing a technetium chelating group onto a molecule or cholinergic agent without drastic lowering of its apparent affinity, to synthesize and develop radiotracers based on m-AChR antagonists selective for one of the subtypes of the receptor. The chemistry service aims were to prepare and characterize (R,R)- and (R,S)-4IQNB and derivatives, to provide the triazene intermediate to other investigators, and to provide ({sup 123}I)4IQNB for in vivo imaging. The biochemistry aims were to characterize the vitro and in vivo properties of novel compounds and to perform the pharmacokinetic studies. 3 refs., 5 tabs.

  20. Anaerobic degradation of naphthalene in a fluvial aquifer: a radiotracer study.

    PubMed

    Bianchin, Mario; Smith, Leslie; Barker, James F; Beckie, Roger

    2006-03-20

    A radiotracer study was conducted in a creosote-contaminated aquifer beneath the Fraser River, British Columbia Canada to investigate the in situ degradation of naphthalene. The groundwater is anaerobic, with abundant methane, ferrous iron and carbon dioxide. This study followed earlier work at the site where the contaminant distribution could only be explained by invoking a mass loss through degradation, even though extensive field and laboratory microcosm studies closer to the source zone onshore could not confirm degradation. Accordingly, 14C-naphthalene was injected into the aquifer offshore, further from the source zone where modeling suggested degradation was occurring. During the 230-day monitoring period, 14CO2 was detected, confirming the degradation of the radio-labeled naphthalene tracer. A zero-order degradation rate of naphthalene of 5 microg/L-day was estimated based on the decrease in 14C-naphthalene concentration with time. While the degradation pathway could not be determined from the radiotracer study alone, the geochemistry of the site suggests that either iron reduction or methanogenesis is the terminal electron accepting processes responsible for naphthalene oxidation. PMID:16487624

  1. 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

  2. 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.

  3. 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.

  4. Designing steriod receptor-based radiotracers to image breast and prostate tumors

    SciTech Connect

    Katzenellenbogen, J.A.

    1995-06-01

    Imaging of breast or prostate cancers based on their content of steroid receptors poses a major challenge in the design of radiotracers. Receptors for steroid hormones are proteins that interact at specific sites in chromatin. Several analogs of estrogens, progestins and androgens have been radiolabeled and evaluated both in vitro and in vivo for receptor binding affinity and selectivity. Breast tumors in patients have been imaged with [{sup 18}F]fluoroestradiol. Scintigraphic images with radiolabeled progestin analogs may be useful for monitoring the efficacy of tamoxifen treatment in breast cancer patients. Tissue distribution and imaging studies in animals with fluorine-substituted androgens indicate that it may be possible to develop a steroid receptor-based radiotracer for staging prostate cancer. Radiochemists are reporting some progress in labeling steroid receptor ligands with {sup 99m}Tc. By using the techniques of molecular nuclear medicine, new imaging procedures could be developed that might provide more precise information to help characterize disease and effect treatment decisions in patients with breast or prostate cancers. 55 refs., 4 figs., 4 tabs.

  5. 64Cu-labeled lissamine rhodamine B: a promising PET radiotracer targeting tumor mitochondria.

    PubMed

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

    2011-08-01

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

  6. 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.

  7. 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.

  8. 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.

  9. Radiotracer studies on calcium ion-selective electrode membranes based on poly(vinyl chloride) matrices.

    PubMed

    Craggs, A; Moody, G J; Thomas, J D; Willcox, A

    Radiotracer studies with (45)Ca and (36)Cl demonstrate that PVC matrix membranes containing Orion 92-20-02 liquid calcium ion-exchanger are permselective to counter-cations. Diffusion coefficients are quoted for the migration of (45)Ca between pairs of calcium solutions and are discussed in terms of solution concentration, membrane thickness and concentration level of sensor in the membrane. Migration of calcium ions from calcium chloride solution to a Group (II) metal chloride solution through a PVC membrane containing calcium liquid ion-exchanger is discussed in terms of solvent extraction and electrode selectivity coefficient parameters. Thus, magnesium, strontium and barium ions appear to inhibit migration through the membrane by their low affinity for the membrane liquid ion-exchanger sites, while the inhibition by beryllium ions is attributed to site blockage by the strong affinity of dialkylphosphate sites for beryllium.

  10. Radiotracer method for residence time distribution study in multiphase flow system.

    PubMed

    Sugiharto, S; Su'ud, Z; Kurniadi, R; Wibisono, W; Abidin, Z

    2009-01-01

    [(131)I] isotope in different chemical compounds have been injected into 24in hydrocarbon transmission pipeline containing approximately 95% water, 3% crude oil, 2% gas and negligible solid material, respectively. The system is operated at the temperature around 70 degrees C enabling fluids flow is easier in the pipeline. The segment of measurement was chosen far from the junction point of the pipeline, therefore, it was reasonably to assume that the fluids in such multiphase system were separated distinctively. Expandable tubing of injector was used to ensure that the isotopes were injected at the proper place in the sense that [(131)I]Na isotope was injected into water layer and iodo-benzene, ([131])IC(6)H(5,) was injected into crude oil regime. The radiotracer selection was based on the compatibility of radiotracer with each of fluids under investigation. [(131)I]Na was used for measuring flow of water while iodo-benzene, ([131])IC(6)H(5,) was used for measuring flow of crude oil. Two scintillation detectors were used and they are put at the distances 80 and 100m, respectively, from injection point. The residence time distribution data were utilized for calculation water and crude oil flows. Several injections were conducted in the experiments. Although the crude oil density is lighter than the density of water, the result of measurement shows that the water flow is faster than the crude oil flow. As the system is water-dominated, water may act as carrier and the movement of crude oil is slowed due to friction between crude oil with water and crude oil with gas at top layer. Above of all, this result was able to give answer on the question why crude oil always arrives behind water as it is checked at gathering station. In addition, the flow patterns of the water in the pipeline calculated by Reynolds number and predicted by simple tank-in-series model is turbulence in character.

  11. 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

  12. 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.

  13. Evaluation of 64Cu-labeled acridinium cation: a PET radiotracer targeting tumor mitochondria.

    PubMed

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

    2011-04-20

    This report presents the synthesis and evaluation of (64)Cu(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 (64)Cu(DO3A-xy-ACR) was excreted mainly through the renal system with >65% of injected radioactivity being recovered from urine samples at 1 h postinjection (p.i.). The tumor uptake of (64)Cu(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. (64)Cu(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 (64)Cu(DO3A-xy-ACR). The high liver radioactivity accumulation was also seen. (64)Cu(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 (64)Cu(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 (64)Cu(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 (64)Cu-labeled acridinium cations are indeed able to localize in the energized mitochondria of tumor cells.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

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

    PubMed

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

    2006-01-01

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

  2. PET and SPECT Radiotracers to Assess Function and Expression of ABC Transporters in Vivo

    PubMed Central

    Mairinger, Severin; Erker, Thomas; Müller, Markus; Langer, Oliver

    2013-01-01

    Adenosine triphosphate-binding cassette (ABC) transporters, such as P-glycoprotein (Pgp, ABCB1), breast cancer resistance protein (BCRP, ABCG2) and multidrug resistance-associated proteins (MRPs) are expressed in high concentrations at various physiological barriers (e.g. blood-brain barrier, blood-testis barrier, blood-tumor barrier), where they impede the tissue accumulation of various drugs by active efflux transport. Changes in ABC transporter expression and function are thought to be implicated in various diseases, such as cancer, epilepsy, Alzheimer’s and Parkinson’s disease. The availability of a non-invasive imaging method which allows for measuring ABC transporter function or expression in vivo would be of great clinical use in that it could facilitate the identification of those patients that would benefit from treatment with ABC transporter modulating drugs. To date three different kinds of imaging probes have been described to measure ABC transporters in vivo: i) radiolabelled transporter substrates ii) radiolabelled transporter inhibitors and iii) radiolabelled prodrugs which are enzymatically converted into transporter substrates in the organ of interest (e.g. brain). The design of new imaging probes to visualize efflux transporters is inter alia complicated by the overlapping substrate recognition pattern of different ABC transporter types. The present article will describe currently available ABC transporter radiotracers for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) and critically discuss strengths and limitations of individual probes and their potential clinical applications. PMID:21434859

  3. Whole lake addition of cadmium-109: radiotracer accumulation in the mussel population in the first season.

    PubMed

    Malley, D F; Chang, P S; Hesslein, R H

    1989-11-01

    Cadmium with the radiotracer 109Cd was added to the epilimnion of Precambrian Shield Lake 382 in the Experimental Lakes Area, northwestern Ontario to monitor pathways of Cd from water to abiotic and biotic components, to quantify Cd accumulation and distribution in biota and to evaluate adverse biological and ecological effects. This experiment will permit evaluation of the adequacy of the water quality guidelines of 0.2 microgram Cd l-1 in protecting aquatic life in softwater lakes. As part of the whole-lake experiment, we monitored the activities of 109Cd in various body parts of the floater mussel Anodonta grandis grandis to determine accumulation and distribution of Cd. Additions of Cd from 23 June to the end of October 1987 (a total of 900 g Cd and 89 mCi of 109Cd) increased the total [Cd] in the water from 1.6 to about 85 ng l-1. Cadmium-109 was accumulated in body parts of the mussels, in increasing concentration: mantle less than foot less than gill less than visceral mass less than kidney. After 4 months exposure to the increased water [Cd], the mussels had increased body burden of Cd by an estimated 5-9 times. At the latter increase, the population of 7330 +/- 2100 mussels in the lake contained an estimated 0.011-0.020% of the added 109Cd.

  4. 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.

  5. Food chains and biogeochemical pathways: contributions of fallout and other radiotracers.

    PubMed

    Whicker, F Ward; Pinder, John E

    2002-05-01

    This paper reviews examples of how measurements of global fallout in the environment and related tracer radionuclides have been used to enhance our basic knowledge of biogeochemical processes and food-chain pathways. Because it is these fundamental, natural processes that control the transport and accumulation of such trace substances in the environment, direct measurements of trace substances over time and space reveal strong insights into these processes. The necessity to monitor global fallout transport, although largely motivated by human health concerns, gave rise to a plethora of new information about plants, animals, and natural and agricultural ecosystems and how they function. This review provides a small selection of examples in the areas of plant and animal physiology, productivity and energy transfer in food chains, biogeochemical cycles of certain elements and their analogues, feeding relationships and movements of organisms, and the agriculture-based human food chain. It is concluded that if society is to cope successfully with continued growth of the human population and resource consumption, more knowledge is still required about these fundamental processes. The use of radiotracers can contribute greatly to this need, but current funding priorities, societal attitudes, and onerous regulations on the use of radioactivity may continue to limit such applications.

  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. 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.

  8. 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.

  9. 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.

  10. Biological evaluation of new [(18) F]F-labeled synthetic amino acid derivatives as oncologic radiotracers.

    PubMed

    Kim, Yeseulmi; Lee, Sang Ju; Yook, Cheol-Min; Oh, Seung Jun; Ryu, Jin-Sook; Lee, Jong Jin

    2016-08-01

    The present study evaluated the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers (S)-2-amino-3-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102), and (S)-2-amino-5-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), all of which are (S)-2-amino-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids. In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. In vitro competitive inhibition tests were performed to identify the involvement of specific amino acid transporters. In vivo dynamic PET images of 9L xenograft tumor-bearing model mice were acquired over 2 h after AMC administration. [(18) F]FDOPA PET studies were performed with and without S-carbidopa pretreatment for comparison. All three AMCs exhibited good in vitro cell uptake through the L and alanine-serine-cysteine transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. Thirty minutes after injection, the mean tumor standardized uptake values were 1.59 ± 0.05, 1.89 ± 0.27, and 1.74 ± 0.13 for AMC-101, AMC-102, and AMC-103, respectively. Although the tumor uptake values of AMCs were lower than that of [(18) F]FDOPA with S-carbidopa pretreatment, AMCs enabled higher contrast images with lower background activity compared with [(18) F]FDOPA with S-carbidopa pretreatment. Our results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers.

  11. 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.

  12. PET studies of binding competition between endogenous dopamine and the D1 radiotracer [11C]NNC 756.

    PubMed

    Abi-Dargham, A; Simpson, N; Kegeles, L; Parsey, R; Hwang, D R; Anjilvel, S; Zea-Ponce, Y; Lombardo, I; Van Heertum, R; Mann, J J; Foged, C; Halldin, C; Laruelle, M

    1999-05-01

    NNC 756 ((+)-8-chloro-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine) is a new high affinity dopamine (DA) D1 receptor antagonist. Labeled with C-11, it has been used as a PET radiotracer to visualize D1 receptors both in striatal and extrastriatal areas, such as the prefrontal cortex. The goal of this study was to evaluate several methods for derivation of D1 receptor binding potential (BP) with [11C]NNC 756 in baboons, and to use these methods to assess the vulnerability of [11C]NNC 756 binding to competition by endogenous DA. A three-compartment model provided a good fit to PET data acquired following a single bolus injection. BP values obtained with this analysis were in good agreement with values derived from in vitro studies. BP values measured following injection of the potent DA releaser amphetamine (1 mg/kg, n=2) were similar to values measured under control conditions. Kinetic parameters derived from single bolus experiments were used to design a bolus plus continuous infusion administration protocol aimed at achieving a state of sustained binding equilibrium. Injection of amphetamine during sustained equilibrium did not affect [11C]NNC 756 binding. Similar results were observed with another D1 radiotracer, [11C]SCH 23390. Doses of amphetamine used in this study are known to reduce by 20-40% the binding potential of several D2 receptors radiotracers. Therefore, the absence of displacement of [11C]NNC 756 by an endogenous DA surge may indicate important differences between D1 and D2 receptors in vivo, such as differences in proportion of high affinity states not occupied by DA at baseline. These findings may also imply that a simple binding competition model is inadequate to account for the effects of manipulation of endogenous DA levels on the in vivo binding of radiolabeled antagonists.

  13. 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

  14. Preclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H

    PubMed Central

    2013-01-01

    Background [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared. Methods Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors. Results Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation. Conclusions This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient

  15. Synthesis, radioiodination and in vivo screening of novel potent iodinated and fluorinated radiotracers as melanoma imaging and therapeutic probes.

    PubMed

    Maisonial, Aurélie; Billaud, Emilie M F; Besse, Sophie; Rbah-Vidal, Latifa; Papon, Janine; Audin, Laurent; Bayle, Martine; Galmier, Marie-Josèphe; Tarrit, Sébastien; Borel, Michèle; Askienazy, Serge; Madelmont, Jean-Claude; Moins, Nicole; Auzeloux, Philippe; Miot-Noirault, Elisabeth; Chezal, Jean-Michel

    2013-05-01

    In order to develop new iodinated and fluorinated matched-pair radiotracers for Single-Photon Emission Computed Tomography (SPECT)/Positron Emission Tomography (PET) imaging and targeted radionuclide therapy of melanoma, we successfully synthesized and radiolabelled with iodine-125 seven new derivatives, starting from our previously described lead structure 3. The relevance of these radiotracers for gamma scintigraphic imaging of melanoma in rodent was assessed. The tumoural radioactivity uptake was most often high and specific even at early time points (12.1-18.3% ID/g at 3 h p.i. for [(125)I]39-42) and a fast clearance from the non-target organs was observed. Also, calculated effective doses that could be delivered to tumours when using corresponding [(131)I]-labelled analogues were generally higher than 100 cGy/MBq injected (98.9-150.5 cGy/MBq for [(131)I]39-42). These results make compounds 39-42 suitable candidates for (i) PET imaging of melanoma after labelling with fluorine-18 and (ii) targeted radionuclide therapy of disseminated melanoma after labelling with iodine-131.

  16. 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.

  17. 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

  18. 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

  19. Isatin sulfonamides: potent caspases-3 and -7 inhibitors, and promising PET and SPECT radiotracers for apoptosis imaging.

    PubMed

    Limpachayaporn, Panupun; Schäfers, Michael; Haufe, Günter

    2015-01-01

    Caspases-3 and -7 play an essential role in apoptosis. Isatin sulfonamides have been identified as potent inhibitors of these executing caspases. Besides pharmacological application, these compounds can also serve as recognition units to target caspases using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) when labeled with a positron or a gamma emitter. Fluorinated, alkylated, arylated isatin derivatives, in addition to derivatives modified with heterocycles, have been prepared in order to improve their binding potency, selectivity and metabolic stability. Structural optimization has led to stable, highly active inhibitors, which after labeling have been applied in PET studies in tumor mouse models and for first preclinical and clinical investigations with healthy human volunteers. The results support further development of such radiotracers for clinical apoptosis imaging. PMID:26132525

  20. 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.

  1. PET radiotracer [18F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation

    PubMed Central

    Uddin, Jashim; Vitale, Paola; Panella, Andrea; Crews, Brenda C.; Daniel, Cristina K.; Ghebreselasie, Kebreab; Nickels, Mike; Tantawy, Mohammed N.; Manning, H. Charles; Marnett, Lawrence J.; Scilimati, Antonio

    2015-01-01

    Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([18/19F]-P6) is the most promising derivative [IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[18F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K18F/Kryptofix 2.2.2 complex, that afforded [18F]-P6 in good radio-chemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [18F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [18F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1. PMID:24832612

  2. UV-photochemical vapor generation of selenium for atomic absorption spectrometry: Optimization and 75Se radiotracer efficiency study

    NASA Astrophysics Data System (ADS)

    Rybínová, Marcela; Musil, Stanislav; Červený, Václav; Vobecký, Miloslav; Rychlovský, Petr

    2016-09-01

    Volatile selenium compounds were generated UV-photochemically in the continuous flow mode using four UV-photoreactors differing in the material of the reaction coil; Teflon tubing and quartz tubes with various inner diameters and wall thicknesses were tested. Atomic absorption spectrometry with an externally heated quartz furnace atomizer was employed as the detector. The relevant experimental generation parameters were optimized and the basic analytical characteristics were determined. Using formic acid as the photochemical agent, limits of detection achieved for selenium were in the range 46-102 ng L- 1 in dependence on the type of UV-photoreactor employed. When nitric acid was also added to the photochemical agent, the limits of detection were reduced to 27-44 ng L- 1. The repeatability did not exceed 2.4% (5 μg L- 1 Se(IV), n = 10). Experiments with 75Se radiotracer have been performed for the first time to quantify the efficiency of UV-photochemical vapor generation (UV-PVG) of selenium. The highest efficiency of 67 ± 1% was obtained for a UV-photoreactor containing a quartz reaction coil (2.0 mm i.d., 4.0 mm o.d.). The generation efficiency of 61 ± 1% was obtained for a Teflon reaction coil (1.0 mm i.d., 1.4 mm o.d.). Mapping of the radiotracer distribution in the individual parts of the apparatus did not reveal substantial transport losses of the analyte in the UV-PVG system.

  3. 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

  4. 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

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

    PubMed

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

    2007-03-01

    Mercury tracers are powerful tools that can be used to study mercury transformations in environmental systems, particularly mercury methylation, demethylation and reduction in sediments and water. However, mercury transformation studies using tracers can be subject to error, especially when used to assess methylation potential. The organic mercury extracted can be as low as 0.01% of the endogenous labeled mercury, and artefacts and contamination present during methylmercury (MeHg) extraction processes can cause interference. Solvent extraction methods based on the use of either KBr/H2SO4 or HCl were evaluated in freshwater sediments using 197Hg radiotracer. Values obtained for the 197Hg tracer in the organic phase were up to 25-fold higher when HCl was used, which is due to the coextraction of 197Hg2+ into the organic phase during MeHg extraction. Evaluations of the production of MeHg gave similar results with both MeHg extraction procedures, but due to the higher Hg2+ contamination of the controls, the uncertainty in the determination was higher when HCl was used. The Hg2+ contamination of controls in the HCl extraction method showed a nonlinear correlation with the humic acid content of sediment pore water. Therefore, use of the KBr/H2SO4 method is recommended, since it is free from these interferences. 197Hg radiotracer (T1/2=2.673 d) has a production rate that is about 50 times higher than that of 203Hg (T1/2=46.595 d), the most frequently used mercury radiotracer. Hence it is possible to obtain a similar level of performance to 203Hg when it is used it in short-term experiments and produced by the irradiation of 196Hg with thermal neutrons, using mercury targets with the natural isotopic composition. However, if the 0.15% natural abundance of the 196Hg isotope is increased, the specific activity of the 197Hg tracer can be significantly improved. In the present work, 197Hg tracer was produced from mercury 51.58% enriched in the 196Hg isotope, and a 340-fold

  6. 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

  7. The [18F]2-Fluoro-1,3-thiazolyl Moiety - an Easily-Accessible Structural Motif for Prospective Molecular Imaging Radiotracers

    PubMed Central

    Siméon, Fabrice G.; Wendahl, Matthew T.; Pike, Victor W.

    2010-01-01

    2-Fluoro-1,3-thiazoles were rapidly and efficiently labeled with no-carrier-added fluorine-18 (t1/2 = 109.7 min) by treatment of readily prepared 2-halo precursors with cyclotron-produced [18F]fluoride ion. The [18F]2-fluoro-1,3-thiazolyl moiety constitutes a new and easily-labeled structural motif for prospective molecular imaging radiotracers. PMID:21057601

  8. 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

  9. 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

  10. Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the agonist radiotracer [(11)C]-(+)-PHNO.

    PubMed

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

    2014-11-01

    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 [(11)C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [(11)C]-(+)-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 [(11)C]-(+)-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). [(11)C]-(+)-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. [(11)C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations.

  11. 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

  12. Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer.

    PubMed

    Shi, Jiyun; Liu, Zhaofei; Jia, Bing; Yu, Zilin; Zhao, Huiyun; Wang, Fan

    2010-06-01

    In this study, we reported the preparation and evaluation of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2 (RGD2 = E[c(RGDfK)](2)) as a potential therapeutic radiotracers for the treatment of integrin alpha(v)beta(3)-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100 degrees C and higher DOTA-conjugate concentration were needed for successful (177)Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of (177)Lu-labeled cyclic RGDfK peptides, and (177)Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin alpha(v)beta(3)-positive tumors.

  13. Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors

    PubMed Central

    Knol, Remco J. J.; van den Bos, Jan C.; Janssen, Anton G. M.; de Bruin, Kora; van Eck-Smit, Berthe L. F.; Booij, Jan

    2011-01-01

    Disturbances of the cerebral cholinergic neurotransmitter system are present in neurodegenerative disorders. SPECT or PET imaging, using radiotracers that selectively target muscarinic receptor subtypes, may be of value for in vivo evaluation of such conditions. 6β-acetoxynortropane, a potent muscarinic M2 receptor agonist, has previously demonstrated nanomolar affinity and high selectivity for this receptor. Based on this compound we synthesized four nortropane derivatives that are potentially suitable for SPECT imaging of the M2 receptor. 6β-acetoxynortropane and the novel derivatives were tested in vitro for affinity to the muscarinic M1−3 receptors. The original 6β-acetoxynortropane displayed high affinity (Ki = 70–90 nM) to M2 receptors and showed good selectivity ratios to the M1 (65-fold ratio) and the M3 (70-fold ratio) receptors. All new derivatives showed reduced affinity to the M2 subtype and loss of subtype selectivity. It is therefore concluded that the newly synthesized derivatives are not suitable for human SPECT imaging of M2 receptors. PMID:21755053

  14. A 1-methyl-4-piperidinyl cytectrene carboxylate labeled by the technetium 99m, a radiotracer for rat brain acetylcholinesterase activity.

    PubMed

    Mejri, Najoua; Barhoumi, Chokri; Trabelsi, Moez; Mekni, Abdelkader; Said, Nadia Malek; Saidi, Mouldi

    2010-02-01

    Alzheimer's disease (AD) is a degenerative neurological disorder that causes progressive and irreversible loss of connections between brain cells and loss of mental functions. Clinical and postmortem studies show that the biochemical changes in brains of AD patients include decrease in acetylcholinesterase (AChE) activity. Our aim was to study AChE activity using piperidinyl ester labelled with technetium-99m. In vivo and in vitro studies demonstrated that labelled piperidinyl ester was a substrate for AChE. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW284c51. The rhenium analogues of the technetium-labelled substrate were used to determine the affinity constant (K(m)) and the maximum reaction velocity (V(max)) because of the high specific activity of technetium. The high hydrolytic rate and high specificity of the substrate for AChE make it suitable as an in vivo radiotracer for studying AChE activity in the brain.

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

    PubMed

    Pant, H J; Sharma, V K

    2016-10-01

    A radiotracer investigation was carried out to measure residence time distribution (RTD) of liquid phase in a trickle bed reactor (TBR). The main objectives of the investigation were to investigate radial and axial mixing of the liquid phase, and evaluate performance of the liquid distributor/redistributor at different operating conditions. Mean residence times (MRTs), holdups (H) and fraction of flow flowing along different quadrants were estimated. The analysis of the measured RTD curves indicated radial non-uniform distribution of liquid phase across the beds. The overall RTD of the liquid phase, measured at the exit of the reactor was simulated using a multi-parameter axial dispersion with exchange model (ADEM), and model parameters were obtained. The results of model simulations indicated that the TBR behaved as a plug flow reactor at most of the operating conditions used in the investigation. The results of the investigation helped to improve the existing design as well as to design a full-scale industrial TBR for petroleum refining applications. PMID:27544314

  16. Grain boundary diffusion and segregation of Bi in Cu: radiotracer measurements in B and C diffusion regimes

    SciTech Connect

    Divinski, Sergiy; Lohmann, Maik; Herzig, Christian

    2004-08-02

    Grain boundary (GB) radiotracer diffusion of {sup 207}Bi in polycrystalline Cu was measured in Harrison's B (1198-843 K) and C (659-536 K) kinetic regimes. In the B regime the triple product P=s{center_dot}{delta}{center_dot}D{sub gb} (where s is the segregation factor and {delta} the GB width) was found to obey the Arrhenius law P=6.6x10{sup -12}xexp (-102.8 kJ mol{sup -1}/RT) m{sup 3} s{sup -1}. The measurements in the C regime yielded the temperature dependence of the Bi GB diffusion coefficient D{sub gb} in Cu, D{sub gb}=0.24xexp (-156.2 kJ mol{sup -1}/RT) m{sup 2} s{sup -1}. Assuming that {delta} congruent with 5x10{sup -10} m the segregation factor s of Bi in Cu was determined in the limit of very dilute solute concentration to follow an Arrhenius dependence s=s{sub 0}exp(-{delta}H{sub s}/RT) with the pre-exponential factor s{sub 0}=0.054 and the segregation enthalpy {delta}H{sub s}=-53.4 kJ mol{sup -1}.

  17. 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

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

    PubMed

    Pant, H J; Sharma, V K

    2016-10-01

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

  19. Radionuclide-labeled red blood cell imaging of vascular malformations in children

    SciTech Connect

    Sloan, G.M.; Bolton, L.L.; Miller, J.H.; Reinisch, J.F.; Nichter, L.S.

    1988-09-01

    Vascular malformations, particularly in the absence of cutaneous changes, can be difficult to distinguish from other soft tissue masses in children. We have used technetium-99m-labeled red blood cell scintigraphy to study 47 lesions in 43 children. Thirty-nine lesions showed increased flow and were, therefore, diagnosed as vascular malformations. Subsequent biopsy of 10 of these lesions confirmed that diagnosis. The other 29 lesions with increased flow were followed for 10 months to 5 years and the clinical course was consistent with vascular malformation in every case. Eight lesions showed no increased flow on technetium scan. One of these subsequently proved to be a hemangioma. The others have turned out not to be vascular malformations. Therefore, in our experience, the technetium-99m-labeled red blood cell scan has had 98% sensitivity and 100% specificity in diagnosing vascular malformations in children.

  20. 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

  1. 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.

  2. Metabolite identification of a radiotracer by electrochemistry coupled to liquid chromatography with mass spectrometric and radioactivity detection.

    PubMed

    Baumann, Anne; Faust, Andreas; Law, Marylin P; Kuhlmann, Michael T; Kopka, Klaus; Schäfers, Michael; Karst, Uwe

    2011-07-01

    Radioligands, which specifically bind to a receptor or enzyme (target), enable molecular imaging of the target expression by positron emission tomography (PET). One very promising PET tracer is (S)-1-(4-(2-[(18)F]-fluoroethoxy)benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (isatin), a caspase-3 inhibitor, which has been developed at the University Hospital of Münster to image cell death (apoptosis). The translation of this novel tracer from preclinical evaluation to clinical examinations requires biodistribution studies, which characterize the pharmakodynamics and metabolic fate of the compound. This information is used to further optimize the radioligands and to interpret radioactive signals from tissues upon injection of the radioligand in vivo with respect to their specificity. The analysis of the metabolism of radioligands is hampered by the low amount of the compound being typically injected (nano/picomolar amount per injection). In the present study, electrochemistry (EC) is applied to elucidate the oxidative metabolism pathway of the radiotracer. Previous studies have demonstrated that EC can be utilized as a complementary tool to conventional in vitro approaches in drug metabolism studies. Thereby, potential oxidative metabolites of the isatin are determined by EC coupled to electrospray ionization mass spectrometry (EC/ESI-MS). Moreover, using EC/liquid chromatography (LC) and ESI-ion trap MS(n), structural elucidation of the oxidation products is performed. Comparatively to EC, in vitro metabolism studies with rat liver microsomes are conducted. Finally, the developed LC/ESI-MS method is applied to determine metabolites in body fluids and cell extracts from in vivo studies with the nonradioactive ((19)F) and radioactive isatin ((18)F). On the basis of the electrochemically generated oxidation products of the radioligand, the major radioactive metabolite occurring in vivo was successfully identified.

  3. 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.

  4. H-CRRETAWAC-OH, a Lead Structure for the Development of Radiotracer Targeting Integrin α5β1?

    PubMed Central

    Maschauer, Simone; Einsiedel, Jürgen; Eder, Iris E.; Gmeiner, Peter; Virgolini, Irene J.

    2014-01-01

    Imaging of angiogenic processes is of great interest in preclinical research as well as in clinical settings. The most commonly addressed target structure for imaging angiogenesis is the integrin αvβ3. Here we describe the synthesis and evaluation of [18F]FProp-Cys*-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys*-OH, a radiolabelled peptide designed to selectively target the integrin α5β1. Conjugation of 4-nitrophenyl-(RS)-2-[18F]fluoropropionate provided [18F]FProp-Cys*-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys*-OH in high radiochemical purity (>95%) and a radiochemical yield of approx. 55%. In vitro evaluation showed α5β1 binding affinity in the nanomolar range, whereas affinity to αvβ3 and αIIbβ3 was >50 μM. Cell uptake studies using human melanoma M21 (αvβ3-positive andα5β1-negative), human melanoma M21-L (αvβ3-negative and α5β1-negative), and human prostate carcinoma DU145 (αvβ3-negative and α5β1-positive) confirmed receptor-specific binding. The radiotracer was stable in human serum and showed low protein binding. Biodistribution studies showed tumour uptake ranging from 2.5 to 3.5% ID/g between 30 and 120 min post-injection. However, blocking studies and studies using mice bearing α5β1-negative M21 tumours did not confirm receptor-specific uptake of [18F]FProp-Cys*-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys*-OH, although this radiopeptide revealed high affinity and substantial selectivity to α5β1 in vitro. Further experiments are needed to study the in vivo metabolism of this peptide and to develop improved radiopeptide candidates suitable for PET imaging of α5β1 expression in vivo. PMID:25374888

  5. 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

  6. Evaluation of focal defects on technetium-99m sulfur colloid scans with new hepatobiliary agents

    SciTech Connect

    Rao, B.K.; Pastakia, B.; Lieberman, L.M.

    1980-08-01

    In 3600 patients evaluated with technetium-99m sulfur colloid for metastatic liver disease, 40 had equivocal scans due to a solitary defect in the inferior margin of the right lobe. In these patients, the authors differentiated the gallbladder fossa from a metastatic focus using one of two new hepatobiliary agents: technetium-99m labeled pyridoxylideneglutamate and paraisopropylacetanilido iminodiacetic acid. The need for laparoscopic biopsy was obviated in a majority (78%) of the patients by identifying the gallbladder fossa.

  7. Environmental biochemistry of current environmental levels of heavy metals: preparation of radiotracers with very high specific radioactivity for metallobiochemical experiments on laboratory animals.

    PubMed

    Sabbioni, E; Goetz, L; Birattari, C; Bonardi, M

    1981-03-01

    Environmental toxicology research on dose-response relationships of heavy metals requires experiments on laboratory animals exposed to "low doses" of trace elements which should reflect "present or actual environmental levels" characteristic of polluted environments. Unfortunately no criteria exist to establish the "low doses" to which laboratory animals must be exposed, in practice the choice of the level used is made in an almost arbitrary manner. In order to define the "present environmental levels" of heavy metals which should be administered to laboratory animals an approach is suggested, based upon knowledge of the concentrations of trace elements in the diet, air and food as well as the fractions absorbed. Today daily intakes of trace elements by man are of the order of few micrograms or nanograms thus requiring the use of extremely sensitive analytical techniques to determine the very low amounts of heavy metals in tissues and cellular components. In these fields of research the use of radiotracers with very high specific radioactivity appears particularly advantageous but requires considerable care during their preparation and use. The first part of this paper deals with a definition of the ranges of concentrations of trace elements which should be used for metabolic studies on laboratory animals when they are exposed via different routes such as ingestion, inhalation in injection; the second part describes the production of radiotracers with very high specific radioactivity by proton activation in the cyclotron and by neutron irradiation in the nuclear reactor. Their use to label present levels of heavy metals under conditions adapted for biochemical purposes, as well as the preparation of different metal-labelled chemical species is also reported. Particular attention is directed to quality control of the radiotracer solutions which are administered to the animals including those of radioactivity concentrations, radioisotopic purity, radiochemical purity

  8. Pre-clinical characterization of [11C]R05013853 as a novel radiotracer for imaging of the glycine transporter type 1 by positron emission tomography.

