WorldWideScience

Sample records for receptor pet tracer

  1. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... these PET tracers further....

  2. RGD-based PET tracers for imaging receptor integrin αv β3 expression.

    Science.gov (United States)

    Cai, Hancheng; Conti, Peter S

    2013-05-15

    Positron emission tomography (PET) imaging of receptor integrin αv β3 expression may play a key role in the early detection of cancer and cardiovascular diseases, monitoring disease progression, evaluating therapeutic response, and aiding anti-angiogenic drugs discovery and development. The last decade has seen the development of new PET tracers for in vivo imaging of integrin αv β3 expression along with advances in PET chemistry. In this review, we will focus on the radiochemistry development of PET tracers based on arginine-glycine-aspartic acid (RGD) peptide, present an overview of general strategies for preparing RGD-based PET tracers, and review the recent advances in preparations of (18) F-labeled, (64) Cu-labeled, and (68) Ga-labeled RGD tracers, RGD-based PET multivalent probes, and RGD-based PET multimodality probes for imaging receptor integrin αv β3 expression.

  3. Inverse agonist histamine H3 receptor PET tracers labelled with carbon-11 or fluorine-18.

    Science.gov (United States)

    Hamill, Terence G; Sato, Nagaaki; Jitsuoka, Makoto; Tokita, Shigeru; Sanabria, Sandra; Eng, Waisi; Ryan, Christine; Krause, Stephen; Takenaga, Norihiro; Patel, Shil; Zeng, Zhizhen; Williams, David; Sur, Cyrille; Hargreaves, Richard; Burns, H Donald

    2009-12-01

    Two histamine H3 receptor (H3R) inverse agonist PET tracers have been synthesized and characterized in preclinical studies. Each tracer has high affinity for the histamine H3 receptor, has suitable lipophilicity, and neither is a substrate for the P-glycoprotein efflux pump. A common phenolic precursor was used to synthesize each tracer with high specific activity and radiochemical purity by an alkylation reaction using either [(11)C]MeI or [(18)F]FCD(2)Br. Autoradiographic studies in rhesus monkey and human brain slices showed that each tracer had a widespread distribution with high binding densities in frontal cortex, globus pallidus and striatum, and lower uptake in cerebellum. The specificity of this expression pattern was demonstrated by the blockade of the autoradiographic signal by either the H3R agonist R-alpha-methylhistamine or a histamine H3R inverse agonist. In vivo PET imaging studies in rhesus monkey showed rapid uptake of each tracer into the brain with the same distribution seen in the autoradiographic studies. Each tracer could be blocked by pretreatment with a histamine H3R inverse agonist giving a good specific signal. Comparison of the in vitro metabolism of each compound showed slower metabolism in human liver microsomes than in rhesus monkey liver microsomes, with each compound having a similar clearance rate in humans. The in vivo metabolism of 1b in rhesus monkey showed that at 60 min, approximately 35% of the circulating counts were due to the parent. These tracers are very promising candidates as clinical PET tracers to both study the histamine H3R system and measure receptor occupancy of H3R therapeutic compounds.

  4. STRATEGIES FOR QUANTIFYING PET IMAGING DATA FROM TRACER STUDIES OF BRAIN RECEPTORS AND ENZYMES.

    Energy Technology Data Exchange (ETDEWEB)

    Logan, J.

    2001-04-02

    A description of some of the methods used in neuroreceptor imaging to distinguish changes in receptor availability has been presented in this chapter. It is necessary to look beyond regional uptake of the tracer since uptake generally is affected by factors other than the number of receptors for which the tracer has affinity. An exception is the infusion method producing an equilibrium state. The techniques vary in complexity some requiring arterial blood measurements of unmetabolized tracer and multiple time uptake data. Others require only a few plasma and uptake measurements and those based on a reference region require no plasma measurements. We have outlined some of the limitations of the different methods. Laruelle (1999) has pointed out that test/retest studies to which various methods can be applied are crucial in determining the optimal method for a particular study. The choice of method will also depend upon the application. In a clinical setting, methods not involving arterial blood sampling are generally preferred. In the future techniques for externally measuring arterial plasma radioactivity with only a few blood samples for metabolite correction will extend the modeling options of clinical PET. Also since parametric images can provide information beyond that of ROI analysis, improved techniques for generating such images will be important, particularly for ligands requiring more than a one-compartment model. Techniques such as the wavelet transform proposed by Turkheimer et al. (2000) may prove to be important in reducing noise and improving quantitation.

  5. Multifocal Head and Neck Paraganglioma Evaluated with Different PET Tracers: Comparison Between Fluorine-18-Fluorodeoxyglucose Between Fluorine-18-Fluorodeoxyglucose and Gallium-68-Somatostatin Receptor PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Castaldi, Paola; Rufini, Vittoria [Catholic Univ. of the Sacred Heart, Rome (Italy); Treglia, G. [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

    2013-09-15

    uptake in the pituitary is also evident (blue arrow). The patient refused surgery and, based on somatostatin receptor PET/CT findings, she underwent therapy with somatostatin analogues. Paragangliomas are rare neuroendocrine tumours arising anywhere along the paraganglial system, with a high frequency of hereditary forms or multifocal disease. Functional imaging with different PET tracers (including F-18-FDG to study the glucose metabolism, F-18-DOPA to study the dopaminergic metabolism and Ga-68-somatostatin analogues to study the somatostatin receptors expression) in combination with morphological imaging may be required to assess the extent of the disease in extra-adrenal paragangliomas. Recent data indicate that the choice of PET tracer should be tailored according to the tumour localisation and the genetic status. Recently, Timmers et al., evaluating a large series of patients with paraganglioma, demonstrated that F-18-FDG-PET/CT is suitable for routine functional imaging of this tumour, particularly in patients with SDH-related tumours. F-18-FDG-PET/CT has the potential to be useful in paraganglioma imaging, not only for detection of metastases but also as a prognostic tool identifying tumours with a high metabolic rate and high metastatic potential. On the other hand, recent studies demonstrated that Ga-68-somatostatin analogue PET/CT is an accurate functional imaging method in patients with neuroendocrine tumours, including those with head and neck paraganglioma. This imaging technique non-invasively provides data on receptor expression on neuroendocrine tumour cells with direct therapeutic implications, identifying those patients who are eligible for a treatment with somatostatin analogues. F-18-DOPA is another PET tracer which has been particularly useful in patients with head and neck paraganglioma. To date, significant studies comparing F-18-DOPA and Ga-68-somatostatin receptor PET/CT in this setting are still lacking. In our case, Ga-68-somatostatin receptor

  6. Developing new PET tracers to image the growth hormone secretagogue receptor 1a (GHS-R1a).

    Science.gov (United States)

    Kawamura, Kazunori; Fujinaga, Masayuki; Shimoda, Yoko; Yamasaki, Tomoteru; Zhang, Yiding; Hatori, Akiko; Xie, Lin; Wakizaka, Hidekatsu; Kumata, Katsushi; Ohkubo, Takayuki; Kurihara, Yusuke; Ogawa, Masanao; Nengaki, Nobuki; Zhang, Ming-Rong

    2017-09-01

    `The growth hormone secretagogue receptor 1a (GHS-R1a) is the orphan G-protein-coupled receptor, and its endogenous ligand is ghrelin. GHS-R1a contributes to regulation of glucose homeostasis, memory and learning, food addiction, and neuroprotection. Several PET tracers for GHS-R1a have been developed, but none have been reported to be clinically applicable to GHS-R1a imaging. In this study, we developed three new PET tracers for GHS-R1a: (18)F-labeled 6-(4-chlorophenyl)-3-((1-(2-fluoroethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (1), (11)C-labeled 6-(4-chlorophenyl)-3-((1-(2-methoxyethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (2), and (11)C-labeled (S)-(4-(1H-indole-6-carbonyl)-3-methylpiperazin-1-yl)(4'-methoxy-[1,1'-biphenyl]-4-yl)methanone (3). [(18)F]1 was synthesized by the (18)F-fluoroethylation; [(11)C]2 or [(11)C]3 was synthesized by the (11)C-methylation. Biodistribution studies and PET studies were conducted in mice. We successfully radiosynthesized [(18)F]1, [(11)C]2, and [(11)C]3 with appropriate radioactivity for the animal study. In the ex vivo biodistribution study, 60min following injection, the radioactivity level of [(18)F]1 was relatively high in the small intestine, that of [(11)C]2 was high in the liver, and that of [(11)C]3 was high in the pancreas. The radioactivity levels of the three PET tracers were relatively low in the brain. Under pretreatment with YIL781 (a selective and high affinity antagonist for GHS-R1a), the pancreas radioactivity level at 30min following [(11)C]3 injection was significantly reduced to 55% of control, but the radioactivity in the brain was not changed. In the PET study under control conditions, high radioactivity levels in the liver and pancreas were observed following [(11)C]3 injection. With YIL781 pretreatment, the accumulated radioactivity in the pancreas 15-60min after [(11)C]3 injection was significantly decreased to 78% of control. [(11)C]3 exhibited relatively high uptake

  7. Current radiosynthesis strategies for 5-HT2A receptor PET tracers

    DEFF Research Database (Denmark)

    Herth, Matthias M; Knudsen, Gitte M

    2015-01-01

    Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been...... made to develop a suitable 5-HT2A R positron emission tomography-tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5-HT2A R radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning...

  8. Microfluidics for Synthesis of Peptide-Based PET Tracers

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2013-01-01

    Full Text Available Positron emission tomography (PET is a powerful noninvasive tool for acquisition of the physiological parameters in human and animals with the help of PET tracers. Among all the PET tracers, radiolabeled peptides have been widely explored for cancer-related receptor imaging due to their high affinity and specificity to receptors. But radiochemistry procedures for production of peptide-based PET tracers are usually complex, which makes large-scale clinical studies relatively challenging. New radiolabeling technologies which could simplify synthesis and purification procedures, are extremely needed. Over the last decade, microfluidics and lab-on-a-chip (LOC technology have boomed as powerful tools in the field of organic chemistry, which potentially provide significant help to the PET chemistry. In this minireview, microfluidic radiolabeling technology is described and its application for synthesis of peptide-based PET tracers is summarized and discussed.

  9. Synthesis and PET imaging of the benzodiazepine receptor tracer [N-methyl-{sup 11}C]iomazenil

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, Ronald M.; Horti, Andrew G.; Bremner, J. Douglas; Stratton, Morgan D.; Dannals, Robert F.; Ravert, Hayden T.; Zea-Ponce, Yolanda; Ng, Chin K.; Dey, Holley M.; Soufer, Robert; Charney, Dennis S.; Mazza, Samuel M.; Sparks, Richard B.; Stubbs, James B.; Innis, Robert B

    1995-07-01

    The central benzodiazepine receptor tracer [N-methyl-{sup 11}C]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with [{sup 11}C]methyl iodide. The [{sup 11}C]CH{sub 3}I (prepared by reduction of [{sup 11}C]CO{sub 2} with LiAlH{sub 4} followed by reaction with HI) was reacted with noriomazenil inN,N -dimethylformamide and Bu{sub 4}N{sup +}OH{sup -} for 1 min at 80 deg. C and purified by HPLC (C{sub 18}, 34% CH{sub 3}CN/H{sub 2}O, 7 mL/min). The product was obtained with synthesis time 35 {+-} 5 min (mean {+-} SD, n = 7), radiochemical yield (EOB) 36 {+-} 16%, radiochemical purity 99 {+-} 1%, and specific activity 5100 {+-} 2800 mCi/{mu}mol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of [{sup 11}C]iomazenil in an adult baboon or healthy human volunteer, radioactivity accumulated in the cortex with time-activity curves in agreement with results obtained with [{sup 11}C]flumazenil PET and [{sup 123}I]iomazenil SPECT studies. The count rate was sufficient to obtain quantitative images up to 2 h post-injection with a 14 mCi injection. These results suggest that [{sup 11}C]iomazenil will be a useful agent for measuring benzodiazepine receptorsin vivo by positron emission tomography.

  10. Kinetic analysis of the cannabinoid-1 receptor PET tracer [{sup 18}F]MK-9470 in human brain

    Energy Technology Data Exchange (ETDEWEB)

    Sanabria-Bohorquez, Sandra Marina; Hamill, Terence G.; Burns, H.D. [Merck Research Laboratories, Imaging, West Point, PA (United States); Goffin, Karolien; Laere, Koen van [University Hospital and K.U. Leuven, Division of Nuclear Medicine, Leuven (Belgium); Lepeleire, Inge de [Merck Research Laboratories, Brussels (Belgium); Bormans, Guy [K.U. Leuven, Laboratory of Radiopharmacy, Leuven (Belgium)

    2010-05-15

    Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [{sup 18}F]MK-9470 in human brain. [{sup 18}F]MK-9470 data were analysed using reversible models and the distribution volume V{sub T} and V{sub ND} k{sub 3} (V{sub ND} k{sub 3} = K{sub 1} k{sub 2}) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K{sub i} and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined. A reversible two-tissue compartment model using a global k{sub 4} value was necessary to describe brain kinetics. Both V{sub T} and V{sub ND} k{sub 3} were estimated satisfactorily and their test-retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K{sub i}. The linear relationship between K{sub i} and V{sub ND} k{sub 3} demonstrated that K{sub i} or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test-retest variability of K{sub i} and FUR was <10% and estimates were independent of blood flow. Brain uptake can be used as a receptor availability index, albeit at the expense of potential bias due to between-subject differences in tracer plasma kinetics. [{sup 18}F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [{sup 18}F]MK-9470 plasma kinetics can be assessed using a few venous samples. (orig.)

  11. Small Molecule PET Tracers for Transporter Imaging.

    Science.gov (United States)

    Kilbourn, Michael R

    2017-09-01

    As the field of PET has expanded and an ever-increasing number and variety of compounds have been radiolabeled as potential in vivo tracers of biochemistry, transporters have become important primary targets or facilitators of radiotracer uptake and distribution. A transporter can be the primary target through the development of a specific high-affinity radioligand: examples are the multiple high-affinity radioligands for the neuronal membrane neurotransmitter or vesicular transporters, used to image nerve terminals in the brain. The goal of a radiotracer might be to study the function of a transporter through the use of a radiolabeled substrate, such as the application of 3-O-[(11)C]methyl]glucose to measure rates of glucose transport through the blood-brain barrier. In many cases, transporters are required for radiotracer distributions, but the targeted biochemistries might be unrelated: an example is the use of 2-deoxy-2-[(18)F]FDG for imaging glucose metabolism, where initial passage of the radiotracer through cell membranes requires the action of specific glucose transporters. Finally, there are transporters such as p-glycoprotein that function to extrude small molecules from tissues, and can effectively work against successful uptake of radiotracers. The diversity of structures and functions of transporters, their importance in human health and disease, and their role in therapeutic drug disposition suggest that in vivo imaging of transporter location and function will continue to be a point of emphasis in PET radiopharmaceutical development. In this review, the variety of transporters and their importance for in vivo PET radiotracer development and application are discussed. Transporters have thus joined the other major protein targets such as G-protein coupled receptors, ligand-gated ion channels, enzymes, and aggregated proteins as of high interest for understanding human health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Synthesis and evaluation of 6-[{sup 18}F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.-S. E-mail: ding@bnl.gov; Liu, N.; Wang, T.; Marecek, J.; Garza, V.; Ojima, I.; Fowler, J.S

    2000-05-01

    Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[{sup 18}F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[{sup 18}F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[{sup 18}F]fluoro-A-85380. Preliminary comparative PET studies of 6-[{sup 18}F]fluoro-A-85380 and 2-[{sup 18}F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system.