    PubMed

    Borroni, Edilio; Zhou, Yun; Ostrowitzki, Susanne; Alberati, Daniela; Kumar, Anil; Hainzl, Dominik; Hartung, Thomas; Hilton, John; Dannals, Robert F; Wong, Dean F

    2013-07-15

    A specific positron emission tomography (PET) radiotracer for the glycine transporter type 1 (GlyT1) would constitute an imaging biomarker to investigate the distribution of GlyT1 in normal individuals and those with neuropsychiatric disorders. In addition it could demonstrate the ability of a novel drug to reach its target in the brain and enable receptor occupancy studies, thus facilitating drug development. In this article we describe the evaluation in non-human primates of two candidate PET radiotracers ([(11)C]RO5013852 and [(11)C]RO5013853) previously characterized in the rat. Both radiotracers showed acceptable uptake in the baboon brain and heterogeneous distribution consistent with that reported for GlyT1. In vivo blockade studies with two specific glycine reuptake inhibitors (GRIs), RO5013853 and bitopertin (RG1678, reduced uptake of both tracers to homogenous levels across brain regions and demonstrated specificity of the signal. [(11)C]RO5013853 showed a larger specific signal and slightly higher brain uptake and was therefore selected for further characterization. Quantitative compartmental analysis of PET data showed that the 2-tissue compartment model with 5 parameters was the most appropriate to describe the kinetics of [(11)C]RO5013853. Two additional methods were used: a) the Logan graphical analysis using plasma input and, b) a linear parametric imaging approach with the 2-tissue compartmental model. These produced VT estimates of comparable magnitude, namely, pons, thalamus and cerebellum>caudate, putamen and cortical regions. High resolution autoradiography with tritiated RO5013853 was used to confirm the binding pattern observed by PET. In vivo metabolism studies in the baboon demonstrated the formation of a single, radiolabeled metabolite more polar than the parent compound. Finally, [(11)C]RO5013853 was used to quantify the degree of cerebral GlyT1 occupancy observed in the baboon following oral administration of bitopertin, a selective GRI

  9. 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

  10. [{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%.

  11. 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

  12. 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

  13. "High specific activity" radiotracers for metallo-toxicological studies: cyclotron and nuclear reactor production, radiochemical separation and "quality control": platinum, iridium, gold, copper and gallium.

    PubMed

    Bonardi, Mauro; Groppi, Flavia; Birattari, Claudio; Arginelli, Dolores

    2002-09-01

    Very High Specific Activity RadioNuclides, HSARN, are a powerful tool to label a wide variety of chemical elements and compounds present in the biosphere in ultra-trace amounts. Medium and high Z radionuclides, can be produced by irradiation in light-ions accelerator and sometimes nuclear reactor. If the nuclear reaction product has atomic number different from irradiated target, it is possible separating the radioactive nuclide from irradiated target, without addition of isotopic carrier. These kinds of radionuclides are named No Carrier Added, NCA, and their specific activity is very high and can reach values close to the theoretical Carrier Free one. The true specific activity must be determined by use of very sensitive radioanalytical techniques. If a low isotopic dilution factor is obtained, these radiotracers are used to label inorganic species and complexes of elements, which are presently introduced into the echo-systems by human activities. New production methods for NCA Pt, Ir, Au, Cu and Ga radiotracers are presented, with some details on radiochemistry and quality controls.

  14. 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.

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

    PubMed

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

    2015-09-01

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

  16. 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.

  17. 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.

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

    PubMed

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

    2016-09-01

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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

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

    PubMed Central

    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/68Ga-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 68Ga(CUR)2+, 68Ga(DAC)2+, and 68Ga(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/68Ga-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

  5. 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.

  6. Metabolism, distribution, and excretion of deoxynivalenol with combined techniques of radiotracing, high-performance liquid chromatography ion trap time-of-flight mass spectrometry, and online radiometric detection.

    PubMed

    Wan, Dan; Huang, Lingli; Pan, Yuanhu; Wu, Qinghua; Chen, Dongmei; Tao, Yanfei; Wang, Xu; Liu, Zhenli; Li, Juan; Wang, Liye; Yuan, Zonghui

    2014-01-01

    Dispositions of deoxynivalenol (DON) in rats and chickens were investigated, using a radiotracer method coupled with a novel γ-accurate radioisotope counting (γ-ARC) radio-high-performance liquid chromatography ion trap time-of-flight tandem mass spectrometry (radio-HPLC-IT-TOF-MS/MS) system. 3β-(3)H-DON was chemically synthesized and orally administrated to both sexes of rats and chickens as single or multiple doses. The results showed that DON was widely distributed and quickly eliminated in all tissues. The highest concentration was found in the gastrointestinal tract at 6 h post-administration. Substantially lower levels were detected in the kidney, liver, heart, lung, spleen, and brain. Three new metabolites were identified tentatively as 10-deoxynivalenol-sulfonate, 10-deepoxy-deoxynivalenol (DOM-1)-sulfonate, and deoxynivalenol-3α-sulfate. Deoxynivalenol-3α-sulfate was a major metabolite in chickens, while the major forms in rats were DOM-1 and DON. Additionally, a higher excretion rate in urine was observed in female rats than in male rats. The differences in metabolite profiles and excretion rates, which suggested diverse ways to detoxify, may relate to the different tolerances in different genders or species.

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

    PubMed

    Pérez Catán, Soledad; Guevara, Sergio Ribeiro; Marvin-DiPasquale, Mark; Magnavacca, Cecilia; Cohen, Isaac Marcos; Arribere, María

    2007-09-01

    Methodological considerations on the determination of benthic methyl-mercury (CH(3)Hg) production potentials were investigated on lake sediment, using (197)Hg radiotracer. Three methods to arrest bacterial activity were compared: flash freezing, thermal sterilization, and gamma-irradiation. Flash freezing showed similar CH(3)Hg recoveries as thermal sterilization, which was both 50% higher than the recoveries obtained with gamma-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 (197)Hg(II) carry-over in the organic extraction and/or [(197)Hg]CH(3)Hg produced via abiotic reactions. Two CH(3)Hg extraction methods from sediment were compared: (a) direct extraction into toluene after sediment leaching with CuSO(4) 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.

  8. 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.

  9. Synthesis and evaluation of inhaled [11C]butane and intravenously injected [11C]acetone as potential radiotracers for studying inhalant abuse.

    PubMed

    Gerasimov, Madina R; Ferrieri, Richard A; Pareto, Deborah; Logan, Jean; Alexoff, David; Ding, Yu-Shin

    2005-02-01

    The phenomenon of inhalant abuse is a growing problem in the US and many countries around the world. Yet, relatively little is known about the pharmacokinetic properties of inhalants that underlie their abuse potential. While the synthesis of 11C-labeled toluene, acetone and butane has been proposed in the literature, none of these compounds has been developed as radiotracers for PET studies. In the present report we extend our previous studies with [11C]toluene to include [11C]acetone and [11C]butane with the goal of comparing the pharmacokinetic profiles of these three volatile abused substances. Both [11C]toluene and [11C]acetone were administered intravenously and [11C]butane was administered via inhalation to anesthesized baboons. Rapid and efficient uptake of radiolabeled toluene and acetone into the brain was followed by fast clearance in the case of toluene and slower kinetics in the case of acetone. [11C]Butane was detected in the blood and brain following inhalation, but the levels of radioactivity in both tissues dropped to half of the maximal values over the period of less than a minute. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman primates. These data provide insight into the pharmacokinetic features possibly associated with the abuse liability of toluene, acetone and butane.

  10. (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.

  11. 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.

  12. (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

  13. Spatially resolved micro-X-ray fluorescence and micro-X-ray absorption fine structure study of a fractured granite bore core following a radiotracer experiment

    NASA Astrophysics Data System (ADS)

    Denecke, Melissa A.; Brendebach, Boris; De Nolf, Wout; Falkenberg, Gerald; Janssens, Koen; Simon, Rolf

    2009-08-01

    Spatially resolved X-ray absorption and fluorescence investigation with a micrometer-scale resolution on actinide-containing samples provide information necessary for safety assessment of nuclear waste disposal. In this paper one example of such an experiment is presented. This example entails neptunium speciation in a fractured granite bore core from the Swedish Äspö Hard Rock Laboratory following a radiotracer experiment using µ-XAFS and µ-XRF. In order to probe micro-volumes below the surface in the granite samples and thereby avoid potential changes in the Np speciation during cutting of the bore core, a confocal irradiation-detection geometry is employed. µ-XAFS results for a selected granite bore core cross section with ~ 3 nmol Np/g reveal that Np, originally introduced as Np(V) in the tracer cocktail, is present in the granite in its reduced Np(IV) form. The Np(IV) is often present as particles, tens of µm in size. Elemental distribution maps show the tracer Np to be located in fissures and permeable channels not larger than 100 µm. The Np distribution appears often correlated with Zn also present in some fissures. We observe small granite fissures containing Fe (presumably Fe(II)), where we do not detect any Np. It is feasible that inflowing Np(V) has a shorter residence time in large fractures, while in the smaller fissures migration is slower, leading to longer residence times, i.e., reaction times, where it is reduced to less soluble Np(IV) and becomes thereby immobilized.

  14. The use of [18F]4-fluorobenzyl iodide (FBI) in PET radiotracer synthesis: model alkylation studies and its application in the design of dopamine D1 and D2 receptor-based imaging agents.

    PubMed

    Mach, R H; Elder, S T; Morton, T E; Nowak, P A; Evora, P H; Scripko, J G; Luedtke, R R; Unsworth, C D; Filtz, T; Rao, A V

    1993-08-01

    [18F]4-Fluorobenzyl iodide ([18F]FBI) was prepared, and a series of model alkylation studies were conducted to determine its chemical reactivity toward nitrogen and sulfur nucleophiles of varying nucleophilicities. [18F]FBI was found to react rapidly with secondary amines and anilines to give the corresponding N-[18F]4-fluorobenzyl analogue in high yield. Amides and thiol groups required the use of a base catalyst. The utility of [18F]FBI was documented by investigation of dopamine D1 and D2 receptor-based radiotracers.

  15. 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.

  16. 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.

  17. Preparation and evaluation of 99mTc-cefuroxime, a potential infection specific imaging agent: a reliable thin layer chromatographic system to delineate impurities from the 99mTc-antibiotic.

    PubMed

    Chattopadhyay, Sankha; Ghosh, Mayuri; Sett, Sucharita; Das, Malay Kanti; Chandra, Susmita; De, Kakali; Mishra, Mridula; Sinha, Samarendu; Ranjan Sarkar, Bharat; Ganguly, Shantanu

    2012-10-01

    Technetium-99m labelled cefuroxime, a second-generation cephalosporin antibiotic and potential bacteria specific infection imaging agent was evaluated. A good radiochemical purity (95%) of the labelled product was obtained after filtering the reaction mixture through a 0.22 μm filter. Scintigraphy study of the purified product showed uptake in infectious lesions 45 min after injection and abscess-to-muscle ratios were found to be 1.80, 1.85 and 1.88 at 45 min, 1.5 hr and 3 hr, respectively. A versatile and reliable chromatographic technique to assess the radiochemical purity of (99m)Tc-cefuroxime has also been described.

  18. Colonoscopic preoperative localization using submucosal injection of radiolabelled colloid

    PubMed Central

    Cho, Carolyn; Jain, Sanjiv; Pilbeam, Mark; Tait, Noel; Thomson, Andrew

    2008-01-01

    Malignant colonic polyps can be removed endoscopically but surgical resection is sometimes required. However, the polypectomy site can be difficult to locate. Current methods use various tattooing agents, with varying degrees of success. A new technique using pre-operative injection of technetium-99m-labelled antimony colloid, with intraoperative localization using a handheld gamma probe, is described. Although unsuccessful in terms of localizing a previously partially resected polyp, the technique itself proved safe and simple, and has some advantages over other endoscopic approaches. PMID:18629395

  19. Technical considerations in gastric ulcer localization using technetium-99m sucralfate

    SciTech Connect

    Garrett, S.G.; Wcislo, W.J.

    1985-09-01

    After the completion and evaluation of 17 patients studies using technetium-99m-labeled sucralfate for the detection of ulcerated areas, the authors felt that the technical aspects of the studies should be evaluated. The factors for evaluation are: the time the patient is kept fasting; the time the patient is being imaged and rotated for various anatomic views; the technologist time and camera time that are involved in one study; and the cost factor of the testing procedure. Based on the findings of their small sample of patients, the sensitivity of the test is uncertain.

  20. 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.

  1. 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.

  2. 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

  3. A fluoro versus a nitro derivative-a high-performance liquid chromatography study of two basic analytes with different reversed phases and silica phases as basis for the separation of a positron emission tomography radiotracer.

    PubMed

    Wenzel, Barbara; Günther, Robert; Brust, Peter; Steinbach, Jörg

    2013-10-11

    To develop a basis for the separation of a (18)F-labeled PET radiotracer from its nitro precursor, we performed an analytical HPLC study using the unlabeled reference compound and the corresponding nitro precursor. Aim of the study was to find a separation in which the fluoro derivative elutes in front of the nitro precursor with appropriate separation parameters. Several RP phases as well as a bare silica column were investigated with ACN and MeOH as organic modifiers and aqueous NH4OAc because of the basic character of the analytes. Four types of separation were observed based on different interaction mechanisms. When ACN/20mM NH4OAc aq. was used mainly cationic-exchange and hydrophobic interactions contributed to the retention. A reversal of elution order could be observed starting from 95% ACN and subsequent increasing of the water content. This phenomenon was observed for all RP phases and seems to be independent of the different spacers bound to the silica. By contrast, using MeOH/20mM NH4OAc aq. the elution order depends on the phase material. Two columns with the potential to perform π-π interactions showed different separation behavior compared to the other RP phases.

  4. Further evaluation of [11C]MP-10 as a radiotracer for phosphodiesterase 10A (PDE10A): PET imaging study in rhesus monkeys and brain tissue metabolite analysis

    PubMed Central

    Lin, Shu-fei; Labaree, David; Chen, Ming-Kai; Holden, Daniel; Gallezot, Jean-Dominique; Kapinos, Michael; Teng, Jo-Ku; Najafzadeh, Soheila; Plisson, Christophe; Rabiner, Eugenii A.; Gunn, Roger N.; Carson, Richard E.; Huang, Yiyun

    2014-01-01

    [11C]MP-10 is a potent and specific PET tracer previously shown to be suitable for imaging the PDE10A in baboons with reversible kinetics and high specific binding. However, another report indicated that [11C]MP-10 displayed seemingly irreversible kinetics in rhesus monkeys, potentially due to the presence of a radiolabeled metabolite capable of penetrating the blood-brain-barrier (BBB) into the brain. This study was designed to address the discrepancies between the species by re-evaluating [11C]MP-10 in vivo in rhesus monkey with baseline scans to assess tissue uptake kinetics and self-blocking scans with unlabeled MP-10 to determine binding specificity. Ex vivo studies with one rhesus monkey and 4 Sprague-Dawley rats were also performed to investigate the presence of radiolabeled metabolites in the brain. Our results indicated that [11C]MP-10 displayed reversible uptake kinetics in rhesus monkeys, albeit slower than in baboons. Administration of unlabeled MP-10 reduced the binding of [11C]MP-10 in a dose-dependent manner in all brain regions including the cerebellum. Consequently, the cerebellum appeared not to be a suitable reference tissue in rhesus monkeys. Regional volume of distribution (VT) was mostly reliably derived with the multilinear analysis (MA1) method. In ex vivo studies in the monkey and rats only negligible (< 2.7%) amount of radiometabolites was seen in the brain of either species. In summary, results from the present study strongly support the suitability of [11C]MP-10 as a radiotracer for PET imaging and quantification of PDE10A in non-human primates. PMID:25450608

  5. The practicality of nanoceria-PAN-based (68)Ge/(68)Ga generator toward preparation of (68)Ga-labeled cyclic RGD dimer as a potential PET radiotracer for tumor imaging.

    PubMed

    Chakraborty, Sudipta; Chakravarty, Rubel; Sarma, Haladhar D; Dash, Ashutosh; Pillai, M R A

    2013-02-01

    Cyclic RGD (Arg-Gly-Asp) peptides radiolabeled with (68)Ga have great potential for the early tumor detection and noninvasive monitoring of tumor metastasis and therapeutic response. Herein, the preparation of (68)Ga-labeled DOTA-E[c(RGDfK)](2) (DOTA=1,4,7,10-tetraazacylododecane-1,4,7,10-tetracetic acid; E=Glutamic acid; R=Arginine; G=Glycine; D=Aspartic acid; f=phenyl alanine; K=lysine) using (68)Ga directly eluted from a nanoceria-polyacrylonitrile (CeO(2)-PAN)-based (68)Ge/(68)Ga generator developed in-house was reported. The (68)Ga complex of DOTA-E[c(RGDfK)](2) was synthesized with >98% radiochemical purity by incubating 20 μg of the conjugate with (68)GaCl(3) (74-111 MBq) in acetate buffer (pH 3.5-4.0) at 90°C for 10 minutes. The complex exhibited excellent in vitro stability in 0.1 M EDTA solution at room temperature upto 1 hour studied (radiochemical purity: 98.0%). The biological efficacy of the radiolabeled conjugate was studied in C57/BL6 mice bearing melanoma tumors. The results of the biodistribution studies revealed significant tumor uptake (4.14±0.54%ID/g) within 10 minutes postinjection (p.i.), which increased further to 4.61±0.31%ID/g at 30 minutes p.i. The tumor-to-blood ratio was found to increase from 1.75±0.42 at 10 minutes p.i. to 2.25±0.20 at 60 minutes p.i., whereas the tumor-to-liver and tumor-to-muscle ratio between the same time points increased from 2.71±0.76 to 3.31±0.84 and 5.37±1.08 to 8.97±1.32, respectively. The study successfully demonstrated the preparation of (68)Ga-DOTA-E[c(RGDfK)](2) as a potential positron-emission tomography radiotracer for possible use in tumor imaging by using (68)Ga eluted from a reliable, easy-to-handle (68)Ge/(68)Ga generator developed in-house, without any postelution purification of (68)Ga.

  6. Automated synthesis and dosimetry of 6-deoxy-6-[18F]fluoro-D-fructose (6-[18F]FDF): a radiotracer for imaging of GLUT5 in breast cancer

    PubMed Central

    Bouvet, Vincent; Jans, Hans S; Wuest, Melinda; Soueidan, Olivier-Mohamad; Mercer, John; McEwan, Alexander JB; West, Frederick G; Cheeseman, Chris I; Wuest, Frank

    2014-01-01

    6-Deoxy-6-[18F]fluoro-D-fructose (6-[18F]FDF) is a promising PET radiotracer for imaging GLUT5 in breast cancer. The present work describes GMP synthesis of 6-[18F]FDF in an automated synthesis unit (ASU) and dosimetry calculations to determine radiation doses in humans. GMP synthesis and dosimetry calculations are important prerequisites for first-in-human clinical studies of 6-[18F]FDF. The radiochemical synthesis of 6-[18F]FDF was optimized and adapted to an automated synthesis process using a Tracerlab FXFN ASU (GE Healthcare). Starting from 30 GBq of cyclotron-produced n.c.a. [18F]fluoride, 2.9 ± 0.1 GBq of 6-[18F]FDF could be prepared within 50 min including HPLC purification resulting in an overall decay-corrected radiochemical yield of 14 ± 3% (n = 11). Radiochemical purity exceeded 95%, and the specific activity was greater than 5.1 GBq/μmol. Sprague-Dawley rats were used for biodistribution experiments, and dynamic and static small animal PET experiments. Biodistribution studies served as basis for allometric extrapolation to the standard man anatomic model and normal organ-absorbed dose calculations using OLINDA/EXM software. The calculated human effective dose for 6-[18F]FDF was 0.0089 mSv/MBq. Highest organ doses with a dose equivalent of 0.0315 mSv/MBq in a humans were found in bone. Injection of 370 MBq (10 mCi) of 6-[18F]FDF results in an effective whole body radiation dose of 3.3 mSv in humans, a value comparable to that of other 18F-labeled PET radiopharmaceuticals. The optimized automated synthesis under GMP conditions, the good radiochemical yield and the favorable human radiation dosimetry estimates support application of 6-[18F]FDF in clinical trials for molecular imaging of GLUT5 in breast cancer patients. PMID:24795839

  7. 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.

  8. Epinephrine kinetics in humans: Radiotracer methodology

    SciTech Connect

    Rosen, S.G.; Linares, O.A.; Sanfield, J.A.; Zech, L.A.; Lizzio, V.P.; Halter, J.B. )

    1989-10-01

    The use of the plasma epinephrine (EPI) level as an index of adrenomedullary activity in humans is complicated by the rapid removal of EPI from plasma by many tissues. To determine whether the kinetics of distribution and metabolism of EPI could be best quantified using the isotope dilution method or a mathematical modeling technique, eight human subjects received a ({sup 3}H)EPI infusion for 50-60 min. Analysis of the steady state arterialized plasma levels of EPI and ({sup 3}H)EPI using the isotope dilution technique showed that the basal plasma EPI appearance rate is 0.87 {plus minus} 0.11 nmol/m2.min, and the basal plasma EPI clearance rate is 1.63 {plus minus} 0.14 L/min.m2. Mathematical modeling of the ({sup 3}H)EPI levels revealed that a biexponential curve fit was superior to monoexponential and triexponential curve fits. A two-compartment model was the minimal compartment model that accurately described EPI kinetics. The basal plasma EPI appearance (0.82 {plus minus} 0.16 nmol/m2.min) and EPI clearance (1.67 {plus minus} 0.15 L/min.m2) rates that were estimated from this two-compartment model are similar to the results derived from the isotope dilution method. Mathematical modeling revealed a large extravascular mass of EPI. We conclude that the isotope dilution and mathematical modeling techniques similarly describe plasma EPI kinetics in humans. Kinetic analysis using mathematical modeling provides new insights into adrenomedullary function in humans.

  9. 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.

  10. 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.

  11. Radiotracer investigation in gold leaching tanks.

    PubMed

    Dagadu, C P K; Akaho, E H K; Danso, K A; Stegowski, Z; Furman, L

    2012-01-01

    Measurement and analysis of residence time distribution (RTD) is a classical method to investigate performance of chemical reactors. In the present investigation, the radioactive tracer technique was used to measure the RTD of aqueous phase in a series of gold leaching tanks at the Damang gold processing plant in Ghana. The objective of the investigation was to measure the effective volume of each tank and validate the design data after recent process intensification or revamping of the plant. I-131 was used as a radioactive tracer and was instantaneously injected into the feed stream of the first tank and monitored at the outlet of different tanks. Both sampling and online measurement methods were used to monitor the tracer concentration. The results of measurements indicated that both the methods provided identical RTD curves. The mean residence time (MRT) and effective volume of each tank was estimated. The tanks-in-series model with exchange between active and stagnant volume was used and found suitable to describe the flow structure of aqueous phase in the tanks. The estimated effective volume of the tanks and high degree of mixing in tanks could validate the design data and confirmed the expectation of the plant engineer after intensification of the process.

  12. Transport rate of arsenic, cadmium, copper and zinc in Potamogeton pectinatus L.: radiotracer experiments with 76As,109,115Cd,64Cu and 65,69mZn.

    PubMed

    Wolterbeek, H Th; van der Meer, A J G M

    2002-03-15

    The present study was aimed at obtaining an insight into possible experimental approaches for providing numerical data on both the accumulation of sediment As, Cd, Cu and Zn in the submerged water plant Potamogeton pectinatus L., and the possible corresponding metal flows into the water phase. A hydroculture two-compartment system was used as the experimental set-up, and the selected metals were followed by measurements of their radioisotopes 76As, 109Cd, 115Cd, 64Cu, 65Zn and 69mZn. All experiments were performed in single plant mode. The results stress the extreme importance of leakage tests, which were performed using 99mTcO4-, and which resulted in approximately 30% of all experiments being discarded. Metal flows were shown as very near the metal limits of detection or obscured by and/or numerically very near the occurring leakage phenomena. Bio-concentration factors BCF (fresh wt. fine root basis) were calculated as 100, 10, 10 and 100-500 l/kg for Cu, Zn, Cd and As, respectively. The mobility, expressed as the shoot/root concentration ratio, CR, was obtained as < 10(-4), < 10(-5), 10(-3) and 10(-3) - 10(-2) for Cu, As, Cd and Zn, respectively. Double-labeling experiments showed that the CR values were due to the exclusive root-mediated transport in radiotracer experiments: results for simultaneous applications of 109Cd and 115Cd or 65Zn and 69mZn showed field-simulated CR values of approximately 0.04 and 14, respectively. Single-tracer experiments, using liquid scintillation counting (LSC) with 109Cd and 65Zn, were shown to strongly improve the sensitivities of flow determinations. Under the applied conditions, metal flows could be determined as <5 x 10(-8), <5 X 10(-8), 3.5+/-1.8 x 10(-10) and <8 x 10(-9) mol/h per kg root fresh wt. for Cu, As, Cd and Zn, respectively. Upscaling calculations, assuming plant steady state behavior, indicate that the metal accumulation in the plants may comprise up to 1% of the sediment metal occurrence, that the major part of

  13. Scintigraphic diagnosis of hepatic hemangioma: its role in the management of hepatic mass lesions

    SciTech Connect

    Moinuddin, M.; Allison, J.R.; Montgomery, J.H.; Rockett, J.F.; McMurray, J.M.

    1985-08-01

    Hepatic cavernous hemangiomas are benign tumors of the liver that are often an incidental finding. They are usually asymptomatic but may cause symptoms when traumatized, may bleed spontaneously, or may produce pain by virtue of their large size and mass effect. A retrospective analysis of the clinical presentation, liver function tests, and diagnostic imaging procedures in 20 patients with hepatic hemangiomas is presented and the literature is reviewed. The 20 patients had 27 mass lesions as seen on liver scintigraphy, computed tomography, or sonography. Technetium-99m-labeled red blood cell flow studies and blood pool scintigrams showed delayed filling of the mass lesions, diagnostic of hemangiomas. This finding was not encountered in any other type of lesion. A new diagnostic algorithm is proposed in which flood-flow and blood-pool scintigraphy play a more prominent role in the diagnostic workup.

  14. Gastric ulcer localization by direct in vivo labeling of sucralfate: work in progress

    SciTech Connect

    Pera, A.; Seevers, R.H.; Meyer, K.; Hall, C.; Bekerman, C.; Anderson, T.M.; Katzen, H.; Laakso, L.; Pinsky, S.M.

    1985-09-01

    The authors developed and evaluated a new procedure for imaging gastric ulcer disease with technetium 99m - labeled sucralfate. The new method employs direct in vivo labeling of sucralfate instead of in vitro labeling using human serum albumin, as previously reported in the literature. In 26 studies using humans with sucralfate labeled directly in vivo, 15 gave true-negative results. Of 14 studies using humans with in vitro labeled sucralfate, three gave true-negative results, three gave true-positive results, and the results of eight were either false-negative or could not be interpreted because of high levels of activity remaining in the stomach. They suggest that the direct in vivo labeling method significantly improves the sucralfate gastric ulcer imaging technique.

  15. Hepatobiliary and gallium imaging findings in gallbladder perforation: A case report and review of the literature

    SciTech Connect

    Yeo, E.; Chen, D.C.; Siegel, M.E.

    1989-02-01

    Gallbladder perforation is an unusual condition with a high mortality rate. Early detection with prompt surgical intervention can increase the survival rate. Hepatobiliary imaging using Technetium-99m-labeled iminodiacetic acid has been used for the diagnosis of gallbladder perforation. However, the results vary and are somewhat confusing. The authors report a case of gallbladder perforation with hepatobiliary imaging and an unusual gallium image; review the literature; and propose a classification of three different imaging patterns: (1) visualization of the gallbladder with bile leakage, (2) nonvisualization of the gallbladder with a photopenic fluid collection, and (3) nonvisualization of the gallbladder with bile leakage. These patterns may provide pathophysiologic information for the surgeon. 27 references.

  16. Spontaneous periodic hypothermia and hyperhidrosis.

    PubMed

    Dundar, Nihal Olgac; Boz, Adil; Duman, Ozgur; Aydin, Funda; Haspolat, Senay

    2008-12-01

    We present a patient diagnosed with Shapiro syndrome without corpus callosum agenesis. A 4-year-old-girl was admitted to the hospital with complaints of sweating, cooling, and drowsiness that continued during the last week of her admission. Attacks occurred almost daily, and lasted for about 1 hour. All laboratory findings, as well as Holter and echocardiography results, were normal. Cranial magnetic resonance imaging demonstrated an intact corpus callosum, and electroencephalography obtained during an attack revealed normal findings. However, technetium 99m-labeled hexamethylpropylene amine oxime brain single-photon emission computed tomography indicated increased perfusion in the right thalamus, basal ganglia, and inferior frontal areas during a hypothermic period. Although oxcarbazepine reduced the frequency of attacks, they were not halted completely. The patient responded better to carbamazepine. PMID:19027594

  17. 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%.

  18. Intrinsically copper-64-labeled organic nanoparticles as radiotracers.

    PubMed

    Liu, Tracy W; MacDonald, Thomas D; Shi, Jiyun; Wilson, Brian C; Zheng, Gang

    2012-12-21

    PET friendly: labels for PET imaging are incorporated into completely organic porphysomes by using a fast (30 min), one-pot, high-yielding (>95 %) procedure to produce highly stable (>48 h) radiolabeled nanoparticles that show the highest specific activity ever reported for a (64) Cu-labeled nanoparticle. These (64) Cu-porphysomes can be accurately and noninvasively tracked in vivo.

  19. Investigation of hydrodynamic behaviour of membranes using radiotracer techniques

    NASA Astrophysics Data System (ADS)

    Miskiewicz, A.; Zakrzewska-Trznadel, G.

    2013-05-01

    The aim of the work was to study membrane devices using short-lived radioisotopes like Ba-137m and Ga-68 as tracers. These radioisotopes were obtained from radionuclide generators: Cs-137/Ba-137m and Ge-68/Ga-68. The first radionuclide, namely Ba-137m with a half-life of 2.55 minutes was applied as a liquid phase tracer for studying hydrodynamic conditions inside the membrane apparatus. The membrane module with ceramic membranes was tested by using Ba-137m. The experiments showed that this radionuclide with a short half-life is a perfect tracer for liquid phase, whereas Ga-68 with longer half-life equal to 68 minutes was considered as a solid phase (bentonite) tracer. Ga-68 was used to gain more knowledge about the phenomena occurring in the membrane boundary layer. After kinetic studies of isotope adsorption into the carrier material, the growth rate of the deposit layer as well as deposit's thickness on the flat-sheet membrane were studied. The influence of such process parameters like pressure, linear velocity of liquid and feed concentration on formation of the bentonite layer on the membrane surface was studied.

  20. 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)

  1. 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.

  2. 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)

  3. 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.

  4. Preparation and evaluation of a /sup 99m/Tc-SnF2 colloid kit for leukocyte labeling

    SciTech Connect

    Hirsch, J.I.; Tatum, J.L.; Fratkin, M.J.; Apostolides, D.L.; Quint, R.I.

    1989-07-01

    Stannous fluoride colloid (SFC) kits for instant radiolabeling with 99mTc were prepared and evaluated for suitability as a leukocyte radiolabeling agent. Technetium-99m labeling for kits stored at -15/degree/C for up to 3 mo was greater than 95% as determined by instant thin layer chromatography while colloid particles of 1-3 microns were measured by electron microscope for these preparations. Canine leukocyte preparations labeled with (/sup 99m/Tc)SFC and characterized by triple density gradients of metrizamide in plasma demonstrated an 83% leukocyte association. Analysis of labeled cell preparation for up to 3 hr demonstrated label stability. Labeled leukocytes, when readministered in normal dogs, demonstrated bi-exponential blood clearance with uptake and subsequent clearance from lung. There was increasing uptake of labeled leukocytes by the liver until steady state was achieved. Furthermore, when whole blood samples were analyzed by the triple density gradient method, an increasing monocyte-to-granulocyte ratio was observed to occur with time. By 3 hr 95% of the whole blood activity was associated with the leukocyte fraction. Dogs in which a 24-hr sterile abscess was created demonstrated elevated blood-pool activity as compared to control with localization of the labeled cells at inflammatory sites within 3 hr following cell readministration.

  5. Improved transnasal transport and brain uptake of tizanidine HCl-loaded thiolated chitosan nanoparticles for alleviation of pain.

    PubMed

    Patel, Deepa; Naik, Sachin; Misra, Ambikanandan

    2012-02-01

    The aim of this study was to prepare and characterize thiolated chitosan (TC) nanoparticles (NPs) of tizanidine HCl (TZ) and to evaluate its transport across monolayer of RPMI 2650 cells (Human nasal septum carcinoma cell line) followed by assessment of their pharmacokinetic and pharmacodynamic attributes, after intranasal (i.n.) administration. Chitosan was thiolated by carbodiimide method and thiolation was confirmed qualitatively and quantitatively. NPs were prepared using ionotropic gelation and evaluated for mucoadhesion using sheep nasal mucosa for drug permeation and cytotoxicity using monolayer of RPMI 2650 cells. Drug biodistribution was evaluated after technetium-99m labeling, visualized using gamma camera, and evaluated pharmacodynamically by measuring antinociceptive activity in mice. High mucoadhesion and permeation of drug were observed for TC NPs with least toxicity to nasal epithelial cells. Brain uptake and antinociceptive effect of the drug were significantly enhanced after thiolation of chitosan. This concludes that TC NPs, after i.n. administration, show significant increase in the mucoadhesion, reduction in cytotoxicity, enhanced permeation across cells monolayer, higher TZ brain uptake, and considerable increase in antinociceptive activity of TZ in mice. These features make TC an interesting polymer for demonstrating appreciable improvement of transnasal permeation of hydrophilic drugs, such as TZ, known to have limited permeation across blood-brain barrier.