  13. [{sup 18}F]FE rate at SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Haeusler, Daniela; Zeilinger, Markus; Wadsak, Wolfgang; Hacker, Marcus; Mitterhauser, Markus [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Kuntner, Claudia; Wanek, Thomas; Langer, Oliver [AIT Austrian Institute of Technology GmbH, Biomedical Systems, Health and Environment Department, Seibersdorf (Austria); Nics, Lukas [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); University of Vienna, Department of Nutritional Sciences, Vienna (Austria); Savli, Markus; Lanzenberger, Rupert R. [Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna (Austria); Karagiannis, Panagiotis [King' s College London, Cutaneous Medicine and Immunotherapy, St. John' s Institute of Dermatology, Division of Genetics and Molecular Medicine King' s College London School of Medicine, Guy' s Hospital, London (United Kingdom); Shanab, Karem; Spreitzer, Helmut [University of Vienna, Department of Drug and Natural Product Synthesis, Vienna (Austria)

    2015-04-01

    The adenosine A{sub 3} receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [{sup 18}F]FE rate at SUPPY. Rats were injected with [{sup 18}F]FE rate at SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE rate at SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [{sup 18}F]FE rate at SUPPY and [{sup 18}F]FDG. Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice). In vitro stability of [{sup 18}F]FE rate at SUPPY in human and rat plasma was also evaluated. [{sup 18}F]FE rate at SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [{sup 18}F]FE rate at SUPPY uptake (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [{sup 18}F]FE rate at SUPPY uptake (p = 0.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [{sup 18}F]FE rate at SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [{sup 18}F]FDG uptake (p = 0.12), the xenograft model showed significantly increased uptake of [{sup 18}F]FE rate at SUPPY in the tissue masses from CHO cells expressing the human A3R (p = 0.03). [{sup 18}F

  14. Small Molecule PET Tracers in Drug Discovery.

    Science.gov (United States)

    Donnelly, David J

    2017-09-01

    The process of discovering and developing a new pharmaceutical is a long, difficult, and risky process that requires numerous resources. Molecular imaging techniques such as PET have recently become a useful tool for making decisions along a drug candidate's development timeline. PET is a translational, noninvasive imaging technique that provides quantitative information about a potential drug candidate and its target at the molecular level. Using this technique provides decisional information to ensure that the right drug candidate is being chosen, for the right target, at the right dose within the right patient population. This review will focus on small molecule PET tracers and how they are used within the drug discovery process. PET provides key information about a drug candidate's pharmacokinetic and pharmacodynamic properties in both preclinical and clinical studies. PET is being used in all phases of the drug discovery and development process, and the goal of these studies are to accelerate the process in which drugs are developed. Copyright © 2017. Published by Elsevier Inc.

  15. Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1'-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine].

    Science.gov (United States)

    Wiese, Christian; Grosse Maestrup, Eva; Schepmann, Dirk; Grimme, Stefan; Humpf, Hans-Ulrich; Brust, Peter; Wünsch, Bernhard

    2011-02-01

    It was shown that racemic (±)-2 [1'-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine], WMS-1813] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ(1) receptors. To study the pharmacological activity of the enantiomers of 2, a preparative HPLC separation of (R)-2 and (S)-2 was performed. The absolute configuration of the enantiomers was determined by CD-spectroscopy together with theoretical calculations of the CD-spectrum of a model compound. In receptor binding studies with the radioligand [(3)H]-(+)-pentazocine, (S)-2 was thrice more potent than its (R)-configured enantiomer (R)-2. The metabolic degradation of the more potent (S)-enantiomer was considerably slower than the metabolism of (R)-2. The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap-LC-MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2. Copyright © 2010 Wiley-Liss, Inc.

  16. Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of chemotherapy : An in vitro study in glioma cells

    NARCIS (Netherlands)

    van Waarde, Aren; Been, Lukas B.; Ishiwata, Kiichi; Dierckx, Rudi A.; Elsinga, Philip H.

    2006-01-01

    The significant presence of nontumor cell populations within tumors can complicate the assessment of in vivo tumor metabolism during therapy. To more clearly define the impact of cytotoxic agents, we compared early changes in the uptake of 6 PET tracers in cultured glioma cells. Doxorubicin (1 mu mo

  17. Effect of tracer metabolism on PET measurement of [[sup 11]C]pyrilamine binding to histamine H[sub 1] receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Eun (Sungkyunkwan Univ., Seoul (Korea, Republic of). School of Medicine); Szabo, Z.; Seki, Chie; Ravert, H.T.; Scheffel, U.; Dannals, R.F.; Wagner, H.N. Jr.

    1999-04-01

    The present study was carried out to investigate the time course of [[sup 11]C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [[sup 11]C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [[sup 11]C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [[sup 11]C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [[sup 11]C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [[sup 11]C]pyrilamine. Based on the rat data, the contribution of [sup 11]C-labeled metabolites to total [[sup 11]C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [[sup 11]C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [[sup 11]C]pyrilamine by brain tissue itself. Therefore, [[sup 11]C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [[sup 11]C]pyrilamine binding to histamine H[sub 1] receptors. (author)

  18. Effect of tracer metabolism on PET measurement of [{sup 11}C]pyrilamine binding to histamine H{sub 1} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Eun [Sungkyunkwan Univ., Seoul (Korea, Republic of). School of Medicine; Szabo, Z.; Seki, Chie; Ravert, H.T.; Scheffel, U.; Dannals, R.F.; Wagner, H.N. Jr.

    1999-04-01

    The present study was carried out to investigate the time course of [{sup 11}C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [{sup 11}C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [{sup 11}C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [{sup 11}C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [{sup 11}C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [{sup 11}C]pyrilamine. Based on the rat data, the contribution of {sup 11}C-labeled metabolites to total [{sup 11}C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [{sup 11}C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [{sup 11}C]pyrilamine by brain tissue itself. Therefore, [{sup 11}C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [{sup 11}C]pyrilamine binding to histamine H{sub 1} receptors. (author)

  19. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid recepto

  20. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid

  1. Development of a Dual Tracer PET Method for Imaging Dopaminergic Neuromodulation

    Science.gov (United States)

    Converse, Alexander K.; Dejesus, Onofre T.; Flores, Leo G.; Holden, James E.; Kelley, Ann E.; Moirano, Jeffrey M.; Nickles, Robert J.; Oakes, Terrence R.; Roberts, Andrew D.; Ruth, Thomas J.; Vandehey, Nicholas T.; Davidson, Richard J.

    2006-04-01

    The modulatory neurotransmittor dopamine (DA) is involved in movement and reward behaviors, and malfunctions in the dopamine system are implicated in a variety of prevalent and debilitating pathologies including Parkinson's disease, attention deficit/hyperactivity disorder, schizophrenia, and addiction. Positron emission tomography (PET) has been used to separately measure changes in DA receptor occupancy and blood flow in response to various interventions. Here we describe a dual tracer PET method to simultaneously measure both responses with the aim of comparing DA release in particular areas of the brain and associated alterations in neural activity throughout the brain. Significant correlations between reductions in DA receptor occupancy and blood flow alterations would be potential signs of dopaminergic modulation, i.e. modifications in signal processing due to increased levels of extracellular DA. Methodological development has begun with rats undergoing an amphetamine challenge while being scanned with the blood flow tracer [17F]fluoromethane and the dopamine D2 receptor tracer [18F]desmethoxyfallypride.

  2. PET and SPET tracers for mapping the cardiac nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska Hospital, 17176 Stockholm (Sweden)

    2002-03-01

    The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[{sup 18}F]fluorodopamine, (-)-6-[{sup 18}F]fluoronorepinephrine and (-)-[{sup 11}C]epinephrine, and radiolabelled catecholamine analogues, such as [{sup 123}I]meta-iodobenzylguanidine, [{sup 11}C]meta-hydroxyephedrine, [{sup 18}F]fluorometaraminol, [{sup 11}C]phenylephrine and meta-[{sup 76}Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[{sup 18}F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility

  3. Microfluidics: A Groundbreaking Technology for PET Tracer Production?

    Directory of Open Access Journals (Sweden)

    Björn Wängler

    2013-07-01

    Full Text Available Application of microfluidics to Positron Emission Tomography (PET tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch- and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed.

  4. PET tracer for imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    2013-01-01

    There is provided a radiolabelled peptide-based compound for diagnostic imaging using positron emission tomography (PET). The compound may thus be used for diagnosis of malignant diseases. The compound is particularly useful for imaging of somatostatin overexpression in tumors, wherein the compound...... is capable of being imaged by PET when administered with a target dose in the range of 150-350 MBq, such as 150-250 MBq, preferable in the range of 191-210 MBq....

  5. Bridging the gaps in 18F PET tracer development

    Science.gov (United States)

    Campbell, Michael G.; Mercier, Joel; Genicot, Christophe; Gouverneur, Véronique; Hooker, Jacob M.; Ritter, Tobias

    2017-01-01

    As compared to the drug discovery process, the development of new 18F PET tracers lacks a well-established pipeline that advances compounds from academic research to candidacy for (pre)clinical imaging. In order to bridge the gaps between methodological advances and clinical success, we must rethink the development process from training to implementation.

  6. Small-molecule PET Tracers for Imaging Proteinopathies.

    Science.gov (United States)

    Mathis, Chester A; Lopresti, Brian J; Ikonomovic, Milos D; Klunk, William E

    2017-09-01

    In this chapter, we provide a review of the challenges and advances in developing successful PET imaging agents for 3 major types of aggregated amyloid proteins: amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn). These 3 amyloids are involved in the pathogenesis of a variety of neurodegenerative diseases, referred to as proteinopathies or proteopathies, that include Alzheimer disease, Lewy body dementias, multiple system atrophy, and frontotemporal dementias, among others. In the Introduction section, we briefly discuss the history of amyloid in neurodegenerative diseases and describe why progress in developing effective imaging agents has been hampered by the failure of crystallography to provide definitive ligand-protein interactions for rational radioligand design efforts. Instead, the field has relied on largely serendipitous, trial-and-error methods to achieve useful and specific PET amyloid imaging tracers for Aβ, tau, and α-syn deposits. Because many of the proteopathies involve more than 1 amyloid protein, it is important to develop selective PET tracers for the different amyloids to help assess the relative contribution of each to total amyloid burden. We use Pittsburgh compound B to illustrate some of the critical steps in developing a potent and selective Aβ PET imaging agent. Other selective Aβ and tau PET imaging compounds have followed similar pathways in their developmental processes. Success for selective α-syn PET imaging agents has not been realized yet, but work is ongoing in multiple laboratories throughout the world. In the tau sections, we provide background regarding 3-repeat (3R) and 4-repeat (4R) tau proteins and how they can affect the binding of tau radioligands in different tauopathies. We review the ongoing efforts to assess the properties of tau ligands, which are useful in 3R, 4R, or combined 3R-4R tauopathies. Finally, we describe in the α-syn sections recent attempts to develop selective tracers to image

  7. Preparation and first evaluation of [{sup 18}F]FE-SUPPY: a new PET tracer for the adenosine A{sub 3} receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wadsak, Wolfgang [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Mien, Leonhard-Key [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Shanab, Karem [Dept. of Drug and Natural Product Synthesis, Faculty of Life Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Ettlinger, Dagmar E. [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Haeusler, Daniela [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Sindelar, Karoline [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Lanzenberger, Rupert R. [Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Spreitzer, Helmut [Dept. of Drug and Natural Product Synthesis, Faculty of Life Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Viernstein, Helmut [Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Keppler, Bernhard K. [Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Dudczak, Robert; Kletter, Kurt [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Mitterhauser, Markus [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria)]|[Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhouser@meduniwien.ac.at

    2008-01-15

    Introduction: Changes of the adenosine A{sub 3} receptor subtype (A3AR) expression have been shown in a variety of pathologies, especially neurological and affective disorders, cardiac diseases and oncological and inflammation processes. Recently, 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE-SUPPY) was presented as a high-affinity ligand for the A3AR with good selectivity. Our aims were the development of a suitable labeling precursor, the establishment of a reliable radiosynthesis for the fluorine-18-labeled analogue [{sup 18}F]FE-SUPPY and a first evaluation of [{sup 18}F]FE-SUPPY in rats. Methods: [{sup 18}F]FE-SUPPY was prepared in a feasible and reliable manner by radiofluorination of the corresponding tosylated precursor. Biodistribution was carried out in rats, and organs were removed and counted. Autoradiography was performed on rat brain slices in the presence or absence of 2-Cl-IB-MECA. Results: Overall yields and radiochemical purity were sufficient for further preclinical and clinical applications. The uptake pattern of [{sup 18}F]FE-SUPPY found in rats mainly followed the described mRNA distribution pattern of the A3AR. Specific uptake in brain was demonstrated by blocking with a selective A3AR agonist. Conclusion: We conclude that [{sup 18}F]FE-SUPPY has the potential to serve as the first positron emission tomography tracer for the A3AR.

  8. Double tracer PET/CT:what is it and what does it mean?

    Institute of Scientific and Technical Information of China (English)

    Mattia Pellicciari; Silvia Ortolani; Elisabetta Grego; Giampaolo Tortora; Sara Cingarlini

    2016-01-01

    68Ga-DOTA-peptide PET/CT is a recommended imaging modality in the workup of neuroendocrine neoplasms (NENs), which shows high diagnostic sensitivity and is a strong predictor of successful somatostatin receptor directed treatments. Although not routinely recommended, reliable evidences show that18F-FDG PET/CT can provide complementary information in this setting with the ability to discriminate slow-proliferating tumors from aggressive, rapidly-proliferating tumors. Further, it has been proposed as an independent prognostic factor for the prediction of either overall survival or progression free survival. In this review, we provide insight into the biologic signiifcance of68Ga-DOTA-peptides and18F-FDG uptake, and of the use of double tracer (68Ga-DOTA-peptides plus18F-FDG) PET/CT in the clinical evaluation of patients affected by NENs.

  9. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Visser, Anniek K.D.; Waarde, Aren van; Willemsen, Antoon T.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Bosker, Fokko J. [University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Luiten, Paul G.M. [University of Groningen, Center for Behavior and Neurosciences, Department of Molecular Neurobiology, Haren (Netherlands); Boer, Johan A. den [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Kema, Ido P. [University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Dierckx, Rudi A.J.O. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

    2011-03-15

    The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are {alpha}-[{sup 11}C]methyltryptophan ([{sup 11}C]AMT) and 5-hydroxy-L-[{beta}-{sup 11}C]tryptophan ([{sup 11}C]5-HTP). Both tracers have advantages and disadvantages. [{sup 11}C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [{sup 11}C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain. (orig.)

  10. Quantitative observation of tracer transport with high-resolution PET

    Science.gov (United States)

    Kulenkampff, Johannes; Gruendig, Marion; Zakhnini, Abdelhamid; Lippmann-Pipke, Johanna

    2016-04-01

    Transport processes in natural porous media are typically heterogeneous over various scales. This heterogeneity is caused by the complexity of pore geometry and molecular processes. Heterogeneous processes, like diffusive transport, conservative advective transport, mixing and reactive transport, can be observed and quantified with quantitative tomography of tracer transport patterns. Positron Emission Tomography (PET) is by far the most sensitive method and perfectly selective for positron-emitting radiotracers, therefore it is suited as reference method for spatiotemporal tracer transport observations. The number of such PET-applications is steadily increasing. However, many applications are afflicted by the low spatial resolution (3 - 5 mm) of the clinical scanners from cooperating nuclear medical departments. This resolution is low in relation to typical sample dimensions of 10 cm, which are restricted by the mass attenuation of the material. In contrast, our GeoPET-method applies a high-resolution scanner with a resolution of 1 mm, which is the physical limit of the method and which is more appropriate for samples of the size of soil columns or drill cores. This higher resolution is achieved at the cost of a more elaborate image reconstruction procedure, especially considering the effects of Compton scatter. The result of the quantitative image reconstruction procedure is a suite of frames of the quantitative tracer distribution with adjustable frame rates from minutes to months. The voxel size has to be considered as reference volume of the tracer concentration. This continuous variable includes contributions from structures far below the spatial resolution, as far as a detection threshold, in the pico-molar range, is exceeded. Examples from a period of almost 10 years (Kulenkampff et al. 2008a, Kulenkampff et al. 2008b) of development and application of quantitative GeoPET-process tomography are shown. These examples include different transport processes

  11. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis.

    Science.gov (United States)

    Gormsen, Lars C; Haraldsen, Ate; Kramer, Stine; Dias, Andre H; Kim, Won Yong; Borghammer, Per

    2016-12-01

    Cardiac sarcoidosis (CS) is a potentially fatal condition lacking a single test with acceptable diagnostic accuracy. (18)F-FDG PET/CT has emerged as a promising imaging modality, but is challenged by physiological myocardial glucose uptake. An alternative tracer, (68)Ga-DOTANOC, binds to somatostatin receptors on inflammatory cells in sarcoid granulomas. We therefore aimed to conduct a proof-of-concept study using (68)Ga-DOTANOC to diagnose CS. In addition, we compared diagnostic accuracy and inter-observer variability of (68)Ga-DOTANOC vs. (18)F-FDG PET/CT. Nineteen patients (seven female) with suspected CS were prospectively recruited and dual tracer scanned within 7 days. PET images were reviewed by four expert readers for signs of CS and compared to the reference standard (Japanese ministry of Health and Welfare CS criteria). CS was diagnosed in 3/19 patients. By consensus, 11/19 (18)F-FDG scans and 0/19 (68)Ga-DOTANOC scans were rated as inconclusive. The sensitivity of (18)F-FDG PET for diagnosing CS was 33 %, specificity was 88 %, PPV was 33 %, NPV was 88 %, and diagnostic accuracy was 79 %. For (68)Ga-DOTANOC, accuracy was 100 %. Inter-observer agreement was poor for (18)F-FDG PET (Fleiss' combined kappa 0.27, NS) and significantly better for (68)Ga-DOTANOC (Fleiss' combined kappa 0.46, p = 0.001). Despite prolonged pre-scan fasting, a large proportion of (18)F-FDG PET/CT images were rated as inconclusive, resulting in low agreement among reviewers and correspondingly poor diagnostic accuracy. By contrast, (68)Ga-DOTANOC PET/CT had excellent diagnostic accuracy with the caveat that inter-observer variability was still significant. Nevertheless, (68)Ga-DOTANOC PET/CT looks very promising as an alternative CS PET tracer. Current Controlled Trials NCT01729169 .