  6. Functional hyposplenism

    PubMed Central

    Kirkineska, L; Perifanis, V; Vasiliadis, T

    2014-01-01

    Abstract Functional hyposplenism is a condition accompanying many diseases such as sickle cell disease, celiac disease, alcoholic liver disease, hepatic cirrhosis, lymphomas and autoimmune disorders. It is characterised mostly by defective immune responses against infectious agents, especially encapsulated organisms, since the spleen is thought to play an important role in the production and maturation of B-memory lymphocytes and other substances like opsonins, both of which are considered crucial elements of the immune system for fighting infections. It is also associated with thrombocytosis, which might lead to thromboembolic events. Functional hyposplenism is diagnosed by the presence of Howell-Jolly bodies and pitted erythrocytes in the peripheral blood smear, and by nuclear imaging modalities such as spleen scintigraphy with the use of Technetium-99m and/or spleen scintigraphy with the use of heat-damaged Technetium-99m labeled erythrocytes. Severe infections accompanying functional hyposplenism can lead to the overwhelming post infection syndrome, which can often be fatal. Identifying patients with functional hyposplenism is important because simple measures such as vaccination against common infective microorganisms (e.g. Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae) and antibiotic therapy when needed are considered beneficial in diminishing the frequency and gravity of the infections accompanying the syndrome. PMID:25125944

  7. Determination of tumour vascularity using selective hepatic angiography as compared with intrahepatic-arterial technetium-99m macroaggregated albumin scan in hepatocellular carcinoma.

    PubMed

    Leung, T W; Lau, W Y; Ho, S K; Chan, M; Leung, N W; Lin, J; Metreweli, C; Johnson, P J; Li, A K

    1994-01-01

    A total of 51 patients with hepatocellular carcinoma (HCC) were studied to determine the tumour vascularity as determined by selective hepatic angiography (HAG) and by intrahepatic-arterial technetium-99m-labeled macroaggregated albumin (Tc99m-MAA) scan. The tumour vascularity was graded on the HAG films by an interventional radiologist using a scale ranging from 1 (hypovascular) to 4 (extremely hypervascular). The grades of vascularity on HAG were grade 1 in 5 patients, grade 2 in 13 patients, grade 3 in 24 patients and grade 4 in 9 patients. The tumour vascularity on scintigraphy was determined by quantifying the count rates over the tumour and normal liver areas by an analog/digital gamma-camera, and the resultant tumour-to-normal ratio (T/N ratio) gave a quantitative measure of the vascularity. The range of the T/N ratio was 0.9 to 11.1, with a median of 3.7. There was no correlation between the tumour vascularity grading on HAG and the T/N ratio on the Tc99m-MAA scan (Wilcoxon rank test, P = 0.83). Thus, we conclude that HAG cannot reveal the true vascularity nor reflect the T/N ratio in HCC.

  8. Preparation and evaluation of a 99mTc-SnF2 colloid kit for leukocyte labeling.

    PubMed

    Hirsch, J I; Tatum, J L; Fratkin, M J; Apostolides, D L; Quint, R I

    1989-07-01

    Stannous fluoride colloid (SFC) kits for instant radiolabeling with 99mTc were prepared and evaluated for suitability as a leukocyte radiolabeling agent. Technetium-99m labeling for kits stored at -15 degrees C for up to 3 mo was greater than 95% as determined by instant thin layer chromatography while colloid particles of 1-3 microns were measured by electron microscope for these preparations. Canine leukocyte preparations labeled with [99mTc]SFC and characterized by triple density gradients of metrizamide in plasma demonstrated an 83% leukocyte association. Analysis of labeled cell preparation for up to 3 hr demonstrated label stability. Labeled leukocytes, when readministered in normal dogs, demonstrated bi-exponential blood clearance with uptake and subsequent clearance from lung. There was increasing uptake of labeled leukocytes by the liver until steady state was achieved. Furthermore, when whole blood samples were analyzed by the triple density gradient method, an increasing monocyte-to-granulocyte ratio was observed to occur with time. By 3 hr 95% of the whole blood activity was associated with the leukocyte fraction. Dogs in which a 24-hr sterile abscess was created demonstrated elevated blood-pool activity as compared to control with localization of the labeled cells at inflammatory sites within 3 hr following cell readministration.

  9. 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.

  10. 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

  11. Definitive diagnosis of hepatic hemangiomas: MR imaging versus Tc-99m-labeled red blood cell SPECT

    SciTech Connect

    Birnbaum, B.A.; Weinreb, J.C.; Megibow, A.J.; Sanger, J.J.; Lubat, E.; Kanamuller, H.; Noz, M.E.; Bosniak, M.A. )

    1990-07-01

    Thirty-seven patients with 69 suspected hemangiomas found by means of computed tomography (CT) and/or ultrasound were studied with both 0.5-T magnetic resonance (MR) imaging and single photon emission CT (SPECT) with technetium-99m-labeled red blood cells. Using a criterion of perfusion-blood pool mismatch, SPECT readers diagnosed 50 of 64 hemangiomas and all five nonhemangiomas (sensitivity, 78% (95% confidence interval, 0.664 - 0.864); accuracy, 80% (0.69 - 0.877)). Qualitative analysis of lesion signal intensity on T2-weighted spin-echo MR images allowed readers to diagnose 58 of 64 hemangiomas and four of five nonhemangiomas (sensitivity, 91% (0.814 - 0.96); accuracy, 90% (0.807 - 0.951)). Because of the significantly higher cost of MR imaging and its inability to categorically differentiate hemangiomas from hypervascular metastases, the authors consider SPECT to be the method of choice for diagnosing hepatic hemangiomas. MR imaging should be reserved for the diagnosis of lesions smaller than 2.0 cm and for those 2.5 cm and smaller adjacent to the heart or major hepatic vessels; in such cases MR imaging was found superior to SPECT.

  12. 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.

  13. 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

  14. 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.

  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. 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.

  17. 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).

  18. Technical Solutions to Ensure Safe Yttrium-90 Radioembolization in Patients With Initial Extrahepatic Deposition of {sup 99m}Technetium-Albumin Macroaggregates

    SciTech Connect

    Barentsz, M. W.; Vente, M. A. D.; Lam, M. G. E. H.; Smits, M. L. J.; Nijsen, J. F. W.; Seinstra, B. A.; Rosenbaum, C. E. N. M.; Verkooijen, H. M.; Zonnenberg, B. A.; Van den Bosch, M. A. A. J.

    2011-10-15

    Purpose: To evaluate the incidence of extrahepatic deposition of technetium-99m-labeled albumin macroaggregates ({sup 99m}Tc-MAA) after pretreatment angiography, before yttrium-90 radioembolizaton ({sup 90}Y-RE), and to report on technical solutions that can be used to ensure safe delivery of {sup 90}Y-microspheres in patients with initial extrahepatic deposition. Materials and Methods: A retrospective analysis of 26 patients with primary and secondary liver malignancies, who were scheduled for treatment with {sup 90}Y-RE in our institution in 2009, was performed. The angiograms and single-photon emission computed tomography images of all patients were reviewed by an interventional radiologist and a nuclear medicine physician, respectively, to identify and localize extrahepatic deposition of {sup 99m}Tc-MAA when present. Subsequently, the technical solutions were used to successfully perform {sup 90}Y-RE in these patients were evaluated and described. Results: Extrahepatic deposition of {sup 99m}Tc-MAA was observed in 8 of 26 patients (31%). In 7 of 8 patients, a second pretreatment angiography was performed to detect the cause of extrahepatic deposition. The technical solutions to enable safe {sup 90}Y microspheres delivery included more distal placement of the microcatheter in the proper/right hepatic artery in 4 of 7 (57%) patients; (super)selective catheterization of multiple segmental branches in 2 of 7 (29%); and additional coiling of a newly detected branch in the remaining patient (14%). This was confirmed by a second MAA procedure. {sup 90}Y-RE was eventually performed in 25 of 26 (96%) patients. No procedure-related complications (<30 days) were observed. Conclusion: Extrahepatic deposition of {sup 99m}Tc-MAA after pretreatment angiography did occur in 8 of 26 (31%) patients. The technical solutions as presented allowed safe {sup 90}Y-RE delivery in 25 of 26 (96%) patients.

  19. 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.

  20. Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion

    SciTech Connect

    Dreyer, W.J.; Michael, L.H.; West, M.S.; Smith, C.W.; Rothlein, R.; Rossen, R.D.; Anderson, D.C.; Entman, M.L. )

    1991-07-01

    The authors have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study they investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism. they concluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region. These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region.

  1. 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

  2. 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.

  3. 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

  4. Small bowel transit of a bran meal residue in humans: sieving of solids from liquids and response to feeding

    PubMed Central

    Hebden, J; Blackshaw, P; Perkins, A; D'Amato, M; Spiller, R

    1998-01-01

    Background—Ileal motor patterns are adapted to the propulsion of viscous meal residue, such as bran, which accumulates in the distal ileum postprandially. 
Aims—To examine the effects of a second liquid/solid meal on ileal emptying. 
Subjects and methods—Eleven healthy fasting subjects consumed a 1.47 MJ pancake containing 15 g bran and 5 MBq Technetium-99m labelled amberlite resin (meal A). Gastric emptying and transit through the left upper quadrant (proximal) and right lower quadrant (distal) small bowel regions and colon were assessed scintigraphically. Transit was compared with and without a second Indium-111 liquid/solid DTPA labelled 2.28 MJ meal (B) given three hours after the first meal. 
Results—Gastric emptying of meal A was slower than meal B (the time for 50% of the activity to leave the stomach (T50) being 113 (11) minutes versus 48 (3) minutes respectively, p<0.01, n=11). Both meals passed rapidly through the proximal small bowel (T50 meal A = 57 (14) minutes versus T50 meal B = 42 (11) minutes). Transit of meal A through the distal small bowel was much slower (T50 more than 390 minutes versus 176 (29) minutes for meal B, p<0.01), resulting in meal B overtaking meal A and entering the colon earlier. Ingestion of the second meal (B) resulted in significantly less meal A marker entering the colon (5 (3)%) at 11 hours than when meal A was taken alone (18 (4)%) (p<0.05, n=8). 
Conclusions—The distal small bowel selectively retains bran, allowing liquid phase markers through to the colon. Consuming a second liquid/solid meal does not stimulate ileal transit of bran which seems to be propelled quicker by fasting motor patterns. 

 Keywords: ileum; motility; bran; feeding PMID:9659165

  5. Utility of (99m)Tc-Hynic-TOC in 131I Whole-Body Scan Negative Thyroid Cancer Patients with Elevated Serum Thyroglobulin Levels.

    PubMed

    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, (99m)Tc-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 ((18)F-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 (99m)Tc-Hynic-TOC scan was higher (93.7%) for patients with advanced stages, that is stages III and IV. (18)F-FDG showed a sensitivity of 93.7%, a specificity of 50% and an accuracy of 89.3%. (18)F-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 (99m)Tc-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.

  6. 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.

  7. Renal caveolin-1 expression in children with unilateral ureteropelvic junction obstruction.

    PubMed

    Vallés, Patricia G; Manucha, Walter; Carrizo, Liliana; Vega Perugorria, José; Seltzer, Alicia; Ruete, Celeste

    2007-02-01

    Caveolae are plasma membrane invaginations that contain a variety of signal transduction molecules and receptors for growth factors and cytokines. This study was performed to examine the in vivo expression and localization of caveolin-1 in kidneys from 19 children who underwent surgery release of ureteropelvic junction obstruction (UPJO) in relation to renal function and degree of tubulointerstitial fibrosis. Renal biopsies were carried out at the time of surgery for obstruction release. Kidney tissue from children of similar age removed because of carcinoma was used as control. Expression of caveolin-1 at the protein level in renal tissue and urine was demonstrated in patients with technetium 99 m labeled diethylene triamine pentaacetate ((99)Tc DTPA) renal scan 28.8+/-2% and increased tubular interstitial fibrosis in seven patients at the time of obstruction release. Colocalization staining of AT(1) angiotensin II receptor with caveolin-1 in basolateral membrane of epithelial tubule cells, enhanced AT(1) messenger ribonucleic acid (mRNA) and decreased endothelial nitric oxide synthase (eNOS), were shown in these patients. In contrast, absence of association of caveolin-1 with AT(1) receptor expression in proximal and collecting tubule membranes with AT(1) receptor mRNA and eNOS mRNA expression near control were demonstrated in 12 patients, with (99)Tc DTPA renal scan 39.7+2.1% and no evidence of tubulointerstitial fibrosis. From our results, the role of caveolin-1 as a factor contributing to the severity of the tubulointerstitial process resulting from obstructive nephropathy could be suggested.

  8. 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.

  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. 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.

  11. 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.

  12. 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.

  13. The diagnosis of periprosthetic infection.

    PubMed

    Del Arco, Alfonso; Bertrand, María Luisa

    2013-01-01

    Periprosthetic infection (PJI) is the most serious joint replacement complication, occurring in 0.8-1.9% of knee arthroplasties and 0.3-1.7% of hip arthroplasties. A definition of PJI was proposed in the November 2011 issue of the journal Clinical Orthopedics and Related Research. The presence of a fistula or of local inflammatory signs is indicative of PJI, but in many cases local pain is the only symptom. In the absence of underlying inflammatory conditions, C-reactive protein measurement is the most useful preoperative blood test for detecting infection associated with a prosthetic joint. The most useful preoperative diagnostic test is the aspiration of synovial joint fluid to obtain a total and differential cell count and culture. Intraoperative frozen sections of periprosthetic tissues produce excellent accuracy in predicting a diagnosis of PJI but only moderate accuracy in ruling out the diagnosis. In this process, obtaining a quality sample is the first step, and determines the quality of microbiological results. Specimens for culture should be obtained prior to the initiation of antibiotic treatment. Sonication of a removed implant may increase the culture yield. Plain radiography has low sensitivity and low specificity for detecting infection associated with a prosthetic joint. Computed tomography and magnetic resonance imaging may be useful in the evaluation of complex cases, but metal inserts interfere with these tests, and abnormalities may be non-specific. Labelled-leucocyte imaging (e.g., leucocytes labelled with indium-111) combined with bone marrow imaging with the use of technetium-99m-labelled sulphur colloid is considered the imaging test of choice when imaging is necessary.

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

    PubMed

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

    2010-01-21

    In this paper, we showed that Cerenkov radiation (CR) escaping from the surface of small living animals injected with (18)F-FDG can be detected with optical imaging techniques. (18)F 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 (18)F-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 (18)F-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 beta(+) but also to pure beta(-) emitters.

  15. (Development of gamma emitting, receptor-binding, radiotracers for imaging the brain and pancreas)

    SciTech Connect

    Not Available

    1989-01-01

    This progress report covers the period from March 1, 1987 to Feb. 28, 1988. In studies to better understand the nature of the m-AChR receptor subtypes, we have generated a manuscript which has been submitted for publication in Life sciences entitled: The effect of chronic atropine and diisopropylfluorophosphate on rat brain muscarinic acetylcholine receptor subtype concentrations. We have also developed a more direct synthesis of 3-quinuclidinyl 4-iodobenzilate and its analogues. During this contract period, we have been involved with the synthesis of analogues 3-quinuclidinyl benzilate (QNB). We have determined the affinity constants of various compounds synthesized this year for the muscarinic receptor from rat corpus striatum. We have continued our investigation of the m-AChR in pancreas. 25 refs., 3 figs., 5 tabs.

  16. Advances in the development of tau PET radiotracers and their clinical applications.

    PubMed

    Okamura, Nobuyuki; Harada, Ryuichi; Furukawa, Katsutoshi; Furumoto, Shozo; Tago, Tetsuro; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka

    2016-09-01

    Alzheimer's disease and other neurodegenerative dementias belong to the family of tauopathies. These diseases are characterized by the deposition of insoluble tau aggregates possessing an enriched β-sheet structure. In vivo imaging of the tau deposits by positron emission tomography (PET) will facilitate the early and accurate diagnosis of these diseases, tracking of disease progression, assessment of disease severity, and prediction of disease prognosis. Furthermore, this technology is expected to play a vital role in the monitoring of treatment outcomes and in the selection of patients for the therapeutic trials of anti-dementia drugs. Recently, several tau PET tracers have been successfully developed and demonstrated as having high binding affinity and selectivity to tau protein deposits. Recent clinical studies using these tracers have demonstrated significant tracer retention in sites susceptible to tau deposition in Alzheimer's disease, as well as correlations with the disease severity and cognitive impairment in cases with dementia. These tracers, thus, have the potential to effectively diagnose the tauopathies. Further longitudinal assessment will clarify the effect of the tau deposition on the neurodegenerative process and cognitive decline and the interaction of tau with amyloid-β in the human brain.

  17. 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.

  18. 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.

  19. 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.

  20. 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)

  1. 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.

  2. 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.

  3. 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

  4. Enantiopure bifunctional chelators for copper radiopharmaceuticals--does chirality matter in radiotracer design?

    PubMed

    Singh, Ajay N; Dakanali, Marianna; Hao, Guiyang; Ramezani, Saleh; Kumar, Amit; Sun, Xiankai

    2014-06-10

    It is well recognized that carbon chirality plays a critical role in the design of drug molecules. However, very little information is available regarding the effect of stereoisomerism of macrocyclic bifunctional chelators (BFC) on biological behaviors of the corresponding radiopharmaceuticals. To evaluate such effects, three enantiopure stereoisomers of a copper radiopharmaceutical BFC bearing two chiral carbon atoms were synthesized in forms of R,R-, S,S-, and R,S-. Their corresponding peptide conjugates were prepared by coupling with a model peptide sequence, c(RGDyK), which targets the αvβ3 integrin for in vitro and in vivo evaluation of their biological behaviors as compared to the racemic conjugate. Despite the chirality differences, all the conjugates showed a similar in vitro binding affinity profile to the αvβ3 integrin (106, 108, 85 and 100 nM for rac-H2-1, RR-H2-1, SS-H2-1, and RS-H2-1 respectively with all p values > 0.05) and a similar level of in vivo tumor uptake (2.72 ± 0.45, 2.60 ± 0.52, 2.45 ± 0.48 and 2.88 ± 0.59 for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 at 1 h p.i. respectively). Furthermore, they demonstrated a nearly identical biodistribution pattern in major organs (e.g. 2.07 ± 0.21, 2.13 ± 0.58, 1.70 ± 0.20 and 1.90 ± 0.46 %ID/g at 24 h p.i. in liver for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively; 1.80 ± 0.46, 2.30 ± 1.49, 1.73 ± 0.31 and 2.23 ± 0.71 at 24 h p.i. in kidneys for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively). Therefore we conclude that the chirality of BFC plays a negligible role in αvβ3-targeted copper radiopharmaceuticals. However, we believe it is still worthwhile to consider the chirality effects of BFCs on other targeted imaging or therapeutic agents.

  5. 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.

  6. 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

  7. 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

  8. Gluconeogenesis in the ruminant fetus: evaluation of conflicting evidence from radiotracer and other experimental techniques

    SciTech Connect

    Prior, R.L.

    1982-01-01

    Conflicting evidence exists as to whether the gluconeogenetic process is active in the late gestation fetal lamb. In vitro evidence based on measurements of enzyme activity and substrate flux into glucose indicates that the capacity for gluconeogenesis exists in fetal liver. The in vivo conversion of (/sup 14/C)lactate and (/sup 14/C)alanine into glucose in the lamb fetus has been demonstrated. Lactate and alanine account for 49 and 2.3% of the fetal glucose pool, respectively. Although gluconeogenesis can occur in the fetal lamb, alterations in net rates of umbilical uptake of glucose or lactate, fetal blood glucose concentrations, fetal or maternal glucose replacement rates, or maternal nutrition may alter the observed rates of fetal gluconeogenesis.

  9. 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

  10. Gallium(III) complexes of NOTA-bis (phosphonate) conjugates as PET radiotracers for bone imaging.

    PubMed

    Holub, Jan; Meckel, Marian; Kubíček, Vojtěch; Rösch, Frank; Hermann, Petr

    2015-01-01

    Ligands with geminal bis(phosphonic acid) appended to 1,4,7-triazacyclonone-1,4-diacetic acid fragment through acetamide (NOTAM(BP) ) or methylenephosphinate (NO2AP(BP) ) spacers designed for (68) Ga were prepared. Ga(III) complexation is much faster for ligand with methylenephosphinate spacer than that with acetamide one, in both chemical (high reactant concentrations) and radiolabeling studies with no-carrier-added (68) Ga. For both ligands, formation of Ga(III) complex was slower than that with NOTA owing to the strong out-of-cage binding of bis(phosphonate) group. Radiolabeling was efficient and fast only above 60 °C and in a narrow acidity region (pH ~3). At higher temperature, hydrolysis of amide bond of the carboxamide-bis(phosphonate) conjugate was observed during complexation reaction leading to Ga-NOTA complex. In vitro sorption studies confirmed effective binding of the (68) Ga complexes to hydroxyapatite being comparable with that found for common bis(phosphonate) drugs such as pamindronate. Selective bone uptake was confirmed in healthy rats by biodistribution studies ex vivo and by positron emission tomography imaging in vivo. Bone uptake was very high, with SUV (standardized uptake value) of 6.19 ± 1.27 for [(68) Ga]NO2AP(BP) ) at 60 min p.i., which is superior to uptake of (68) Ga-DOTA-based bis(phosphonates) and [(18) F]NaF reported earlier (SUV of 4.63 ± 0.38 and SUV of 4.87 ± 0.32 for [(68) Ga]DO3AP(BP) and [(18) F]NaF, respectively, at 60 min p.i.). Coincidently, accumulation in soft tissue is generally low (e.g. for kidneys SUV of 0.26 ± 0.09 for [(68) Ga]NO2AP(BP) at 60 min p.i.), revealing the new (68) Ga complexes as ideal tracers for noninvasive, fast and quantitative imaging of calcified tissue and for metastatic lesions using PET or PET/CT.

  11. Validation of methodology for determination of the mercury methylation potential in sediments using radiotracers.

    PubMed

    Zizek, Suzana; Ribeiro Guevara, Sergio; Horvat, Milena

    2008-04-01

    Experiments to determine the mercury methylation potential were performed on sediments from two locations on the river Idrijca (Slovenia), differing in ambient mercury concentrations. The tracer used was the radioactive isotope (197)Hg. The benefit of using this tracer is its high specific activity, which enables spikes as low as 0.02 ng Hg(2+) g(-1) of sample to be used. It was therefore possible to compare the efficiency of the methylation potential experiments over a range of spike concentrations from picogram to microgram levels. The first part of the work aimed to validate the experimental blanks and the second part consisted of several series of incubation experiments on two different river sediments using a range of tracer additions. The results showed high variability in the obtained methylation potentials. Increasing Hg(2+) additions gave a decrease in the percentage of the tracer methylated during incubation; in absolute terms, the spikes that spanned four orders of magnitude (0.019-190 pg g(-1) of sediment slurry) resulted in MeHg formation between 0.01 and 0.1 ng MeHg g(-1) in Podroteja and Kozarska Grapa. Higher spikes resulted in slightly elevated MeHg production (up to a maximum of 0.27 ng g(-1)). The values of methylation potential were similar in both sediments. The results imply that the experimental determination of mercury methylation potential strongly depends on the experimental setup itself and the amount of tracer added to the system under study. It is therefore recommended to use different concentrations of tracer and perform the experiments in several replicates. The amount of mercury available for methylation in nature is usually very small. Therefore, adding very low amounts of tracer in the methylation potential studies probably gives results that have a higher environmental relevance. It is also suggested to express the results obtained in absolute amounts of MeHg produced and not just as the percentage of the added tracer.

  12. 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.

  13. 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/.

  14. Development of a PET Radiotracer for Noninvasive Imaging of the Reactive Oxygen Species, Superoxide, in vivo

    PubMed Central

    Chu, Wenhua; Chepetan, Andre; Zhou, Dong; Shoghi, Kooresh I.; Xu, Jinbin; Dugan, Laura L.; Gropler, Robert J.; Mintun, Mark A.; Mach, Robert H.

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide range of human disease states and drug toxicities, but development of imaging tools to study ROS biology in vivo remains a challenge. Here we synthesized and validated a novel PET tracer (12) and its 18F radiolabeled version [18F]12 to allow PET (positron emission tomography) imaging of superoxide in vivo. Initial analysis of ROS reaction kinetics found that compound 12 was rapidly and selectively oxidized by superoxide, but not other ROS. Cell culture studies in EMT6 cells exposed to the cancer chemotherapeutic agent Doxorubicin (DOX), which activates the superoxide-generating enzyme, NADPH oxidase, showed that compound 12 was a sensitive and specific probe for superoxide in cells. The microPET imaging of heart in mice with DOX-induced cardiac inflammation observed 2-fold greater oxidation of [18F]12 in the DOX-treated mice compared to controls (p=0.02), the results were confirmed by distribution studies on organs subsequently removed from the mice and HPLC analysis of [18F] radioactivity compounds. These data indicate that compound 12 is a useful PET tracer to imaging ROS in vivo. PMID:24847866

  15. 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

  16. Normal Solid Gastric Emptying Values Measured by Scintigraphy Using Asian-style Meal:A Multicenter Study in Healthy Volunteers

    PubMed Central

    Vasavid, Pataramon; Chaiwatanarat, Tawatchai; Pusuwan, Pawana; Sritara, Chanika; Roysri, Krisana; Namwongprom, Sirianong; Kuanrakcharoen, Pichit; Premprabha, Teerapon; Chunlertrith, Kitti; Thongsawat, Satawat; Sirinthornpunya, Siam; Ovartlarnporn, Bancha; Kachintorn, Udom; Leelakusolvong, Somchai; Kositchaiwat, Chomsri; Chakkaphak, Suriya; Gonlachanvit, Sutep

    2014-01-01

    Background/Aims To report gastric emptying scintigraphy, normal values should be established for a specific protocol. The aim of this study was to provide normal gastric emptying values and determine factors affecting gastric emptying using Asian rice-based meal in healthy volunteers. Methods One hundred and ninety-two healthy volunteers were included at 7 tertiary care centers across Thailand. Gastric emptying scintigraphy was acquired in 45 degree left anterior oblique view immediately after ingestion of a 267 kcal steamed-rice with technetium-99m labeled-microwaved egg meal with 100 mL water for up to 4 hours. Results One hundred and eighty-nine volunteers (99 females, age 43 ± 14 years) completed the study. The medians (5–95th percentiles) of lag time, gastric emptying half time (GE T1/2) and percent gastric retentions at 2 and 4 hours for all volunteers were 18.6 (0.5–39.1) minutes, 68.7 (45.1–107.8) minutes, 16.3% (2.7–49.8%) and 1.1% (0.2–8.8%), respectively. Female volunteers had significantly slower gastric emptying compared to male (GE T1/2, 74 [48–115] minutes vs. 63 (41–96) minutes; P < 0.05). Female volunteers who were in luteal phase of menstrual cycle had significantly slower gastric emptying compared to those in follicular phase or menopausal status (GE T1/2, 85 [66–102] mintes vs. 69 [50–120] minutes or 72 [47–109] minutes, P < 0.05). All of smoking volunteers were male. Smoker male volunteers had significantly faster gastric emptying compared to non-smoker males (GE T1/2, 56 [44–80] minutes vs. 67 [44–100] minutes, P < 0.05). Age, body mass index and alcohol consumption habits did not affect gastric emptying values. Conclusions A steamed-rice with microwaved egg meal was well tolerated by healthy volunteers. Gender, menstrual status and smoking status were found to affect solid gastric emptying. PMID:24948129

  17. Safety and Efficacy Assessment of Flow Redistribution by Occlusion of Intrahepatic Vessels Prior to Radioembolization in the Treatment of Liver Tumors

    SciTech Connect

    Bilbao, Jose I.; Garrastachu, Puy; Herraiz, Maria J.; Rodriguez, Macarena; Inarrairaegui, Mercedes; Rodriguez, Javier; Hernandez, Carmen; Cuesta, Antonio Martinez de la; Arbizu, Javier; Sangro, Bruno

    2010-06-15

    We evaluated the feasibility, safety, and efficacy of radioembolization (administered from one or two vascular points) after the redistribution of arterial blood flow in the liver in patients with hepatic neoplasms and arterial anatomic peculiarities (AAP). Twenty-four patients with liver neoplasms and AAP (graded according to Michel's classification) were included in the study. During pretreatment angiographic planning, all extrahepatic vessels that could feed the tumor were embolized and the intrahepatic vessels occluded in order to redistribute blood flow. The distribution of microspheres was initially assessed by using technetium-99m-labeled macroaggregated albumin ({sup 99m}Tc-MAA) from one of two vascular points before the administration of yttrium-90 ({sup 90}Y)-radiolabeled resin microspheres. Perfusion of lesions situated in the redistributed segments (L-RS) and nonredistributed segments (L-NRS) were compared by assessing the distribution of {sup 99m}Tc-MAA by SPECT/CT. Perfusion was graded as normal, reduced, or absent. {sup 90}Y resin microspheres were then injected from the same arterial sites as {sup 99m}Tc-MAA and the tumor response recorded 3 months later. The tumor response in L-RS was compared with that in L-NRS and graded as better, similar, or worse. Among 11 patients with type I AAP in whom mainly vessels in segments I-III or IV were occluded, perfusion of L-RS was graded as similar (n = 7) or reduced (n = 4). Among the remaining 13 patients with AAP types III (n = 3), V (n = 4), VIII (n = 3), and others (n = 3) in which aberrant arteries were occluded, perfusion of L-RS was graded as similar (n = 9), reduced (n = 3), or absent (n = 1). Overall, {sup 99m}Tc-MAA was present in the L-RS of 95.8% patients and the distribution of {sup 99m}Tc-MAA in L-RS and L-NRS were graded as similar in 66.6% of patients. Compared with lesions in the L-NRS, tumor response in L-RS was similar in 23 cases and worse in 1 case. No complications were recorded after the

  18. Lung Dose Calculation With SPECT/CT for {sup 90}Yittrium Radioembolization of Liver Cancer

    SciTech Connect

    Yu, Naichang; Srinivas, Shaym M.; DiFilippo, Frank P.; Shrikanthan, Sankaran; Levitin, Abraham; McLennan, Gordon; Spain, James; Xia, Ping; Wilkinson, Allan

    2013-03-01

    Purpose: To propose a new method to estimate lung mean dose (LMD) using technetium-99m labeled macroaggregated albumin ({sup 99m}Tc-MAA) single photon emission CT (SPECT)/CT for {sup 90}Yttrium radioembolization of liver tumors and to compare the LMD estimated using SPECT/CT with clinical estimates of LMD using planar gamma scintigraphy (PS). Methods and Materials: Images of 71 patients who had SPECT/CT and PS images of {sup 99m}Tc-MAA acquired before TheraSphere radioembolization of liver cancer were analyzed retrospectively. LMD was calculated from the PS-based lung shunt assuming a lung mass of 1 kg and 50 Gy per GBq of injected activity shunted to the lung. For the SPECT/CT-based estimate, the LMD was calculated with the activity concentration and lung volume derived from SPECT/CT. The effect of attenuation correction and the patient's breathing on the calculated LMD was studied with the SPECT/CT. With these effects correctly taken into account in a more rigorous fashion, we compared the LMD calculated with SPECT/CT with the LMD calculated with PS. Results: The mean dose to the central region of the lung leads to a more accurate estimate of LMD. Inclusion of the lung region around the diaphragm in the calculation leads to an overestimate of LMD due to the misregistration of the liver activity to the lung from the patient's breathing. LMD calculated based on PS is a poor predictor of the actual LMD. For the subpopulation with large lung shunt, the mean overestimation from the PS method for the lung shunt was 170%. Conclusions: A new method of calculating the LMD for TheraSphere and SIR-Spheres radioembolization of liver cancer based on {sup 99m}Tc-MAA SPECT/CT is presented. The new method provides a more accurate estimate of radiation risk to the lungs. For patients with a large lung shunt calculated from PS, a recalculation of LMD based on SPECT/CT is recommended.