  12. Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers

    DEFF Research Database (Denmark)

    Ettrup, Anders; Hansen, Martin; Santini, Martin A

    2011-01-01

    Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer....... In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig...

  13. Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers

    DEFF Research Database (Denmark)

    Ettrup, Anders; Hansen, Martin; Santini, Martin A;

    2011-01-01

    Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer....... In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig...

  14. Radiosynthesis and in vivo evaluation of N-[{sup 11}C]methylated imidazopyridineacetamides as PET tracers for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sekimata, Katsuhiko [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Hatano, Kentaro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)], E-mail: hatanok@nils.go.jp; Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Abe, Junichiro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Biggio, Giovanni; Serra, Mariangela [Department of Experimental Biology, University of Cagliari, Cagliari 09100 (Italy); Laquintana, Valentino; Denora, Nunzio; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano [Pharmaco-Chemistry Department, University of Bari, Bari 70125 (Italy); Ito, Kengo [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)

    2008-04-15

    Imidazopyridineacetoamide 5-8, a series of novel and potentially selective peripheral benzodiazepine receptor (PBR) ligands with affinities comparable to those of known PBR ligands, was investigated. Radiosyntheses of [{sup 11}C]5, 6, 7 or 8 was accomplished by N-methylation of the corresponding desmethyl precursors with [{sup 11}C]methyl iodide in the presence of NaH in dimethylformamide (DMF), resulting in 25% to 77% radiochemical yield and specific activitiy of 20 to 150 MBq/nmol. Each of the labeled compounds was injected in ddY mice, and the radioactivity and weight of dissected peripheral organs and brain regions were measured. Organ distribution of [{sup 11}C]7 was consistent with the known PBR distribution. Moreover, [{sup 11}C]7 showed the best combination of brain uptake and PBR binding, leading to its high retention in the olfactory bulb and cerebellum, areas where PBR density is high in mouse brain. Coinjection of PK11195 or unlabeled 7 significantly reduced the brain uptake of [{sup 11}C]7. These results suggest that [{sup 11}C]7 could be a useful radioligand for positron emission tomography imaging of PBRs.

  15. Synthesis and preclinical evaluation of [{sup 11}C]PAQ as a PET imaging tracer for VEGFR-2

    Energy Technology Data Exchange (ETDEWEB)

    Samen, Erik; Stone-Elander, Sharon [Karolinska University Hospital Solna, Karolinska Pharmacy, Stockholm (Sweden); Karolinska Institutet, Clinical Neurosciences, Stockholm (Sweden); Thorell, Jan-Olov [Karolinska University Hospital Solna, Karolinska Pharmacy, Stockholm (Sweden); Lu, Li [Karolinska Institutet, Clinical Neurosciences, Stockholm (Sweden); Tegnebratt, Tetyana; Holmgren, Lars [Karolinska Institutet, Cancer Center Karolinska, Oncology-Pathology, Stockholm (Sweden)

    2009-08-15

    (R,S)-N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-3-piperidinyl)methoxy)-4-quinazolinamine (PAQ) is a tyrosine kinase inhibitor with high affinity for the vascular endothelial growth factor receptor 2 (VEGFR-2), which plays an important role in tumour angiogenesis. The aim of this work was to develop and evaluate in mice the {sup 11}C-labelled analogue as an in vivo tracer for VEGFR-2 expression in solid tumours. [{sup 11}C]PAQ was synthesized by an N-methylation of desmethyl-PAQ using [{sup 11}C]methyl iodide. The tracer's pharmacokinetic properties and its distribution in both subcutaneous and intraperitoneal tumour models were evaluated with positron emission tomography (PET). [{sup 18}F]FDG was used as a reference tracer for tumour growth. PET results were corroborated by ex vivo and in vitro phosphor imaging and immunohistochemical analyses. In vitro assays and PET in healthy animals revealed low tracer metabolism, limited excretion over 60 min and a saturable and irreversible binding. Radiotracer uptake in subcutaneous tumour masses was low, while focal areas of high uptake (up to 8% ID/g) were observed in regions connecting the tumour to the host. Uptake was similarly high but more distributed in tumours growing within the peritoneum. The pattern of radiotracer uptake was generally different from that of the metabolic tracer [{sup 18}F]FDG and correlated well with variations in VEGFR-2 expression determined ex vivo by immunohistochemical analysis. These results suggest that [{sup 11}C]PAQ has potential as a noninvasive PET tracer for in vivo imaging of VEGFR-2 expression in angiogenic ''hot spots''. (orig.)

  16. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    Energy Technology Data Exchange (ETDEWEB)

    Sako, Takeo [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Senda, Michio [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)

    2013-12-06

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  17. Application of separable parameter space techniques to multi-tracer PET compartment modeling

    Science.gov (United States)

    Zhang, Jeff L.; Morey, A. Michael; Kadrmas, Dan J.

    2016-02-01

    Multi-tracer positron emission tomography (PET) can image two or more tracers in a single scan, characterizing multiple aspects of biological functions to provide new insights into many diseases. The technique uses dynamic imaging, resulting in time-activity curves that contain contributions from each tracer present. The process of separating and recovering separate images and/or imaging measures for each tracer requires the application of kinetic constraints, which are most commonly applied by fitting parallel compartment models for all tracers. Such multi-tracer compartment modeling presents challenging nonlinear fits in multiple dimensions. This work extends separable parameter space kinetic modeling techniques, previously developed for fitting single-tracer compartment models, to fitting multi-tracer compartment models. The multi-tracer compartment model solution equations were reformulated to maximally separate the linear and nonlinear aspects of the fitting problem, and separable least-squares techniques were applied to effectively reduce the dimensionality of the nonlinear fit. The benefits of the approach are then explored through a number of illustrative examples, including characterization of separable parameter space multi-tracer objective functions and demonstration of exhaustive search fits which guarantee the true global minimum to within arbitrary search precision. Iterative gradient-descent algorithms using Levenberg-Marquardt were also tested, demonstrating improved fitting speed and robustness as compared to corresponding fits using conventional model formulations. The proposed technique overcomes many of the challenges in fitting simultaneous multi-tracer PET compartment models.

  18. Extracting a respiratory signal from raw dynamic PET data that contain tracer kinetics

    Science.gov (United States)

    Schleyer, P. J.; Thielemans, K.; Marsden, P. K.

    2014-08-01

    Data driven gating (DDG) methods provide an alternative to hardware based respiratory gating for PET imaging. Several existing DDG approaches obtain a respiratory signal by observing the change in PET-counts within specific regions of acquired PET data. Currently, these methods do not allow for tracer kinetics which can interfere with the respiratory signal and introduce error. In this work, we produced a DDG method for dynamic PET studies that exhibit tracer kinetics. Our method is based on an existing approach that uses frequency-domain analysis to locate regions within raw PET data that are subject to respiratory motion. In the new approach, an optimised non-stationary short-time Fourier transform was used to create a time-varying 4D map of motion affected regions. Additional processing was required to ensure that the relationship between the sign of the respiratory signal and the physical direction of movement remained consistent for each temporal segment of the 4D map. The change in PET-counts within the 4D map during the PET acquisition was then used to generate a respiratory curve. Using 26 min dynamic cardiac NH3 PET acquisitions which included a hardware derived respiratory measurement, we show that tracer kinetics can severely degrade the respiratory signal generated by the original DDG method. In some cases, the transition of tracer from the liver to the lungs caused the respiratory signal to invert. The new approach successfully compensated for tracer kinetics and improved the correlation between the data-driven and hardware based signals. On average, good correlation was maintained throughout the PET acquisitions.

  19. Comparison of dual-biomarker PIB-PET and dual-tracer PET in AD diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Liping; Zhang, Jinming; Xu, Baixuan; Tian, Jiahe [General Hospital of the Chinese People' s Liberation Army, Department of Nuclear Medicine, Beijing (China); Liu, Linwen; Fan, Yong [Institute of Automation, Chinese Academy of Sciences, National Laboratory of Pattern Recognition, Beijing (China)

    2014-11-15

    To identify the optimal time window for capturing perfusion information from early {sup 11}C-PIB imaging frames (perfusion PIB, {sup 11}C-pPIB) and to compare the performance of {sup 18}F-FDG PET and ''dual biomarker'' {sup 11}C-PIB PET [{sup 11}C-pPIB and amyloid PIB ({sup 11}C-aPIB)] for classification of AD, MCI and CN subjects. Forty subjects (14 CN, 12 MCI and 14 AD patients) underwent {sup 18}F-FDG and {sup 11}C-PIB PET studies. Pearson correlation between the {sup 18}F-FDG image and sum of early {sup 11}C-PIB frames was maximised to identify the optimal time window for {sup 11}C-pPIB. The classification power of imaging parameters was evaluated with a leave-one-out validation. A 7-min time window yielded the highest correlation between {sup 18}F-FDG and {sup 11}C-pPIB. {sup 11}C-pPIB and {sup 18}F-FDG images shared a similar radioactive distribution pattern. {sup 18}F-FDG performed better than {sup 11}C-pPIB for the classification of both AD vs. CN and MCI vs. CN. {sup 11}C-pPIB + {sup 11}C-aPIB and {sup 18}F-FDG + {sup 11}C-aPIB yielded the highest classification accuracy for the classification of AD vs. CN, and {sup 18}F-FDG + {sup 11}C-aPIB had the best classification performance for the classification of MCI vs. CN. C-pPIB could serve as a useful biomarker of rCBF for measuring neural activity and improve the diagnostic power of PET for AD in conjunction with {sup 11}C-aPIB. {sup 18}F-FDG and {sup 11}C-PIB dual-tracer PET examination could better detect MCI. (orig.)

  20. Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase.

    Science.gov (United States)

    Liu, Ping; Hamill, Terence G; Chioda, Marc; Chobanian, Harry; Fung, Selena; Guo, Yan; Chang, Linda; Bakshi, Raman; Hong, Qingmei; Dellureficio, James; Lin, Linus S; Abbadie, Catherine; Alexander, Jessica; Jin, Hong; Mandala, Suzanne; Shiao, Lin-Lin; Li, Wenping; Sanabria, Sandra; Williams, David; Zeng, Zhizhen; Hajdu, Richard; Jochnowitz, Nina; Rosenbach, Mark; Karanam, Bindhu; Madeira, Maria; Salituro, Gino; Powell, Joyce; Xu, Ling; Terebetski, Jenna L; Leone, Joseph F; Miller, Patricia; Cook, Jacquelynn; Holahan, Marie; Joshi, Aniket; O'Malley, Stacey; Purcell, Mona; Posavec, Diane; Chen, Tsing-Bau; Riffel, Kerry; Williams, Mangay; Hargreaves, Richard; Sullivan, Kathleen A; Nargund, Ravi P; DeVita, Robert J

    2013-06-13

    We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH-specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH in the brain.

  1. Multi-contrast attenuation map synthesis for PET/MR scanners: assessment on FDG and Florbetapir PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Burgos, Ninon [University College London, Translational Imaging Group, Centre for Medical Image Computing, London (United Kingdom); Cardoso, M.J.; Modat, Marc; Ourselin, Sebastien [University College London, Translational Imaging Group, Centre for Medical Image Computing, London (United Kingdom); University College London, Dementia Research Centre, Institute of Neurology, London (United Kingdom); Thielemans, Kris; Dickson, John [University College London, Institute of Nuclear Medicine, London (United Kingdom); Schott, Jonathan M. [University College London, Dementia Research Centre, Institute of Neurology, London (United Kingdom); Atkinson, David [University College London, Centre for Medical Imaging, London (United Kingdom); Arridge, Simon R. [University College London, Centre for Medical Image Computing, London (United Kingdom); Hutton, Brian F. [University College London, Institute of Nuclear Medicine, London (United Kingdom); University of Wollongong, Centre for Medical Radiation Physics, Wollongong, NSW (Australia)

    2015-08-15

    Positron Emission Tomography/Magnetic Resonance Imaging (PET/MR) scanners are expected to offer a new range of clinical applications. Attenuation correction is an essential requirement for quantification of PET data but MRI images do not directly provide a patient-specific attenuation map. Methods We further validate and extend a Computed Tomography (CT) and attenuation map (μ-map) synthesis method based on pre-acquired MRI-CT image pairs. The validation consists of comparing the CT images synthesised with the proposed method to the original CT images. PET images were acquired using two different tracers ({sup 18}F-FDG and {sup 18}F-florbetapir). They were then reconstructed and corrected for attenuation using the synthetic μ-maps and compared to the reference PET images corrected with the CT-based μ-maps. During the validation, we observed that the CT synthesis was inaccurate in areas such as the neck and the cerebellum, and propose a refinement to mitigate these problems, as well as an extension of the method to multi-contrast MRI data. Results With the improvements proposed, a significant enhancement in CT synthesis, which results in a reduced absolute error and a decrease in the bias when reconstructing PET images, was observed. For both tracers, on average, the absolute difference between the reference PET images and the PET images corrected with the proposed method was less than 2%, with a bias inferior to 1%. Conclusion With the proposed method, attenuation information can be accurately derived from MRI images by synthesising CT using routine anatomical sequences. MRI sequences, or combination of sequences, can be used to synthesise CT images, as long as they provide sufficient anatomical information. (orig.)

  2. Fluorine-18 labeled tracers for PET studies in the neurosciences

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yu-Shin; Fowler, J.S.

    1995-12-31

    This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18 labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments.

  3. Development of N-substituted quinolinimides, as potential PET tracers for the visualisation of {delta}-opioid receptors; Developpement de quinoleinimides N-substitues, traceurs potentiels des recepteurs opiaces de type {delta} pour l'imagerie medicale par TEP

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, Th.

    2005-12-15

    In order to develop radiotracers for in vivo studies of {delta}-opioid receptors by Positron Emission Tomography (PET) or Single Photon Emission computed Tomography (SPECT), we undertook the synthesis of halogenated analogues (chlorinated and brominated) of compound 12. These analogues were prepared by a convergent synthesis and from these novel structures a halogen exchange reaction has been performed to complete this series. These molecules were tested to determine their in vitro affinity and selectivity toward {delta} opioid receptors. The compounds 12 and 15 were labelled with carbon-11. The radiosynthesis of compound 12, in weak radioactivity chemistry, was performed first by the Stille reaction and second by a new methodology based on the transfer reaction of [{sup 11}C]-methyl group. This new methodology used a mono-organotin compound prepared by addition of [{sup 11}C]-iodomethane onto Lappert's stannylene. The compound [{sup 11}C]-12 was obtained with 60 and 10% radiochemical yield respectively. In order to produce higher radioactivity quantities, the Stille reaction was automated. The compounds [{sup 11}C]-12 and [{sup 11}C]-15 were obtained in 40 minutes with a specific radioactivity ranging from 322 to 747 mCi/{mu}mol. (author)

  4. Characterizing Tumors Using Metabolic Imaging: PET Imaging of Cellular Proliferation and Steroid Receptors

    Directory of Open Access Journals (Sweden)

    David A. Mankoff

    2000-01-01

    Full Text Available Treatment decisions in oncology are increasingly guided by information on the biologic characteristics of tumors. Currently, patient-specific information on tumor biology is obtained from the analysis of biopsy material. Positron emission tomography (PET provides quantitative estimates of regional biochemistry and receptor status and can overcome the sampling error and difficulty in performing serial studies inherent with biopsy. Imaging using the glucose metabolism tracer, 2-deoxy-2-fluoro-D-glucose (FDG, has demonstrated PET's ability to guide therapy in clinical oncology. In this review, we highlight PET approaches to imaging two other aspects of tumor biology: cellular proliferation and tumor steroid receptors. We review the biochemical and biologic processes underlying the imaging, positron-emitting radiopharmaceuticals that have been developed, quantitative image-analysis considerations, and clinical studies to date. This provides a basis for evaluating future developments in these promising applications of PET metabolic imaging.