  19. Spontaneous periodic hypothermia.

    PubMed

    Kloos, R T

    1995-09-01

    Spontaneous periodic hypothermia is a rare syndrome of recurrent, centrally mediated hypothermia without an identifiable systemic cause or brain lesion. Most patients defend a temporarily lowered temperature "set point" during episodes of hypothermia, despite manifesting many well-known systemic consequences of core temperature hypothermia. No case of death directly attributable to an episode of spontaneous periodic hypothermia has been reported, although many of the serious systemic effects of hypothermia have been documented in these cases, so it is not unlikely that death may occur. The syndrome's cause, and that of Shapiro syndrome, remains unknown. Pharmacologic trials to date have been only modestly successful. Anticonvulsant agents, clonidine, and cyproheptadine appear the most likely to succeed, with cyproheptadine being a reasonable first choice. Given that the term "spontaneous periodic hypothermia" describes a syndrome, and not a pathophysiologic mechanism, it is likely to encompass a common eventuality, arrived at via several different pathways. One can postulate mechanisms such as structural abnormalities, trauma, infection, irritation, and degeneration involving strategic locations which create a focus for epileptic or other periodic dysfunction whose scope involves the centers for thermoregulation. The existence of 2 distinct, oppositional thermoregulatory centers would allow for speculation of similar mechanisms accounting for cases of both periodic hypo- and hyperthermia (61). Postmortem data regarding the hypothalamic and surrounding areas from future cases of Shapiro syndrome and spontaneous periodic hypothermia would be of great interest. Further, more sensitive in vivo testing methods are clearly needed. The role of PET or single photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) performed acutely during an episode remains to be characterized (64, 103, 105). The term

  20. [¹¹C]Phosgene: a versatile reagent for radioactive carbonyl insertion into medicinal radiotracers for positron emission tomography.

    PubMed

    Roeda, Dirk; Dollé, Frédéric

    2010-01-01

    [¹¹C]Phosgene has been playing a relatively modest but continuous and manifest role all along the history of radiochemistry for Positron Emission Tomography. It acts as a radiolabelling agent through carbonyl insertion, usually between heteroatoms, and benefits from a high chemical reactivity allowing for short reaction times. The aim of this review is to give an overview of this radiochemistry from its beginning until the present day. After drawing up the inventory of the various ways of its production, the reactions in which it has been employed and the labelled products that have been synthesised with it are catalogued. This comprises the reactions of [¹¹C]phosgene with primary, secondary and tertiary amines to labelled isocyanates and carbamoyl chlorides, which serve as intermediates for symmetrical and unsymmetrical [¹¹C]ureas and [¹¹C]carbamates, reactions with alcohols leading to labelled carbamates and carbonates via [¹¹C]chloroformates, cyclisation reactions to heterocycles and the radiochemistry of the secondary radiolabelling agents [¹¹C]urea and diethyl- or dimethyl [¹¹C]carbonate. Apart from this already vast field of chemical possibilities there should be room for extension of the use of [¹¹C]phosgene to other chemistry, notably that of C-¹¹C bond formation. PMID:20583989

  1. Studies on In-situ Chelation/Supercritical Fluid Extraction of Lanthanides and Actinides Using a Radiotracer Technique

    SciTech Connect

    Lin, Yuehe; Wu, Hong; Smart, Neil G.; Wai, Chien M.

    2001-06-01

    Radioisotope tracer techniques were used to study the process of in-situ chelation/supercritical fluid extraction(SFE) of La3+ and Lu3+ from solid matrix using mixed ligand hexafluoroacetylacetone (HFA) and tributylphosphate (TBP) as chelating agents. A lab-built SFE extactor was used in this study and the extractor design was optimized based on the experimental results. Quantitative recovery of La and Lu was achieved when the extrator design was optimized. Extraction of uranium from real world samples was also investigated to demonstrate the capability of this chelation/SFE technology for environmental remediation applications. A novel on-line back extraction technique for the recovery of metal ions and regeneration of ligands is also reported.

  2. The western Mediterranean basin as an aged aerosols reservoir. Insights from an old-fashioned but efficient radiotracer

    NASA Astrophysics Data System (ADS)

    Brattich, E.; Hernández-Ceballos, M. A.; Orza, J. A. G.; Bolívar, J. P.; Tositti, L.

    2016-09-01

    The long-term contemporary 210Pb time series acquired during the period 2004-2011 at two distant sites of different altitude in the Mediterranean basin, El Arenosillo (40 m a.s.l. in southwestern Spain) and Mt. Cimone (2165 m a.s.l. in northern Italy), are analyzed and compared. Besides being considered a tracer of continental air masses, 210Pb radionuclide is also a proxy of fine stable aerosol. For this reason, the measurements of PM10 mass concentrations collected at the same time and the corresponding 210Pb/PM10 ratio at the two sites are considered to gain better insights into the origin and size of the particles. Three statistical trajectory methods are applied to identify and characterize the 210Pb source regions at the two sites. The three methods yield similar outcomes in the source identification, which strengthens the robustness of our results. In addition to the importance of the transport from areas of continental Europe, this study highlights the relevant role of the Mediterranean Sea as a major 210Pb reservoir layer associated to the aged air masses that accumulate in the western Mediterranean basin. The analysis of the sources points out the significant influence of northern Africa to 210Pb increases at both sites as well, even though the most intensive episodes are not of Saharan origin.

  3. Bioconcentration of the anionic surfactant linear alkylbenzene sulfonate (LAS) in the marine shrimp Palaemonetes varians: a radiotracer study.

    PubMed

    Renaud, Florent; Warnau, Michel; Oberhänsli, François; Teyssié, Jean-Louis; Temara, Ali; Rouleau, Claude; Metian, Marc

    2014-08-15

    Uptake and depuration kinetics of dissolved [(14)C]C₁₂-6-linear alkylbenzene sulfonate (LAS) were determined in the shrimp Palaemonetes varians using environmentally relevant exposure concentration. The shrimp concentrated LAS from seawater with a mean BCF value of 120 L kg(-1) after a 7-day exposure. Uptake biokinetics were best described by a saturation model, with an estimated BCFss, of 159 ± 34 L kg(-1), reached after 11.5 days. Shrimp weight influenced significantly BCF value with smaller individuals presenting higher affinity to LAS. To the light of a whole body autoradiography, major accumulation of LAS occurred in the cephalothorax circulatory system (gills, heart, hepatopancreas) and ocular peduncle, but not in the flesh, limiting potential transfer to human consumers. LAS depuration rate constant value of the shrimp was 1.18 ± 0.08 d(-1) leading to less than 1% of remaining LAS in its tissues after 8 days of depuration.

  4. 99mTc-low density lipoprotein: intracellularly trapped radiotracer for noninvasive imaging of low density lipoprotein metabolism in vivo.

    PubMed

    Vallabhajosula, S; Goldsmith, S J

    1990-01-01

    Low density lipoprotein (LDL) is the major transport protein for endogenous cholesterol in human plasma. LDL can be radiolabeled with 99mTc using sodium dithionite as a reducing agent. Biodistribution studies of 99mTc-LDL in normal rabbits confirm that 99mTc-LDL acts as an intracellularly "trapped ligand" similar to radioiodinated tyramine cellobiose-LDL (the previously validated trapped radioligand). In addition, studies performed in hypercholesterolemic rabbit models demonstrated the feasibility of imaging hepatic LDL-receptor concentration noninvasively. 99mTc-LDL imaging studies in a number of hypercholesterolemic and hypocholesterolemic patients have proven useful in understanding the abnormal uptake and metabolism of LDL. In patients with hypercholesterolemia (HC), 99mTc-LDL appears to be taken up well by the actively evolving atherosclerotic lesions and xanthomata that contained foam cells and macrophages. In patients with myeloproliferative disease and chronic hypocholesterolemia, 99mTc-LDL images showed intense accumulation of radioactivity in the spleen and bone marrow; this demonstrated extensive proliferation of the macrophage population suggesting that hypocholesterolemia in these patients may be due to increased uptake of LDL uptake by the macrophages. 99mTc-LDL is a powerful tool for the noninvasive exploration of a variety of disorders of lipoprotein metabolism in patients.

  5. Atmospheric flux, transport and mass balance of (210)Pb and (137)Cs radiotracers in different regions of Romania.

    PubMed

    Begy, R Cs; Kovacs, T; Veres, D; Simon, H

    2016-05-01

    This study focuses on the determination of (210)Pb and (137)Cs fluxes from different areas in Transylvania, Romania and on the determination of transport and mass balance within the lacustrine system of Red Lake. In order to achieve this, samples were taken from six different locations (Bihor County area, Ighiel area, Red Lake area, Mluha Peatbog, Mohos Peatbog and Zanoaga Rosie Peat bog in the Semenic Mountains) throughout Romania, these being compared to the values of the Danube Delta area. The activity concentrations of the soil samples were measured by gamma spectrometry (HPGe detector) for both (210)Pbtotal, (210)Pbsup ((226)Ra) and (137)Cs, while peat samples were measured by both alpha ((210)Po) spectrometry (PIPS detectors) as well. The mean value for the (210)Pb flux was measured in the Danube Delta region (42±8Bqm(-2) yr(-1)), while the highest was measured in the Semenic Peatbog (227±54Bqm(-2) yr(-1)); the average being 132±8Bqm(-2) yr(-1). In case of (137)Cs the mean was 298±3Bqm(-2) yr(-1), maximum being 1683±15Bqm(-2) yr(-1) in case of Ighiel area and minimum being 32±1Bqm(-2) yr(-1) in the Danube Delta region. In case of the Red Lake, from the total inventory of 410±23Bqm(-2) yr(-1) in the sediments, the loss by outflows is 100±12Bqm(-2) yr(-1), the catchment to lake transfer factor being 0.84%. PMID:26922393

  6. [Mean elimination time of the impulse radiotracer (131I-hippurate) as a marker of renal function].

    PubMed

    Kowalczyk, M

    1990-01-01

    A possibility of assessment of renal excretory function using mean time of the impulse tracer (131I-hippurate) dose elimination has been shown on the basis of theoretical analysis of hippurate kinetics. Such an index was calculated during classic hippurate renography from time/activity curve over precordium. Other traces and different regions of monitoring might also be employed. The mean time of tracer elimination obtained in this manner only indirectly reflects the hippurate clearance, yet can be easily achieved. Moreover, this entity is not influenced by errors related to quantitative measurements of radioactivity and to hypothetical assumptions, which are common for more sophisticated isotope clearance methods. The enlisted characteristics seem to predispose the proposed method of renal function evaluation for application in screening isotope tests. PMID:2135901

  7. Muonium--the second radioisotope of hydrogen: a remarkable and unique radiotracer in the chemical, materials, biological and environmental sciences.

    PubMed

    Rhodes, Christopher J

    2012-01-01

    Muonium (Mu), may be regarded as a radioactive hydrogen atom with a positive muon as its nucleus, and is formed in a range of media which are irradiated with positive muons. This exotic atom can be considered as a second radioisotope of hydrogen, along with tritium. Addition of this light atom (with a mass 1/9th that of a normal hydrogen, protium, atom) to unsaturated organic molecules forms free radicals, in which the muon serves as a radioactive and magnetic probe of their kinetic and structural properties. Suitable examples are chosen to illustrate the very large functionality of organic radicals which have been measured using muons and various methods of muSR, where mu stands for muon, S for spin and R may refer to rotation, resonance or relaxation. The principal techniques illustrated are transverse-field muon spin rotation (TF-muSR), avoided level crossing muon spin resonance (ALC-muSR) and longitudinal-field muon spin relaxation (LF-muSRx). Structural studies of radicals, the determination of mechanisms for radical formation, the measurement of radical stabilisation energies, the determination of the kinetics of reactions of free muonium atoms and of free radicals have all been accomplished using TF-muSR methods. It is further shown that TF-muSR is most useful in measuring radical reaction rates in non-aqueous media, to provide information of relevance to cell membrane damage and repair Muonium may further be used as a mechanistic probe since it determines a true pattern of H-atom reactivity in molecules, against which results from similar radiolysed materials may be compared. [In many solid materials that are exposed to ionising radiation, apparent H-atom adduct radicals are detected but which originate from charge-neutralisation of positive holes (radical cations) and ejected electrons, without free H-atoms being formed. DNA is the superlative example of this. Free H-atoms normally feature in the province of radiolysed aqueous media]. The applications of ALC-muSR and LF-muSRx in studying the reorientation of reactive radicals on reactive surfaces forms the substantive proportion of the review: considered specifically are radicals sorbed in zeolites, in clays and in porous silica, in porous carbons and on ice-surfaces, in connection with their role as intermediates in catalytic systems, particularly hydrocarbon cracking and oxidation processes, and in atmospheric aerosol chemistry. The formation of muonium and other muon species in cation-exchanged zeolite-X samples are also considered, according to the evidence of longitudinal field repolarisation measurements. Finally, mention is given of the use of muSR techniques for studying radicals in the gas-phase.

  8. An Improved Antagonist Radiotracer for the Kappa Opioid Receptor: Synthesis and Characterization of 11C-LY2459989

    PubMed Central

    Zheng, Ming-Qiang; Kim, Su Jin; Holden, Daniel; Lin, Shu-fei; Need, Anne; Rash, Karen; Barth, Vanessa; Mitch, Charles; Navarro, Antonio; Kapinos, Michael; Maloney, Kathleen; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun

    2016-01-01

    The kappa opioid receptors (KOR) are implicated in a number of neuropsychiatric diseases and addictive disorders. Positron Emission Tomography (PET) with radioligands provides a means to image the KOR in vivo and investigate its function in health and disease. The purpose of this study was to develop the selective KOR antagonist 11C-LY2459989 as a PET radioligand and characterize its imaging performance in non-human primates. Methods LY2459989 was synthesized and assayed for in vitro binding to opioid receptors. Ex vivo studies in rodents were conducted to assess its potential as a tracer candidate. 11C-LY2459989 was synthesized by reaction of its iodophenyl precursor with 11C-cyanide followed by partial hydrolysis of the resulting 11C-cyanophenyl intermediate. Imaging experiments with 11C-LY2459989 were carried out in rhesus monkeys with arterial input function measurement. Imaging data were analyzed with kinetic models to derive in vivo binding parameters. Results LY2459989 is a full antagonist with high binding affinity and selectivity for KOR (Ki = 0.18, 7.68, and 91.3 nM, respectively, for κ, μ, and δ receptors). Ex vivo studies in rats indicated LY2459989 as an appropriate tracer candidate with high specific binding signals, and confirmed its KOR binding selectivity in vivo. 11C-LY2459989 was synthesized in high radiochemical purity and good specific activity. In rhesus monkeys, 11C-LY2459989 displayed a fast rate of peripheral metabolism. Similarly, 11C-LY2459989 displayed fast uptake kinetics in the brain and an uptake pattern consistent with the distribution of KOR in primates. Pretreatment with naloxone (1 mg/kg, i.v.) resulted in a uniform distribution of radioactivity in the brain. Further, specific binding of 11C-LY2459989 was dose-dependently reduced by the selective KOR antagonist LY2456302 and the unlabeled LY2459989. Regional binding potential (BPND) values derived from the multilinear analysis method (MA1), as a measure of in vivo specific binding signal, were 2.18, 1.39, 1.08, 1.04, 1.03, 0.59, 0.51, 0.50, respectively, for the globus pallidus, cingulate cortex, insula, caudate, putamen, frontal cortex, temporal cortex, and thalamus. Conclusion The novel PET radioligand 11C-LY2459989 displayed favorable pharmacokinetic properties, specific and KOR-selective binding profile, and high specific binding signals in vivo, thus making it a promising PET imaging agent for KOR. PMID:24854795

  9. Enhanced copper-mediated (18)F-fluorination of aryl boronic esters provides eight radiotracers for PET applications.

    PubMed

    Preshlock, Sean; Calderwood, Samuel; Verhoog, Stefan; Tredwell, Matthew; Huiban, Mickael; Hienzsch, Antje; Gruber, Stefan; Wilson, Thomas C; Taylor, Nicholas J; Cailly, Thomas; Schedler, Michael; Collier, Thomas Lee; Passchier, Jan; Smits, René; Mollitor, Jan; Hoepping, Alexander; Mueller, Marco; Genicot, Christophe; Mercier, Joël; Gouverneur, Véronique

    2016-06-28

    [(18)F]FMTEB, [(18)F]FPEB, [(18)F]flumazenil, [(18)F]DAA1106, [(18)F]MFBG, [(18)F]FDOPA, [(18)F]FMT and [(18)F]FDA are prepared from the corresponding arylboronic esters and [(18)F]KF/K222 in the presence of Cu(OTf)2py4. The method was successfully applied using three radiosynthetic platforms, and up to 26 GBq of non-carrier added starting activity of (18)F-fluoride.

  10. 18F-FP-PEG2-β-Glu-RGD2: A Symmetric Integrin αvβ3-Targeting Radiotracer for Tumor PET Imaging

    PubMed Central

    Tang, Ganghua; Yao, Shaobo; Yao, Baoguo; Wang, Hongliang; Nie, Dahong; Liang, Xiang; Tang, Caihua; He, Shanzhen

    2015-01-01

    Radiolabeled cyclic arginine-glycine-aspartic (RGD) peptides can be used for noninvasive determination of integrin αvβ3 expression in tumors. In this study, we performed radiosynthesis and biological evaluation of a new 18F-labeled RGD homodimeric peptide with one 8-amino-3,6-dioxaoctanoic acid (PEG2) linker on the glutamate β-amino group (18F-FP-PEG2-β-Glu-RGD2) as a symmetric PET tracer for tumor imaging. Biodistribution studies showed that radioactivity of 18F-FP-PEG2-β-Glu-RGD2 was rapidly cleared from blood by predominately renal excretion. MicroPET-CT imaging with 18F-FP-PEG2-β-Glu-RGD2 revealed high tumor contrast and low background in A549 human lung adenocarcinoma-bearing mouse models, PC-3 prostate cancer-bearing mouse models, and orthotopic transplanted C6 brain glioma models. 18F-FP-PEG2-β-Glu-RGD2 exhibited good stability in vitro and in vivo. The results suggest that this tracer is a potential PET tracer for tumor imaging. PMID:26397833

  11. Rapid radiotracer washout from the heart: effect on image quality in SPECT performed with a single-headed gamma camera system.

    PubMed

    O'Connor, M K; Cho, D S

    1992-06-01

    Technetium-99m-teboroxime demonstrates high extraction and rapid washout from the myocardium. To evaluate the feasibility of performing SPECT with this agent using a single-headed gamma camera system, a series of phantom studies were performed that simulated varying degrees of washout from normal and "ischemic" regions of the myocardium. In the absence of ischemic regions, short axis profiles were relatively unaffected by washout of less than 50% of activity over the duration of a SPECT acquisition. However, significant corruption of the SPECT data was observed when large (greater than a factor of 2) differences existed in the washout of activity from normal and "ischemic" myocardium. This corruption was observed with 30%-40% washout of activity from normal regions of the heart. Based on published washout rates, these results indicate that clinical studies with 99mTc-teboroxime may need to be completed within 2-4 min to order to prevent degradation of image quality due to differential washout effects.

  12. 21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography

    SciTech Connect

    Pomper, M.G.; Katzenellenbogen, J.A.; Welch, M.J.; Brodack, J.W.; Mathias, C.J.

    1988-07-01

    We have synthesized 21-(/sup 18/F)fluoro-16 alpha-ethyl-19-norprogesterone (FENP), a high affinity ligand for the progesterone receptor, labeled with the positron-emitting radionuclide fluorine-18 (t1/2 = 110 min). The synthesis proceeds in two steps from 21-hydroxy-16 alpha-ethyl-19-norprogesterone and involves (/sup 18/F)fluoride ion displacement of the 21-trifluoromethanesulfonate (21-triflate). This material is purified by HPLC and is obtained in 4-30% overall yield (decay corrected) within 40 min after the end of bombardment to produce (/sup 18/F)fluoride ion. The effective specific activity, determined by competitive radioreceptor binding assays, is 700-1400 Ci/mmol. In vivo, (/sup 18/F)FENP demonstrates highly selective, receptor-mediated uptake by the uterus of estrogen-primed rats; the uterus to blood and uterus to muscle ratios were respectively 26 and 16 at 1 h and 71 and 41 at 3 h after injection. The high target tissue selectivity of this uptake suggests that this compound may be useful for the in vivo imaging of progestin target tissues and receptor-rich tumors (such as human breast tumors) by positron emission tomography.

  13. Investigations of (99m)Tc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism.

    PubMed

    Meng, Lanfang; Xiu, Yan; Li, Yanli; Xu, Xiaobo; Li, Shanqun; Li, Xiao; Pak, Koon Y; Shi, Hongcheng; Cheng, Dengfeng

    2015-07-01

    This study attempted to evaluate the feasibility of (99m)Tc-labeled glucarate ((99m)Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of (99m)Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of (99m)Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in (99m)Tc-GLA uptake by H292 and H1975 cells when fructose was added. The (99m)Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. (99m)Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of (99m)Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that (99m)Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation. PMID:25890861

  14. Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations

    SciTech Connect

    Vallabhajosula, S.; Paidi, M.; Badimon, J.J.; Le, N.A.; Goldsmith, S.J.; Fuster, V.; Ginsberg, H.N.

    1988-07-01

    In an attempt to characterize the in vivo behavior of (99mTc) low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of (99mTc)LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these organs. In both normal and HC rabbits, less than 17% of 99mTc activity appeared in the 24-hr urine following injection of (99mTc)LDL, suggesting that in vivo, (99mTc)LDL is trapped and accumulated within the tissues. Direct comparison of (99mTc)LDL, 125I-native-LDL and (131I)tyramine cellobiose-LDL (the previously validated trapped radioligand) in normal rabbits, demonstrated that the biodistribution of (99mTc)LDL was similar to that of (131I)tyramine cellobiose-LDL. The adrenal glands, liver, and spleen accumulated significantly greater quantities of 99mTc and 131I activity per gram of tissue than 125I (from native-LDL). In addition, imaging studies in monkeys, showed that the hepatic uptake and retention of (99mTc) LDL was similar to that of (131I)tyramine cellobiose LDL. In contrast, radioiodine from native-LDL was deiodinated in liver with subsequent excretion into the intestine. These results suggest that (99mTc)LDL acts as a trapped ligand in vivo and should therefore, be a good tracer for noninvasive quantitative biodistribution studies of LDL.

  15. Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations.

    PubMed

    Vallabhajosula, S; Paidi, M; Badimon, J J; Le, N A; Goldsmith, S J; Fuster, V; Ginsberg, H N

    1988-07-01

    In an attempt to characterize the in vivo behavior of [99mTc] low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of [99mTc]LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these organs. In both normal and HC rabbits, less than 17% of 99mTc activity appeared in the 24-hr urine following injection of [99mTc]LDL, suggesting that in vivo, [99mTc]LDL is trapped and accumulated within the tissues. Direct comparison of [99mTc]LDL, 125I-native-LDL and [131I]tyramine cellobiose-LDL (the previously validated trapped radioligand) in normal rabbits, demonstrated that the biodistribution of [99mTc]LDL was similar to that of [131I]tyramine cellobiose-LDL. The adrenal glands, liver, and spleen accumulated significantly greater quantities of 99mTc and 131I activity per gram of tissue than 125I (from native-LDL). In addition, imaging studies in monkeys, showed that the hepatic uptake and retention of [99mTc] LDL was similar to that of [131I]tyramine cellobiose LDL. In contrast, radioiodine from native-LDL was deiodinated in liver with subsequent excretion into the intestine. These results suggest that [99mTc]LDL acts as a trapped ligand in vivo and should therefore, be a good tracer for noninvasive quantitative biodistribution studies of LDL.

  16. Quantification of regional ventilation in humans using a short-lived radiotracer--theoretical evaluation of the steady-state model

    SciTech Connect

    Valind, S.O.; Rhodes, C.G.; Jonson, B.

    1987-07-01

    The accuracy of the steady-state measurement of ventilation by means of a short-lived insoluble inert gas tracer rests with the validity of the steady-state flow equation. This has previously been applied to the qualitative assessment of regional ventilation using krypton-81m, but may potentially be used for the calculation of regional alveolar ventilation per unit alveolar gas volume--(VA/VA)cal--from measurements of the alveolar concentration of the tracer. The steady-state alveolar tracer concentration was calculated for the course of a breathing cycle, using a lung model featuring airways dead space and tidal gas flow. The calculations were made by computer simulations of a lung, characterized by predefined values of parameters describing the lung structure and the mode of ventilation. In the normal lung of supine man at rest (specific alveolar ventilation, ranging from 1.0 to 3.5 min-1) the errors of (VA/VA)cal relative to the predefined true values range from an overestimation by some 3% in the low ventilation regions to an underestimation by 8% in the best ventilated regions. The errors mainly result from ventilation of the airways dead space, which will influence the distribution of tracer in the lung by the transfer of tracer between regions by way of the common dead space and by the decay of tracer during its transport through the bronchial tree.

  17. Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor

    PubMed Central

    Bauer, Florian; Kuntner, Claudia; Bankstahl, Jens P.; Wanek, Thomas; Bankstahl, Marion; Stanek, Johann; Mairinger, Severin; Dörner, Bernd; Löscher, Wolfgang; Müller, Markus; Erker, Thomas; Langer, Oliver

    2013-01-01

    The aim of this study was to develop a positron emission tomography (PET) tracer based on the dual P-glycoprotein (P-gp) breast cancer resistance protein (BCRP) inhibitor tariquidar (1) to study the interaction of 1 with P-gp and BCRP in the blood-brain barrier (BBB) in vivo. O-desmethyl-1 was synthesized and reacted with [11C]methyl triflate to afford [11C]-1. Small-animal PET imaging of [11C]-1 was performed in naïve rats, before and after administration of unlabeled 1 (15 mg/kg, n=3) or the dual P-gp/BCRP inhibitor elacridar (5 mg/kg, n=2), as well as in wild-type, Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice (n=3). In vitro autoradiography was performed with [11C]-1 using brain sections of all 4 mouse types, with and without co-incubation with unlabeled 1 or elacridar (1 μM). In PET experiments in rats, administration of unlabeled 1 or elacridar increased brain activity uptake by a factor of 3-4, whereas blood activity levels remained unchanged. In Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice, brain-to-blood ratios of activity at 25 min after tracer injection were 3.4, 1.8 and 14.5 times higher, respectively, as compared to wild-type animals. Autoradiography showed approximately 50% less [11C]-1 binding in transporter knockout mice compared to wild-type mice and significant displacement by unlabeled elacridar in wild-type and Mdr1a/b(−/−) mouse brains. Our data suggest that [11C]-1 interacts specifically with P-gp and BCRP in the BBB. However, further investigations are needed to assess if [11C]-1 behaves in vivo as a transported or a non-transported inhibitor. PMID:20621487

  18. Synthesis, Radiolabeling, and Biological Evaluation of 5-Hydroxy-2-[(18)F]fluoroalkyl-tryptophan Analogues as Potential PET Radiotracers for Tumor Imaging.

    PubMed

    Chiotellis, Aristeidis; Müller Herde, Adrienne; Rössler, Simon L; Brekalo, Ante; Gedeonova, Erika; Mu, Linjing; Keller, Claudia; Schibli, Roger; Krämer, Stefanie D; Ametamey, Simon M

    2016-06-01

    Aiming at developing mechanism-based amino acid (18)F-PET tracers for tumor imaging, we synthesized two (18)F-labeled analogues of 5-hydroxy-l-[β-(11)C]tryptophan ([(11)C]5HTP) whose excellent in vivo performance in neuroendocrine tumors is mainly attributed to its decarboxylation by aromatic amino acid decarboxylase (AADC), an enzyme overexpressed in these malignancies. Reference compounds and precursors were synthesized following multistep synthetic approaches. Radiosynthesis of tracers was accomplished in good radiochemical yields (15-39%), high specific activities (45-95 GBq/μmol), and excellent radiochemical purities. In vitro cell uptake was sodium-independent and was inhibited ≥95% by 2-amino-2-norbornanecarboxylic acid (BCH) and ∼30% by arginine. PET imaging in mice revealed distinctly high tumor/background ratios for both tracers, outperforming the well-established O-(2-[(18)F]fluoroethyl)tyrosine ([(18)F]FET) tracer in a head-to-head comparison. Biological evaluation revealed that the in vivo performance is most probably independent of any interaction with AADC. Nevertheless, the excellent tumor visualization qualifies the new tracers as interesting probes for tumor imaging worthy for further investigation. PMID:27191773

  19. Kinetic modeling of 11C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans

    PubMed Central

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

    2014-01-01

    11C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of 11C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the best models to provide reliable measures of binding parameters. The rank order of 11C-LY2795050 distribution volume (VT) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for 11C-LY2795050. Three methods for calculation of the nondisplaceable distribution volume (VND) were assessed: (1) individual VND estimated from naltrexone occupancy plots, (2) mean VND across subjects, and (3) a fixed fraction of cerebellum VT. Approach (3) produced the lowest intersubject variability in the calculation of binding potentials (BPND, BPF, and BPP). Therefore, binding potentials of 11C-LY2795050 can be determined if the specific binding fraction in the cerebellum is presumed to be unchanged by diseases and experimental conditions. In conclusion, results from the present study show the suitability of 11C-LY2795050 to image and quantify KOR in humans. PMID:25182664

  20. Preparation of radioactive core-shell type 198Au@SiO2 nanoparticles as a radiotracer for industrial process applications.

    PubMed

    Jung, Sung-Hee; Kim, Kyo-Il; Ryu, Jung-Ho; Choi, Seong-Ho; Kim, Jong-Bum; Moon, Jin-Ho; Jin, Joon-Ha

    2010-06-01

    Silica-coated gold nanoparticles produced by gamma-ray irradiation were bombarded with neutrons in a nuclear reactor in order to activate gold nuclides into Au-198 emitting gamma radiation of 0.412-1.088 MeV. The particle size ranges from 20 to 200 nm. The physical integrity of the particles was examined by TEM before and after the neutron irradiation and the silica-gold particles were not affected in terms of structural appearance under gamma radiation environment. The gamma emitting NPs can be utilized as a tracer in petrochemical and refinery industrial processes where the internal temperature is extremely high and the conventional organic radioactive labeled compound would be decomposed.

  1. Synthesis of radiotracers for studying muscarinic cholinergic receptors in the living human brain using positron emission tomography: [11C]dexetimide and [11C]levetimide.

    PubMed

    Dannals, R F; Långström, B; Ravert, H T; Wilson, A A; Wagner, H N

    1988-01-01

    Dexetimide (Fig. 1a), a potent muscarinic cholinergic receptor antagonist, and levetimide (Fig. 1b), its pharmacologically inactive enantiomer, were labeled with 11C for non-invasive in vivo studies of muscarinic cholinergic receptors in the human brain using positron emission tomography. The syntheses were completed in approximately 32 min using [alpha-11C]benzyl iodide as the precursor. The synthesis, purification, characterization and determination of specific activity are presented and discussed. PMID:2838435

  2. The effect of resuspension on chemical exchanges at the sediment-water interface in the deep sea — A modelling and natural radiotracer approach

    NASA Astrophysics Data System (ADS)

    Rutgers van der Loeff, Michiel M.; Boudreau, Bernard P.

    1997-06-01

    We review the processes responsible for the formation of vertical gradients in the chemical composition of suspended particles across the benthic nepheloid layer. Such gradients have usually explained by resuspension of surface sediments, but it is shown here that these gradients can only be understood as part of a dynamic exchange between the water column and the sediments. A coupled model, developed in a companion paper, is expanded to include chemical reactions above and below the sediment-water interface. Three cases are discussed: A tracer with first-order decay (Model 1), the dissolution of a major constituent (Model 2), and a particle-reactive tracer with first-order decay and production in the water column (Model 3). Using typical parameter values for a well-developed benthic nepheloid layer, the three models reproduce typical distributions of C org (organic carbon), opal, and 234Th, respectively, on particles above and below the sediment-water interface. Sensitivity analyses illustrate how bioturbation can cause the large discrepancy observed between suspended and surface sediment C org values (Model 1). The model also reconciles this observed discrepancy with observations that the major part of the decomposition takes place within the sediment. For opal (Model 2), the influence of resuspension on the burial rate of opal is shown to be negligible, as long as dissolution follows first-order kinetics and is not enhanced by turbulence in the suspended phase. The modelling of 234Th (Model 3) successfully links the depletion of 234Th in bottom waters with the distribution of excess 234Th in surface sediments and on resuspended particles. 234Th is a powerful example of the tools supplied by the radioactive daughters of the natural U and Th decay series in studying fluxes and exchange rates of solutes and particles across the sediment-water interface. A short review is given of these tools, and it is shown how they can be used to obtain rate information required to apply and calibrate specific resuspension models.

  3. Development of a freeze-dried kit formulation for the preparation of 99mTc-NTP 15-5, a radiotracer for scintigraphic imaging of proteoglycans.

    PubMed

    Vidal, Aurélien; Gaumet, Vincent; Galmier, Marie-Josèphe; Besse, Sophie; Leal, Fernand; Gachon, Françoise; Viot, Gilles; Métin, Jacques; Chezal, Jean-Michel; Miot-Noirault, Elisabeth; Auzeloux, Philippe

    2015-07-01

    The cartilage-targeting strategy is based on the strong affinity of quaternary ammonium (QA) functions for cartilage proteoglycans. We use a bifunctional agent containing QA moiety and a polyazamacrocycle structure able to complex technetium-99m. (99m)Tc-NTP 15-5 was selected for its high stability and its high affinity for proteoglycans in vivo. Labeling conditions of NTP 15-5 were optimized, and a lyophilized kit was developed for radiolabeling of (99m)Tc-NTP 15-5 (radiochemical yields 94.6±1.8%). (99m)Tc-NTP 15-5 was stable and resulted in favorable biological evaluations.

  4. Detection of brain metastasis with 68Ga-labeled PSMA ligand PET/CT: a novel radiotracer for imaging of prostate carcinoma.

    PubMed

    Chakraborty, Partha Sarathi; Kumar, Rajiv; Tripathi, Madhavi; Das, Chandan Jyoti; Bal, Chandrasekhar

    2015-04-01

    Brain metastasis in prostate cancer is rare and not expected at initial presentation especially when the patient is asymptomatic for the same. A 45-year-old male patient undergoing initial evaluation for newly diagnosed prostatic adenocarcinoma was referred to our department for 99mTc-MDP bone scintigraphy. As part of the study protocol, he also underwent Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)] (68Ga-PSMA) PET/CT, which revealed tracer accumulation in brain lesions, apart from localization in the primary, lymph node, and bone metastases. A subsequent MR evaluation confirmed brain metastases.

  5. No effect of dopamine depletion on the binding of the high-affinity D 2/3 radiotracer [11C]FLB 457 in the human cortex.

    PubMed

    Frankle, W Gordon; Mason, N Scott; Rabiner, Eugenii A; Ridler, Khanum; May, Maureen A; Asmonga, Deanna; Chen, Chi-Min; Kendro, Steve; Cooper, Thomas B; Mathis, Chester A; Narendran, Rajesh

    2010-12-01

    The use of PET and SPECT endogenous competition-binding techniques has contributed to the understanding of the role of dopamine (DA) in several neuropsychiatric disorders. An important limitation of these imaging studies is the fact that measurements of changes in synaptic DA have been restricted to the striatum. The ligands previously used, such as [(11)C]raclopride and [(123)I]IBZM, do not provide sufficient signal-to-noise ratio to quantify D(2) receptors in extrastriatal areas, such as cortex, where the concentration of D(2) receptors is much lower than that in the striatum. Recently, we published a comparison study of the ability of two high-affinity DA D(2) radioligands [(11)C]FLB 457 and [(11)C]fallypride to measure amphetamine-induced changes in DA transmission in the human cortex. Our findings support the use of [(11)C]FLB 457 to measure changes in cortical synaptic DA induced by amphetamine. The goal of this study is to examine the effects of DA depletion with α-methyl-para-tyrosine (α-MPT) on [(11)C]FLB 457 binding in the cortex. Six healthy volunteers underwent two PET scans, first under control conditions and subsequently after DA depletion. The simplified reference tissue model as well as kinetic modeling with an arterial input function was used to derive the binding potential (BP(ND)) in seven cortical regions. We found no effect of DA depletion with α-MPT on [(11)C]FLB 457 binding in any of the regions examined. In contrast to the measurement of DA release, the combination of low D(2) receptor density and low basal DA levels in the cortex greatly reduce the power to detect alterations in [(11)C]FLB 457 binding secondary to DA depletion.

  6. Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer.

    PubMed

    Choi, Ji Young; Iacobazzi, Rosa Maria; Perrone, Mara; Margiotta, Nicola; Cutrignelli, Annalisa; Jung, Jae Ho; Park, Do Dam; Moon, Byung Seok; Denora, Nunzio; Kim, Sang Eun; Lee, Byung Chul

    2016-01-01

    The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)₃(H₂O)₃]⁺ and (NEt₄)₂[Re(CO)₃Br₃] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.

  7. Confocal {mu}-XRF, {mu}-XAFS, and {mu}-XRD Studies of Sediment from a Nuclear Waste Disposal Natural Analogue Site and Fractured Granite Following a Radiotracer Migration Experiment

    SciTech Connect

    Denecke, Melissa A.; Brendebach, Boris; Rothe, Joerg; Simon, Rolf; Janssens, Koen; Nolf, Wout de; Vekemans, Bart; Falkenberg, Gerald; Somogyi, Andrea; Noseck, Ulrich

    2007-02-02

    Combined {mu}-XRF, {mu}-XAFS, and {mu}-XRD investigations of a uranium-rich tertiary sediment, from a nuclear repository natural analogue site, and a fractured granite bore core section after a column tracer experiment using a Np(V) containing cocktail have been performed. Most {mu}-XRF/{mu}-XAFS measurements are recorded in a confocal geometry to provide added depth information. The U-rich sediment results show uranium to be present as a tetravalent phosphate and that U(IV) is associated with As(V). Arsenic present is either As(V) or As(0). The As(0) forms thin coatings on the surface of pyrite nodules. A hypothesis for the mechanism of uranium immobilization is proposed, where arsenopyrite acted as reductant of ground water dissolved U(VI) leading to precipitation of less soluble U(IV) and thereby forming As(V). Results for the granite sample show the immobilized Np to be tetravalent and associated with facture material.

  8. Synthesis and small-animal positron emission tomography evaluation of [11C]-elacridar as a radiotracer to assess the distribution of P-glycoprotein at the blood-brain barrier

    PubMed Central

    Dörner, Bernd; Kuntner, Claudia; Bankstahl, Jens P.; Bankstahl, Marion; Stanek, Johann; Wanek, Thomas; Stundner, Gloria; Mairinger, Severin; Löscher, Wolfgang; Müller, Markus; Langer, Oliver; Erker, Thomas

    2013-01-01

    With the aim to develop a positron emission tomography (PET) tracer to assess the distribution of P-glycoprotein (P-gp) at the blood-brain barrier (BBB) in vivo, the potent third-generation P-gp inhibitor elacridar (1) was labeled with 11C by reaction of O-desmethyl 1 with [11C]-methyl triflate. In vitro autoradiography and small-animal PET imaging of [11C]-1 was performed in rats (n=3), before and after administration of unlabeled 1, as well as in wild-type, Mdr1a/b(−/−) and Bcrp1(−/−) mice (n=3). In PET experiments in rats, administration of unlabeled 1 increased brain activity uptake 5.4-fold, whereas blood activity levels remained unchanged. In Mdr1a/b(−/−) mice, brain activity uptake was 2.5-fold higher compared to wild-type animals, whereas in Bcrp1(−/−) mice brain activity uptake was only 1.3-fold higher. In vitro autoradiography showed that 63% of [11C]-1 binding was displaceable by an excess of unlabeled 1. As the signal obtained with [11C]-1 appeared to be specific for P-gp at the BBB, its utility for the visualization of cerebral P-gp merits further investigation. PMID:19711894

  9. Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer.

    PubMed

    Choi, Ji Young; Iacobazzi, Rosa Maria; Perrone, Mara; Margiotta, Nicola; Cutrignelli, Annalisa; Jung, Jae Ho; Park, Do Dam; Moon, Byung Seok; Denora, Nunzio; Kim, Sang Eun; Lee, Byung Chul

    2016-07-07

    The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)₃(H₂O)₃]⁺ and (NEt₄)₂[Re(CO)₃Br₃] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.

  10. Radiosynthesis of an opiate receptor-binding radiotracer for positron emission tomography: (C-11 methyl)-methyl-4-(N-(1-oxopropyl)-N-phenylamino)-4-piperidine carboxylate (C-11 4-carbomethoxyfentanyl)

    SciTech Connect

    Dannals, R.F.; Ravert, H.T.; Frost, J.J.; Wilson, A.A.; Burns, H.D.; Wagner, H.N. Jr.

    1984-01-01

    The development of high affinity, high specific activity tritium-labeled neurotransmitter receptor ligands has made it possible to determine the spatial distribution and relative regional concentration of several neuroreceptors by means of in vivo receptor labeling techniques in animals. This development made possible the biochemical identification of opiate receptors by autoradiographic visualization in experimental animals. The quantitation and localization of opiate receptors in man using non-invasive methods, such as positron emission tomography, could provide a means of obtaining information about a variety of receptor-linked neuropsychiatric diseases as well as normal brain mechanisms regulating pain and emotions. As part of a continuing program to identify and radiolabel high affinity, highly specific ligands for the opiate receptor, the authors have selected two derivatives of fentanyl, a well-known analgesic, as candidates for radiolabeling: R-31,833 (4-carbomethoxy-fentanyl) and R-34,995 (lofentanil). Carbon-11 labeled R-31,833 was synthesized by the methylation of the appropriate carboxylate with C-11 methyl iodide in dimethylformamide at room temperature and purified by high performance liquid chromatography. The average synthesis time from end-of-bombardment (E.O.B.) was 30 minutes. The average specific activity was determined by ultraviolet spectroscopy to be 890 mCi/..mu..mole end-of-synthesis (approx. 2500 mCi/..mu..mole E.O.B.).

  11. Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer.

    PubMed

    Choi, Ji Young; Iacobazzi, Rosa Maria; Perrone, Mara; Margiotta, Nicola; Cutrignelli, Annalisa; Jung, Jae Ho; Park, Do Dam; Moon, Byung Seok; Denora, Nunzio; Kim, Sang Eun; Lee, Byung Chul

    2016-01-01

    The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)₃(H₂O)₃]⁺ and (NEt₄)₂[Re(CO)₃Br₃] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation. PMID:27409602

  12. Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer.

    PubMed

    Choi, Ji Young; Iacobazzi, Rosa Maria; Perrone, Mara; Margiotta, Nicola; Cutrignelli, Annalisa; Jung, Jae Ho; Park, Do Dam; Moon, Byung Seok; Denora, Nunzio; Kim, Sang Eun; Lee, Byung Chul

    2016-01-01

    The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)₃(H₂O)₃]⁺ and (NEt₄)₂[Re(CO)₃Br₃] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation. PMID:27399688

  13. Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer.

    PubMed

    Choi, Ji Young; Iacobazzi, Rosa Maria; Perrone, Mara; Margiotta, Nicola; Cutrignelli, Annalisa; Jung, Jae Ho; Park, Do Dam; Moon, Byung Seok; Denora, Nunzio; Kim, Sang Eun; Lee, Byung Chul

    2016-01-01

    The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)₃(H₂O)₃]⁺ and (NEt₄)₂[Re(CO)₃Br₃] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation. PMID:27457557

  14. Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

    PubMed Central

    Choi, Ji Young; Iacobazzi, Rosa Maria; Perrone, Mara; Margiotta, Nicola; Cutrignelli, Annalisa; Jung, Jae Ho; Park, Do Dam; Moon, Byung Seok; Denora, Nunzio; Kim, Sang Eun; Lee, Byung Chul

    2016-01-01

    The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. 99mTc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [99mTc(CO)3(H2O)3]+ and (NEt4)2[Re(CO)3Br3] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that 99mTc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.

  15. Development of robotic plasma radiochemical assays for positron emission tomography

    SciTech Connect

    Alexoff, D.L.; Shea, C.; Fowler, J.S.; Gatley, S.J.; Schlyer, D.J.

    1995-12-01

    A commercial laboratory robot system (Zymate PyTechnology II Laboratory Automation System; Zymark Corporation, Hopkinton, MA) was interfaced to standard and custom laboratory equipment and programmed to perform rapid radiochemical analyses for quantitative PET studies. A Zymark XP robot arm was used to carry out the determination of unchanged (parent) radiotracer in plasma using only solid phase extraction methods. Robotic throughput for the assay of parent radiotracer in plasma is 4--6 samples/hour depending on the radiotracer. Robotic assays of parent compound in plasma were validated for the radiotracers [{sup 11}C]Benztropine, [{sup 11}C]cocaine, [{sup 11}C]clorgyline, [{sup 11}C]deprenyl, [{sup 11}C]methadone, [{sup 11}C]methylphenidate, [{sup 11}C]raclorpride, and [{sup 11}C]SR46349B. A simple robot-assisted methods development strategy has been implemented to facilitate the automation of plasma assays of new radiotracers.

  16. Peptide targeted copper-64 radiopharmaceuticals.

    PubMed

    Ma, Michelle T; Donnelly, Paul S

    2011-01-01

    Peptide targeted ⁶⁴Cu-labelled diagnostic agents for positron emission tomography are viable candidates for molecular imaging of cancer. In a clinical setting, optimal image quality relies on selective tumor uptake of the ⁶⁴Cu-labelled radiotracer. The three components of the radiotracer construct--the chelate group, linker and targeting peptide--all influence the biodistribution of the ⁶⁴Cu-labelled radiotracer in vivo. Low or moderate Cu complex stability in vivo results in transmetallation of ⁶⁴Cu to endogenous proteins, giving rise to high background activity. The length and the nature of the linker group affect the affinity of the ⁶⁴Cu-labelled radiotracer for the target receptor. Variations in the peptide sequence can impact on the metabolic stability and therefore the bioavailability and tumor retention of the ⁶⁴Cu-labelled radiotracer in vivo. Lastly, the hydrophilicity of the construct can influence radiotracer metabolism and clearance pathways. Recent advances in the field of peptide targeted ⁶⁴Cu-labelled radiopharmaceuticals involve GRPR-targeted and αvβ3 integrin receptor-targeted constructs. These constructs are based on the bombesin peptide sequence and the RGD recognition motif respectively. These examples are reviewed as case studies in the optimisation of ⁶⁴Cu radiotracer design.

  17. General Nuclear Medicine

    MedlinePlus

    ... the examination table which slides in between the parallel gamma camera heads which are suspended over the ... energy from the radiotracer in your body. A computer aids in creating the images from the data ...

  18. Addiction Studies with Positron Emission Tomography

    SciTech Connect

    Joanna Fowler

    2008-10-13

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

  19. The Role of Chemistry in Positron Emission Tomography.

    ERIC Educational Resources Information Center

    Feliu, Anthony L.

    1988-01-01

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

  20. Addiction Studies with Positron Emission Tomography

    ScienceCinema

    Joanna Fowler

    2016-07-12

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

  1. Three-dimensional reconstructions from low-count SPECT data using deformable models

    SciTech Connect

    Cunningham, G.S.; Hanson, K.M.; Battle, X.L.

    1998-03-01

    The authors demonstrate the reconstruction of a 3D, time-varying bolus of radiotracer from first-pass data obtained at the dynamic SPECT imager, FASTSPECT, built by the University of Arizona. The object imaged is a CardioWest Total Artificial Heart. The bolus is entirely contained in one ventricle and its associated inlet and outlet tracts. The model for the radiotracer distribution is a time-varying closed surface parameterized by 162 vertices that are connected to make 960 triangles, with uniform intensity of radiotracer inside. The total curvature of the surface is minimized through the use of a weighted prior in the Bayesian framework. MAP estimates for the vertices, interior intensity and background scatter are produced for diastolic and systolic frames, the only two frames analyzed.

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

    NASA Astrophysics Data System (ADS)

    Xie, Tianwu; Zaidi, Habib

    2014-03-01

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

  3. Molecular Imaging of Urogenital Diseases

    PubMed Central

    Cho, Steve Y.; Szabo, Zsolt; Morgan, Russell H.

    2013-01-01

    There is an expanding and exciting repertoire of PET imaging radiotracers for urogenital diseases, particularly in prostate cancer, renal cell cancer, and renal function. Prostate cancer is the most commonly diagnosed cancer in men. With growing therapeutics options for the treatment of metastatic and advanced prostate cancer, improved functional imaging of prostate cancer beyond the limitations of conventional computed tomography (CT) and bone scan (BS) is becoming increasingly important for both clinical management and drug development. PET radiotracers beyond 18F-Fluorodeoxyglucose (FDG) for prostate cancer include 18F-Sodium Fluoride, 11C-Choline and 18F-Fluorocholine and 11C-Acetate. Other emerging and promising PET radiotracers include a synthetic L-leucine amino acid analog (anti-18F-FACBC), dihydrotestosterone analog (18F-FDHT) and prostate specific membrane antigen (PSMA) based PET radiotracers (ex. 18F-DCFBC, 89Zr-DFO-J591, 68Ga(HBED-CC)). Larger prospective and comparison trials of these PET radiotracers are needed to establish the role of PET/CT in prostate cancer. Renal cell cancer imaging with FDG PET/CT although available can be limited, especially for detection of the primary tumor. Improved renal cell cancer detection with carbonic anhydrase IX (CAIX) based antibody (124I-girentuximab) and radioimmunotherapy targeting with 177Lu-cG250 appear promising. Evaluation of renal injury by imaging renal perfusion and function with novel PET radiotracers include p-18F-fluorohippurate (18F-PFH) and hippurate m-cyano-p-18F-fluorohippurate (18F-CNPFH) and Rubidium-82 chloride (typically used for myocardial perfusion imaging). Renal receptor imaging of the renal renin angiotensin system with a variety of selective PET radioligands are also becoming available for clinical translation. PMID:24484747

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

    PubMed

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

    2016-09-01

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

  5. Scintigraphic findings in ankylosing spondylitis.

    PubMed

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

    1977-06-01

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

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

    DOEpatents

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

    1989-01-01

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

  7. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy.

  8. Measuring Oncogenic Signaling Pathways in Cancer with PET: An Emerging Paradigm from Studies in Castration Resistant Prostate Cancer

    PubMed Central

    2012-01-01

    As parallel advances in cancer biology and drug development continue to elevate the role of targeted therapies in oncology, the need for imaging biomarkers that systematically measure the biology associated with therapeutic intervention has become more urgent. Although the molecular imaging community has a commitment to develop technologies to this end, few investigational radiotracers directly measure the biology of common oncogenic signaling pathways often addressed by targeted therapies. Visible progress has been achieved with a handful of radiotracers rationally designed to intercalate the patho-biology of prostate cancer, a molecularly heterogeneous disease nevertheless broadly defined by a fairly small repertoire of recurrent oncogenic lesions. PMID:23043150

  9. Preparation of the Metabotropic Glutamate Receptor 5 (mGluR5) PET Tracer [18F]FPEB for Human Use: An Automated Radiosynthesis and a Novel One-Pot Synthesis of its Radiolabeling Precursor

    PubMed Central

    Lim, Keunpoong; Labaree, David; Li, Songye; Huang, Yiyun

    2014-01-01

    The radiotracer 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile, or [18F]FPEB, is a promising PET imaging agent for the metabotropic glutamate subtype 5 receptor (mGluR5). In an effort to develop a routine production method of this radiotracer for use in clinical research we adapted its radiosynthesis to an automated chemistry module. In the meanwhile, we also developed a simplified “one-pot” method for the preparation of the nitrobenzonitrile radiolabeling precursor for [18F]FPEB and its reference standard to replace the existing multi-step synthetic approach. PMID:25305528

  10. A data sheet for the simultaneous assessment of dual radioactive tracer uptake in the heart.

    PubMed

    Kato, Takao

    2016-01-01

    The myocardium takes up two major substrates: glucose and fatty acids, and various methods have been used to evaluate this uptake. Despite extensive study of radiotracer uptake-based methods, however, an easily applicable datasheet has not previously been provided. In this manuscript, an example of a method involving an easily modified data sheet based on dual tracer methods is presented. This method, with its data sheet: •Is applicable to all radiotracers, regardless of decay time•Is useful, simple, and modifiable; and•Is applicable to small animal studies.

  11. A data sheet for the simultaneous assessment of dual radioactive tracer uptake in the heart.

    PubMed

    Kato, Takao

    2016-01-01

    The myocardium takes up two major substrates: glucose and fatty acids, and various methods have been used to evaluate this uptake. Despite extensive study of radiotracer uptake-based methods, however, an easily applicable datasheet has not previously been provided. In this manuscript, an example of a method involving an easily modified data sheet based on dual tracer methods is presented. This method, with its data sheet: •Is applicable to all radiotracers, regardless of decay time•Is useful, simple, and modifiable; and•Is applicable to small animal studies. PMID:27114927

  12. Improving cancer treatment with cyclotron produced radionuclides. Progress report

    SciTech Connect

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

    1993-11-01

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

  13. Deep Vein Thrombosis Presenting on Pulmonary Ventilation and Perfusion Scintigraphy.

    PubMed

    Itani, Malak; Fair, Joanna; Hillman, Zachary; Behnia, Fatemeh; Elojeimy, Saeed

    2016-10-01

    A 52-year-old woman presenting with dyspnea was referred for a ventilation and perfusion scan (VQ). VQ images (with Tc-DTPA [diethylene triamine pentaacetic acid aerosol] and Tc-MAA [macroaggregated albumin]) initially appeared normal; however, count rates on perfusion images were similar to ventilation images, implying little Tc-MAA had reached the lungs. Spot images of the injected extremity demonstrated focal Tc-MAA accumulation worrisome for a venous thrombus, subsequently confirmed by Doppler ultrasound. Careful attention to relative radiotracer count rates on VQ scans is crucial to ensure diagnostic utility. In addition, abnormal low perfusion radiotracer counts may unveil other pathology with important clinical implications. PMID:27556796

  14. A data sheet for the simultaneous assessment of dual radioactive tracer uptake in the heart

    PubMed Central

    Kato, Takao

    2016-01-01

    The myocardium takes up two major substrates: glucose and fatty acids, and various methods have been used to evaluate this uptake. Despite extensive study of radiotracer uptake-based methods, however, an easily applicable datasheet has not previously been provided. In this manuscript, an example of a method involving an easily modified data sheet based on dual tracer methods is presented. This method, with its data sheet: • Is applicable to all radiotracers, regardless of decay time • Is useful, simple, and modifiable; and • Is applicable to small animal studies. PMID:27114927

  15. The changing role of imaging in clinical care

    PubMed Central

    Aggarwal, Rahul; Kurhanewicz, John

    2014-01-01

    Considerable developments in prostate cancer in 2013 have emerged from the imaging field. Hyperpolarized 13C-MRI can monitor metabolic activity to identify high-grade disease and treatment response, and novel PET radiotracers might identify distinct subsets of patients with advanced disease. These examples highlight the progress made at all stages of care. PMID:24418808

  16. Diagnosing protein losing enteropathy: A new approach using Tc-99m human immunoglobulin

    SciTech Connect

    Bhatnagar, A.; Kashyap, R.; Chopra, M.K.

    1995-11-01

    Tc-99m HIG has recently come into prominence as an inflammation seeking radiotracer. The authors describe a novel use of the agent for imaging protein-losing enteropathy. The agent may have certain advantages over Tc-99m HSA, which is currently being used for imaging protein loss. 19 refs., 2 figs.

  17. Comparative evaluation of quantitative glomerular filtration rate measured by isotopic and nonisotopic methods

    SciTech Connect

    Balachandran, S.; Toguri, A.G.; Petrusick, T.W.; Abbott, L.C.

    1981-04-01

    Good correlation of glomerular filtration rate measured isotopically from plasma disappearance of Tc-99m-DTPA was shown with inulin clearance, creatinine clearance, and graded radionuclide imaging. The isotopic GFR is a simple, urineless technique not requiring continuous infusion that enables one to perform simultaneous renal imaging with one radiotracer.

  18. Comparative evaluation of quantitative glomerular filtration rate measured by isotopic and nonisotopic methods

    SciTech Connect

    Balachandran, S.; Toguri, A.G.; Petrusick, T.W.; Abbott, L.C.

    1981-04-01

    Good correlation of glomerular filtration rate (GFR) measured isotopically from plasma disappearance of Tc-99m-DTPA (Sn) was shown with inulin clearance, creatinine clearance, and graded radionuclide imaging. The isotopic GFR is a simple, urineless technique not requiring continuous infusion that enables one to perform simultaneous renal imaging with one radiotracer.

  19. Improved Arene Fluorination Methodology for I(III) Salts

    PubMed Central

    Wang, Bijia; Qin, Linlin; Neumann, Kiel D.; Uppaluri, ShriHarsha; Cerny, Ronald L.; DiMagno, Stephen G.

    2010-01-01

    The use of low polarity aromatic solvents (benzene or toluene) and/or the removal of inorganic salts results in dramatically improved yields of fluorinated arenes from diaryliodonium salts. This methodology is shown to “scale down” to the conditions used typically for radiotracer synthesis. PMID:20617820

  20. Growth and Decay: An Experiment Demonstrating Radioactivity Relationships and Chelate Solvent Extraction Separations.

    ERIC Educational Resources Information Center

    Downey, D. M.; And Others

    1984-01-01

    The separation of lead and bismuth by chelate solvent extraction is of interest because of the simplicity which the use of radiotracers allows in its demonstration. Theoretical background information, procedures, materials needed, and typical results are provided for an experiment involving the extraction. (JN)

  1. Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?

    PubMed

    Vivash, Lucy; O'Brien, Terence J

    2016-02-01

    Neuroinflammation is implicated in the pathogenesis of a wide range of neurologic and neuropsychiatric diseases. For over 20 years, (11)C-PK11195 PET, which aims to image expression of the translocator protein (TSPO) on activated microglia in the brain, has been used in preclinical and clinical research to investigate neuroinflammation in vivo in patients with brain diseases. However, (11)C-PK11195 suffers from two major limitations: its low brain permeability and high nonspecific and plasma binding results in a low signal-to-noise ratio, and the use of (11)C restricts its use to PET research centers and hospitals with an on-site cyclotron. In recent years, there has been a great deal of work into the development of new TSPO-specific PET radiotracers. This work has focused on fluorinated radiotracers, which would enable wider use and improved signal-to-noise ratios. These radiotracers have been utilized in preclinical and clinical studies of several neurologic diseases with varying degrees of success. Unfortunately, the application of these second-generation TSPO radiotracers has revealed additional problems, including a polymorphism that affects TSPO binding. In this review, the developments in TSPO imaging are discussed, and current limitations and suggestions for future directions are explored.

  2. Behavior of mercury in bio-systems. II. Depuration of /sup 203/Hg/sup 2 +/ in various trophic levels

    SciTech Connect

    Hamdy, M.K.; Prabhu, N.V.

    1984-01-01

    Using radiotracer techniques, the depuration rates for methylmercury at three trophic levels in an aquatic ecosystem are examined. Bacteria (decomposers), mosquito larvae (primary consumers), and fish (secondary consumers) were studied. Results indicated that depuration rates for mercury were temperature dependent - the rate of depuration increased with increase in temperature (up to 45/sup 0/C)

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  4. ²⁰¹Tl⁺-labelled Prussian blue nanoparticles as contrast agents for SPECT scintigraphy.

    PubMed

    Perrier, M; Busson, M; Massasso, G; Long, J; Boudousq, V; Pouget, J-P; Peyrottes, S; Perigaud, Ch; Porredon-Guarch, C; de Lapuente, J; Borras, M; Larionova, J; Guari, Y

    2014-11-21

    Prussian blue (PB) and its analogues on the nanometric scale are exciting nano-objects that combine the advantages of molecular-based materials and nanochemistry. Herein, we demonstrate that ultra-small PB nanoparticles of 2-3 nm can be easily labelled with radioactive (201)Tl(+) to obtain new nanoprobes as radiotracers for 201-thallium-based imaging.

  5. Different patterns for bile leakage following cholecystectomy demonstrated by hepatobiliary imaging

    SciTech Connect

    Siddiqui, A.R.; Ellis, J.H.; Madura, J.A.

    1986-11-01

    Tc-99m labeled iminodiacetic acid (Tc-99m IDA) studies were performed in three patients with bile leaks. The radiotracer distribution was different in all three. A diffuse peritoneal pattern was seen in one patient. Localized radioactivity was seen in two; in one in the gallbladder bed and in the other in the perihepatic region.

  6. Ga-67 positivity in sarcoidosis of the skin with coincident thyroid uptake of uncertain etiology

    SciTech Connect

    Moreno, A.J.; Brown, J.M.; Salinas, J.A.; Feaster, B.L.; Brown, T.J.

    1984-03-01

    Gallium-67 citrate scintigraphy of a 26-year-old woman with systemic sarcoidosis demonstrated abnormal radiotracer uptake within multiple biopsy-proven sarcoidal cutaneous lesions and within both lobes of the thyroid gland. The etiology of the thyroidal uptake of the Ga-67 was uncertain but it may represent sarcoidal involvement of the gland.

  7. 453rd Brookhaven Lecture

    ScienceCinema

    Richard Ferrieri

    2016-07-12

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

  8. 4D RECONSTRUCTIONS FROM LOW-COUNT SPECT DATA USING DEFORMABLE MODELS WITH SMOOTH INTERIOR INTENSITY VARIATIONS

    SciTech Connect

    G. S. CUNNINGHAM; A. LEHOVICH

    2000-01-01

    The Bayes Inference Engine (BIE) has been used to perform a 4D reconstruction of a first-pass radiotracer bolus distribution inside a CardioWest Total Artificial Heart, imaged with the University of Arizona's FastSPECT system. The BIE estimates parameter values that define the 3D model of the radiotracer distribution at each of 41 times spanning about two seconds. The 3D models have two components: a closed surface, composed of hi-quadratic Bezier triangular surface patches, that defines the interface between the part of the blood pool that contains radiotracer and the part that contains no radiotracer, and smooth voxel-to-voxel variations in intensity within the closed surface. Ideally, the surface estimates the ventricular wall location where the bolus is infused throughout the part of the blood pool contained by the right ventricle. The voxel-to-voxel variations are needed to model an inhomogeneously-mixed bolus. Maximum a posterior (MAP) estimates of the Bezier control points and voxel values are obtained for each time frame. We show new reconstructions using the Bezier surface models, and discuss estimates of ventricular volume as a function of time, ejection fraction, and wall motion. The computation time for our reconstruction process, which directly estimates complex 3D model parameters from the raw data, is performed in a time that is competitive with more traditional voxel-based methods (ML-EM, e.g.).

  9. Estimating the effect of endogenous dopamine on baseline [(11) C]-(+)-PHNO binding in the human brain.

    PubMed

    Caravaggio, Fernando; Kegeles, Lawrence S; Wilson, Alan A; Remington, Gary; Borlido, Carol; Mamo, David C; Graff-Guerrero, Ariel

    2016-11-01

    Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3 R) have been quantified in the living human brain using the agonist radiotracer [(11) C]-(+)-PHNO. As an agonist radiotracer, [(11) C]-(+)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [(11) C]-(+)-PHNO binding to D2/3 Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BPND ) and the change in BPND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [(11) C]-(+)-PHNO BPND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42-59%. These results indicate that lower baseline values of [(11) C]-(+)-PHNO BPND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D2/3 R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [(11) C]-(+)-PHNO can detect the impact of endogenous DA levels at D2/3 R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers. PMID:27341789

  10. A dual-tracer study of extrastriatal 6-[18F]fluoro-m-tyrosine and 6-[18F]-Fluoro-L-dopa uptake in Parkinson's disease

    PubMed Central

    Li, Clarence; Palotti, Matthew; Holden, James E.; Oh, Jen; Okonkwo, Ozioma; Christian, Bradley T.; Bendlin, Barbara B.; Buyan-Dent, Laura; Harding, Sandra J.; Stone, Charles K.; Dejesus, Onofre T.; Nickles, Robert J.; Gallagher, Catherine L

    2014-01-01

    6-[18F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism—its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6-[18F]fluoro-m-tyrosine (FMT), which also targets L-amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol-O-methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. 15 Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high-resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer (http://surfer.nmr.mgh.harvard.edu); region-specific uptake rate constants (Kocc) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional Kocc were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT Kocc were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical Kocc were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD. PMID:24710997

  11. Bayesian estimation of regularization parameters for deformable surface models

    SciTech Connect

    Cunningham, G.S.; Lehovich, A.; Hanson, K.M.

    1999-02-20

    In this article the authors build on their past attempts to reconstruct a 3D, time-varying bolus of radiotracer from first-pass data obtained by the dynamic SPECT imager, FASTSPECT, built by the University of Arizona. The object imaged is a CardioWest total artificial heart. The bolus is entirely contained in one ventricle and its associated inlet and outlet tubes. The model for the radiotracer distribution at a given time is a closed surface parameterized by 482 vertices that are connected to make 960 triangles, with nonuniform intensity variations of radiotracer allowed inside the surface on a voxel-to-voxel basis. The total curvature of the surface is minimized through the use of a weighted prior in the Bayesian framework, as is the weighted norm of the gradient of the voxellated grid. MAP estimates for the vertices, interior intensity voxels and background count level are produced. The strength of the priors, or hyperparameters, are determined by maximizing the probability of the data given the hyperparameters, called the evidence. The evidence is calculated by first assuming that the posterior is approximately normal in the values of the vertices and voxels, and then by evaluating the integral of the multi-dimensional normal distribution. This integral (which requires evaluating the determinant of a covariance matrix) is computed by applying a recent algorithm from Bai et. al. that calculates the needed determinant efficiently. They demonstrate that the radiotracer is highly inhomogeneous in early time frames, as suspected in earlier reconstruction attempts that assumed a uniform intensity of radiotracer within the closed surface, and that the optimal choice of hyperparameters is substantially different for different time frames.

  12. Oral antioxidants for radioprotection during medical imaging examinations

    NASA Astrophysics Data System (ADS)

    Velauthapillai, Nivethan

    The oncogenic effect of ionizing radiation (IR) is clearly established and occurs in response to DNA damage. Many diagnostic imaging exams make use of IR and the oncogenic risk of IR-based imaging has been calculated. We hypothesized that the DNA damage sustained from IR exposure during medical imaging exams could be reduced by pre-medicating patients with antioxidants. First, we tested and validated a method for measuring DNA double-strand breaks (DSBs) in peripheral blood mononuclear cells (PBMCs) exposed to low doses of ionizing radiation. Afterwards, we conducted a pilot clinical study in which we administered oral antioxidants to patients undergoing bone scans, prior to radiotracer injection. We showed that oral antioxidant pre-medication reduced the number of DSBs in PBMCs induced by radiotracer injection. Our study shows proof-of-principle for this simple and inexpensive approach to radioprotection in the clinical setting.

  13. Cross-fused renal ectopia associated with vesicoureteral reflux; a case report.

    PubMed

    Naseri, Mitra

    2016-01-01

    Crossed renal ectopia is a rare urinary system anomaly which mostly is asymptomatic and is diagnosed incidentally. Urinary obstruction, infection, and neoplasia of the urinary system and nephrolithiasis are main complications of this anomaly. A 6-year-old boy admitted to the hospital with colicky abdominal pain and nausea. Abdominal examination revealed tenderness in right lower quadrant. Urine analysis and culture were normal. Kidney ultrasonography showed right kidney in pelvis cavity with no kidney tissue in left side. TC 99-DMSA scan demonstrated no radiotracer accumulation in the normal renal area. Radiotracer accumulation was seen in the pelvis area with a deviation to the left. Voiding cystoureterogram revealed right sided grade II vesicoureteral reflux. Severe urological anomalies in children may be asymptomatic or have nonspecific symptoms such as abdominal pain. PMID:27689123

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

    PubMed Central

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

    2014-01-01

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

  15. Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC

    NASA Astrophysics Data System (ADS)

    Parra, Pamela Ochoa; Veloza, Stella

    2016-07-01

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

  16. Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors.