  5. Astrocytic tracer dynamics estimated from [1-11C]-acetate PET measurements

    DEFF Research Database (Denmark)

    Arnold, Andrea; Calvetti, Daniela; Gjedde, Albert

    2014-01-01

    We address the problem of estimating the unknown parameters of a model of tracer kinetics from sequences of positron emission tomography (PET) scan data using a statistical sequential algorithm for the inference of magnitudes of dynamic parameters. The method, based on Bayesian statistical...... inference, is a modification of a recently proposed particle filtering and sequential Monte Carlo algorithm, where instead of preassigning the accuracy in the propagation of each particle, we fix the time step and account for the numerical errors in the innovation term. We apply the algorithm to PET images...

  6. Mass dose effects and in vivo affinity in brain PET receptor studies--a study of cerebral 5-HT4 receptor binding with [11C]SB207145

    DEFF Research Database (Denmark)

    Madsen, Karine; Marner, Lisbeth; Haahr, Mette;

    2011-01-01

    Attention to tracer dose principles is crucial in positron emission tomography (PET), and deviations can induce serious errors. In this study, we devise a method for determining receptor occupancy of the mass dose of the radioligand itself and the in vivo affinity.......Attention to tracer dose principles is crucial in positron emission tomography (PET), and deviations can induce serious errors. In this study, we devise a method for determining receptor occupancy of the mass dose of the radioligand itself and the in vivo affinity....

  7. Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers

    Energy Technology Data Exchange (ETDEWEB)

    Vanasschen, Christian; Brandt, Marie; Ermert, Johannes [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany); Neumaier, Bernd [Institute for Radiochemistry and Experimental Molecular Imaging, Medical Clinics, University of Cologne (Germany); Coenen, Heinz H [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany)

    2015-05-18

    The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn. N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps. [52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%. [52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.

  8. Multiparametric PET imaging in thyroid malignancy characterizing tumour heterogeneity: somatostatin receptors and glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Traub-Weidinger, Tatjana [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Putzer, Daniel; Bale, Reto [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Guggenberg, Elisabeth von; Dobrozemsky, Georg; Nilica, Bernhard; Kendler, Dorota; Virgolini, Irene Johanna [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

    2015-12-15

    Radiolabelled somatostatin (SST) analogues have proven useful in diagnosing tumours positive for SST receptor (SSTR). As different subtypes of SSTR are expressed on the tumour cell surface, the choice of appropriate therapeutic SST analogue is crucial. We evaluated the SSTR status of thyroid cancer patients who had signs of progressive disease comparing different SSTR ligands for PET imaging to evaluate possible further therapeutic options. PET with {sup 68}Ga-radiolabelled SSTR ligands DOTA lanreotide (DOTA-LAN), DOTA-Tyr{sup 3} octreotide (DOTA-TOC) and {sup 18}F-FDG was performed in 31 patients with thyroid cancer (TC). These 31 patients comprised 18 with radioiodine non-avid differentiated TC (DTC) including 6 papillary TC (PTC), 8 follicular TC (FTC) and 4 oxyphilic TC (oxyTC), 5 with anaplastic TC (ATC), and 8 with medullary TC (MTC). The PET results were compared in a region-based evaluation. All patients underwent a PET study with {sup 68}Ga-DOTA-LAN, 28 patients with {sup 68}Ga-DOTA-TOC and 28 patients with {sup 18}F-FDG. A lack of SSTR expression was found in 13 of the 31 patients (42 %) with negative results with both SSTR tracers in 12 patients. Ambiguous results with both SSTR tracers were observed in one patient. High tracer uptake in SSTR PET images was seen in seven DTC patients (39 %; two PTC, three FTC, two oxyTC), in four ATC patients (80 %) and in six MTC patients (75 %). Lesions showing aerobic glycolysis on {sup 18}F-FDG PET were found in 24 of 28 patients (86 %) with corresponding positive results with {sup 68}Ga-DOTA-LAN in 35 % and with {sup 68}Ga-DOTA-TOC in 29 %. The heterogeneous SSTR profile of TC tumour lesions needs to be evaluated using different SSTR PET tracers to characterize more closely the SSTR subtype affinities in patients with progressive TC in order to further stratify therapy with SSTR therapeutics. (orig.)

  9. Radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET

    DEFF Research Database (Denmark)

    Ettrup, Anders; Palner, Mikael; Gillings, Nicolas;

    2010-01-01

    PET brain imaging of the serotonin 2A (5-hydroxytryptamine 2A, or 5-HT(2A)) receptor has been widely used in clinical studies, and currently, several well-validated radiolabeled antagonist tracers are used for in vivo imaging of the cerebral 5-HT(2A) receptor. Access to 5-HT(2A) receptor agonist...... PET tracers would, however, enable imaging of the active, high-affinity state of receptors, which may provide a more meaningful assessment of membrane-bound receptors. In this study, we radiolabel the high-affinity 5-HT(2A) receptor agonist 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-[(11)C-OCH(3...

  10. Radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET

    DEFF Research Database (Denmark)

    Ettrup, Anders; Palner, Mikael; Gillings, Nic;

    2010-01-01

    PET tracers would, however, enable imaging of the active, high-affinity state of receptors, which may provide a more meaningful assessment of membrane-bound receptors. In this study, we radiolabel the high-affinity 5-HT(2A) receptor agonist 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-[(11)C-OCH(3...

  11. A Investigation of Partially Extracted Tracers Used to Determine Myocardial Blood Flow with PET.

    Science.gov (United States)

    Christian, Bradley Thomas

    Positron Emission Tomography (PET) provides the ability to quantitatively measure mass-specific blood flow to myocardial tissue (ml/min/g tissue). The partially extracted tracers ^{62}Cu -PTSM and two single photon emission computed tomography(SPECT) agents, teboroxime and sestamibi were studied. The latter two demonstrate the effectiveness of PET as a pharmacological tool for SPECT perfusion tracer development. The characteristics of these tracers were compared to commonly used partially extracted tracers ^{13}rm NH_3 and ^{82} Rb. Positron emitting ^{rm 94m}Tc was used to label ligands originally developed for ^{rm 99m} Tc labeling. ^{rm 94m }Tc can be produced by the bombardment of a natural molybdenum foil with an 11Mev proton beam, via the ^{94}rm Mo(p,n)^ {94m}Tc reaction. The production of ^{rm94m}Tc is accompanied by ^{92}Tc, ^ {94}Tc, ^{95} Tc, ^{rm 95m}Tc, ^{96}Tc, and ^{rm 99m}Tc due to the isotopic mixture of natural Mo. The presence of these radionuclidic impurities increase the radiation dose received by the patient and radio chemist. The elimination of these impurities was achieved by irradiating an isotopically enriched target material, ^{94}rm MoO_3. The ability to reclaim the enriched target is essential due to the high cost of the material. Recovery was accomplished by a solvent extraction technique yielding an activity recovery of 80% and target material recovery of 95%. Preliminary data was measured for the myocardial perfusion tracer ^{62}Cu -PTSM. It was found that the uptake of ^ {62}Cu-PTSM is linear for resting flows but a high degree of variability is observed at stress induced flows. This same result was found in the human studies when compared to ^{13} rm NH_3 measured myocardial perfusion values. The dynamic analysis of multiple tracers in the sequence of protocols: (1) acute canine prep ( ^{11}rm CO, ^{82 }Rb, ^{62}Cu-PTSM, ^{13}rm NH_3, ^{94m,99m}Tc-BATO, H_2 ^{14}rm O, ^{18 }FCH_3), (2) chronic canine prep ( ^{82}rm Rb, ^{13 }NH_3

  12. In vivo PET imaging of brain nicotinic cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bottlaender, M.; Valette, H.; Saba, W.; Schollhorn-Peyronneau, M.A.; Dolle, F.; Syrota, A. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), 91 - Orsay (France)

    2006-07-01

    Neuronal acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system where they modulate a number of CNS functions including neurotransmitter release, cognitive function, anxiety, analgesia and control of cerebral blood flow. In the brain, a major subtype is composed of the {alpha}4{beta}2 subunit combination. Density of this subtype has been shown to be decreased in patients with neuro-degenerative disease such as Alzheimer and Parkinson's disease (AD and PD), and mutated receptors has been described in some familial epilepsy. Thus, in vivo mapping of the nicotinic nAChRs by Positron Emission Tomography (PET) are of great interest to monitor the evolution of these pathologies and changes in the neuronal biochemistry induced by therapeutic agents. Recently, a new compound, 3-[2(S)-2-azetidinyl-methoxy]pyridine (A-85380) has been synthesised and labelled with fluorine-18, [{sup 18}F]fluoro-A-85380 (Dolle et al., 1999). The [{sup 18}F]fluoro-A-85380 has been shown to bind with high affinity t o nAChRs in vitro (Saba et al., 2004), and its toxicity was low and compatible with it s use at tracer dose in human PET studies (Valette, 2002). PET studies in baboons showed that, after in vivo administration of [ {sup 18}F]fluoro-A-85380 at a tracer dose, the distribution of the radioactivity in the brain reflect the distribution of the < 4R2 nAChRs. Competition and pre-blocking studies, using nicotinic agonists, confirm that the radiotracer binds specifically to the heteromeric nAChRs in the brain (Valette et al., 1999). The in vivo, characteristics of the [{sup 18}F]fluoro-A-8538 0 combined with its low toxicity make possible the imaging of the nicotinic receptor s in human by PET (Bottlaender 2003). Studies were performed in healthy non-smoker volunteers to evaluate the brain kinetics of [{sup 18}F]fluoro-A-85380 and to assess the quantification of its nAChRs binding in the human brain with PET (Gallezot et a., 2005). The [{sup 18}F

  13. PET imaging of human cardiac opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2002-10-01

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  14. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: a critical analysis of literature.

    Science.gov (United States)

    Yu, Chung Yao; Desai, Bhushan; Ji, Lingyun; Groshen, Susan; Jadvar, Hossein

    2014-01-01

    Positron emission tomography (PET) with a number of tracers targeted to particular biological features of cancer has been explored for the imaging evaluation of patients with biochemical recurrence of prostate cancer after curative primary treatment. However, these reports are often heterogeneous in study design, patient cohorts, standards of reference for the imaging findings, data analysis, and data reporting. The aim of our study was to address these limitations by extracting and re-analyzing the PET detection data only from studies that satisfied pre-defined sets of patient selection criteria and verification standards. Our investigation analyzed the effects of 5 tracers ((18)F-fluorodeoxyglucose (FDG), (11)C-acetate (ACET), (11)C- or (18)F-choline (CHOL), anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid (FACBC), and radiolabeled ligand targeted to prostate-specific membrane antigen (PSMA)), 2 treatment types (radical prostatectomy and radiation therapy), and whether the detected disease was local or metastatic, including lesion type (bone, lymph node, soft tissue). FDG exhibited the lowest detection rate for any suspected disease. ACET tended to be advantageous over CHOL in detecting local recurrence and lymph node lesions, even though the difference was not statistically significant. FACBC had greater likelihood of detecting local recurrence, when compared to CHOL, though this difference was not statistically significant. PSMA tended to show a higher proportion of patients with suspected disease compared to the other four tracers. Patients treated with radiation therapy had greater odds of displaying local recurrence on PET than those treated with radical prostatectomy. We also provide suggestions for future investigations that facilitate communication and the impact of the findings.

  15. Direct 4D parametric imaging for linearized models of reversibly binding PET tracers using generalized AB-EM reconstruction

    Science.gov (United States)

    Rahmim, Arman; Zhou, Yun; Tang, Jing; Lu, Lijun; Sossi, Vesna; Wong, Dean F.

    2012-02-01

    Due to high noise levels in the voxel kinetics, development of reliable parametric imaging algorithms remains one of most active areas in dynamic brain PET imaging, which in the vast majority of cases involves receptor/transporter studies with reversibly binding tracers. As such, the focus of this work has been to develop a novel direct 4D parametric image reconstruction scheme for such tracers. Based on a relative equilibrium (RE) graphical analysis formulation (Zhou et al 2009b Neuroimage 44 661-70), we developed a closed-form 4D EM algorithm to directly reconstruct distribution volume (DV) parametric images within a plasma input model, as well as DV ratio (DVR) images within a reference tissue model scheme (wherein an initial reconstruction was used to estimate the reference tissue time-activity curves). A particular challenge with the direct 4D EM formulation is that the intercept parameters in graphical (linearized) analysis of reversible tracers (e.g. Logan or RE analysis) are commonly negative (unlike for irreversible tracers, e.g. using Patlak analysis). Subsequently, we focused our attention on the AB-EM algorithm, derived by Byrne (1998, Inverse Problems 14 1455-67) to allow inclusion of prior information about the lower (A) and upper (B) bounds for image values. We then generalized this algorithm to the 4D EM framework, thus allowing negative intercept parameters. Furthermore, our 4D AB-EM algorithm incorporated and emphasized the use of spatially varying lower bounds to achieve enhanced performance. As validation, the means of parameters estimated from 55 human 11C-raclopride dynamic PET studies were used for extensive simulations using a mathematical brain phantom. Images were reconstructed using conventional indirect as well as proposed direct parametric imaging methods. Noise versus bias quantitative measurements were performed in various regions of the brain. Direct 4D EM reconstruction resulted in notable qualitative and quantitative accuracy

  16. Radiosynthesis and in vivo evaluation of a series of substituted {sup 11}C-phenethylamines as 5-HT{sub 2A} agonist PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Ettrup, Anders; Santini, Martin A.; Palner, Mikael; Knudsen, Gitte M. [Copenhagen University Hospital, Neurobiology Research Unit, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Hansen, Martin; Paine, James; Kristensen, Jesper; Begtrup, Mikael [University of Copenhagen, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Gillings, Nic; Herth, Matthias M.; Madsen, Jacob [Copenhagen University Hospital, Rigshospitalet, PET and Cyclotron Unit, Copenhagen (Denmark); Copenhagen University Hospital, Rigshospitalet, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen (Denmark); Lehel, Szabolcs [Copenhagen University Hospital, Rigshospitalet, PET and Cyclotron Unit, Copenhagen (Denmark)

    2011-04-15

    Positron emission tomography (PET) imaging of serotonin 2A (5-HT{sub 2A}) receptors with agonist tracers holds promise for the selective labelling of 5-HT{sub 2A} receptors in their high-affinity state. We have previously validated [{sup 11}C]Cimbi-5 and found that it is a 5-HT{sub 2A} receptor agonist PET tracer. In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [{sup 11}C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT{sub 2A} receptor agonist PET tracers in the pig brain. Each radiotracer was injected intravenously into anaesthetized Danish Landrace pigs, and the pigs were subsequently scanned for 90 min in a high-resolution research tomography scanner. To evaluate 5-HT{sub 2A} receptor binding, cortical nondisplaceable binding potentials (BP{sub ND}) were calculated using the simplified reference tissue model with the cerebellum as a reference region. After intravenous injection, all compounds entered the brain and distributed preferentially into the cortical areas, in accordance with the known 5-HT{sub 2A} receptor distribution. The largest target-to-background binding ratio was found for [{sup 11}C]Cimbi-36 which also had a high brain uptake compared to its analogues. The cortical binding of [{sup 11}C]Cimbi-36 was decreased by pretreatment with ketanserin, supporting 5-HT{sub 2A} receptor selectivity in vivo. [{sup 11}C]Cimbi-82 and [{sup 11}C]Cimbi-21 showed lower cortical BP{sub ND}, while [{sup 11}C]Cimbi-27, [{sup 11}C]Cimbi-29, [{sup 11}C]Cimbi-31 and [{sup 11}C]Cimbi-88 gave rise to cortical BP{sub ND} similar to that of [{sup 11}C]Cimbi-5. [{sup 11}C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT{sub 2A} receptor agonist binding in the living human brain with PET. (orig.)

  17. 11C-harmine as a potential PET tracer for ductal pancreas cancer: in vitro studies.

    Science.gov (United States)

    Herlin, G; Persson, B; Bergström, M; Långström, B; Aspelin, P

    2003-04-01

    Our objective was to find a tracer in diagnosing human pancreatic cancer using positron emission tomography (PET). For this purpose in vitro test of pancreatic tissues with autoradiography was used. Autoradiography was performed with (11)C-harmine (a MAO-A-inhibitor) with and without competitive inhibition. Tissue preparations were obtained from normal human pancreas and pancreatic cancer. The uptake was compared with rat brain or pig brain, tissues with high expression of MAO-A. Nine autoradiography studies on 16 samples from five different human pancreatic cancers gave a significant level of specific binding of (11)C-harmine in 13, and 3 samples did not give a significant level of specific binding of (11)C-harmine. All 16 samples were analysed with autoradiography. Compared with rat brain, the uptake in the human cancers varied between 9 and 43% except for one tissue preparation which had a too low value for measurement. This study shows expression of MAO-A in human pancreatic cancer. This is readily characterised in vitro. The potential use of (11)C-harmine in the diagnosis of pancreatic cancer using PET might be limited, but further PET studies are necessary.