    PubMed

    Wuest, F

    2007-01-01

    The favourable long-half life, the ease of production and the low energy of the emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry of 18F basically relies on two distinctive types of reactions: nucleophilic and electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling precursors which are obtained directly from the cyclotron. They can be applied either directly to the radiosynthesis or they can be transformed into more complex labeling precursors enabling the multi-step build-up of organic tracer molecules. The topic of this review is a survey on the application of several 18F-labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.) [18F] fluoride to build up small monomeric PET radiotracers at high specific radioactivity by multi-step synthesis procedures.

  17. Cross-fused renal ectopia associated with vesicoureteral reflux; a case report

    PubMed Central

    Naseri, Mitra

    2016-01-01

    Crossed renal ectopia is a rare urinary system anomaly which mostly is asymptomatic and is diagnosed incidentally. Urinary obstruction, infection, and neoplasia of the urinary system and nephrolithiasis are main complications of this anomaly. A 6-year-old boy admitted to the hospital with colicky abdominal pain and nausea. Abdominal examination revealed tenderness in right lower quadrant. Urine analysis and culture were normal. Kidney ultrasonography showed right kidney in pelvis cavity with no kidney tissue in left side. TC 99-DMSA scan demonstrated no radiotracer accumulation in the normal renal area. Radiotracer accumulation was seen in the pelvis area with a deviation to the left. Voiding cystoureterogram revealed right sided grade II vesicoureteral reflux. Severe urological anomalies in children may be asymptomatic or have nonspecific symptoms such as abdominal pain. PMID:27689123

  18. Cerenkov Luminescence Tomography for In Vivo Radiopharmaceutical Imaging

    PubMed Central

    Zhong, Jianghong; Qin, Chenghu; Yang, Xin; Zhu, Shuping; Zhang, Xing; Tian, Jie

    2011-01-01

    Cerenkov luminescence imaging (CLI) is a cost-effective molecular imaging tool for biomedical applications of radiotracers. The introduction of Cerenkov luminescence tomography (CLT) relative to planar CLI can be compared to the development of X-ray CT based on radiography. With CLT, quantitative and localized analysis of a radiopharmaceutical distribution becomes feasible. In this contribution, a feasibility study of in vivo radiopharmaceutical imaging in heterogeneous medium is presented. Coupled with a multimodal in vivo imaging system, this CLT reconstruction method allows precise anatomical registration of the positron probe in heterogeneous tissues and facilitates the more widespread application of radiotracers. Source distribution inside the small animal is obtained from CLT reconstruction. The experimental results demonstrated that CLT can be employed as an available in vivo tomographic imaging of charged particle emitters in a heterogeneous medium. PMID:21747821

  19. A Review on Segmentation of Positron Emission Tomography Images

    PubMed Central

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

    2014-01-01

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

  20. Cross-fused renal ectopia associated with vesicoureteral reflux; a case report

    PubMed Central

    Naseri, Mitra

    2016-01-01

    Crossed renal ectopia is a rare urinary system anomaly which mostly is asymptomatic and is diagnosed incidentally. Urinary obstruction, infection, and neoplasia of the urinary system and nephrolithiasis are main complications of this anomaly. A 6-year-old boy admitted to the hospital with colicky abdominal pain and nausea. Abdominal examination revealed tenderness in right lower quadrant. Urine analysis and culture were normal. Kidney ultrasonography showed right kidney in pelvis cavity with no kidney tissue in left side. TC 99-DMSA scan demonstrated no radiotracer accumulation in the normal renal area. Radiotracer accumulation was seen in the pelvis area with a deviation to the left. Voiding cystoureterogram revealed right sided grade II vesicoureteral reflux. Severe urological anomalies in children may be asymptomatic or have nonspecific symptoms such as abdominal pain.

  1. Performance evaluation of advanced industrial SPECT system with diverging collimator.

    PubMed

    Park, Jang Guen; Jung, Sung-Hee; Kim, Jong Bum; Moon, Jinho; Yeom, Yeon Soo; Kim, Chan Hyeong

    2014-12-01

    An advanced industrial SPECT system with 12-fold-array diverging collimator was developed for flow visualization in industrial reactors and was discussed in the previous study. The present paper describes performance evaluation of the SPECT system under both static- and dynamic- flow conditions. Under static conditions, the movement of radiotracer inside the test reactor was compared with that of color tracer (blue ink) captured with a high-speed camera. The comparison of the reconstructed images obtained with the radiotracer and the SPECT system showed fairly good agreement with video-frames of the color tracer obtained with the camera. Based on the results of the performance evaluation, it is concluded that the SPECT system is suitable for investigation and visualization of flows in industrial flow reactors.

  2. Radiosynthesis of Carbon-11 Labeled Puromycin as a Potential PET Candidate for Imaging Protein Synthesis in Vivo.

    PubMed

    Milicevic Sephton, Selena; Aigbirhio, Franklin I

    2016-06-01

    In order to address the limitations associated with the present range of PET radiotracers used for imaging protein synthesis in vivo we have synthesized a candidate PET radiotracer based on Puromycin (3, PURO), a protein synthesis inhibitor. The desmethylPURO 9 precursor for radiolabeling with carbon-11 radioisotope was synthesized in two steps employing EDC/HOBt amide coupling in overall 76% yield. Optimal conditions for radiolabeling were then established via methylation/deprotection sequence. Under these conditions as determined by NMR analysis 9 showed partial stability (ca. 80%) under acidic conditions. Limited evidence of stereochemical stability of 3 was also found. The radiolabeling of intermediate [(11)C]12 was accomplished with up to 57% conversion from [(11)C]iodomethane. An automated method was then developed for high radioactivity radiosynthesis to produce [(11)C]3 ([(11)C]PURO) in 16 ± 6% (n = 3) decay corrected radiochemical yields. PMID:27326342

  3. Quantitative imaging of coronary blood flow

    PubMed Central

    Alessio, Adam M.; Butterworth, Erik; Caldwell, James H.; Bassingthwaighte, James B.

    2010-01-01

    Positron emission tomography (PET) is a nuclear medicine imaging modality based on the administration of a positron-emitting radiotracer, the imaging of the distribution and kinetics of the tracer, and the interpretation of the physiological events and their meaning with respect to health and disease. PET imaging was introduced in the 1970s and numerous advances in radiotracers and detection systems have enabled this modality to address a wide variety of clinical tasks, such as the detection of cancer, staging of Alzheimer's disease, and assessment of coronary artery disease (CAD). This review provides a description of the logic and the logistics of the processes required for PET imaging and a discussion of its use in guiding the treatment of CAD. Finally, we outline prospects and limitations of nanoparticles as agents for PET imaging. PMID:22110860

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

    DOEpatents

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

    1992-11-10

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

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

    DOEpatents

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

    1995-01-01

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

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

    DOEpatents

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

    1992-01-01

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

  7. Improving cancer treatment with cyclotron produced radionuclides

    SciTech Connect

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

    1992-08-04

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

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

    SciTech Connect

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

    1992-08-04

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

  9. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy. PMID:26874530

  10. Factors limiting microbial activity in volcanic tuff at Yucca Mountain

    SciTech Connect

    Kieft, T.L.; Kovacik, W.P.; Taylor, J.

    1996-09-01

    Samples of tuff aseptically collected from 10 locations in the Exploratory Shaft Facility at the site of the proposed high-level nuclear waste repository at Yucca Mountain, Nevada Test Site were analyzed for microbiological populations, activities, and factors limiting microbial activity. Radiotracer assays ({sup 14}C-labeled organic substrate mineralization), direct microscopic counts, and plate counts were used. Radiolabeled substrates were glucose, acetate, and glutamate. Radiotracer experiments were carried out with and without moisture and inorganic nutrient amendments to determine factors limiting to microbial activities. Nearly all samples showed the presence of microorganisms with the potential to mineralize organic substrates. Addition of inorganic nutrients stimulated activities in a small number of samples. The presence of viable microbial communities within the tuff has implications for transport of contaminants.

  11. 201Tl+-labelled Prussian blue nanoparticles as contrast agents for SPECT scintigraphy

    NASA Astrophysics Data System (ADS)

    Perrier, M.; Busson, M.; Massasso, G.; Long, J.; Boudousq, V.; Pouget, J.-P.; Peyrottes, S.; Perigaud, Ch.; Porredon-Guarch, C.; de Lapuente, J.; Borras, M.; Larionova, J.; Guari, Y.

    2014-10-01

    Prussian blue (PB) and its analogues on the nanometric scale are exciting nano-objects that combine the advantages of molecular-based materials and nanochemistry. Herein, we demonstrate that ultra-small PB nanoparticles of 2-3 nm can be easily labelled with radioactive 201Tl+ to obtain new nanoprobes as radiotracers for 201-thallium-based imaging.Prussian blue (PB) and its analogues on the nanometric scale are exciting nano-objects that combine the advantages of molecular-based materials and nanochemistry. Herein, we demonstrate that ultra-small PB nanoparticles of 2-3 nm can be easily labelled with radioactive 201Tl+ to obtain new nanoprobes as radiotracers for 201-thallium-based imaging. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, PXRD, TEM images, kinetics and adsorption isotherms, SPECT/CT images, Tl+ captation profiles. See DOI: 10.1039/c4nr03044c

  12. Carbon-11 labeled cathepsin K inhibitors: syntheses and preliminary in vivo evaluation.

    PubMed

    Rodnick, Melissa E; Shao, Xia; Kozloff, Kenneth M; Scott, Peter J H; Kilbourn, Michael R

    2014-01-01

    Cathepsin K is a cysteine peptidase primarily located in osteoclasts, cells involved in normal growth and remodeling of bone but that are also responsible for bone loss in osteolytic diseases such as osteoporosis. In vivo imaging of cathepsin K may provide a method to assess changes in osteoclast numbers in such disease states. To that end, two high-affinity and selective cathepsin K inhibitors were radiolabeled with carbon-11. In vivo microPET imaging studies demonstrated uptake and prolonged retention of radioactivity in actively growing or remodeling bone regions (e.g., distal ulnar, carpal, distal and proximal humeral, distal femur, proximal tibia, tail vertebrae). Uptake into bone could be blocked by pre- or co-injection of unlabeled ligand, supporting a specific and saturable binding mechanism for radiotracer localization. These proof-of-concept studies indicate that radiolabeled cathepsin K inhibitors may have potential as in vivo imaging radiotracers for assessing changes of osteoclast numbers in osteolytic diseases.

  13. Radiosynthesis and in vivo evaluation of a ¹⁸F-labelled styryl-benzoxazole derivative for β-amyloid targeting.

    PubMed

    Ribeiro Morais, G; Gano, L; Kniess, T; Bergmann, R; Abrunhosa, A; Santos, I; Paulo, A

    2013-12-01

    The formation of β-amyloid deposits is considered a histopathological feature of Alzheimer's disease (AD). In vivo molecular imaging by means of amyloid-avid radiotracers will allow for an early and conclusive diagnostic of AD. Herein, we describe the radiosynthesis of the radiofluorinated styryl benzoxazole derivative [¹⁸F]-[2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole] ([¹⁸F]-1) and its pre-clinical evaluation, including metabolic and biodistribution studies in male Wistar rats. The in vivo biological evaluation of [¹⁸F]-1 showed that this new radiotracer has a moderate brain uptake with a slow brain washout and a poor in vivo stability.

  14. Nurse exposure doses resulted from bone scintigraphy patient

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  15. Performance evaluation of advanced industrial SPECT system with diverging collimator.

    PubMed

    Park, Jang Guen; Jung, Sung-Hee; Kim, Jong Bum; Moon, Jinho; Yeom, Yeon Soo; Kim, Chan Hyeong

    2014-12-01

    An advanced industrial SPECT system with 12-fold-array diverging collimator was developed for flow visualization in industrial reactors and was discussed in the previous study. The present paper describes performance evaluation of the SPECT system under both static- and dynamic- flow conditions. Under static conditions, the movement of radiotracer inside the test reactor was compared with that of color tracer (blue ink) captured with a high-speed camera. The comparison of the reconstructed images obtained with the radiotracer and the SPECT system showed fairly good agreement with video-frames of the color tracer obtained with the camera. Based on the results of the performance evaluation, it is concluded that the SPECT system is suitable for investigation and visualization of flows in industrial flow reactors. PMID:25169132

  16. Imaging Monoamine Oxidase in the Human Brain

    SciTech Connect

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  17. Synthesis optimization of 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB), β-amyloid PET imaging tracer for Alzheimer's disease diagnosis.

    PubMed

    Coliva, A; Monterisi, C; Apollaro, A; Gatti, D; Penso, M; Gianolli, L; Perani, D; Gilardi, M C; Carpinelli, A

    2015-11-01

    [11C]PIB is the most used amyloid plaques-specific positron-emitting radiotracers. The radiosynthesis of this compound, carried out by methylation of its precursor with [11C]methyl triflate in 2-butanone, has been improved optimizing the initial concentration and the purification method. Two HPLC methods were compared: good radiochemical yields, specific activities, and chemical purity above 98% were achieved by using as eluant acetonitrile/citrate and formulation in 10% ethanol.

  18. Understanding the cause of an unreadable nuclear medicine image: a case of unexpected results with 123I whole-body scintigraphy.

    PubMed

    Skweres, Justin; Yang, Zhiyun; Gonzalez-Toledo, Eduardo

    2014-12-01

    When unexpected results are obtained with standard image collection, the nuclear medicine physician must consider many technical factors that may have contributed. When image quality is poor, prior radiotracer administration, among other things, should always be considered. Our case demonstrates how knowledge of patient history and basic principles of nuclear medicine physics allows recognition of the septal penetration artifact. This allows the nuclear medicine physician to tailor the exam to an individual patient and obtain the most useful diagnostic information for the clinician.

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

    SciTech Connect

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

    1986-01-01

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

  20. [The clinical management guidelines of the Sociedad Española de Cardiología. Nuclear cardiology: the technical bases and clinical applications].

    PubMed

    Candell Riera, J; Castell Conesa, J; Jurado López, J A; López de Sá, E; Nuño de la Rosa, J A; Ortigosa Aso, F J; Valle Tudela, V

    1999-11-01

    Although the role of nuclear cardiology is currently well consolidated, the addition of new radiotracers and modern techniques prompt us to permanently update the requirements, equipment and clinical applications of these isotopic tests. Radioisotopic drugs, instrumentation and characteristics of radionuclide tests that are presently used are explained in the first part of this text. In the second part, diagnostic and prognostic indications of these tests are presented in detail.

  1. Radiopharmaceuticals for diagnosis

    SciTech Connect

    Kuhl, D.E.

    1990-06-01

    During this grant period 1 January 1988--31 December 1990, we have successfully developed a number of new approaches to fluorine-18 labeled compounds, prepared several new radiotracers for both animal studies and eventual clinical trials, and explored the utility of a high-quality industrial robot in radiopharmaceutical applications. The progress during the last grant period is summarized briefly in the following sections. Publications arising from this research are listed below and can be found in Appendix I. 1 fig.

  2. External Imaging of Cerebral Muscarinic Acetylcholine Receptors

    NASA Astrophysics Data System (ADS)

    Eckelman, William C.; Reba, Richard C.; Rzeszotarski, Waclaw J.; Gibson, Raymond E.; Hill, Thomas; Holman, B. Leonard; Budinger, Thomas; Conklin, James J.; Eng, Robert; Grissom, Michael P.

    1984-01-01

    A radioiodinated ligand that binds to muscarinic acetylcholine receptors was shown to distribute in the brain by a receptor-mediated process. With single-photon-emission imaging techniques, radioactivity was detected in the cerebrum but not in the cerebellum, whereas with a flow-limited radiotracer, radioactivity was detected in cerebrum and cerebellum. Single-photon-emission computed tomography showed good definition of the caudate putamen and cortex in man.

  3. External imaging of cerebral muscarinic acetylcholine receptors

    SciTech Connect

    Eckelman, W.C.; Reba, R.C.; Rzeszotarski, W.J.; Gibson, R.E.; Hill, T.; Holman, B.L.; Budinger, T.; Conklin, J.J.; Eng, R.; Grissom, M.P.

    1984-01-20

    A radioiodinated ligand that binds to muscarinic acetylcholine receptors was shown to distribute in the brain by a receptor-mediated process. With single-photon-emission imaging techniques, radioactivity was detected in the cerebrum but not in the cerebellum, whereas with a flow-limited radiotracer, radioactivity was detected in cerebrum and cerebellum. Single-photon-emission computed tomography showed good definition of the caudate putamen and cortex in man.

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

    SciTech Connect

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

    2014-08-05

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

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

    DOEpatents

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

    2014-08-12

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  7. Quantitative autoradiographic microimaging in the development and evaluation of radiopharmaceuticals

    SciTech Connect

    Som, P.; Oster, Z.H.

    1994-04-01

    Autoradiographic (ARG) microimaging is the method for depicting biodistribution of radiocompounds with highest spatial resolution. ARG is applicable to gamma, positron and negatron emitting radiotracers. Dual or multiple-isotope studies can be performed using half-lives and energies for discrimination of isotopes. Quantitation can be performed by digital videodensitometry and by newer filmless technologies. ARG`s obtained at different time intervals provide the time dimension for determination of kinetics.

  8. Synthesis of [18F]Arenes via the Copper-Mediated [18F]Fluorination of Boronic Acids

    PubMed Central

    2015-01-01

    A copper-mediated radiofluorination of aryl- and vinylboronic acids with K18F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [18F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors. PMID:26568457

  9. Image Reconstruction in Higher Dimensions: Myocardial Perfusion Imaging of Tracer Dynamics with Cardiac Motion Due to Deformation and Respiration

    PubMed Central

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

    2015-01-01

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases due to redistribution of the counts over the cardiac-respiratory gates. However, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images. PMID:26450115

  10. Secondary Ion Mass Spectrometry for Mg Tracer Diffusion: Issues and Solutions

    SciTech Connect

    Tuggle, Jay; Giordani, Andrew; Kulkarni, Nagraj S; Warmack, Robert J Bruce; Coffey, Kevin; Sohn, Yong Ho; HunterJr., Jerry

    2014-01-01

    A Secondary Ion Mass Spectrometry (SIMS) method has been developed to measure stable Mg isotope tracer diffusion. This SIMS method was then used to calculate Mg self- diffusivities and the data was verified against historical data measured using radio tracers. The SIMS method has been validated as a reliable alternative to the radio-tracer technique for the measurement of Mg self-diffusion coefficients and can be used as a routine method for determining diffusion coefficients.

  11. Gallium-67 imaging in muscular sarcoidosis

    SciTech Connect

    Edan, G.; Bourguet, P.; Delaval, P.; Herry, J.Y.

    1984-07-01

    A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

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

    DOE PAGES

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

    2015-10-09

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

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

    SciTech Connect

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

    2015-10-09

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

  14. Synthesis of [18F]Arenes via the Copper-Mediated [18F]Fluorination of Boronic Acids.

    PubMed

    Mossine, Andrew V; Brooks, Allen F; Makaravage, Katarina J; Miller, Jason M; Ichiishi, Naoko; Sanford, Melanie S; Scott, Peter J H

    2015-12-01

    A copper-mediated radiofluorination of aryl- and vinylboronic acids with K(18)F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [(18)F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors. PMID:26568457

  15. Imaging of experimental myocardial infarction with technetium-99m 2,3-dimercaptosuccinic acid

    SciTech Connect

    Karlsberg, R.P.; Milne, N.; Lyons, K.P.; Aronow, W.S.

    1981-03-01

    We have studied the use of Tc-99m-labeled 2,3-dimercaptosuccinic acid(Tc-99m DMSA) to scintigraph acute myocardial infaction after coronary occlusion in dogs. Optimal images were obtained 5 hr after injection of radiotracer, with consistent delineation 48 hr after occlusion. Delivery of tracer was dependent on blood flow. Uptake of tracer correlated to extent of infarction as determined by the myocardial depletion of creatine kinase. Myocardial Tc-99m DMSA was protein-bound.

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

    PubMed

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

    2015-11-01

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images. PMID:26450115

  17. Abdominal varices mimicking an acute gastrointestinal hemorrhage during technetium-99m red blood cell scintigraphy

    SciTech Connect

    Moreno, A.J.; Byrd, B.F.; Berger, D.E.; Turnbull, G.L.

    1985-04-01

    Abdominal varices consisting of a caput medusae and dilated mesenteric veins resulted in pooling of Tc-99m tagged red blood cells (RBC) within these dilated vessels in a 57-year-old man with severe Laennec's cirrhosis. The atypical radiotracer localization within the abdomen mimicked an acute gastrointestinal hemorrhage. Clinical suspicion and careful evaluation of scintigraphic gastrointestinal bleeding studies will avoid false-positive interpretations.

  18. Radiogallium scan in P. carinii pneumonia

    SciTech Connect

    Parthasarathy, K.L.; Bakshi, S.P.; Bender, M.A.

    1982-02-01

    A gallium scan performed on a patient with fever of unknown origin (FUO) revealed an abnormal uptake of radiotracer in the lungs despite negative chest roentgenographic examination and other routine diagnostic studies. Subsequent lung biopsy results confirmed the presence of Pneumocystis (P.) carinii infection. A repeat gallium scan obtained following appropriate antibiotic therapy was essentially normal. The importance of radiogallium scanning in an immunosuppressed patient with FUO is emphasized.

  19. In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography.

    PubMed

    Rojas, Santiago; Herance, José Raúl; Gispert, Juan Domingo; Abad, Sergio; Torrent, Elia; Jiménez, Xavier; Pareto, Deborah; Perpiña, Unai; Sarroca, Sara; Rodríguez, Elisenda; Ortega-Aznar, Arantxa; Sanfeliu, Coral

    2013-07-01

    Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [(18)F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [(11)C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [(18)F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [(11)C]-PIB, and [(18)F]-Florbetapir could quantify the amyloid deposition in vivo and if [(18)F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [(18)F]-Florbetapir, [(11)C]-PIB, and [(18)F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [(18)F]-FDG is a consequence of glial activation that occurs in 5XFAD mice.

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

    PubMed Central

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

    2016-01-01

    Amyloidosis is a protein-misfolding disorder characterized by the extracellular deposition of amyloid, a complex matrix composed of protein fibrils, hyper-sulphated glycosaminoglycans and serum amyloid P component (SAP). Accumulation of amyloid in visceral organs results in the destruction of tissue architecture leading to organ dysfunction and failure. Early differential diagnosis and disease monitoring are critical for improving patient outcomes; thus, whole body amyloid imaging would be beneficial in this regard. Non-invasive molecular imaging of systemic amyloid is performed in Europe by using iodine-123-labelled SAP; however, this tracer is not available in the US. Therefore, we evaluated synthetic, poly-basic peptides, designated p5 and p5+14, as alternative radiotracers for detecting systemic amyloidosis. Herein, we perform a comparative effectiveness evaluation of radiolabelled peptide p5+14 with p5 and SAP, in amyloid-laden mice, using dual-energy SPECT imaging and tissue biodistribution measurements. All three radiotracers selectively bound amyloid in vivo; however, p5+14 was significantly more effective as compared to p5 in certain organs. Moreover, SAP bound principally to hepatosplenic amyloid, whereas p5+14 was broadly distributed in numerous amyloid-laden anatomic sites, including the spleen, liver, pancreas, intestines and heart. These data support clinical validation of p5+14 as an amyloid radiotracer for patients in the US. PMID:26936002

  1. Imaging pathological tau in atypical parkinsonian disorders

    PubMed Central

    Coakeley, Sarah; Strafella, Antonio P.

    2016-01-01

    Purpose of review This review examines the current literature on tau imaging in atypical parkinsonian disorders and other tauopathies. Recent findings There are a number of tau PET radiotracers that have demonstrated promising preliminary results in atypical parkinsonian disorders, such as progressive supranuclear palsy and corticobasal degeneration. These radiotracers were capable of selectively labeling tau in vitro and in vivo, with high affinity. Other radiotracers tested more extensively in patients with Alzheimer’s disease have also been able to successfully image tau deposition. Summary The development of tau radioligands for PET has led to the current testing of these tracers in clinical studies, many of which concentrate on patients with Alzheimer’s disease. Atypical parkinsonian disorders such as progressive supranuclear palsy and corticobasal degeneration are now being investigated as well. These disorders can be very difficult to diagnose, because of their clinical overlap with other parkinsonian disorders. Imaging tau using PET could serve as a diagnostic biomarker for these tauopathies and provide a means of assessing treatment that targets tau burden. PMID:26110795

  2. First true initial ictal SPECT in partial epilepsy verified by electroencephalography

    PubMed Central

    Pastor, Jesús; Domínguez-Gadea, Luis; Sola, Rafael G; Hernando, Virgilio; Meilán, María Luisa; Dios, Eva De; Martínez-Chacón, José Luis; Martínez, Marcos

    2008-01-01

    Drug-resistant epilepsy can sometimes be treated by surgery. In these cases, an accurate identification of the epileptogenic area must be addressed before resection. Ictal SPECT is one of the presurgical evaluations that can be performed, but usually, the increase in the regional cerebral perfusion observed is produced by diffusion of ictal activity. Here we describe a patient studied with v-EEG and foramen ovale electrodes that suffered a seizure after intravenous infusion of etomidate. The sequence of etomidate administration, followed by radiotracer and seizure was good enough for us to suspect that a true initial ictal SPECT was observed. We have implemented a kinetic model with four compartments, previously described (Andersen 1989), in order to estimate the fraction of hydrophilic radiotracer in the brain during the pre-ictal and ictal periods. This model has shown that the fraction of hydrophilic radiotracer during the seizure into the brain would be between 18.9% and 42.3% of total infused. We show the first true initial ictal SPECT demonstrated by bioelectrical recordings of the brain activity, obtained by a correct succession of events and compatible with theoretical data obtained from the kinetic model. PMID:18728803

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

    PubMed

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

    2013-08-01

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

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

    SciTech Connect

    Shuang Liu

    2012-10-24

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

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

    PubMed

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

    2016-03-03

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

  6. The application of positron emission tomography (PET/CT) in diagnosis of breast cancer. Part II. Diagnosis after treatment initiation, future perspectives.

    PubMed

    Jodłowska, Elżbieta; Czepczyński, Rafał; Czarnywojtek, Agata; Rewers, Amanda; Jarząbek, Grażyna; Kędzia, Witold; Ruchała, Marek

    2016-01-01

    Similarly to the applications described in the first part of this publication, positron emission tomography with computed tomography (PET/CT) is also gaining importance in monitoring a tumour's response to therapy and diagnosing breast cancer recurrences. This is additionally caused by the fact that many new techniques (dual-time point imaging, positron emission tomography with magnetic resonance PET/MR, PET/CT mammography) and radiotracers (16α-18F-fluoro-17β-estradiol, 18F-fluorothymidine) are under investigation. The highest sensitivity and specificity when monitoring response to treatment is achieved when the PET/CT scan is made after one or two chemotherapy courses. Response to anti-hormonal treatment can also be monitored, also when new radiotracers, such as FES, are used. When monitoring breast cancer recurrences during follow-up, PET/CT has higher sensitivity than conventional imaging modalities, making it possible to monitor the whole body simultaneously. New techniques and radiotracers enhance the sensitivity and specificity of PET and this is why, despite relatively high costs, it might become more widespread in monitoring response to treatment and breast cancer recurrences. PMID:27647983

  7. Molecular Imaging of Inflammation in the ApoE −/− Mouse Model of Atherosclerosis with IodoDPA

    PubMed Central

    Foss, Catherine A.; Bedja, Djahida; Mease, Ronnie C.; Wang, Haofan; Kass, David A.; Chatterjee, Subroto; Pomper, Martin G.

    2015-01-01

    Background Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and Results We previously developed a low-molecular-weight imaging agent, [125I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE−/− mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE−/− mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions IodoDPA is a promising, new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. PMID:25858322

  8. Optimization of nucleophilic ¹⁸F radiofluorinations using a microfluidic reaction approach.

    PubMed

    Pascali, Giancarlo; Matesic, Lidia; Collier, Thomas L; Wyatt, Naomi; Fraser, Benjamin H; Pham, Tien Q; Salvadori, Piero A; Greguric, Ivan

    2014-09-01

    Microfluidic techniques are increasingly being used to synthesize positron-emitting radiopharmaceuticals. Several reports demonstrate higher incorporation yields, with shorter reaction times and reduced amounts of reagents compared with traditional vessel-based techniques. Microfluidic techniques, therefore, have tremendous potential for allowing rapid and cost-effective optimization of new radiotracers. This protocol describes the implementation of a suitable microfluidic process to optimize classical (18)F radiofluorination reactions by rationalizing the time and reagents used. Reaction optimization varies depending on the systems used, and it typically involves 5-10 experimental days of up to 4 h of sample collection and analysis. In particular, the protocol allows optimization of the key fluidic parameters in the first tier of experiments: reaction temperature, residence time and reagent ratio. Other parameters, such as solvent, activating agent and precursor concentration need to be stated before the experimental runs. Once the optimal set of parameters is found, repeatability and scalability are also tested in the second tier of experiments. This protocol allows the standardization of a microfluidic methodology that could be applied in any radiochemistry laboratory, in order to enable rapid and efficient radiosynthesis of new and existing [(18)F]-radiotracers. Here we show how this method can be applied to the radiofluorination optimization of [(18)F]-MEL050, a melanoma tumor imaging agent. This approach, if integrated into a good manufacturing practice (GMP) framework, could result in the reduction of materials and the time required to bring new radiotracers toward preclinical and clinical applications. PMID:25079426

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

    SciTech Connect

    Jolley, R.L.; Begovich, J.M.; Brashear, H.R.; Case, N.; Clark, T.G.; Emery, J.F.; Patton, B.D.; Rodgers, B.R.; Villiers-Fisher, J.F.; Watson, J.S.

    1983-12-01

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

  10. High Affinity Radiopharmaceuticals Based Upon Lansoprazole for PET Imaging of Aggregated Tau in Alzheimer’s Disease and Progressive Supranuclear Palsy: Synthesis, Preclinical Evaluation, and Lead Selection

    PubMed Central

    2014-01-01

    Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity for tau would allow noninvasive quantification of tau burden using positron emission tomography (PET) imaging. We have synthesized [18F]lansoprazole, [11C]N-methyl lansoprazole, and [18F]N-methyl lansoprazole and identified them as high affinity radiotracers for tau with low to subnanomolar binding affinities. Herein, we report radiosyntheses and extensive preclinical evaluation with the aim of selecting a lead radiotracer for translation into human PET imaging trials. We demonstrate that [18F]N-methyl lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid brain entry in nonhuman primates, favorable kinetics, low white matter binding, and selectivity for binding to tau over amyloid, is the lead compound for progression into clinical trials. PMID:24896980

  11. Radiolabelling diverse positron emission tomography (PET) tracers using a single digital microfluidic reactor chip.

    PubMed

    Chen, Supin; Javed, Muhammad Rashed; Kim, Hee-Kwon; Lei, Jack; Lazari, Mark; Shah, Gaurav J; van Dam, R Michael; Keng, Pei-Yuin; Kim, Chang-Jin C J

    2014-03-01

    Radiotracer synthesis is an ideal application for microfluidics because only nanogram quantities are needed for positron emission tomography (PET) imaging. Thousands of radiotracers have been developed in research settings but only a few are readily available, severely limiting the biological problems that can be studied in vivo via PET. We report the development of an electrowetting-on-dielectric (EWOD) digital microfluidic chip that can synthesize a variety of (18)F-labeled tracers targeting a range of biological processes by confirming complete syntheses of four radiotracers: a sugar, a DNA nucleoside, a protein labelling compound, and a neurotransmitter. The chip employs concentric multifunctional electrodes that are used for heating, temperature sensing, and EWOD actuation. All of the key synthesis steps for each of the four (18)F-labeled tracers are demonstrated and characterized with the chip: concentration of fluoride ion, solvent exchange, and chemical reactions. The obtained fluorination efficiencies of 90-95% are comparable to, or greater than, those achieved by conventional approaches.

  12. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    PubMed Central

    Bernard-Gauthier, Vadim; Wängler, Carmen; Wängler, Bjoern; Schirrmacher, Ralf

    2014-01-01

    Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE) approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA) via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014) shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry. PMID:25157357

  13. The application of positron emission tomography (PET/CT) in diagnosis of breast cancer. Part II. Diagnosis after treatment initiation, future perspectives

    PubMed Central

    Jodłowska, Elżbieta; Czarnywojtek, Agata; Rewers, Amanda; Jarząbek, Grażyna; Kędzia, Witold; Ruchała, Marek

    2016-01-01

    Similarly to the applications described in the first part of this publication, positron emission tomography with computed tomography (PET/CT) is also gaining importance in monitoring a tumour's response to therapy and diagnosing breast cancer recurrences. This is additionally caused by the fact that many new techniques (dual-time point imaging, positron emission tomography with magnetic resonance PET/MR, PET/CT mammography) and radiotracers (16α-18F-fluoro-17β-estradiol, 18F-fluorothymidine) are under investigation. The highest sensitivity and specificity when monitoring response to treatment is achieved when the PET/CT scan is made after one or two chemotherapy courses. Response to anti-hormonal treatment can also be monitored, also when new radiotracers, such as FES, are used. When monitoring breast cancer recurrences during follow-up, PET/CT has higher sensitivity than conventional imaging modalities, making it possible to monitor the whole body simultaneously. New techniques and radiotracers enhance the sensitivity and specificity of PET and this is why, despite relatively high costs, it might become more widespread in monitoring response to treatment and breast cancer recurrences. PMID:27647983

  14. The application of positron emission tomography (PET/CT) in diagnosis of breast cancer. Part II. Diagnosis after treatment initiation, future perspectives

    PubMed Central

    Jodłowska, Elżbieta; Czarnywojtek, Agata; Rewers, Amanda; Jarząbek, Grażyna; Kędzia, Witold; Ruchała, Marek

    2016-01-01

    Similarly to the applications described in the first part of this publication, positron emission tomography with computed tomography (PET/CT) is also gaining importance in monitoring a tumour's response to therapy and diagnosing breast cancer recurrences. This is additionally caused by the fact that many new techniques (dual-time point imaging, positron emission tomography with magnetic resonance PET/MR, PET/CT mammography) and radiotracers (16α-18F-fluoro-17β-estradiol, 18F-fluorothymidine) are under investigation. The highest sensitivity and specificity when monitoring response to treatment is achieved when the PET/CT scan is made after one or two chemotherapy courses. Response to anti-hormonal treatment can also be monitored, also when new radiotracers, such as FES, are used. When monitoring breast cancer recurrences during follow-up, PET/CT has higher sensitivity than conventional imaging modalities, making it possible to monitor the whole body simultaneously. New techniques and radiotracers enhance the sensitivity and specificity of PET and this is why, despite relatively high costs, it might become more widespread in monitoring response to treatment and breast cancer recurrences.

  15. Radionuclide thyroid imaging in the newborn with suspected hypothyroidism

    SciTech Connect

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

    1985-05-01

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

  16. PET radiopharmaceuticals for probing enzymes in the brain

    PubMed Central

    Holland, Jason P; Cumming, Paul; Vasdev, Neil

    2013-01-01

    Biologically important processes in normal brain function and brain disease involve the action of various protein-based receptors, ion channels, transporters and enzymes. The ability to interrogate the location, abundance and activity of these entities in vivo using non-invasive molecular imaging can provide unprecedented information about the spatio-temporal dynamics of brain function. Indeed, positron emission tomography (PET) imaging is transforming our understanding of the central nervous system and brain disease. Great emphasis has historically been placed on developing radioligands for the non-invasive detection of neuroreceptors. In contrast, relatively few enzymes have been amenable to examination by PET imaging procedures based upon trapping or accumulation of enzymatic products, because only a subset of enzymes have sufficient catalytic rate to produce measureable accumulation within the practical time-limit of PET recordings. However, high affinity inhibitors are now serving as tracers for enzymes, particularly for measuring the abundance of enzymes mediating intracellular signal transduction in the brain, which offer a rich diversity of potential targets for drug discovery. The purpose of this review is to summarize well-known radiotracers for brain enzymes, and draw attention to recent developments in PET radiotracers for imaging signal transduction pathways in the brain. The review is organized by target class and focuses on structural chemistry of the best-established radiotracers identified in each class. PMID:23638333

  17. 18F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy

    PubMed Central

    Kong, Xiang; Luo, Song; Wu, Jin Rong; Wu, Shawn; De Cecco, Carlo N.; Schoepf, U. Joseph; Spandorfer, Adam J.; Wang, Chun Yan; Tian, Ying; Chen, Hui Juan; Lu, Guang Ming; Yang, Gui Fen; Zhang, Long Jiang

    2016-01-01

    Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. 11C-PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, 18F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE. This study was divided into two parts. The first part compared 18F-DPA-714 and 11C-PK11195 radiotracers in ten HE induced rats [bile duct ligation (BDL) and fed hyperammonemic diet (HD)] and 6 control rats. The animal subjects underwent dynamic positron emission tomography (PET) during 2-day intervals. The 11C-PK11195 PET study showed no differences in whole brain average percent injected dose per gram (%ID/g) values at all time points (all P>0.05), while the 18F-DPA-714 PET study showed higher whole brain average %ID/g values in HE rats compared to control group rats at 900 s to 3300 s after injecting radiotracer (all P<0.05). The second part of the study evaluated the effectiveness of ibuprofen (IBU) treatment to chronic HE. Forty rats were classified into six groups, including Sham+normal saline (NS), Sham+IBU, BDL+NS, BDL+HD+NS, BDL+IBU, and BDL+HD+IBU groups. 18F-DPA-714 PET was used to image neuroinflammation. Whole and regional brain average %ID/g values, neurological features, inflammatory factors and activated microglia showed better in the IBU groups than in the NS groups (all P<0.05) and no difference was seen in the Sham groups compared to IBU groups (all P>0.05). In conclusion, this study demonstrated that 18F-DPA-714 is an ideal TPSO radiotracer for imaging neuroinflammation and monitoring anti-neuroinflammation treatment efficacy of chronic HE. PMID:27279913

  18. (18)F, (64)Cu, and (68)Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer.

    PubMed

    Liu, Zhaofei; Yan, Yongjun; Liu, Shuanglong; Wang, Fan; Chen, Xiaoyuan

    2009-05-20

    Radiolabeled RGD (Arg-Gly-Asp) and bombesin (BBN) radiotracers that specifically target integrin alpha(v)beta(3) and gastrin releasing peptide receptor (GRPR) are both promising radiopharmaceuticals for tumor imaging. We recently designed and synthesized a RGD-BBN heterodimeric peptide with both RGD and BBN motifs in one single molecule. The (18)F-labeled RGD-BBN heterodimer exhibited dual integrin alpha(v)beta(3) and GRPR targeting in a PC-3 prostate cancer model. In this study we investigated whether radiolabeled RGD-BBN tracers can be used to detect breast cancer by using microPET. Cell binding assay demonstrated that the high GRPR expressing breast cancer cells typically express low to moderate level of integrin alpha(v)beta(3), while high integrin alpha(v)beta(3) expressing breast cancer cells have negligible level of GRPR. We labeled RGD-BBN heterodimer with three positron emitting radionuclides (18)F, (64)Cu, and (68)Ga and investigated the corresponding PET radiotracers in both orthotopic T47D (GRPR(+)/low integrin alpha(v)beta(3)) and MDA-MB-435 (GRPR(-)/integrin alpha(v)beta(3)(+)) breast cancer models. The three radiotracers all possessed in vitro dual integrin alpha(v)beta(3) and GRPR binding affinity. The advantages of the RGD-BBN radiotracers over the corresponding BBN analogues are obvious for imaging MDA-MB-435 (GRPR(-)/integrin alpha(v)beta(3)(+)) tumor. (18)F-FB-PEG(3)-RGD-BBN showed lower tumor uptake than (64)Cu-NOTA-RGD-BBN and (68)Ga-NOTA-RGD-BBN but was able to visualize breast cancer tumors with high contrast. Synthesis of (64)Cu-NOTA-RGD-BBN and (68)Ga-NOTA-RGD-BBN is much faster and easier than (18)F-FB-PEG(3)-RGD-BBN. (64)Cu-NOTA-RGD-BBN showed prolonged tumor uptake but also higher liver retention and kidney uptake than (68)Ga-NOTA-RGD-BBN and (18)F-FB-PEG(3)-RGD-BBN. (68)Ga-NOTA-RGD-BBN possessed high tumor signals but also relatively high background uptake compared with the other two radiotracers. In summary, the prosthetic labeling

  19. Miscellaneous cancers (lung, thyroid, renal cancer, myeloma, and neuroendocrine tumors): role of SPECT and PET in imaging bone metastases.

    PubMed

    Chua, Sue; Gnanasegaran, Gopinath; Cook, Gary J R

    2009-11-01

    In this review, we assess the current role of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in the imaging of skeletal metastatic disease from a miscellaneous group of malignancies, including lung, thyroid, and renal carcinomas; multiple myeloma; and neuroendocrine tumors, and consider how recent advances may enhance their effectiveness in this area. Bone scintigraphy using technetium-labeled diphosphonates has long been the mainstay of functional imaging of bony metastases, but is of limited value in myeloma and aggressive osteolytic metastases, and has the limitation of relatively poor specificity. SPECT, as a tomographic imaging technique, produces three-dimensional images of tracer distribution from multiplanar images. Its application to bone scintigrams greatly aids accurate anatomic localization and sensitivity in detection of foci of tracer uptake. SPECT can equally be applied to scintigrams using radiotracers, which are specific for particular groups of tumors, such as somatostatin analogs for neuroendocrine tumors. The advent of combined SPECT/computed tomography (CT) systems has further enhanced the accuracy of SPECT in all these malignancies. PET uses positron-emitting radiotracers and achieves a higher spatial resolution than single-photon imaging. Its high resolution and coverage of the entire body have made it a highly effective technique for the evaluation of skeletal metastatic disease, particularly when combined with CT. (18)F-fluorodeoxyglucose ((18)F-FDG)-PET/CT now forms part of routine staging for many carcinomas, such as non-small-cell lung carcinomas, and may obviate the need for routine staging scintigraphy in these patients. As uptake of the most common PET radiotracer, (18)F-FDG, is dependent on the increased cellular metabolism of most tumors, it may enable earlier detection of metastatic foci than bone scintigraphy, which relies on detecting an osteoblastic response. Another significant

  20. Agonist and antagonist bind differently to 5-HT1A receptors during Alzheimer's disease: A post-mortem study with PET radiopharmaceuticals.

    PubMed

    Vidal, Benjamin; Sebti, Johan; Verdurand, Mathieu; Fieux, Sylvain; Billard, Thierry; Streichenberger, Nathalie; Troakes, Claire; Newman-Tancredi, Adrian; Zimmer, Luc

    2016-10-01

    PET imaging studies using 5-HT1A receptor radiotracers show a decreased density of this receptor in hippocampi of patients with Alzheimer's disease (AD) at advanced stages. However, current 5-HT1A receptor radiopharmaceuticals used in neuroimaging are antagonists, thought to bind to 5-HT1A receptors in different functional states (i.e., both the one which displays high affinity for agonists and is thought to mediate receptor activation, as well as the state which has low affinity for agonists). Comparing the PET imaging obtained using an agonist radiotracer, which binds selectively to functional receptors, with the PET imaging obtained using an antagonist radiotracer would therefore provide original information on 5-HT1A receptor impairment during AD. Quantitative autoradiography using [(18)F]F13640 and [(18)F]MPPF, a 5-HT1A agonist and antagonist, respectively, was measured in hippocampi of patients with AD (n = 25, at different Braak stages) and control subjects (n = 9). The neuronal density was measured in the same tissues by NeuN immunohistochemistry. The specific binding of both radiotracers was determined by addition of WAY-100635, a selective 5-HT1A receptor antagonist. The autoradiography distribution of both 5-HT1A PET radiotracers varied across hippocampus regions. The highest binding density was in the pyramidal layer of CA1. Incubation with Gpp(NH)p, a non-hydrolysable analogue of GTP, reduced significantly [(18)F]F13640 binding in hippocampal regions, confirming its preferential interaction with G-coupled receptors, and slightly increased [(18)F]MPPF binding. In the CA1 subfield, [(18)F]F13640 binding was significantly decreased at Braak stages I/II (-19%), Braak stages III/IV (-23%), and Braak stages V/VI (-36%) versus control. In contrast, [(18)F]MPPF binding was statistically reduced only at the most advanced Braak stages V/VI compared to control (-33%). Since [(18)F]F13640 and [(18)F]MPPF can be used in vivo in humans, this

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

    PubMed Central

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

    2016-01-01

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

  2. Positron Emission Tomography for the Assessment of Myocardial Viability

    PubMed Central

    2010-01-01

    , harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability. Stress Echocardiography with Contrast Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium. SPECT SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images. The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%. There are two technetium-99 m tracers: sestamibi (MIBI

  3. [18F]- and [11C]-Labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging of apoptosis in Fas-treated mice

    PubMed Central

    Zhou, Dong; Chu, Wenhua; Chen, Delphine L.; Wang, Qi; Reichert, David E.; Rothfuss, Justin; D'Avignon, Andre; Welch, Michael J.; Mach, Robert H.

    2011-01-01

    Summary The radiolabeled isatin sulfonamide caspase-3 inhibitor, [18F]2 (WC-II-89), is a potential PET radiotracer for noninvasive imaging of apoptosis. The radiolabeling mechanism was studied by 13C NMR, ESI/MS, and computational calculations. It was found that the high electrophilicity of the C3 carbonyl group in the isatin ring, which served as a trap for [18F]fluoride, was responsible for the failure of the radiolabeling via nucleophilic substitution of the mesylate group in 7a by [18F]fluoride. Once treated with a strong base, 7a opened the isatin ring completely to form an isatinate intermediate 16, which lost the ability to trap [18F]fluoride, thereby allowing the displacement of the mesylate group to afford the 18F-labeled isatinate 17. [18F]17 can be converted to isatin [18F]2 efficiently under acidic conditions. The ring-opening and re-closure of the isatin ring under basic and acidic conditions were confirmed by reversed phase HPLC analysis, ESI/MS and 13C NMR studies. Computational studies of model compounds also support the above proposed mechanism. Similarly, the ring-opening and re-closure method was used successfully in the synthesis of the 11C labeled isatin sulfonamide analogue [11C]4 (WC-98). A microPET imaging study using [11C]4 in the Fas liver apoptosis model demonstrated retained activity in the target organ (liver) of the treated mice. Increased caspase-3 activation in the liver was verified by the fluorometric caspase-3 enzyme assay. Therefore, this study provides a useful method for radio-synthesis of isatin derivative radiotracers for PET and SPECT studies, and [11C]4 is a potential PET radiotracer for noninvasive imaging of apoptosis. PMID:19300818

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

    PubMed

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

    2016-01-01

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

  5. The history of cerebral PET scanning

    PubMed Central

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

    2013-01-01

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

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

    SciTech Connect

    Lee, Dong-Chang; Jans, Hans; McEwan, Sandy; Riauka, Terence; Martin, Wayne; Wieler, Marguerite

    2014-08-15

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

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

    PubMed

    Vallabhajosula, Shankar

    2007-11-01

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

  8. Assessment of radiation dose in nuclear cardiovascular imaging using realistic computational models

    SciTech Connect

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

    2015-06-15

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

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

    DOE PAGES

    Converse, Alexander K.; Ahlers, Elizabeth O.; Bryan, Tom W.; Hetue, Jackson D.; Lake, Katherine A.; Ellison, Paul A.; Engle, Jonathan W.; Barnhart, Todd E.; Nickles, Robert J.; Williams, Paul H.; et al

    2015-03-15

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

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

    SciTech Connect

    Chen, K.; Reiman, E.M. |; Lawson, M.; Yun, L.S.; Bandy, D.

    1996-12-01

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

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

    SciTech Connect

    McCall, Keisha C.; Humm, John L.; Bartlett, Rachel; Reese, Megan; Carlin, Sean

    2012-11-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

    Foss, Catherine A.; Bedja, Djahida; Mease, Ronnie C.; Wang, Haofan; Kass, David A.; Chatterjee, Subroto; Pomper, Martin G.

    2015-05-22

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

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

    SciTech Connect

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

    1984-01-01

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

  15. Uptake and/or utilization of two simple phenolic acids by Cucumis sativus

    SciTech Connect

    Shann, J.R.

    1986-01-01

    The uptake of ferulic acid (FA) and p-hydroxybenzoic acid (p-HBA) from solutions (0.1 to 1.00 mM, pH 4.0 to 7.0), was determined for intact and excised roots of Cucumis sativus. Uptake methods based on high performance liquid chromatographic (HPLC) analysis of phenolic acid depletion from solution were compared to those radioisotopic methods employing (U-ring-/sup 14/C)FA or p-HBA. Although radiotracer methods more accurately reflected actual uptake of the compounds by cucumber seedlings, HPLC solution depletion methods may be useful in the elucidation of trends over very limited periods of time. The uptake of FA was unaffected by the presence of p-HBA. The uptake of p-HBA was reduced by 30% in the presence of FA when compared to the uptake from solutions containing p-HBA alone. Ferulic acid acts both as an allelopathic agent and precursor in the endogenous process of lignification. To evaluate the involvement of exogenous FA in lignin biosynthesis, roots of hydroponically grown cucumber seedlings were exposed to concentrations of FA labeled with (U-ring-/sup 14/C)FA. Radiotracer was distributed throughout the seedling. A quantitative change in lignification occurred in treated seedlings. In roots and stems, the level of lignin increased with the number of exposures and as the concentrations of exogenous FA increased. Radiotracer was found in the residues of lignin isolated from seedling tissue treated with (U-ring-/sup 14/C)FA. This suggested the utilization of the exogenously applied FA in the endogenous process of lignification.

  16. Potential Role of Tc-99m DTPA Diuretic Renal Scan in the Diagnosis of Calyceal Diverticulum in Children

    PubMed Central

    Lin, Chun-Chen; Shih, Bing-Fu; Shih, Shin-Lin; Tsai, Jeng-Daw

    2015-01-01

    Abstract The aim of the study was to assess the usefulness of Technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) diuretic scan to diagnose calyceal diverticulum (CD). From January 2000 to June 2014, children with evidence of renal cystic lesions of undetermined diagnosis on ultrasound were enrolled. Computed tomography urography (CTU) and Tc-99m DTPA diuretic scan were performed to characterize the precise anatomy. The diagnosis of CD depended on visualization of a renal cystic lesion with filling of contrast material or radiotracer from the collecting system on CTU or diuretic renal scan. Children who had positive findings of CD on 1 or both imaging studies were selected and analyzed. Both CTU and Tc-99m DTPA diuretic renal scan were performed in 39 children. A total of 9 (23.1 %) children with CD were diagnosed. All 9 children had positive diagnosis of CD on diuretic renal scan. Only 6 (66.7%) children could be diagnosed by CTU, and CD was missed by CTU in 3 subjects. The differential renal functions in patients with CD were 46% to 55%. The time of radiotracer appearance in the CD ranged from the 8th to the 24th minute. Seven patients had persistent accumulation of radiotracer in their CD at the end of the study. Tc-99m DTPA diuretic renal scan seems to be more sensitive than CTU in diagnosing CD. The possible reasons of higher sensitivity are discussed. Additional advantages that Tc-99m DTPA diuretic renal scan provides include the following: continuous monitoring, less radiation doses, and information on renal function, making it an attractive alternative to CTU for diagnosis of CD. PMID:26091475

  17. Potential Role of Tc-99m DTPA Diuretic Renal Scan in the Diagnosis of Calyceal Diverticulum in Children

    PubMed Central

    Lin, Chun-Chen; Shih, Bing-Fu; Shih, Shin-Lin; Tsai, Jeng-Daw

    2015-01-01

    Abstract The aim of the study was to assess the usefulness of Technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) diuretic scan to diagnose calyceal diverticulum (CD). From January 2000 to June 2014, children with evidence of renal cystic lesions of undetermined diagnosis on ultrasound were enrolled. Computed tomography urography (CTU) and Tc-99m DTPA diuretic scan were performed to characterize the precise anatomy. The diagnosis of CD depended on visualization of a renal cystic lesion with filling of contrast material or radiotracer from the collecting system on CTU or diuretic renal scan. Children who had positive findings of CD on 1 or both imaging studies were selected and analyzed. Both CTU and Tc-99m DTPA diuretic renal scan were performed in 39 children. A total of 9 (23.1 %) children with CD were diagnosed. All 9 children had positive diagnosis of CD on diuretic renal scan. Only 6 (66.7%) children could be diagnosed by CTU, and CD was missed by CTU in 3 subjects. The differential renal functions in patients with CD were 46% to 55%. The time of radiotracer appearance in the CD ranged from the 8th to the 24th minute. Seven patients had persistent accumulation of radiotracer in their CD at the end of the study. Tc-99m DTPA diuretic renal scan seems to be more sensitive than CTU in diagnosing CD. The possible reasons of higher sensitivity are discussed. Additional advantages that Tc-99m DTPA diuretic renal scan provides include the following: continuous monitoring, less radiation doses, and information on renal function, making it an attractive alternative to CTU for diagnosis of CD.

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

    SciTech Connect

    Converse, Alexander K.; Ahlers, Elizabeth O.; Bryan, Tom W.; Hetue, Jackson D.; Lake, Katherine A.; Ellison, Paul A.; Engle, Jonathan W.; Barnhart, Todd E.; Nickles, Robert J.; Williams, Paul H.; DeJesus, Onofre T.

    2015-03-15

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

  19. Classification of M/sub 1/ and M/sub 2/ receptor subtypes in vivo by autoradiography using (/sup 125/I) (R,R) 4IQNB: Implications for imaging receptor subtypes

    SciTech Connect

    Gibson, R.E.; Moody, T.; Kzeszotarski, W.J.; Schneidau, T.S.; Jagoda, E.M.; Reba, R.C.

    1985-05-01

    (/sup 125/I) (R,R) 3-Quinuclidinyl 4-Iodobenzilate (4IQNB) is a high affinity radiotracer for the muscarinic acetylcholine receptor which exhibits differential kinetics of dissociation from the receptor subtypes, M/sub 1/ and M/sub 2/. The authors have determined the relative percentages of M/sub 1/ to M/sub 2/-receptor subtype in six structures of rat brain by equilibrium competition using the selective antagonist, QNX, and by analysis of the off-rate profiles for 4IQNB. The results are comparable and provide: (% M/sub 1/) caudate nucleus - 100%, hippocampus - 92%, cortex - 82%, thalamus - 6%, superior + inferior colliculi - 41%, and pons - 23%. To determine the relative proportions of M/sub 1/ to M/sub 2/ receptors in vivo we examined the distribution of 4IQNB at 2 h and 24 h by autoradiography. At 2 h, both M/sub 1/ and M/sub 2/ receptors will be labeled but at 24 h only the M/sub 1/ receptor will retain radiotracer. At 2 h, all structures of the brain are variably labeled with the cortex, hippocampus, caudate nucleus, olfactory nuclei, nucleus accumbens, pontine nuclei, and anteroventral thalamic nucleus (AV) most heavily labeled. At 24 h, both the pontine and AV, as well as the less heavily labeled hypothalamus, superior colliculus and mesencephalic nuclei, are devoid of radiotracer thus indicating predominantly M/sub 2/ receptor. Quantitation is necessary to determine possible washout of activity from the M/sub 2/ receptors in cortex. Similar time studies in man should provide distinctions between the M/sub 1/ and M/sub 2/ receptor rich structures and the preferential loss of a subtype of receptor due to disease.

  20. Anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid: Physiologic Uptake Patterns, Incidental Findings, and Variants That May Simulate Disease

    PubMed Central

    Schuster, David M.; Nanni, Cristina; Fanti, Stefano; Oka, Shuntaro; Okudaira, Hiroyuki; Inoue, Yusuke; Sörensen, Jens; Owenius, Rikard; Choyke, Peter; Turkbey, Baris; Bogsrud, Trond V.; Bach-Gansmo, Tore; Halkar, Raghuveer K.; Nye, Jonathon A.; Odewole, Oluwaseun A.; Savir-Baruch, Bital; Goodman, Mark M.

    2016-01-01

    Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone 18F-FACBC PET. Methods Sixteen clinical trials involving 611 18F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. Results The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though 18F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%–10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. Conclusion Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid–based PET radiotracers. As with other PET radiotracers such as 18F-FDG, focal nonphysiologic uptake may represent incidental malignancy

  1. Diverse bone scan abnormalitites in "shin splints".

    PubMed

    Spencer, R P; Levinson, E D; Baldwin, R D; Sziklas, J J; Witek, J T; Rosenberg, R

    1979-12-01

    Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of the foot.

  2. Metastatic superscan in prostate carcinoma on gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography scan

    PubMed Central

    Agarwal, Krishan Kant; Tripathi, Madhavi; Kumar, Rajeev; Bal, Chandrasekhar

    2016-01-01

    We describe the imaging features of a metastatic superscan on gallium-68 Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)], abbreviated as gallium-68-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging. 68Ga-PSMA is novel radiotracer undergoing evaluation for PET/CT imaging of prostate carcinoma. This patient had a superscan of metastases on conventional bone scintigraphy and was referred for 68Ga-PSMA PET/CT to evaluate the feasibility of 177Lu-PSMA therapy. PMID:27095868

  3. Contemporary approaches for imaging skeletal metastasis

    PubMed Central

    Ulmert, David; Solnes, Lilja; Thorek, Daniel LJ

    2015-01-01

    The skeleton is a common site of cancer metastasis. Notably high incidences of bone lesions are found for breast, prostate, and renal carcinoma. Malignant bone tumors result in significant patient morbidity. Identification of these lesions is a critical step to accurately stratify patients, guide treatment course, monitor disease progression, and evaluate response to therapy. Diagnosis of cancer in the skeleton typically relies on indirect bone-targeted radiotracer uptake at sites of active bone remodeling. In this manuscript, we discuss established and emerging tools and techniques for detection of bone lesions, quantification of skeletal tumor burden, and current clinical challenges. PMID:26273541

  4. Image-derived biomarkers and multimodal imaging strategies for lung cancer management.

    PubMed

    Sauter, Alexander W; Schwenzer, Nina; Divine, Mathew R; Pichler, Bernd J; Pfannenberg, Christina

    2015-04-01

    Non-small-cell lung cancer is the most common type of lung cancer and one of the leading causes of cancer-related death worldwide. For this reason, advances in diagnosis and treatment are urgently needed. With the introduction of new, highly innovative hybrid imaging technologies such as PET/CT, staging and therapy response monitoring in lung cancer patients have substantially evolved. In this review, we discuss the role of FDG PET/CT in the management of lung cancer patients and the importance of new emerging imaging technologies and radiotracer developments on the path to personalized medicine.

  5. Unusual appearance for urinary bladder obstruction detected with 99mTc-MDP bone scintigraphy.

    PubMed

    Wright, Chadwick L; Sharma, Akash

    2015-12-01

    Unanticipated but clinically significant nonosseous findings can be detected during routine bone scintigraphy. We present a case of an 83-year-old man who presented with a pathologic fracture of the right femur. Whole-body bone scintigraphy for osseous staging revealed intense radiotracer accumulation in the kidneys and ureters but no activity within the urinary bladder. The patient had not voided for 14 hours. A Foley catheter was inserted, and more than 2000 mL of urine was drained, most consistent with urinary bladder obstruction. Subsequent repeat images demonstrated marked reduction of the renal and ureteral activity with trace activity in the urinary bladder.

  6. Method for image reconstruction of moving radionuclide source distribution

    DOEpatents

    Stolin, Alexander V.; McKisson, John E.; Lee, Seung Joon; Smith, Mark Frederick

    2012-12-18

    A method for image reconstruction of moving radionuclide distributions. Its particular embodiment is for single photon emission computed tomography (SPECT) imaging of awake animals, though its techniques are general enough to be applied to other moving radionuclide distributions as well. The invention eliminates motion and blurring artifacts for image reconstructions of moving source distributions. This opens new avenues in the area of small animal brain imaging with radiotracers, which can now be performed without the perturbing influences of anesthesia or physical restraint on the biological system.

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

    PubMed

    Martínez-Rodríguez, I; Carril, J M

    2013-01-01

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

  8. Dissociation of reticuloendothelial cell and hepatocyte functions in alcoholic liver disease: a clinical study with a new Tc-99m-labeled hepatobiliary agent

    SciTech Connect

    Rao, B.K.; Weir, G.J. Jr.; Lieberman, L.M.

    1981-07-01

    Tc-99m-sulfur colloid scintigrams were abnormal in four patients with hepatic dysfunction due to chronic alcohol abuse. Minimal uptake of radiocolloid in the liver suggested local reticuloendothelial (RE) cell failure. Imaging with a new hepatobiliary agent, Tc-99m-PIPIDA, revealed rapid hepatic accumulation and excretion of radiotracer with adequate visualization of the organ. Scintigraphic findings in these patients indicated a dissociation of hepatocyte and RE cell functions. Demonstration of adequate hepatocyte function with severe RE failure in alcoholic liver disease using a Tc-99m-labeled hepatobiliary agent has not been previously reported.

  9. Robin Hood caught in Wonderland: brain SPECT findings.

    PubMed

    Morland, David; Wolff, Valérie; Dietemann, Jean-Louis; Marescaux, Christian; Namer, Izzie Jacques

    2013-12-01

    We present the case of a 53-year-old woman presenting several episodes of body image distortions, ground deformation illusions, and problems assessing distance in the orthostatic position corresponding to the Alice in Wonderland syndrome. No symptoms were reported when sitting or lying down. She had uncontrolled hypertension, hyperglycemia, hypercholesterolemia, and a history of head trauma. Her condition had been diagnosed with left internal carotid artery dissection 2 years earlier. Brain SPECT with 99mTc-ECD performed after i.v. injection of the radiotracer in supine and in standing positions showed hypoperfusion in the healthy contralateral frontoparietal operculum (Robin Hood syndrome), deteriorating when standing up. PMID:24152648

  10. Pelvis: normal variants and benign findings in FDG-PET/CT imaging.

    PubMed

    Kohan, Andres; Avril, Norbert E

    2014-04-01

    With the widespread use of whole-body fluorodeoxyglucose (FDG)-PET/computed tomography as a diagnostic tool in patients with cancer, incidental findings are of increasing importance. This is particularly true within the pelvis, where several benign findings might present with increased FDG uptake. In addition, physiologic excretion of radiotracer by way of the urinary tract can complicate image analysis. This article reviews potential incidental benign findings in the pelvis that one should be aware of when interpreting FDG-PET/computed tomography scans.

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

    SciTech Connect

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

    2014-11-07

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

  12. Radiolabeled Phosphonium Salts as Mitochondrial Voltage Sensors for Positron Emission Tomography Myocardial Imaging Agents.

    PubMed

    Kim, Dong-Yeon; Min, Jung-Joon

    2016-09-01

    Despite substantial advances in the diagnosis of cardiovascular disease, (18)F-labeled positron emission tomography (PET) radiopharmaceuticals remain necessary to diagnose heart disease because clinical use of current PET tracers is limited by their short half-life. Lipophilic cations such as phosphonium salts penetrate the mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to negative inner-transmembrane potentials. Radiolabeled tetraphenylphosphonium cation derivatives have been developed as myocardial imaging agents for PET. In this review, a general overview of these radiotracers, including their radiosynthesis, in vivo characterization, and evaluation is provided and clinical perspectives are discussed. PMID:27540422

  13. Being Relevant in Tough Times: TRIUMF's Five-Year Plan

    ScienceCinema

    Tim, Mayer [TRIUMF

    2016-07-12

    Perhaps better known to the international community than its own neighbors, TRIUMF is Canada's national laboratory for particle and nuclear physics.  Working with the Canadian scientific community, TRIUMF has formulated a new vision to transform the laboratory and deliver a whole new level of performance and impact.  The plan capitalizes on platform technologies (superconducting RF cavities for accelerator physics and radiotracers in nuclear medicine) and exploits Canada's role in ATLAS and the LHC.  I will describe the key elements of the plan and discuss the science-policy landscape in which TRIUMF must make its case.

  14. [Capabilities of positron emission tomography to study mecha-nisms of multiple sclerosis: own data and literature].

    PubMed

    Stolyarov, I D; Petrov, A M; Shkil'nyuk, G G; Kataeva, G V; Prakhova, L N

    2016-01-01

    The article presents the literature data and results of our own researchon the use of positron emission tomography (PET) with different radiotracersin multiple sclerosis (MS). Informationon the operating principles of PET and PET studies with different radiotracers are considered. The results of PET studiesin different typesof MS, including determinationof the localization of neuronal damagein the corticalgray matter, assessmentof microglial activation, study of the relationship between glucose metabolismin the brain and the severity of cognitive impairmentin MS, can providenew information about the pathogenesis ofMS.

  15. Copper-Mediated Radiofluorination of Arylstannanes with [18F]KF

    PubMed Central

    2016-01-01

    A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [18F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [18F]F-phenylalanine and [18F]F-DOPA. In addition, an automated synthesis of [18F]MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol. PMID:27718581

  16. Ectopic Lingual Thyroid

    PubMed Central

    Khamassi, Khaled; Jaafoura, Habib; Masmoudi, Fahmi; Lahiani, Rim; Bougacha, Lobna; Ben Salah, Mamia

    2015-01-01

    Ectopy of the thyroid gland is an abnormal embryological development. Its occurrence in children is rare. In this study, we report the case of a 12-year-old girl that presented with dysphagia and nocturnal dyspnea. Magnetic resonance imaging confirmed the presence of a lingual thyroid. Thyroid scintigraphy showed intense and elective uptake of radiotracer at the base of the tongue. Hormonal tests revealed hypothyroidism. Treatment consisted of opotherapy based on levothyroxine. Evolution has been favourable and the patient showed significant improvement with reduction of the dyspnea and the dysphagia and normalization of thyroid hormone tests. PMID:25893126

  17. 99m-Tc-ubiquicidin scintigraphy in diagnosis of knee prosthesis infection and comparison with F-18 fluorodeoxy-glucose positron emission tomography/computed tomography.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Rajkumar, N; Mohanan, Vyshak; Kalarikal, Radhakrishnan; Shinto, Ajit Sugunan

    2015-01-01

    Total knee arthroplasty has witnessed a significant increase in recent years. Despite the advantages of this surgical procedure, it has some complications, the most serious of which is prosthetic infection. The discrimination of bacterial infections from sterile inflammatory processes is of great importance in the management of periprosthetic infection (PPI). Ubiquicidin (UBI) is a synthetic antimicrobial peptide fragment reported to be highly infection-specific. Tc99m-UBI has recently been reported to be a promising radiotracer for infection imaging. We report a case of left knee PPI diagnosed using 99mTc-UBI scintigraphy and compared with F-18 fluorodeoxy-glucose positron emission tomography.