  18. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs;

    2011-01-01

    Small-molecule α(7) nicotinic acetylcholine receptor (α(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled α(7)nAChR PET tracer would be important for in vivo quantification of α(7)nAChR bind......Small-molecule α(7) nicotinic acetylcholine receptor (α(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled α(7)nAChR PET tracer would be important for in vivo quantification of α(7)n...

  19. PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments

    Directory of Open Access Journals (Sweden)

    Roland Haubner

    2014-01-01

    Full Text Available Noninvasive determination of integrin expression has become an interesting approach in nuclear medicine. Since the discovery of the first 18F-labeled cyclic RGD peptide as radiotracer for imaging integrin αvβ3 expression in vivo, there have been carried out enormous efforts to develop RGD peptides for PET imaging. Moreover, in recent years, additional integrins, including α5β1 and αvβ6, came into the focus of pharmaceutical radiochemistry. This review will discuss the tracers already evaluated in clinical trials and summarize the preliminary outcome. It will also give an overview on recent developments to further optimize the first-generation compounds such as [18F]Galacto-RGD. This includes recently developed 18F-labeling strategies and also new approaches in 68Ga-complex chemistry. Furthermore, the approaches to develop radiopharmaceuticals targeting integrin α5β1 and αvβ6 will be summarized and discussed.

  20. Analysis of metabolism of 6FDG: a PET glucose transport tracer

    Energy Technology Data Exchange (ETDEWEB)

    Muzic, Raymond F., E-mail: raymond.muzic@case.edu [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Chandramouli, Visvanathan [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Huang, Hsuan-Ming [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Wu Chunying; Wang Yanming [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Ismail-Beigi, Faramarz [Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2011-07-15

    Introduction: We are developing {sup 18}F-labeled 6-fluoro-6-deoxy-D-glucose ([{sup 18}F]6FDG) as a tracer of glucose transport. As part of this process it is important to characterize and quantify putative metabolites. In contrast to the ubiquitous positron emission tomography (PET) tracer {sup 18}F-labeled 2-fluoro-2-deoxy-D-glucose ([{sup 18}F]2FDG) which is phosphorylated and trapped intracellularly, the substitution of fluorine for a hydroxyl group at carbon-6 in [{sup 18}F]6FDG should prevent its phosphorylation. Consequently, [{sup 18}F]6FDG has the potential to trace the transport step of glucose metabolism without the confounding effects of phosphorylation and subsequent steps of metabolism. Herein the focus is to determine whether, and the degree to which, [{sup 18}F]6FDG remains unchanged following intravenous injection. Methods: Biodistribution studies were performed using 6FDG labeled with {sup 18}F or with the longer-lived radionuclides {sup 3}H and {sup 14}C. Tissues were harvested at 1, 6, and 24 h following intravenous administration and radioactivity was extracted from the tissues and analyzed using a combination of ion exchange columns, high-performance liquid chromatography, and chemical reactivity. Results: At the 1 h time-point, the vast majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood was identified as 6FDG. At the 6-h and 24-h time points, there was evidence of a minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D-sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. Conclusion: On the time scale typical of PET imaging studies radioactive metabolites of [{sup 18}F]6FDG are negligible.

  1. A pharmacokinetic PET study of NK{sub 1} receptor occupancy

    Energy Technology Data Exchange (ETDEWEB)

    Zamuner, Stefano [GlaxoSmithKline, Clinical Pharmacology Modeling and Simulation, Stockley Park (United Kingdom); Rabiner, Eugenii A. [Hammersmith Hospital, GlaxoSmithKline, Clinical Imaging Centre, London (United Kingdom); Fernandes, Sofia A.; Bani, Massimo; Ratti, Emilangelo [GlaxoSmithKline, Neurosciences CEDD, Verona (Italy); Gunn, Roger N. [Hammersmith Hospital, GlaxoSmithKline, Clinical Imaging Centre, London (United Kingdom); University of Oxford, Department of Engineering Science, Oxford (United Kingdom); Gomeni, Roberto [GlaxoSmithKline, Pharmacometrics, Upper Merion, PA (United States); Cunningham, Vincent J. [Hammersmith Hospital, GlaxoSmithKline, Clinical Imaging Centre, London (United Kingdom); University of Aberdeen, School of Medical Sciences, Aberdeen Biomedical Imaging Centre, Aberdeen, Scotland (United Kingdom)

    2012-02-15

    There is growing recognition of the importance of integrating drug occupancy data acquired by positron emission tomography (PET) with the plasma pharmacokinetics of the drug, in order to establish proper dose selection in subsequent clinical trials. Here we present a study in human subjects of the occupancy of NK{sub 1} receptors achieved following different doses of casopitant, a selective NK{sub 1} antagonist. Two PET scans were carried out in each of eight human subjects, with the PET radioligand [{sup 11}C]GR205171, a high-affinity and selective NK{sub 1} receptor antagonist. The first scan was under baseline conditions and the second 24 h after a single oral dose of casopitant (2-120 mg). Arterial blood was collected throughout the scans for determination of plasma and whole blood input functions. Venous blood samples were taken prior to and following oral dosing up to 24 h for a pharmacokinetic study of casopitant concentration in plasma. It was first necessary to establish a suitable kinetic model for the estimation of [{sup 11}C]GR205171 NK{sub 1} receptor binding parameters in human brain tissue. A three-tissue compartment model with simultaneous estimation of multiple regions sharing common variables across regions was found suitable for the analysis. Because of the injected cold mass of the tracer and the high affinity of [{sup 11}C]GR205171 a correction for tracer occupancy effects was also incorporated into the analysis. We then developed a pharmacokinetic-receptor occupancy (PK-RO) model of the relationship between casopitant plasma concentrations and receptor binding, using a population approach. These results indicate that after chronic dosing, casopitant can achieve a degree of NK{sub 1} receptor occupancy higher than those that have previously been tested in studies of clinical depression. (orig.)

  2. Biocompatible branched copolymer nanoparticles prepared by RAFT polymerization as MRI/PET bimodal tracers

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chang-Tong [Lee Kong Chian School of Medicine, Nanyang Technological University (Singapore); Tao, He; Jackson, Alexander W [Institute of Chemical and Engineering Sciences, Agency for Science Technology and Research (Singapore); Chandrasekharan, Prashant [Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (Singapore); Padmanabhan, Parasuraman [Lee Kong Chian School of Medicine, Nanyang Technological University (Singapore); Gulyás, Balázs; Halldin, Christer [Lee Kong Chian School of Medicine, Nanyang Technological University (Singapore); Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden)

    2015-05-18

    Stable branched copolymer nanoparticles of varying size (Dh = 20 – 35 nm) have been developed and employed as MRI nano-sized contrast agents. RAFT polymerization has been employed to prepare these novel nanoparticles possessing DO3A macrocycles within their cores and succinimidyl ester benzoate functionalities within their coronas. It has been demonstrated that these nanoparticles can chelate gadolinium and in vitro cytotoxicity studies using HK-2 cells established their negligible toxicity profile. In vivo MRI experiments showed that these nanoparticles have a high relaxivity and a long blood retention time. Xenograft experiments further illustrated the ability of these nanoparticles to perfuse and passively accumulate in tumor cells, presumably through the enhanced EPR effect. The presence of the succinimidyl ester benzoate functionalities within the nanoparticle coronas will permit future surface modification with fluorophores or targeting moieties to generate nanoparticles to study opportunities for bimodal imaging nano-probes or active cell targeting contrast agents. The chelation with PET radioisotopes (68Ga(III) or 64Cu(II)) can afford various PET tracers.

  3. Defining optimal tracer activities in pediatric oncologic whole-body {sup 18}F-FDG-PET/MRI

    Energy Technology Data Exchange (ETDEWEB)

    Gatidis, Sergios; Schmidt, Holger; Nikolaou, Konstantin; Schwenzer, Nina F.; Schaefer, Juergen F. [University of Tuebingen, Department of Radiology, Diagnostic and Interventional Radiology, Tuebingen (Germany); La Fougere, Christian [University of Tuebingen, Department of Radiology, Nuclear Medicine, Tuebingen (Germany)

    2016-12-15

    To explore the feasibility of reducing administered tracer activities and to assess optimal activities for combined {sup 18}F-FDG-PET/MRI in pediatric oncology. 30 {sup 18}F-FDG-PET/MRI examinations were performed on 24 patients with known or suspected solid tumors (10 girls, 14 boys, age 12 ± 5.6 [1-18] years; PET scan duration: 4 min per bed position). Low-activity PET images were retrospectively simulated from the originally acquired data sets using randomized undersampling of list mode data. PET data of different simulated administered activities (0.25-2.5 MBq/kg body weight) were reconstructed with or without point spread function (PSF) modeling. Mean and maximum standardized uptake values (SUV{sub mean} and SUV{sub max}) as well as SUV variation (SUV{sub var}) were measured in physiologic organs and focal FDG-avid lesions. Detectability of organ structures and of focal {sup 18}F-FDG-avid lesions as well as the occurrence of false-positive PET lesions were assessed at different simulated tracer activities. Subjective image quality steadily declined with decreasing tracer activities. Compared to the originally acquired data sets, mean relative deviations of SUV{sub mean} and SUV{sub max} were below 5 % at {sup 18}F-FDG activities of 1.5 MBq/kg or higher. Over 95 % of anatomic structures and all pathologic focal lesions were detectable at 1.5 MBq/kg {sup 18}F-FDG. Detectability of anatomic structures and focal lesions was significantly improved using PSF. No false-positive focal lesions were observed at tracer activities of 1 MBq/kg {sup 18}F-FDG or higher. Administration of {sup 18}F-FDG activities of 1.5 MBq/kg is, thus, feasible without obvious diagnostic shortcomings, which is equivalent to a dose reduction of more than 50 % compared to current recommendations. Significant reduction in administered {sup 18}F-FDG tracer activities is feasible in pediatric oncologic PET/MRI. Appropriate activities of {sup 18}F-FDG or other tracers for specific clinical

  4. Multiple Neoplasms Simultaneously Diagnosed by Complementary Triple-Tracer PET/CT and 123I-MIBG Scintigraphy.

    Science.gov (United States)

    Søndergaard, Esben; Ebbehoj, Andreas; Poulsen, Per Løgstrup; Gormsen, Lars Christian

    2017-01-01

    A 51-year-old woman with recurrent paragangliomas and catecholamine hypersecretion underwent F-FDG PET/CT for localization and evaluation of extent of disease. This revealed multiple F-FDG avid tumors with localization pattern suggesting multiple primary neoplasms of different origin rather than disseminated paraganglioma. Three additional nuclear medicine investigations were performed (F-DOPA PET/CT, Ga-DOTATOC PET/CT and I-MIBG scintigraphy) to further characterize tumor biology, guide diagnostic workup, and decide treatment strategy. Biopsies showed benign paraganglioma, mucinous adenocarcinoma of the cecum, renal cell carcinoma, and thyroid colloid nodule. Treatment strategy was based on tumor biology determined by the various PET and SPECT tracers used.

  5. Automatic extraction of forward stroke volume using dynamic PET/CT: a dual-tracer and dual-scanner validation in patients with heart valve disease

    OpenAIRE

    Harms, Hendrik Johannes; Tolbod, Lars Poulsen; Hansson, Nils Henrik Stubkjær; Kero, Tanja; Örndahl, Lovisa Holm; Kim, Won Yong; Bjerner, Tomas; Bouchelouche, Kirsten; Wiggers, Henrik; Frøkiær, Jørgen; Sörensen, Jens

    2015-01-01

    BACKGROUND: The aim of this study was to develop and validate an automated method for extracting forward stroke volume (FSV) using indicator dilution theory directly from dynamic positron emission tomography (PET) studies for two different tracers and scanners. METHODS: 35 subjects underwent a dynamic (11)C-acetate PET scan on a Siemens Biograph TruePoint-64 PET/CT (scanner I). In addition, 10 subjects underwent both dynamic (15)O-water PET and (11)C-acetate PET scans on a GE Discovery-ST PET...

  6. Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]tracers, [11C]/[18F]-HTP).

    Science.gov (United States)

    Ambrosini, V; Morigi, J J; Nanni, C; Castellucci, P; Fanti, S

    2015-03-01

    Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate.

  7. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs

    2011-01-01

    Small-molecule a(7) nicotinic acetylcholine receptor (a(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled a(7)nAChR PET tracer would be important for in vivo quantification of a(7)n...

  8. Quantification of 5-HT{sub 1A} receptors in human brain using p-MPPF kinetic modelling and PET

    Energy Technology Data Exchange (ETDEWEB)

    Sanabria-Bohorquez, S.M.; Veraart, C. [Neural Rehabilitation Engineering Lab., Univ. Catholique de Louvain, Brussels (Belgium); Biver, F.; Damhaut, P.; Wikler, D.; Goldman, S. [PET/Biomedical Cyclotron Unit, Univ. Libre de Bruxelles (Belgium)

    2002-01-01

    Serotonin-1A (5-HT{sub 1A}) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-[{sup 18}F]fluorobenzamido] ethyl] piperazine (p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT{sub 1A} receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT{sub 1A} receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT{sub 1A} receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT{sub 1A} receptor human studies. (orig.)

  9. Small Prosthetic Groups in (18)F-Radiochemistry: Useful Auxiliaries for the Design of (18)F-PET Tracers.

    Science.gov (United States)

    Schirrmacher, Ralf; Wängler, Björn; Bailey, Justin; Bernard-Gauthier, Vadim; Schirrmacher, Esther; Wängler, Carmen

    2017-09-01

    Prosthetic group (PG) applications in (18)F-radiochemistry play a pivotal role among current (18)F(-)labeling techniques for the development and availability of (18)F-labeled imaging probes for PET (Wahl, 2002) ((1)). The introduction and popularization of PGs in the mid-80s by pioneers in (18)F-radiochemistry has profoundly changed the landscape of available tracers for PET and has led to a multitude of new imaging agents based on simple and efficiently synthesized PGs. Because of the chemical nature of anionic (18)F(-) (apart from electrophilic low specific activity (18)F-fluorine), radiochemistry before the introduction of PGs was limited to simple nucleophilic substitutions of leaving group containing precursor molecules. These precursors were not always available, and some target compounds were either hard to synthesize or not obtainable at all. Even with the advent of recently introduced "late-stage fluorination" techniques for the (18)F-fluorination of deactivated aromatic systems, PGs will continue to play a central role in (18)F-radiochemistry because of their robust and almost universal usability. The importance of PGs in radiochemistry is shown by its current significance in tracer development and exemplified by an overview of selected methodologies for PG attachment to PET tracer molecules. Especially, click-chemistry approaches to PG conjugation, while furthering the historical evolution of PGs in PET tracer design, play a most influential role in modern PG utilization. All earlier and recent multifaceted approaches in PG development have significantly enriched the contingent of modern (18)F-radiochemistry procedures and will continue to do so. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, Atsushi B.; Sogawa, Chizuru; Sugyo, Aya [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Sudo, Hitomi [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Toyohara, Jun [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 206-8670 (Japan); Koizumi, Mitsuru [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Abe, Masaaki; Hino, Okio [Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Harada, Yoshi-nobu; Furukawa, Takako [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Suzuki, Kazutoshi [Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Saga, Tsuneo [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: saga@nirs.go.jp

    2009-05-15

    Introduction: Malignant mesothelioma is a highly aggressive tumor originating in the pleura, peritoneum and pericardium, and the prognosis of patients undergoing current treatment remains poor. To develop new therapies, it is important to have a noninvasive imaging system for evaluating the efficacy of such prospective treatments. We have established clinically relevant mouse models and evaluated conventional and novel positron emission tomography (PET) tracers. Methods: Epithelioid and sarcomatoid mesothelioma cells were inoculated subcutaneously and intrapleurally into nude mice. Biodistribution and PET imaging studies were conducted by injecting [{sup 18}F]fluoro-2-deoxy-D-glucose (FDG), 3'-[{sup 18}F]fluoro-3'-doxythymidine (FLT) or 4'-methyl-[{sup 11}C]thiothymidine (S-dThd) into the mouse models. In vitro cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and thymidine kinase 1 (TK{sub 1}) activity in both cell lines were measured. Expression of glucose transporter 1 (GLUT-1) and Ki-67 in xenografted tumors was evaluated by immunohistochemical staining. Results: In epithelioid mesothelioma models, biodistribution experiments showed that tumor uptake of [{sup 11}C]S-dThd was significantly higher than that of [{sup 18}F]FDG. On the other hand, in sarcomatoid models, [{sup 18}F]FDG showed significantly higher accumulation than the other two tracers. These differential uptakes of the three tracers were confirmed by PET imaging. The cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and TK{sub 1} activity in sarcomatoid cells were higher than those of epithelioid cells. GLUT-1 protein was strongly expressed in sarcomatoid but not in epithelioid tumor. We observed a high percentage of Ki-67-positive cells in both epithelioid and sarcomatoid tumors. Conclusions: We established nude mouse models of epithelioid and sarcomatoid subtypes of mesothelioma. PET tracers applicable for the evaluation of epithelioid and sarcomatoid mesothelioma would vary

  11. Complementary roles of tumour specific PET tracer {sup 18}F-FAMT to {sup 18}F-FDG PET/CT for the assessment of bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Motoho [Gunma University Hospital, Department of General Medicine, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Achmad, Arifudin [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gadjah Mada University, Department of Radiology, Faculty of Medicine, Yogyakarta (Indonesia)

    2013-10-15

    The usefulness of {sup 18}F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [{sup 18}F]-3-fluoro-alpha-methyl tyrosine ({sup 18}F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of {sup 18}F-FAMT PET/CT to complement {sup 18}F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both {sup 18}F-FDG and {sup 18}F-FAMT PET/CT within 1 month of each other. {sup 18}F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the {sup 18}F-FAMT in the corresponding lesions were evaluated. A total of 72 {sup 18}F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. {sup 18}F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of {sup 18}F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher {sup 18}F-FAMT uptake than those of adenocarcinoma. No significant difference in {sup 18}F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of {sup 18}F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that {sup 18}F-FAMT uptake was confirmed by {sup 18}F-FDG uptake suggests that {sup 18}F-FAMT PET/CT has the potential to complement {sup 18}F-FDG PET/CT for the detection of bone metastases. (orig.)

  12. Evaluation of [{sup 11}C]rofecoxib as PET tracer for cyclooxygenase 2 overexpression in rat models of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Erik F.J. de [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen (Netherlands)], E-mail: e.f.j.de.vries@ngmb.umcg.nl; Doorduin, Janine; Dierckx, Rudi A.; Waarde, Aren van [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen (Netherlands)

    2008-01-15

    Background: Overexpression of cyclooxygenase type 2 (COX-2) is triggered by inflammatory stimuli, but it also plays a prominent role in the initiation and progression of various diseases. This study aims to investigate [{sup 11}C]rofecoxib as a positron emission tomography (PET) tracer for COX-2 expression. Methods: [{sup 11}C]Rofecoxib was prepared by methylation of its sulphinate precursor. Regional brain distribution and specific binding of [{sup 11}C]rofecoxib in healthy rats was studied by ex vivo biodistribution and autoradiography. Regional brain distribution and PET imaging studies were also performed on rats with severe encephalitis, caused by nasal infection with herpes simplex virus (HSV). Finally, ex vivo biodistribution and blocking studies were carried in rats with a sterile inflammation, induced by intramuscular turpentine injection. Results: [{sup 11}C]rofecoxib brain uptake in control animals corresponded with the known distribution of COX-2. Pretreatment with NS398 significantly reduced tracer uptake in the cingulate/frontopolar cortex, whereas the reduction in hippocampus approached significance. Ex vivo autoradiography also revealed preferential tracer uptake in hippocampus and cortical areas that could be blocked by NS398. In HSV-infected animals, [{sup 11}C]rofecoxib uptake was moderately increased in all brain regions, but it could not be blocked with indomethacin. Yet, some PET images revealed increased tracer uptake in brain areas with microglia activation. In turpentine-injected animals, [{sup 11}C]rofecoxib uptake in inflamed muscle was not higher than in control muscle and could not be blocked with NS398. Indomethacin caused a slight reduction in muscle uptake. Conclusions: Despite the apparent correlation between [{sup 11}C]rofecoxib uptake and COX-2 distribution in healthy rats, [{sup 11}C]rofecoxib could not unambiguously detect COX-2 overexpression in two rat models of inflammation.

  13. The potential use of 2-[{sup 18}F]fluoro-2-deoxy-D-galactose as a PET/CT tracer for detection of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen, Michael; Keiding, Susanne [Aarhus University Hospital, PET Centre, Aarhus C (Denmark); Aarhus University Hospital, Department of Medicine V (Hepatology and Gastroenterology), Aarhus (Denmark); Frisch, Kim; Bender, Dirk [Aarhus University Hospital, PET Centre, Aarhus C (Denmark)

    2011-09-15

    The aim of the study was to evaluate the feasibility of using the hepatocyte-specific positron emission tomography (PET) tracer 2-[{sup 18}F]fluoro-2-deoxy-D-galactose (FDGal) as a tracer for hepatocellular carcinoma (HCC). In addition to standard clinical investigations, 39 patients with known HCC or suspected of having HCC underwent a partial-body FDGal PET/CT (from base of skull to mid-thigh). Diagnosis of HCC was based on internationally approved criteria. FDGal PET/CT images were analysed for areas with high (hot spots) or low (cold spots) tracer accumulation when compared to surrounding tissue. Seven patients did not have HCC and FDGal PET/CT was negative in each of them. Twenty-three patients had HCC and were included before treatment. FDGal PET/CT correctly identified 22 of these patients, which was comparable to contrast-enhanced CT. Interestingly, FDGal PET/CT was conclusive in 12 patients in whom conventional imaging techniques were inconclusive and required additional diagnostic investigations or close follow-up. Nine patients were included after treatment of HCC and in these patients FDGal PET/CT was able to distinguish between viable tumour tissue as hot spots and areas with low metabolic activity as cold spots. FDGal PET/CT detected extrahepatic disease in nine patients which was a novel finding in eight patients. FDGal PET/CT has great clinical potential as a PET tracer for detection of extra- but also intrahepatic HCC. In the present study, the specificity of FDGal PET/CT was 100%, which is very promising but needs to be confirmed in a larger, prospective study. (orig.)

  14. Dual Tracer PET Imaging with FDG and FLT Differentiates Tuberculous Lymphadenopathy from Metastases in a Case of Carcinoma Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Prathamesh; Lele, Vikram; Aland, Parag; Gemawat, Shilpa [Jaslok Hospital and Research Centre, Woril (India)

    2013-09-15

    A forty-year-old woman with a known case of carcinoma cervix underwent 18-fluorodeoxyglucose positron emission tomography.computed tomography (18-FDG PET/CT) for evaluation of abdominal lymphadenopathy. Her treatment history included radical hysterectomy and radiotherapy 6 months ago. She complained of weight loss of 7 kg over last 5 months. The maximum intensity projection (MIP) image (Fig. 1a, arrows) revealed multiple areas of intense FDG uptake, which on CT and fused PET/CT images were localized to multiple lymph nodes in bilateral cervical region, right axilla, mediastinum and abdomen. The SUVmax of right axillary lymph nodes (most FDG avid of all lymph node groups) was 15.3. There was no evidence of metabolically active disease or CT demonstrable abnormality in rest of the body. Presence of metabolically active disease in extensive supradiaphramatic lymphadenopathy was unusual for a case of carcinoma cervix. This finding, along with history of significant weight loss and absence of extranodal disease, was suspicious for unrelated pathology like lymphoproliferative disorder or granulomatous disease. Mixed malignant and benign lymphadenopathy was also considered a possibility. To solve the conundrum, 18-fluoro-L-thymidine (FLT) PET/CT was performed on the next day. This scan was performed to assess the proliferation rate in various above-mentioned lymph nodes, and to plan the optimum site of biopsy. The FLT PET scan (Fig. 1b) showed physiological distribution of the tracer in bone marrow, liver, gall bladder and urinary bladder. There was minimal FLT uptake in the enlarged, FDG avid lymph nodes (Fig. 1c and d). SUVmax of FLT uptake in right axillary lymph nodes was 1.4 (SUVmax of FDG uptake = 15.8). The SUVmax of FLT uptake in cervical, mediastinal and abdominal lymph nodes were 1.3, 1.4 and 1.0 respectively. (SUVmax of FDG uptake 12.1, 12.7 and 11.9, respectively). Considering avidity for FDG and non-avidity of proliferation marker tracer (FLT), possibility of

  15. Development of new peripheral benzodiazepine receptor ligands for SPECT and PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, A.; Fookes, C.; Pham, T.; Holmes, T.; Mattner, F.; Berghoffer, P.; Gregoire, M.C.; Loc' h, C.; Greguric, I. [Radiopharmaceuticas Research Institute, ANSTO, Menai, N.S.W. Sydney (Australia); Thominiaux, C.; Boutin, H.; Chauveau, F.; Gregoire, M.C.; Hantraye, Ph.; Tavitain, B.; Dolle, F. [Service Hospitalier Frederic Joliot, CEA/DSV, 91 - Orsay (France); Arlicot, N.; Chalon, S.; Guilloteau, D. [Universite Francois Rabelais, Inserm U619, 37 - Tours (France)

    2008-02-15

    This study aims to demonstrate that a number of radiolabelled ({sup 123}I,{sup 11}C, {sup 18}F) imidazo pyridines, imidazo pyridazines and indolglyoxylamides can be developed as potential tracers for SPECT and PET imaging. (N.C.)

  16. Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis.

    Science.gov (United States)

    Pillai, Sekhar C; Gill, Deepak; Webster, Richard; Howman-Giles, Robert; Dale, Russell C

    2010-09-01

    N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2) with relapsing NMDA receptor encephalitis each had the classic clinical features of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia, and mild autonomic dysfunction. Both patients had persistent neuropsychiatric disability, despite immune therapies. Positron emission tomography (PET) scans were performed during clinical relapse at 6 weeks (case 1) and 5 months (case 2). In both cases, the scans demonstrated reduced fluorodeoxyglucose metabolism in the cerebral cortex, with the temporal regions being most affected. PET imaging was more sensitive than magnetic resonance imaging in these patients. In contrast, the one previous report of acute NMDA receptor encephalitis indicated cortical hypermetabolism. Thus, NMDA receptor encephalitis may be associated with variable PET findings, possibly dependent upon the timing of the study, or other factors. Future studies should investigate whether cortical hypometabolism is associated with a relapsing course, and whether it is predictive of a poorer outcome in NMDA receptor encephalitis.

  17. PET neuroimaging of extrastriatal dopamine receptors and prefrontal cortex functions.

    Science.gov (United States)

    Takahashi, Hidehiko

    2013-12-01

    The role of prefrontal dopamine D1 receptors in prefrontal cortex (PFC) functions, including working memory, is widely investigated. However, human (healthy volunteers and schizophrenia patients) positron emission tomography (PET) studies about the relationship between prefrontal D1 receptors and PFC functions are somewhat inconsistent. We argued that several factors including an inverted U-shaped relationship between prefrontal D1 receptors and PFC functions might be responsible for these inconsistencies. In contrast to D1 receptors, relatively less attention has been paid to the role of D2 receptors in PFC functions. Several animal and human pharmacological studies have reported that the systemic administration of D2 receptor agonist/antagonist modulates PFC functions, although those studies do not tell us which region(s) is responsible for the effect. Furthermore, while prefrontal D1 receptors are primarily involved in working memory, other PFC functions such as set-shifting seem to be differentially modulated by dopamine. PET studies of extrastriatal D2 receptors including ours suggested that orchestration of prefrontal dopamine transmission and hippocampal dopamine transmission might be necessary for a broad range of normal PFC functions. In order to understand the complex effects of dopamine signaling on PFC functions, measuring a single index related to basic dopamine tone is not sufficient. For a better understanding of the meanings of PET indices related to neurotransmitters, comprehensive information (presynaptic, postsynaptic, and beyond receptor signaling) will be required. Still, an interdisciplinary approach combining molecular imaging techniques with cognitive neuroscience and clinical psychiatry will provide new perspectives for understanding the neurobiology of neuropsychiatric disorders and their innovative drug developments.

  18. MRI combined with PET-CT of different tracers to improve the accuracy of glioma diagnosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Yang, Yihan; He, Mike Z; Li, Tao; Yang, Xuejun

    2017-09-16

    Based on studies focusing on positron emission tomography (PET)-computed tomography (CT) combined with magnetic resonance imaging (MRI) in the diagnosis of glioma, we conducted a systematic review and meta-analysis evaluating the pros and cons and the accuracy of different examinations. PubMed and Cochrane Library were searched. The search was conducted until April 2017. Two reviewers independently conducted the literature search according to the criteria set initially. Based on the exclusion criteria, 15 articles are included in this study. Of all studies that used MRI examination, there are five involving 18F-fluorodeoxyglucose-PET, five involving 11C-methionine-PET, five involving 18F-fluoro-ethyl-tyrosine-PET, and three involving 18F-fluorothymidine-PET. Due to the limitations such as lack of data, small sample size, and unrepresentative studies, we use a non-quantitative methodology. MRI examination can provide the anatomy information of glioma more clearly. PET-CT examinations based on tumor metabolism using different tracers have more advantages in determining the degree of glioma malignancy and boundaries. However, information provided by PET-CT of different tracers is not the same. With respect to the novel hybrid MRI/PET examination equipment proposed in recent years, the combination of MRI and PET-CT can definitively improve the diagnostic accuracy of glioma.

  19. Prognostic value of bone marrow tracer uptake pattern in baseline PET scan in Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Zwarthoed, Colette; El-Galaly, Tarec Cristoffer; Canepari, Maria

    2017-01-01

    RATIONALE: Positron Emission Tomography/Computed Tomography (PET/CT)-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analysed the clinico.......03). The kappa-values for inter-observer agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. CONCLUSION: We confirmed that FDG-PET scan is a reliable tool for BMI assessment in HL and BMB is no longer needed for routine staging. Moreover, the inter-observer agreement for BMI in this study proved...

  20. Kinetic modelling of [{sup 123}I]CNS 1261--a potential SPET tracer for the NMDA receptor

    Energy Technology Data Exchange (ETDEWEB)

    Erlandsson, Kjell E-mail: k.erlandsson@nucmed.ucl.ac.uk; Bressan, Rodrigo A.; Mulligan, Rachel S.; Gunn, Roger N; Cunningham, Vincent J.; Owens, Jonathan; Wyper, David; Ell, Peter J.; Pilowsky, Lyn S

    2003-05-01

    N-(1-napthyl)-N'-(3-[{sup 123}I]-iodophenyl)-N-methylguanidine ([{sup 123}I]CNS 1261) is a novel SPET ligand developed for imaging the NMDA receptor intra-channel MK 801/PCP/ketamine site. Data was acquired in 7 healthy volunteers after bolus injection of [{sup 123}I]CNS 1261. Kinetic modeling showed reversible tracer binding. Arterial and venous time-activity curves overlapped after 90 min. The rank order of binding was: Thalamus > striatum > cortical regions > white matter. This distribution concurs with [{sup 11}C]-ketamine and [{sup 18}F]-memantine PET studies . These data provide a methodological basis for further direct in vivo challenge studies.

  1. Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Hudson, Brian D; Hansen, Anders Højgaard;

    2016-01-01

    The free fatty acid receptor 1 (FFA1/GPR40) is a potential target for treatment of type 2 diabetes. Although several potent agonists have been described, there remains a strong need for suitable tracers to interrogate ligand binding to this receptor. We address this by exploring fluorophore-tethe...