  18. 99m-Tc-ubiquicidin scintigraphy in diagnosis of knee prosthesis infection and comparison with F-18 fluorodeoxy-glucose positron emission tomography/computed tomography

    PubMed Central

    Kamaleshwaran, Koramadai Karuppusamy; Rajkumar, N; Mohanan, Vyshak; Kalarikal, Radhakrishnan; Shinto, Ajit Sugunan

    2015-01-01

    Total knee arthroplasty has witnessed a significant increase in recent years. Despite the advantages of this surgical procedure, it has some complications, the most serious of which is prosthetic infection. The discrimination of bacterial infections from sterile inflammatory processes is of great importance in the management of periprosthetic infection (PPI). Ubiquicidin (UBI) is a synthetic antimicrobial peptide fragment reported to be highly infection-specific. Tc99m-UBI has recently been reported to be a promising radiotracer for infection imaging. We report a case of left knee PPI diagnosed using 99mTc-UBI scintigraphy and compared with F-18 fluorodeoxy-glucose positron emission tomography. PMID:26170572

  19. Complementary roles of brain scintigraphy and computed tomography in multiple sclerosis

    SciTech Connect

    Moreno, A.J.; Brown, J.M.; Waller, S.F.; Lundy, M.M.; Brown, T.J.

    1983-12-01

    Cerebral computed tomography, with and without iodinated contrast, revealed the appearance and evolution of lesions in a 32-year-old man with multiple sclerosis. Two areas were enhanced with contrast, with one showing a mild mass effect and rim of enhancement. Serial brain scintigraphy using technetium-/sub 99m/ glucoheptonate, following the computed tomography, showed the appearance and regression of corresponding regions of increased uptake. Computed tomography one day prior to brain scintigraphy failed to demonstrate a region of increased accumulation of radiotracer. One week later, however, evidence of a corresponding unenhanced defect was noted on computed tomography. Clinical correlation is given additionally.

  20. Modular Strategies for PET Imaging Agents

    PubMed Central

    Hooker, Jacob M

    2009-01-01

    Summary of Recent Advances In recent years, modular and simplified chemical and biological strategies have been developed for the synthesis and implementation of positron emission tomography (PET) radiotracers. New developments in bioconjugation and synthetic methodologies, in combination with advances in macromolecular delivery systems and gene-expression imaging, reflect a need to reduce radiosynthesis burden in order to accelerate imaging agent development. These new approaches, which are often mindful of existing infrastructure and available resources, are anticipated to provide a more approachable entry point for researchers interested in using PET to translate in vitro research to in vivo imaging. PMID:19880343

  1. SPECT Imaging: Basics and New Trends

    NASA Astrophysics Data System (ADS)

    Hutton, Brian F.

    Single Photon Emission Computed Tomography (SPECT) is widely used as a means of imaging the distribution of administered radiotracers that have single-photon emission. The most widely used SPECT systems are based on the Anger gamma camera, usually involving dual detectors that rotate around the patient. Several factors affect the quality of SPECT images (e.g., resolution and noise) and the ability to perform absolute quantification (e.g., attenuation, scatter, motion, and resolution). There is a trend to introduce dual-modality systems and organ-specific systems, both developments that enhance diagnostic capability.

  2. A systemic review of PET and biology in lung cancer

    PubMed Central

    Kaira, Kyoichi; Oriuchi, Noboru; Sunaga, Noriaki; Ishizuka, Tamotsu; Shimizu, Kimihiro; Yamamoto, Nobuyuki

    2011-01-01

    Positron emission tomography imaging with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) has been established as a significant molecular imaging technique in the management of lung cancer. However, 18F-FDG accumulation is not specific, therefore several other radiotracers targeting hypoxia, cell proliferation and amino acid metabolism have been developed for the imaging of human cancers. This review summarizes the current data on the correlation between the underlying molecular biology and tumor PET accumulation in lung cancer. PMID:21904658

  3. Unusual presentations of metastatic prostate carcinoma as detected by anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F] FACBC) PET-CT

    PubMed Central

    Amzat, Rianot; Taleghani, Pooneh; Savir-Baruch, Bital; Nieh, Peter T.; Master, Viraj A.; Halkar, Raghuveer K.; Lewis, Melinda M.; Faurot, Michelle; Bellamy, Leah M.; Goodman, Mark M.; Schuster, David M.

    2013-01-01

    Prostate carcinoma is the second most common cause of cancer related mortality in males in the United States. The pattern of metastatic disease of prostate cancer is well recognized, frequently involving sclerotic bone lesions and abdomino-pelvic lymph nodes. Anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F] FACBC) is a synthetic amino acid analog positron emission tomography (PET) radiotracer with reported utility in the detection of prostate carcinoma. We present two cases of unusual presentations of prostate carcinoma, one with malignant ascitis and omental implants and the other with lytic bone lesions detected with anti-3-[18F]FACBC. PMID:21825855

  4. An assessment of the immunofluorescence technique as a method for demonstrating the histological localization of tetrahydrocannabinol in mammalian tissues

    SciTech Connect

    Morley, M.; Gee, D.J.

    1982-10-01

    The use of the indirect immunofluorescence technique as a method for demonstrating the histological localization of tetrahydrocannabinol (delta-THC) has been examined. The experimental protocol was designed in order that optimal staining conditions with respect to temperature, the length of time of incubations and washes, and the dilution of the antisera should be defined. No marked differences were detected between frozen sections of liver from normal and delta-THC-injected mice. Results from radiotracer experiments using human liver suggest that the success of the method is dependent upon the solubility characteristics of the antigen-antibody complex.

  5. Gallium-67 imaging in muscular sarcoidosis

    SciTech Connect

    Edan, G.; Bourguet, P.; Delaval, P.; Herry, J.Y.

    1984-07-01

    A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid muscle disease but is consistent with the rarity of clinical evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

  6. Increased FDG activity in a dermatofibroma in esophageal cancer patient.

    PubMed

    Bingham, Brigid A; Hatef, Daniel A; Chevez-Barrios, Patricia; Blackmon, Shanda H; Kim, Min P

    2013-03-01

    PET using the radiotracer (18)F-FDG is used for staging patients with esophageal cancer. Nonmalignant conditions, mainly inflammation and some benign tumors, however, can cloud the clinical picture by taking up FDG and producing a false-positive result. We report the case of a 46 year-old man with squamous cell carcinoma of the thoracic esophagus who underwent combined PET/CT and had false-positive uptake in a chest wall dermatofibroma. Dermatofibroma is a benign skin lesion with a characteristic large presence of fibroblasts and macrophages. Macrophage uptake of FDG is likely responsible for the false-positive result on PET/CT. PMID:23357820

  7. Radioactive nanoparticles and their main applications: recent advances.

    PubMed

    Kharisov, Boris I; Kharissova, Oxana V; Berdonosov, Sergei S

    2014-01-01

    Selected nanoparticles and nanocomposites on the basis of radioactive elements are reviewed. Isotopes of metallic gold, iodine and technetium salts, CeO2 and other lanthanide and actinide compounds, as well as several p- (P, C, F, Te) and d- (Fe, Co, Cu, Cd, Zn) elements form most common radioactive nanoparticles. Methods for their fabrication, including dopation with radionuclides and neutron/proton/deuteron activation, are discussed. These nanocomposites possess a series of useful applications, in particular in biology and medicine, including cancer therapeutics, drug delivery systems and radiotracers, as well as in the studies of several catalytic processes and materials structure.

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

    USGS Publications Warehouse

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

    2003-01-01

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

  9. Unusual mediastinal lymph node uptake and peritoneopleural fistula demonstrated on Technetium-99m macro-aggregated human serum albumin (Tc-99m MAA) peritoneal scintigraphy in a patient with portal hypertension.

    PubMed

    Tan, C J; Thang, S P; Lam, W W

    2016-04-01

    Peritoneal radionuclide scan is an established imaging modality for evaluating peritoneopleural communications. In this case report, unusual mediastinal lymph node radiotracer uptake is seen in a patient with portal hypertension on peritoneal scintigraphy. This was suspected to be due to marked lymphatic enlargement from longstanding portal hypertension since childhood, permitting passage of the large Tc-99m MAA particle. The nodes were morphologically benign on CT. Mediastinal lymph node uptake on peritoneal scintigraphy is rare but should not raise undue clinical concern, particularly in a patient with chronic portal hypertension. Anatomic correlation with SPECT-CT can provide reassurance. PMID:27326945

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  11. [Rest gated-SPECT myocardial perfusion post (99m)Tc-MIBI injection in a patient with acute chest pain and with no medical history of ischemic heart disease].

    PubMed

    Negre-Busó, M; Muntaner-Muñoz, L; Rubió-Rodríguez, A; Marin-Buriticá, A; Ferran-Sureda, N; Bassaganyas-Vilarrasa, J

    2015-01-01

    Gated-SPECT myocardial perfusion imaging is a widely used technique indicated for assessment of patients with no clear diagnosis of ischemic heart disease. Early rest gated-SPECT myocardial perfusion study in patients with acute chest pain has high sensitivity and high negative predictive value for ruling out coronary disease. We report a case of a patient admitted for the study of her chest pain. She underwent a myocardial perfusion stress-rest whose interpretation could have been equivocal due to the clinical status of the patient during the injection of the radiotracer. PMID:25759109

  12. Biogeochemical Cycle of Methanol in Anoxic Deep-Sea Sediments

    PubMed Central

    Yanagawa, Katsunori; Tani, Atsushi; Yamamoto, Naoya; Hachikubo, Akihiro; Kano, Akihiro; Matsumoto, Ryo; Suzuki, Yohey

    2016-01-01

    The biological flux and lifetime of methanol in anoxic marine sediments are largely unknown. We herein reported, for the first time, quantitative methanol removal rates in subsurface sediments. Anaerobic incubation experiments with radiotracers showed high rates of microbial methanol consumption. Notably, methanol oxidation to CO2 surpassed methanol assimilation and methanogenesis from CO2/H2 and methanol. Nevertheless, a significant decrease in methanol was not observed after the incubation, and this was attributed to the microbial production of methanol in parallel with its consumption. These results suggest that microbial reactions play an important role in the sources and sinks of methanol in subseafloor sediments. PMID:27301420

  13. Sodium 18F-Fluoride Bone Scintigraphy in Deep Ocean Diver.

    PubMed

    Lim, Jin T E; Moncayo, Valeria M; Alazraki, Naomi

    2015-07-01

    Sodium ¹⁸F-fluoride (NaF) is a diagnostic marker for new bone formation in bone scintigraphy that was approved by US FDA in 1972 but discontinued in 1984. We report a case of a US naval officer who spent time living and working in an oceanic lab, 205 feet below the surface. Plain skeletal films of femurs 4 years later demonstrate bilateral bone infarcts. Corresponding sodium ¹⁸F-fluoride bone scintigraphy demonstrates low-normal to decreased tracer activity. This rectilinear scan image is of historical interest. Other bone scintigraphic radiotracers used in the past and present will be briefly discussed.

  14. Radioecological studies in Korea atomic energy research institute, KAERI.

    PubMed

    Choi, Yong-Ho; Lim, Kwang-Muk; Jun, In; Keum, Dong-Kwon; Han, Moon-Hee

    2011-07-01

    Regarding the assessment of the terrestrial food chain dose to man, radioecology may be the field that is focused on the transfer of radionuclides from environmental media to food crops. In Korea, the environmental transfer of radionuclides to staple food crops have been investigated at Korea Atomic Energy Research Institute (KAERI) for the last 25 y mainly through radiotracer experiments in greenhouses. As a result, several hundreds of parameter values for the prediction of the radionuclide transfer have been produced. Many of them appear in two recent publications of International Atomic Energy Agency. This paper outlines the KAERI's past radioecological work and introduces the ongoing research and future plans. PMID:21525043

  15. Synthesis and characterization of radioisotope nanospheres containing two gamma emitters.

    PubMed

    Jung, Jin-Hyuck; Jung, Sung-Hee; Kim, Sang-Ho; Choi, Seong-Ho

    2012-12-01

    Silica-coated gold-silver alloy nanospheres prepared by Stöber's method were irradiated in a nuclear reactor to prepare radioisotope nanospheres for use as radiotracers. The radioisotope nanospheres included two gamma nuclides: (i) Au-198, emitting major photons with 0.412 MeV and (ii) Ag-108, emitting photons with 0.434 and 0.633 MeV. The nanospheres shell and core diameters were 100-112 nm and 20-50 nm, respectively, depending on their preparation. The gamma-emitting nanospheres could be used as tracers in high-temperature petrochemical and refinery processes in which conventional organic radioactive labels will decompose.

  16. Incidental Detection of Shoulder Peripheral T-Cell Lymphoma During the Redistribution Phase of 201Tl Myocardial Perfusion Scintigraphy.

    PubMed

    Chen, Yu-Ren; Hsieh, Te-Chun; Yen, Kuo-Yang; Kao, Chia-Hung

    2015-10-01

    A 74-year-old woman underwent Tl myocardial perfusion scan for cardiac symptoms; increased radiotracer accumulation in the left shoulder was found in the redistribution images only, and the shoulder was normal in the stress images. Suspecting septic arthritis subsequent investigations were performed, and peripheral T-cell lymphoma was diagnosed. Attention should also be paid to extracardiac sites in interpreting redistribution images taken as late as 4 hours apart from stress images because some clinically pertinent ancillary findings may be found in redistribution images only. PMID:26018700

  17. Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT.

    PubMed

    Hassan, Aamna; Khalid, Madeeha; Khawar, Saquib

    2016-01-01

    Melorheostosis is a benign, noninheritable bone dysplasia characterized by its classic radiographic features of dense, flowing hyperostosis. It frequently affects one limb, usually the lower extremity and rarely the axial skeleton. A 26-year-old lady with obesity, polycystic ovarian syndrome and scalp dandruff presented with a long standing history of upper extremity pain and inability to adduct the arm completely. A Tc-99m MDP whole body and SPECT/CT scan performed for suspected fibrous dysplasia showed increased radiotracer uptake in densely sclerotic humeral and radial melorheostosis. This case highlighted the role of SPECT/CT imaging in this rare condition. PMID:27252746

  18. Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT

    PubMed Central

    Hassan, Aamna; Khalid, Madeeha; Khawar, Saquib

    2016-01-01

    Summary Melorheostosis is a benign, noninheritable bone dysplasia characterized by its classic radiographic features of dense, flowing hyperostosis. It frequently affects one limb, usually the lower extremity and rarely the axial skeleton. A 26-year-old lady with obesity, polycystic ovarian syndrome and scalp dandruff presented with a long standing history of upper extremity pain and inability to adduct the arm completely. A Tc-99m MDP whole body and SPECT/CT scan performed for suspected fibrous dysplasia showed increased radiotracer uptake in densely sclerotic humeral and radial melorheostosis. This case highlighted the role of SPECT/CT imaging in this rare condition. PMID:27252746

  19. Image presentation and normal SPECT rCBF

    SciTech Connect

    Devous, M.D. Sr.

    1991-12-31

    The appearance of images of normal regional cerebral blood flow (rCBF) obtained from single photon emission computed tomography (SPECT) is influenced by several factors, including (1) the environmental conditions at the time of administration of the radiotracer, (2) the characteristics of the subject (eg. age, gender, and handedness), (3) the format used for image presentation, (4) the quality of the tomographic device, (5) the choices of image-processing techniques, and (6) the radiopharmaceutical used. The first three of these topics are briefly reviewed here; topics 4, 5 and 6 are reviewed by others in this workshop summary. 27 refs.

  20. Positron emission tomographic investigations of central muscarinic cholinergic receptors with three isomers of [76Br]BrQNP.

    PubMed

    Strijckmans, V; Bottlaender, M; Luo, H; Ottaviani, M; McPherson, D W; Loc'h, C; Fuseau, C; Knapp, F F; Mazière, B

    1997-05-01

    We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[76Br]BrQNP, E(-,-)-[76Br]BrQNP and E(-,+)-[76Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [76Br]BrNH4 and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M2 selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M1 selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., the E(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively. Z(-,-)-[76Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for the E(-, +)-[76Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors. Z(-, -)-[76Br]BrQNP, which is displaced in higher amounts from M2 mAChR-enriched structures, reveals an M2 affinity. The two isomers

  1. Preliminary observations on californium-252 behaviour in sea water, sediments and zooplankton.

    PubMed

    Aston, S R; Fowler, S W

    1983-04-01

    We carried out radiotracer experiments on the behaviour of 252Cf in the marine environment. The particulate fraction of californium in sea water approached 45% after four days. Californium rapidly adsorbed onto marine coastal and deep-sea sediments with Kd values from 1.4 X 10(4) to greater than or equal to 1 X 10(5). The concentration of 252Cf in euphausiids reached near-equilibrium factors of 3 X 10(2) in water after one week; in contrast, the assimilation from food was very low. Excreted fecal pellets, molts and zooplankton carcasses are potentially important vectors for californium re-distribution in the oceans.

  2. Microbial degradation of natural and pollutionally-derived lignocelluosic detritus in wetland ecosystems

    SciTech Connect

    Hodson, R.E.; Maccubbin, A.E.; Benner, R.

    1982-12-01

    Wetlands have been characterized as detritus-based ecosystems. Most of the standing stock of plant biomass is not directly eaten by grazing animals, but first must be decomposed by the sediment and water microflora. In this study, the composition of a variety of wetland plants serving as sources of detritus was determined. Most of the dry weight was found to be lignocellulose. A radiotracer procedure was developed to specifically label the lignin and cellulosic moieties of lignocellulose from a variety of wetland plants.

  3. Nuclear Breast Imaging: Clinical Results and Future Directions.

    PubMed

    Berg, Wendie A

    2016-02-01

    Interest in nuclear breast imaging is increasing because of technical improvements in dedicated devices that allow the use of relatively low doses of radiotracers with high sensitivity for even small breast cancers. For women with newly diagnosed cancer, primary chemotherapy is often recommended, and improved methods of assessing treatment response are of interest. With widespread breast density notification, functional rather than anatomic methods of screening are of increasing interest as well. For a cancer imaging technology to be adopted, several criteria must be met that will be discussed: evidence of clinical benefit with minimal harm, standardized interpretive criteria, direct biopsy guidance, and acceptable cost-effectiveness.

  4. Imaging in drug development.

    PubMed

    Nairne, James; Iveson, Peter B; Meijer, Andreas

    2015-01-01

    Imaging has played an important part in the diagnosis of disease and development of the understanding of the underlying disease mechanisms and is now poised to make an impact in the development of new pharmaceuticals. This chapter discusses the underlying technologies that make the field ready for this challenge. In particular, the potentials of magnetic resonance imaging and functional magnetic resonance imaging are outlined, including the new methods developed to provide additional information from the scans carried out. The field of nuclear medicine has seen a rapid increase in interest as advances in radiochemistry have enabled a wide range of new radiotracers to be synthesised. PMID:25727706

  5. Approaches to reducing radiation dose from radionuclide myocardial perfusion imaging.

    PubMed

    Dorbala, Sharmila; Blankstein, Ron; Skali, Hicham; Park, Mi-Ae; Fantony, Jolene; Mauceri, Charles; Semer, James; Moore, Stephen C; Di Carli, Marcelo F

    2015-04-01

    Radionuclide myocardial perfusion imaging (MPI) plays a vital role in the evaluation and management of patients with coronary artery disease. However, because of a steep growth in MPI in the mid 2000s, concerns about inappropriate use of MPI and imaging-related radiation exposure increased. In response, the professional societies developed appropriate-use criteria for MPI. Simultaneously, novel technology, image-reconstruction software for traditional scanners, and dedicated cardiac scanners emerged and facilitated the performance of MPI with low-dose and ultra-low-dose radiotracers. This paper provides a practical approach to performing low-radiation-dose MPI using traditional and novel technologies. PMID:25766891

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

    PubMed Central

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

    2016-01-01

    Prostate-specific membrane antigen (PSMA)-targeted PET imaging is an emerging technique for evaluating patients with prostate cancer (PCa) in a variety of clinical contexts. As with any new imaging modality, there are interpretive pitfalls that are beginning to be recognized. In this image report, we describe the findings in a 63-year-old male with biochemically recurrent PCa after radical prostatectomy who was imaged with 18F-DCFPyL, a small molecule inhibitor of PSMA. Diffuse radiotracer uptake was noted throughout the sacrum, corresponding to imaging findings on contrast-enhanced CT, bone scan, and pelvic MRI consistent with Paget’s disease of bone. The uptake of 18F-DCFPyL in Paget’s disease is most likely due to hyperemia and increased radiotracer delivery. In light of the overlap in patients affected by PCa and Paget’s, it is important for nuclear medicine physicians and radiologists interpreting PSMA PET/CT scans to be aware of the potential for this diagnostic pitfall. Correlation to findings on conventional imaging such as diagnostic CT and bone scan can help confirm the diagnosis. PMID:26807444

  7. Theoretical dosimetry estimations for radioisotopes produced by proton-induced reactions on natural and enriched molybdenum targets

    NASA Astrophysics Data System (ADS)

    Hou, X.; Celler, A.; Grimes, J.; Bénard, F.; Ruth, T.

    2012-03-01

    This study presents a summary of the dosimetry calculations performed for three technetium agents most commonly used in nuclear medicine diagnostic studies, namely sestamibi™, phosphonates and pertechnetate, labeled with cyclotron-produced technetium. Calculated patient doses were compared to those that would be delivered by the same radiotracers labeled with technetium obtained from a generator produced in a reactor. The main difference is that technetium from a generator is pure, i.e. contains only 99mTc and its decay product 99gTc, while in a cyclotron a large number of other stable and radioactive isotopes are created. In our calculations only technetium radioisotopes (ground and isomeric states) were considered as they will be included in the radiotracer labeling process and will contribute to the patient dose. Other elements should be removed by chemical purification. These dose estimates are based on our theoretical calculations of the proton-induced reaction cross sections and radioisotope production yields. Thick targets of enriched (three different compositions) and natural molybdenum, and three initial beam energies (16, 19 and 24 MeV) were considered for irradiation times of 3, 6 and 12 h with a beam current of 200 µA. The doses were calculated for injection times corresponding to 0, 2, 8, 12 and 24 h after the end of beam.

  8. Nuclear Imaging of Amyloidosis

    PubMed Central

    Cytawa, Wojciech; Teodorczyk, Jacek; Lass, Piotr

    2014-01-01

    Summary Amyloidosis is a clinical condition caused by deposition of various protein fibrills in extracellular space. The presented symptoms depend on the type of deposits and the organ or organs involved. The correct diagnosis is often difficult, due to lack of nonivasive imaging techniques and insufficiency of morphological imaging procedures delievered by radiology. We presented a list of potential radiopharmaceuticals that can be used in detecting various types of amyloidoses. 123I-SAP proved to have high sensitivity in imaging of AA and AL amyloidosis in visceral organs. 99mTc-Aprotinin was found to be useful in detecting cardiac amyloidosis. A couple of classical radiotracers, such as 201Tl, 123I-mIBG, together with 111In-antimyosin were also tested for accuracy in cardiac imaging, however the main problem was low specificity. Potential applicability was also found in case of some bone-seeking agents and other radiotracers, e.g. 67Ga-citrate and 99mTc-penta-DMSA. High sensitivity and specificity was achieved with β2-microglobulin labeled with 131I or 111In. Among PET tracers, 11C-PIB deserves more attention, because it may have an important role in diagnosing of AD in the near future. Further clinical studies are expected to take place, because noninvasive diagnosing and monitoring of amyloidosis is still a challenge. PMID:25071873

  9. [Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use].

    PubMed

    Arbizu, J; Luquin, M R; Abella, J; de la Fuente-Fernández, R; Fernandez-Torrón, R; García-Solís, D; Garrastachu, P; Jiménez-Hoyuela, J M; Llaneza, M; Lomeña, F; Lorenzo-Bosquet, C; Martí, M J; Martinez-Castrillo, J C; Mir, P; Mitjavila, M; Ruiz-Martínez, J; Vela, L

    2014-01-01

    Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson's disease progression.

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

    PubMed

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

    2015-01-01

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

  11. Theoretical dosimetry estimations for radioisotopes produced by proton-induced reactions on natural and enriched molybdenum targets.

    PubMed

    Hou, X; Celler, A; Grimes, J; Bénard, F; Ruth, T

    2012-03-21

    This study presents a summary of the dosimetry calculations performed for three technetium agents most commonly used in nuclear medicine diagnostic studies, namely sestamibi™, phosphonates and pertechnetate, labeled with cyclotron-produced technetium. Calculated patient doses were compared to those that would be delivered by the same radiotracers labeled with technetium obtained from a generator produced in a reactor. The main difference is that technetium from a generator is pure, i.e. contains only (99m)Tc and its decay product (99g)Tc, while in a cyclotron a large number of other stable and radioactive isotopes are created. In our calculations only technetium radioisotopes (ground and isomeric states) were considered as they will be included in the radiotracer labeling process and will contribute to the patient dose. Other elements should be removed by chemical purification. These dose estimates are based on our theoretical calculations of the proton-induced reaction cross sections and radioisotope production yields. Thick targets of enriched (three different compositions) and natural molybdenum, and three initial beam energies (16, 19 and 24 MeV) were considered for irradiation times of 3, 6 and 12 h with a beam current of 200 µA. The doses were calculated for injection times corresponding to 0, 2, 8, 12 and 24 h after the end of beam.

  12. Comparison of short-lived medical isotopes activation by laser thin target induced protons and conventional cyclotron proton beams

    NASA Astrophysics Data System (ADS)

    Murray, Joseph; Dudnikova, Galina; Liu, Tung-Chang; Papadopoulos, Dennis; Sagdeev, Roald; Su, J. J.; UMD MicroPET Team

    2014-10-01

    Production diagnostic or therapeutic nuclear medicines are either by nuclear reactors or by ion accelerators. In general, diagnostic nuclear radioisotopes have a very short half-life varying from tens of minutes for PET tracers and few hours for SPECT tracers. Thus supplies of PET and SPECT radiotracers are limited by regional production facilities. For example 18F-fluorodeoxyglucose (FDG) is the most desired tracer for positron emission tomography because its 110 minutes half-life is sufficient long for transport from production facilities to nearby users. From nuclear activation to completing image taking must be done within 4 hours. Decentralized production of diagnostic radioisotopes will be idea to make high specific activity radiotracers available to researches and clinicians. 11 C, 13 N, 15 O and 18 F can be produced in the energy range from 10-20 MeV by protons. Protons of energies up to tens of MeV generated by intense laser interacting with hydrogen containing targets have been demonstrated by many groups in the past decade. We use 2D PIC code for proton acceleration, Geant4 Monte Carlo code for nuclei activation to compare the yields and specific activities of short-lived isotopes produced by cyclotron proton beams and laser driven protons.

  13. Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, A Calcium Channel Antagonist

    PubMed Central

    Rotstein, Benjamin H.; Liang, Steven H.; Belov, Vasily V.; Livni, Eli; Levine, Dylan B.; Bonab, Ali A.; Papisov, Mikhail I.; Perlis, Roy H.; Vasdev, Neil

    2016-01-01

    In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·μmol−1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08 %ID/cc (percent of injected dose per cubic centimeter) at peak, 15–60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg−1, i.p.), whole brain radioactivity uptake was diminished by 25–40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned. PMID:26016546

  14. Biotin radioligand assay with an /sup 125/I-labeled biotin derivative, avidin, and avidin double-antibody reagents

    SciTech Connect

    Livaniou, E.; Evangelatos, G.P.; Ithakissios, D.S.

    1987-11-01

    We describe a new radioligand assay for determining biotin in biological fluids by using a mixture of N-(beta-(4-OH-3-125I-phenyl)ethyl)- and N-(beta-(4-OH-3,5-di-125I-phenyl)ethyl)biotinamides as radiotracer, avidin as a binding protein, and an avidin double-antibody as a separation reagent. The radiotracer is synthesized by coupling (at pH 8.5, 20-22 degrees C, 90 min) N-hydroxysuccinimidobiotin to radioiodinated tyramine. The assay curve is linear and the assay itself is sensitive (less than 10 ng/L), reproducible (intra- and interassay CVs 4.1% and 7.0%, respectively), and allows the simultaneous handling of more than 100 samples in less than 4 h. Serum samples from apparently normal subjects contained 100-840 ng of biotin per liter (mean 340 ng/L). Pregnant women had low concentrations of biotin (100-300 ng/L) in their serum. Patients undergoing chronic hemodialysis treatment showed high concentrations (0.5-3.0 micrograms/L), which may be ascribable to the inability of avidin, which was used as the assay binding protein, to distinguish biotin from biotinyl derivatives with an intact ureido ring.

  15. Indirect Oxidation of Co(II) in the Presence of the Marine Mn(II)-Oxidizing Bacterium Bacillus Sp. Strain SG-1

    SciTech Connect

    Murray, K.J.; Webb, S.M.; Bargar, J.R.; Tebo, B.M.; /Scripps Inst. Oceanography /SLAC, SSRL /Oregon Health Sci. U.

    2009-04-29

    Cobalt(II) oxidation in aquatic environments has been shown to be linked to Mn(II) oxidation, a process primarily mediated by bacteria. This work examines the oxidation of Co(II) by the spore-forming marine Mn(II)-oxidizing bacterium Bacillus sp. strain SG-1, which enzymatically catalyzes the formation of reactive nanoparticulate Mn(IV) oxides. Preparations of these spores were incubated with radiotracers and various amounts of Co(II) and Mn(II), and the rates of Mn(II) and Co(II) oxidation were measured. Inhibition of Mn(II) oxidation by Co(II) and inhibition of Co(II) oxidation by Mn(II) were both found to be competitive. However, from both radiotracer experiments and X-ray spectroscopic measurements, no Co(II) oxidation occurred in the complete absence of Mn(II), suggesting that the Co(II) oxidation observed in these cultures is indirect and that a previous report of enzymatic Co(II) oxidation may have been due to very low levels of contaminating Mn. Our results indicate that the mechanism by which SG-1 oxidizes Co(II) is through the production of the reactive nanoparticulate Mn oxide.

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

    PubMed

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

    2015-06-01

    For the growth and spread of a tumor beyond 2 mm, angiogenesis plays a crucial role, and association of various integrins with angiogenesis is evidential. The aim of the study was radiolabeling of DOTA-chelated RGD (arginine-glycine-aspartic acid) peptide with (68)Ga for PET imaging in locally advanced breast carcinoma. DOTA-RGD was incubated with (68)GaCl3, eluted in 0.05 m HCl. Elution volume, peptide amount, and reaction pH were studied. Radio-ITLC, gas chromatography, endotoxin, and sterility testing were performed. Serial (n=3) and whole-body (n=2) PET/CT imaging was done on patients post i.v. injection of 111-185 MBq of (68)Ga-DOTA-RGD. Maximum radiolabeling yield was achieved with 3 mL elution volume of 15-20 μg peptide at pH 3.5-4.0 with 10 minutes of incubation at 95°C. Product samples were sterile having 99.5% radiochemical purity with residual ethanol content and endotoxins in injectable limits. Intense radiotracer uptake was noticed in the tumor with SUVmax 15.3 at 45 minutes in serial images. Physiological radiotracer uptake was seen in the liver, spleen, ventricles, and thyroid with excretion through the kidneys. The authors concluded that (68)Ga-DOTA-RGD has the potential for imaging α,vβ3 integrin-expressing tumors. PMID:26083951

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

    PubMed

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

    2015-06-01

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

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

    SciTech Connect

    Fink-Bennett, D.

    1982-10-01

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

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

    PubMed

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

    2015-01-01

    Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging. PMID:25633335

  20. Identification and in vivo evaluation of a fluorine-18 rolipram analogue, [(18) F]MNI-617, as a radioligand for PDE4 imaging in mammalian brain.

    PubMed

    Thomae, David; Morley, Thomas J; Lee, Hsiaoju S; Barret, Olivier; Constantinescu, Cristian; Papin, Caroline; Baldwin, Ronald M; Tamagnan, Gilles D; Alagille, David

    2016-05-15

    Phosphodiesterase (PDE) 4 is the most prevalent PDE in the central nervous system (CNS) and catalyzes hydrolysis of intracellular cAMP, a secondary messenger. By therapeutic inhibition of PDE4, intracellular cAMP levels can be stabilized, and the symptoms of psychiatric and neurodegenerative disorders including depression, memory loss and Parkinson's disease can be ameliorated. Radiotracers targeting PDE4 can be used to study PDE4 density and function, and evaluate new PDE4 therapeutics, in vivo in a non-invasive way, as has been shown using the carbon-11 labeled PDE4 inhibitor R-(-)-rolipram. Herein we describe a small series of rolipram analogs that contain fluoro- or iodo-substituents that could be used as fluorine-18 PET or iodine-123 SPECT PDE4 radiotracers. This series was evaluated with an in vitro binding assay and a 4-(fluoromethyl) derivative of rolipram, MNI-617, was identified, with a five-fold increase in affinity for PDE4 (Kd  = 0.26 nM) over R-(-)-rolipram (Kd  = 1.6 nM). A deutero-analogue d2 -[(18) F]MNI-617 was radiolabeled and produced in 23% yield with high (>5 Ci/µmol) specific activity and evaluated in non-human primate, where it rapidly entered the brain, with SUVs between 4 and 5, and with a distribution pattern consistent with that of PDE4. PMID:27006107