  2. New targets for the development of PET tracers for imaging neurodegeneration in Alzheimer disease.

    Science.gov (United States)

    Mach, Robert H

    2014-08-01

    The field of molecular imaging has experienced significant advances in the area of Alzheimer disease (AD), the most significant being the development of PET radiotracers for imaging β-amyloid burden in the brain of individuals at risk for or in the early stages of AD. More recent advances include the development of PET radiotracers for imaging aggregates of hyperphosphorylated tau protein in neurofibrillary tangles, a process that occurs late in the disease process. This article highlights advances in the neurobiology of AD and describes how PET can be used to study the mechanisms of neurodegeneration in AD. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  3. {sup 11}C-harmine as a potential PET tracer for ductal pancreas cancer: in vitro studies

    Energy Technology Data Exchange (ETDEWEB)

    Herlin, G.; Persson, B.; Laangstroem, B.; Aspelin, P. [Department of Diagnostic Radiology, Huddinge University Hospital, 141-86 Stockholm (Sweden); Bergstroem, M. [Uppsala University PET Centre, Uppsala (Sweden)

    2003-04-01

    Our objective was to find a tracer in diagnosing human pancreatic cancer using positron emission tomography (PET). For this purpose in vitro test of pancreatic tissues with autoradiography was used. Autoradiography was performed with {sup 11}C-harmine (a MAO-A-inhibitor) with and without competitive inhibition. Tissue preparations were obtained from normal human pancreas and pancreatic cancer. The uptake was compared with rat brain or pig brain, tissues with high expression of MAO-A. Nine autoradiography studies on 16 samples from five different human pancreatic cancers gave a significant level of specific binding of {sup 11}C-harmine in 13, and 3 samples did not give a significant level of specific binding of {sup 11}C-harmine. All 16 samples were analysed with autoradiography. Compared with rat brain, the uptake in the human cancers varied between 9 and 43% except for one tissue preparation which had a too low value for measurement. This study shows expression of MAO-A in human pancreatic cancer. This is readily characterised in vitro. The potential use of {sup 11}C-harmine in the diagnosis of pancreatic cancer using PET might be limited, but further PET studies are necessary. (orig.)

  4. Synthesis, in vitro and in vivo pharmacology of a C-11 labeled analog of CP-101,606, ({+-})threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[{sup 11}C]methoxyphenyl) peridino]-1-propanol, as a PET tracer for NR2B subunit-containing NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Haradahira, Terushi E-mail: terushi@nirs.go.jp; Maeda, Jun; Okauchi, Takashi; Zhang, Ming-Rong; Hojo, Junko; Kida, Takayo; Arai, Takuya; Yamamoto, Fumihiko; Sasaki, Shigeki; Maeda, Minoru; Suzuki, Kazutoshi; Suhara, Tetsuya

    2002-07-01

    A carbon-11 labeled methoxyl analog of CP-101,606, ({+-})threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[{sup 11}C]methoxyphenyl) piperidino]-1-propanol [({+-})[{sup 11}C]1], was synthesized as a new subtype-selective PET radioligand for NMDA receptors. The in vitro binding studies using rat brain slices demonstrated that ({+-})[{sup 11}C]1 shows an extremely high-specific binding to the NR2B subunit of NMDA receptors. In contrast to the in vitro binding, the in vivo binding to mouse and monkey brains showed no apparent specific localization of the radioactivity in any of the brain regions. Metabolism and physicochemical properties such as the lipophilicity of ({+-})[{sup 11}C]1 seemed unlikely to affect the in vivo ({+-})[{sup 11}C]1 binding. Among the various endogenous ligands acting at the NMDA receptors, polyamines (spermine and spermidine) and divalent cations (Mg{sup 2+,} Zn{sup 2+,} and Ca{sup 2+}) strongly inhibited the in vitro ({+-})[{sup 11}C]1 binding. Thus, the present studies point to the possibility that the polyamines and cations behave as endogenous inhibitors for ({+-})[{sup 11}C]1 binding, leading to the loss of the specific binding in vivo.

  5. Graphical Analysis of PET Data Applied to Reversible and Irreversible Tracers

    Energy Technology Data Exchange (ETDEWEB)

    Logan, Jean

    1999-11-18

    Graphical analysis refers to the transformation of multiple time measurements of plasma and tissue uptake data into a linear plot, the slope of which is related to the number of available tracer binding sites. This type of analysis allows easy comparisons among experiments. No particular model structure is assumed, however it is assumed that the tracer is given by bolus injection and that both tissue uptake and the plasma concentration of unchanged tracer are monitored following tracer injection. The requirement of plasma measurements can be eliminated in some cases when a reference region is available. There are two categories of graphical methods which apply to two general types of ligands--those which bind reversibly during the scanning procedure and those which are irreversible or trapped during the time of the scanning procedure.

  6. Application and research progress of PET positron tracers associated with Alzheimer disease%阿尔茨海默病PET正电子药物应用与研究进展

    Institute of Scientific and Technical Information of China (English)

    段小艺; 李淼; 王黎; 李宏利; 赵周社; 郭佑民

    2014-01-01

    阿尔茨海默病(AD)严重危害人们的身心健康。伴随PET分子成像的发展,出现了一系列针对AD的正电子药物,其中匹兹堡化合物B(PIB)及其衍生物类PET正电子药物研究最为成熟,部分已获准应用于临床,在AD诊断与治疗方面显示出重要价值。随着人们对AD发生机制研究的不断深入,近年又相继出现了包括蛋白类、受体类以及肽类在内的更多种类AD相关PET正电子药物。该文就此类正电子药物的应用与研究进展做一综述。%Alzheimer disease(AD) harms human being′s health seriously. With the development progress of PET molecular imaging, a series of PET positron tracers associated with AD appeard. Among them, pittsburgh compound-B(PIB) and PIB derivatives are studied more deeply and part of them have been used in clinic which are showing great value in diagnosis and therapy of AD. Recently, with the deep-er research of AD mechanism , more kinds of PET tracers related to AD are developed, including protein , receptor and peptide radiotracers. This article reviews the current application and research progress of those PET positron tracers which associated with AD.

  7. Comparison of [11C]cocaine binding at tracer and pharmacological doses of baboon brain: A PET study

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.S.; Logan, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1994-05-01

    In vitro studies have shown that cocaine (C) binds to both high and low affinity sites on the dopamine transporter (DAT). We have previously characterized the binding of tracer doses of [{sup 11}C]cocaine (C*)to a high affinity site on the DAT. To assess if in vivo C also binds to low affinity sites we used PET to compare binding of tracer doses (17.8{plus_minus}12.2 {mu}g C) of C* to pharmacological doses (8 mg of C coadministered with C*). Sixteen paired studies were done to assess test/retest variability, specific versus non specific binding and to characterize binding profile. Dynamic scans were started immediately after injection of C* (5-8 mCi) for 50 min on the CTI-931 (6 x 6 x 6.5 mm FWHM). Time activity curves for tissue concentration and for unchanged tracer in plasma were used to calculate the transport constant between plasma and tissue (K1) and to obtain the distribution volume (DV). The ratio of the DV in striatum (ST) to that in cerebellum (CB) (which corresponds to Bmax/Kd-1) was used as model parameter. Peak brain uptake of C* was significantly higher for tracer than for pharmacological doses (0.041 versus 0.033 % dose/cc), as were the values for K1 (1.07{plus_minus}0.21 versus 0.68{plus_minus}0.26 (t=3.0 p<0.01)). Repeated measures were reproducible for tracer ({plus_minus}2%) and pharmacological doses of C* ({plus_minus}4%). Tracer dose C* showed highest binding and slowest clearance in ST which was reduced by C (0.5-2.0 mg/kg iv, -25 to -30%) and by drugs that inhibit DAT (2mg/kg nomifensine - 21%, 0.5 mg/kg methylphenidate -12%) and was increased by serotonin transporter inhibitors (5HT-Ti) (2 mg/kg citalopram +11%, 0.5 mg/kg fluoxetine +6%) and not changed by NE transporter inhibitors (0.5 mg/kg desipramine or 2 mg/kg tomoxetine). The increase with (5HT-Ti) may reflect neurotransmitter interactions or changes in bioavailability. At pharmacological doses C* showed homogeneous distribution and was not changed by C nor by any of the above drugs.

  8. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    Science.gov (United States)

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  9. 89Zr-bevacizumab PET visualizes heterogeneous tracer accumulation in tumor lesions of renal cell carcinoma patients and differential effects of antiangiogenic treatment

    NARCIS (Netherlands)

    Oosting, Sjoukje F; Brouwers, Adrienne H; van Es, Suzanne C; Nagengast, Wouter B; Oude Munnink, Thijs H; Lub-de Hooge, Marjolijn N; Hollema, Harry; de Jong, Johan R; de Jong, Igle J; de Haas, Sanne; Scherer, Stefan J; Sluiter, Wim J; Dierckx, Rudi A; Bongaerts, Alfons H H; Gietema, Jourik A; de Vries, Elisabeth G E

    2015-01-01

    UNLABELLED: No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before

  10. A Standardized Method for the Construction of Tracer Specific PET and SPECT Rat Brain Templates : Validation and Implementation of a Toolbox

    NARCIS (Netherlands)

    Vállez Garcia, David; Casteels, Cindy; Schwarz, Adam J.; Dierckx, Rudi A. J. O.; Koole, Michel; Doorduin, Janine

    2015-01-01

    High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present l

  11. 89Zr-bevacizumab PET visualizes heterogeneous tracer accumulation in tumor lesions of renal cell carcinoma patients and differential effects of antiangiogenic treatment

    NARCIS (Netherlands)

    Oosting, Sjoukje F; Brouwers, Adrienne H; van Es, Suzanne C; Nagengast, Wouter B; Oude Munnink, Thijs H; Lub-de Hooge, Marjolijn N; Hollema, Harry; de Jong, Johan R; de Jong, Igle J; de Haas, Sanne; Scherer, Stefan J; Sluiter, Wim J.; Dierckx, Rudi A; Bongaerts, Alfons H H; Gietema, Jourik A; de Vries, Elisabeth G E

    UNLABELLED: No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before

  12. Evaluation of S-([{sup 18}F]fluoromethyl)-(+)-McN5652 (FMcN) as a PET tracer for the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Brust, P.; Zessin, J.; Pawelke, B.; Steinbach, J. [Inst. fuer Interdisziplinaere Isotopenforschung, Leipzig (Germany)

    2002-01-01

    The suitability of FMcN as a PET tracer was studied in six-week-old piglets. The binding equilibrium in piglet brain was reached about 60 min after i.v. administration of FMcN. The binding was significantly reduced by citalopram but not by maprotiline. It was concluded that FMcN may be suitable for use in humans. (orig.)

  13. First evaluation of PET based human biodistribution and dosimetry of (18)F-FAZA, a tracer for imaging tumor hypoxia.

    Science.gov (United States)

    Savi, Annarita; Incerti, Elena; Fallanca, Federico; Bettinardi, Valentino; Rossetti, Francesca; Monterisi, Cristina; Compierchio, Antonia; Negri, Giampiero; Zannini, Piero; Gianolli, Luigi; Picchio, Maria

    2017-02-16

    humans. Therefore, estimated organ radiation doses from animal data could exhibit a moderate underestimation. Our data showed that dosimetry of (18)F-FAZA, for an injection of 370 MBq of tracer, is safe for its clinical use and it is almost similar to other widely used PET ligands. In particular, the ED is not appreciably different from those obtained with other hypoxia tracers, such as (18)F-fluoromisonidazole ((18)F-FMISO).

  14. A pictoral review on somatostatin receptor scintigraphy in neuroendocrine tumors: The role of multimodality imaging with SRS and GLUT receptor imaging with FDG PET-CT

    Directory of Open Access Journals (Sweden)

    Sneha Shah

    2012-01-01

    Full Text Available Somatostatin receptor scintigraphy is considered as a comprehensive imaging modality for many neuroendocrine tumors. Multiple radiotracers using combinations of gamma or positron emitting radionuclides and tracers are now available. Newer radiopharmaceuticals using 99m Tc labeled with TOC, TATE, NOC are good alternatives to the 68 - Gallium radiotracers where the PET facility is not available. The pictoral depicts the role of SRS using 99m TC - HYNIC -TOC radiotracers in staging and treatment planning of NETs. Characterization of the tumor biology using combined SRS and FDG PET/CT is also demonstrated with a proposed categorization method. The emerging role of SRS in tailored targeted radionuclide therapy is outlined in brief.

  15. 68Ga-DOTA-NOC PET and peptide receptor radionuclide therapy in management of bilateral ovarian metastases from gastrointestinal carcinoid.

    Science.gov (United States)

    Singla, Suhas; Gupta, Santosh; Reddy, Rama Mohan; Durgapal, Prashant; Bal, C S

    2012-12-01

    The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

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

    Directory of Open Access Journals (Sweden)

    Ahmed Haider

    2016-07-01

    Full Text Available Over the past two decades, our understanding of the endocannabinoid system has greatly improved due to the wealth of results obtained from exploratory studies. Currently, two cannabinoid receptor subtypes have been well characterized. The cannabinoid receptor type 1 (CB1 is widely expressed in the central nervous system, while the levels of the cannabinoid receptor type 2 (CB2 in the brain and spinal cord of healthy individuals are relatively low. However, recent studies demonstrated a CB2 upregulation on activated microglia upon neuroinflammation, an indicator of neurodegeneration. Our research group aims to develop a suitable positron emission tomography (PET tracer to visualize the CB2 receptor in patients suffering from neurodegenerative diseases. Herein we report two novel thiophene-based 11C-labeled PET ligands designated [11C]AAT-015 and [11C]AAT-778. The reference compounds were synthesized using Gewald reaction conditions to obtain the aminothiophene intermediates, followed by amide formation. Saponification of the esters provided their corresponding precursors. Binding affinity studies revealed Ki values of 3.3 ± 0.5 nM (CB2 and 1.0 ± 0.2 µM (CB1 for AAT-015. AAT-778 showed similar Ki values of 4.3 ± 0.7 nM (CB2 and 1.1 ± 0.1 µM (CB1. Radiosynthesis was carried out under basic conditions using [11C]iodomethane as methylating agent. After semi-preparative HPLC purification both radiolabeled compounds were obtained in 99% radiochemical purity and the radiochemical yields ranged from 12 to 37%. Specific activity was between 96 - 449 GBq/µmol for both tracers. In order to demonstrate CB2 specificity of [11C]AAT-015 and [11C]AAT-778, we carried out autoradiography studies using CB2-positive mouse/rat spleen tissues. The obtained results revealed unspecific binding in spleen tissue that was not blocked by an excess of CB2-specific ligand GW402833. For in vivo analysis, [11C]AAT-015 was administered to healthy rats via tail

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

    Science.gov (United States)

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

    2016-01-01

    Over the past two decades, our understanding of the endocannabinoid system has greatly improved due to the wealth of results obtained from exploratory studies. Currently, two cannabinoid receptor subtypes have been well-characterized. The cannabinoid receptor type 1 (CB1) is widely expressed in the central nervous system, while the levels of the cannabinoid receptor type 2 (CB2) in the brain and spinal cord of healthy individuals are relatively low. However, recent studies demonstrated a CB2 upregulation on activated microglia upon neuroinflammation, an indicator of neurodegeneration. Our research group aims to develop a suitable positron emission tomography (PET) tracer to visualize the CB2 receptor in patients suffering from neurodegenerative diseases. Herein we report two novel thiophene-based 11C-labeled PET ligands designated [11C]AAT-015 and [11C]AAT-778. The reference compounds were synthesized using Gewald reaction conditions to obtain the aminothiophene intermediates, followed by amide formation. Saponification of the esters provided their corresponding precursors. Binding affinity studies revealed Ki-values of 3.3 ± 0.5 nM (CB2) and 1.0 ± 0.2 μM (CB1) for AAT-015. AAT-778 showed similar Ki-values of 4.3 ± 0.7 nM (CB2) and 1.1 ± 0.1 μM (CB1). Radiosynthesis was carried out under basic conditions using [11C]iodomethane as methylating agent. After semi-preparative HPLC purification both radiolabeled compounds were obtained in 99% radiochemical purity and the radiochemical yields ranged from 12 to 37%. Specific activity was between 96 and 449 GBq/μmol for both tracers. In order to demonstrate CB2 specificity of [11C]AAT-015 and [11C]AAT-778, we carried out autoradiography studies using CB2-positive mouse/rat spleen tissues. The obtained results revealed unspecific binding in spleen tissue that was not blocked by an excess of CB2-specific ligand GW402833. For in vivo analysis, [11C]AAT-015 was administered to healthy rats via tail-vein injection

  18. Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation

    NARCIS (Netherlands)

    van Waarde, A; Jager, PL; Ishiwata, K; Dierckx, RA; Elsinga, PH

    2006-01-01

    Novel radiopharmaceuticals for the detection of tumors and their metastases may be of clinical interest if they are more tumor selective than F-18-FDG. Increased glucose metabolism of inflammatory tissues is the main source of false-positive F-18-FDG PET findings in oncology. Methods: We compared th

  19. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage

    Energy Technology Data Exchange (ETDEWEB)

    Busk, Morten; Horsman, Michael R.; Overgaard, Jens [Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus C (Denmark); Jakobsen, Steen [Aarhus University Hospital, PET Centre, Aarhus (Denmark); Bussink, Johan; Kogel, Albert van der [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

    2008-12-15

    Tumour hypoxia and elevated glycolysis (Warburg effect) predict poor prognosis. Each parameter is assessable separately with positron emission tomography, but they are linked through anaerobic glycolysis (Pasteur effect). Here, we compare the oxygenation-dependent retention of fluoroazomycin arabinoside ([{sup 18}F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([{sup 18}F]FDG) in four carcinoma cell lines. Cells seeded on coverslips were positioned in modified Petri dishes that allow physically separated cells to share the same tracer-containing medium pool. Following oxic, hypoxic or anoxic tracer incubation, coverslips were analysed for radioactivity ([{sup 18}F]FDG+[{sup 18}F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([{sup 18}F]FAZA). Next, we tested the reliability of [{sup 18}F]FDG as a relative measure of glucose metabolic rate. Finally, from two cell lines, xenografts were established in mice, and the tracer distribution between hypoxic and well-oxygenated areas were deduced from tissue sections. Three hours of anoxia strongly stimulated [{sup 18}F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [{sup 18}F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [{sup 18}F]FDG varied considerably. Although less pronounced, [{sup 18}F]FAZA also showed superior in vivo hypoxia specificity compared with [{sup 18}F]FDG. [{sup 18}F]FAZA displays excellent in vitro characteristics for hypoxia imaging including modest cell-to-cell line variability and no binding in oxic cells. In contrast, the usability of [{sup 18}F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects. (orig.)

  20. Evaluation of 89Zr-rituximab tracer by Cerenkov luminescence imaging and correlation with PET in a humanized transgenic mouse model to image NHL.

    Science.gov (United States)

    Natarajan, Arutselvan; Habte, Frezghi; Liu, Hongguang; Sathirachinda, Ataya; Hu, Xiang; Cheng, Zhen; Nagamine, Claude M; Gambhir, Sanjiv Sam

    2013-08-01

    This research aimed to study the use of Cerenkov luminescence imaging (CLI) for non-Hodgkin's lymphoma (NHL) using 89Zr-rituximab positron emission tomography (PET) tracer with a humanized transgenic mouse model that expresses human CD20 and the correlation of CLI with PET. Zr-rituximab (2.6 MBq) was tail vein-injected into transgenic mice that express the human CD20 on their B cells (huCD20TM). One group (n=3) received 2 mg/kg pre-dose (blocking) of cold rituximab 2 h prior to tracer; a second group (n=3) had no pre-dose (non-blocking). CLI was performed using a cooled charge-coupled device optical imager. We also performed PET imaging and ex vivo studies in order to confirm the in vivo CLI results. At each time point (4, 24, 48, 72, and 96 h), two groups of mice were imaged in vivo and ex vivo with CLI and PET, and at 96 h, organs were measured by gamma counter. huCD20 transgenic mice injected with 89Zr-rituximab demonstrated a high-contrast CLI image compared to mice blocked with a cold dose. At various time points of 4-96 h post-radiotracer injection, the in vivo CLI signal intensity showed specific uptake in the spleen where B cells reside and, hence, the huCD20 biomarker is present at very high levels. The time-activity curve of dose decay-corrected CLI intensity and percent injected dose per gram of tissue of PET uptake in the spleen were increased over the time period (4-96 h). At 96 h, the 89Zr-rituximab uptake ratio (non-blocking vs blocking) counted (mean±standard deviation) for the spleen was 1.5±0.6 for CLI and 1.9±0.3 for PET. Furthermore, spleen uptake measurements (non-blocking and blocking of all time points) of CLI vs PET showed good correlation (R2=0.85 and slope=0.576), which also confirmed the corresponding correlations parameter value (R2=0.834 and slope=0.47) obtained for ex vivo measurements. CLI and PET of huCD20 transgenic mice injected with 89Zr-rituximab demonstrated that the tracer was able to target huCD20-expressing B cells. The in

  1. Biodistribution study of [61Cu] pyruvaldehyde-bis (N-4-methylthiosemicarbazone) in normal rats as a PET tracer

    Institute of Scientific and Technical Information of China (English)

    Amir Reza JALILIAN; Saeed SHANESAZZADEH; Pejaman ROWSHANFARZAD; Fatemeh BOLOURINOVIN; Abbas MAJDABADI

    2008-01-01

    [61Cu]-labeled pyruvaldehyde-bis (N-4-methylthiosemicarbazone) (61Cu-PTSM), a promising agent made for imaging blood perfusion, was produced via the natZn(p,x)61Cu nuclear reaction in a 30 MeV cyclotron, and separated by a two-step column chromatography method developed in our laboratory using a cation and an anion exchange resin. After 150μA irradiation for 76 min, about 6.006 Ci of 61Cu2+ was obtained with a radiochemical separation yield of 95% and a radionuclidic purity of 99%. 61Cu-PTSM was prepared using an optimized method with in-house synthesized PTSM ligand for radiolabeling following quality control procedures using RTLC and HPLC. The tracer is mostly incorporated in heart, kidneys and brain compared to free copper cation as a control. These are in agreement with former reports. In conclusion, [61Cu]-PTSM was prepared at the radiopharmaceutical scales with high quality and is a potential PET tracer in the perfusion study of the heart, kidney, brain and tumors.

  2. [68Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - Comparison to [18F]FDG and laboratory values

    Science.gov (United States)

    Lapa, Constantin; Schreder, Martin; Schirbel, Andreas; Samnick, Samuel; Kortüm, Klaus Martin; Herrmann, Ken; Kropf, Saskia; Einsele, Herrmann; Buck, Andreas K.; Wester, Hans-Jürgen; Knop, Stefan; Lückerath, Katharina

    2017-01-01

    Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [68Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [68Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [18F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [68Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [18F]FDG was available, [68Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [18F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [18F]FDG-PET positivity correlated with [68Ga]Pentixafor-PET positivity (p=0.018). [68Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma. PMID:28042328

  3. Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach.

    Science.gov (United States)

    Werner, Rudolf A; Weich, Alexander; Higuchi, Takahiro; Schmid, Jan S; Schirbel, Andreas; Lassmann, Michael; Wild, Vanessa; Rudelius, Martina; Kudlich, Theodor; Herrmann, Ken; Scheurlen, Michael; Buck, Andreas K; Kropf, Saskia; Wester, Hans-Jürgen; Lapa, Constantin

    2017-01-01

    C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [(68)Ga]Pentixafor in comparison to (68)Ga-DOTA-D-Phe-Tyr3-octreotide ([(68)Ga]DOTATOC) and (18)F-fluorodeoxyglucose ([(18)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [(68)Ga]DOTATOC, [(18)F]FDG, and [(68)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [(68)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [(18)F]FDG revealed sites of disease in 10/12 and [(68)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [(68)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [(68)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.

  4. Heart PET scan

    Science.gov (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  5. Discovery of [¹¹C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors.

    Science.gov (United States)

    Cox, Christopher D; Hostetler, Eric D; Flores, Broc A; Evelhoch, Jeffrey L; Fan, Hong; Gantert, Liza; Holahan, Marie; Eng, Waisi; Joshi, Aniket; McGaughey, Georgia; Meng, Xiangjun; Purcell, Mona; Raheem, Izzat T; Riffel, Kerry; Yan, Youwei; Renger, John J; Smith, Sean M; Coleman, Paul J

    2015-11-01

    Phosphodiesterase 10A (PDE10A) inhibition has recently been identified as a potential mechanism to treat multiple symptoms that manifest in schizophrenia. In order to facilitate preclinical development and support key proof-of-concept clinical trials of novel PDE10A inhibitors, it is critical to discover positron emission tomography (PET) tracers that enable plasma concentration/PDE10A occupancy relationships to be established across species with structurally diverse PDE10A inhibitors. In this Letter, we describe how a high-throughput screening hit was optimized to provide [(11)C]MK-8193 (8j), a PET tracer that supports the determination of plasma concentration/PDE10A occupancy relationships for structurally diverse series of PDE10A inhibitors in both rat and rhesus monkey.

  6. PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer {sup 18}F-AlF-NOTA-PRGD2

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Haokao [The Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China); National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Lang, Lixin; Guo, Ning; Quan, Qimeng; Hu, Shuo; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Cao, Feng [The Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China)

    2012-04-15

    The {alpha}{sub v}{beta}{sub 3} integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin {alpha}{sub v}{beta}{sub 3}-targeting positron emission tomography (PET) probe, {sup 18}F-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infarction/reperfusion (MI/R) animal model. Male Sprague-Dawley rats underwent 45-min transient left coronary artery occlusion followed by reperfusion. The myocardial infarction was confirmed by ECG, {sup 18}F-fluorodeoxyglucose (FDG) imaging, and cardiac ultrasound. In vivo PET imaging was used to determine myocardial uptake of {sup 18}F-AlF-NOTA-PRGD2 at different time points following reperfusion. The control peptide RAD was labeled with a similar procedure and used to confirm the specificity. Ex vivo autoradiographic analysis and CD31/CD61 double immunofluorescence staining were performed to validate the PET results. Myocardial origin of the {sup 18}F-AlF-NOTA-PRGD2 accumulation was confirmed by {sup 18}F-FDG and autoradiography. PET imaging demonstrated increased focal accumulation of {sup 18}F-AlF-NOTA-PRGD2 in the infarcted area which started at day 3 (0.28 {+-} 0.03%ID/g, p < 0.05) and peaked between 1 and 3 weeks (0.59 {+-} 0.16 and 0.55 {+-} 0.13%ID/g, respectively). The focal accumulation decreased but still kept at a higher level than the sham group after 4 months of reperfusion (0.31 {+-} 0.01%ID/g, p < 0.05). Pretreatment with unlabeled arginine-glycine-aspartic acid (RGD) peptide significantly decreased tracer uptake, indicating integrin specificity of this tracer. At 1 week after MI/R, uptake of the control tracer {sup 18}F-AlF-NOTA-RAD that does not bind to integrin, in the infarcted area, was only 0.21 {+-} 0.01%ID/g. Autoradiographic imaging showed the same trend of uptake in the myocardial infarction area. The time course of focal tracer uptake was consistent with the pattern of vascular density and integrin {beta

  7. Tetra- and mono-organotin reagents in palladium-mediated cross-coupling reactions for the labeling with carbon-11 of PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, T.; Huiban, M.; Sobrio, F.; Perrio, C.; Barre, E. [Groupe de Dev Methodol en Tomographie par Emission de Positons, UMR CEA 2E, Universite deCaen, Centre Cyceron, F-14070 Caen Cedex (France); Fouquet, A.; Huet, A. [Laboratoire de Chimie Organique et Organometallique, UMR CNRS 3802, Univ Bordeaux I, F-33405 Talence Cedex (France)

    2008-07-01

    The palladium-catalyzed cross-coupling reactions between a (trimethylstannyl)arene and [{sup 11}C]methyl iodide (Stille reaction) or between an aryl halide and a [{sup 11}C]monomethyltin reagent issued from Lappert's stannylene, were developed for the synthesis of polyfunctional [{sup 11}C]methyl quinolines and quinoline-imides as potential tracers for positron emission tomography (PET). (authors)

  8. Kinetic Modeling of the Tau PET Tracer (18)F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects.

    Science.gov (United States)

    Barret, Olivier; Alagille, David; Sanabria, Sandra; Comley, Robert A; Weimer, Robby M; Borroni, Edilio; Mintun, Mark; Seneca, Nicholas; Papin, Caroline; Morley, Thomas; Marek, Ken; Seibyl, John P; Tamagnan, Gilles D; Jennings, Danna

    2017-07-01

    (18)F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate (18)F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods:(18)F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BPND), and SUVR. BPND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results: AD demonstrated increased (18)F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R(2) > 0.93 was found between BPND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although (18)F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BPND, whereas SUVR sensitivity to regional cerebral blood changes needs further investigation. © 2017 by the Society of Nuclear Medicine and

  9. Evaluation of the Hsp90 inhibitor NVP-AUY922 in multicellular tumour spheroids with respect to effects on growth and PET tracer uptake

    Energy Technology Data Exchange (ETDEWEB)

    Monazzam, Azita [Institute of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, SE-751 85 Uppsala (Sweden); Uppsala Applied Science Lab (UASL), GE Healthcare, SE-752 28 Uppsala (Sweden)], E-mail: azita.monazzam@ge.com; Razifar, Pasha [Uppsala Applied Science Lab (UASL), GE Healthcare, SE-752 28 Uppsala (Sweden); Molecular Imaging and CT Research, GE Healthcare, SE-53188 Waukesha, Wisconsin (United States); Ide, Susan [Novartis Institutes for Biomedical Research Oncology Biomarkers, 260C Cambridge, MA 02139-4299 (United States); Rugaard Jensen, Michael [Novartis Institutes for Biomedical Research, Novartis Pharma AG, Klybeckstrasse 141, 4057 Basel (Switzerland); Josephsson, Raymond [Department of Medical Sciences, Uppsala Academic Hospital, SE-75105 Uppsala (Sweden); Blomqvist, Carl [Institute of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, SE-751 85 Uppsala (Sweden); Langstroem, Bengt [Department of Biochemistry and Organic Chemistry, SE-751 24 Uppsala (Sweden); Bergstroem, Mats [Department of Pharmaceutical Biosciences, Uppsala University, SE-751 24 Uppsala (Sweden)

    2009-04-15

    Background: Molecular targeting has become a prominent concept in cancer treatment and heat shock protein 90 (Hsp90) inhibitors are suggested as promising anticancer drugs. The Hsp90 complex is one of the chaperones that facilitate the refolding of unfolded or misfolded proteins and plays a role for key oncogenic proteins such as Her2, Raf-1, Akt/PKB, and mutant p53. NVP-AUY922 is a novel low-molecular Hsp90 inhibitor, currently under clinical development as an anticancer drug. Disruption of the Hsp90-client protein complexes leads to proteasome-mediated degradation of client proteins and cell death. The aim of the current study was to use a combination of the multicellular tumour spheroid (MTS) model and positron emission tomography (PET) to investigate the effects of NVP-AUY922 on tumour growth and its relation to PET tracer uptake for the selection of appropriate PET tracer. A further aim was to evaluate the concentration and time dependence in the relation between growth inhibition and PET tracer uptake as part of translational imaging activities. Methods: MTS of two breast cancer cell lines (MCF-7 and BT474), one glioblastoma cell line (U87MG) and one colon carcinoma cell line (HCT116) were prepared. Initially, we investigated MTS growth pattern and {sup 3}H-thymidine incorporation in MTS after continuous exposure to NVP-AUY922 in order to determine dose response. Then the short-term effect of the drug on the four PET tracers 2-[{sup 18}F] fluoro-2-deoxyglucose (FDG), 3'-deoxy-3'-fluorothymidine (FLT), methionine and choline was correlated to the long-term effect (changes in growth pattern) to determine the adequate PET tracer with high predictability. Next, the growth inhibitory effect of different dose schedules was evaluated to determine the optimal dose and time. Finally, the effect of a 2-h exposure to the drug on growth pattern and FDG/FLT uptake was evaluated. Results: A dose-dependent inhibition of growth and decrease of {sup 3}H

  10. Small Molecule Receptor Ligands for PET Studies of the Central Nervous System-Focus on G Protein Coupled Receptors.

    Science.gov (United States)

    Mach, Robert H

    2017-09-01

    G protein-coupled receptors (GPRCs) are a class of proteins that are expressed in high abundance and are responsible for numerous signal transduction pathways in the central nervous system. Consequently, alterations in GPRC function have been associated with a wide variety of neurologic and neuropsychiatric disorders. The development of PET probes for imaging GPRCs has served as a major emphasis of PET radiotracer development and PET imaging studies over the past 30 years. In this review, a basic description of the biology of G proteins and GPRCs is provided. This includes recent evidence of the existence of dimeric and multimeric species of GPRCs that have been termed "receptor mosaics," with an emphasis on the different GPRCs that form complexes with the dopamine D2 receptor. An overview of the different PET radiotracers for imaging the component GPRC within these different multimeric complexes of the D2 receptor is also provided. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Somatostatin receptor PET in neuroendocrine tumours: {sup 68}Ga-DOTA{sup 0},Tyr{sup 3}-octreotide versus {sup 68}Ga-DOTA{sup 0}-lanreotide

    Energy Technology Data Exchange (ETDEWEB)

    Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Uprimny, Christian; Guggenberg, Elisabeth von; Decristoforo, Clemens; Warwitz, Boris; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Traub-Weidinger, Tatjana [Vienna Medical University, Department of Nuclear Medicine, Vienna (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-03-15

    The aim of this study was to evaluate the impact of {sup 68}Ga-labelled DOTA{sup 0}-lanreotide ({sup 68}Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or {sup 68}Ga-labelled DOTA{sup 0},Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or {sup 68}Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent {sup 68}Ga-DOTA-LAN PET to evaluate a treatment option with {sup 90}Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 {+-} 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. {sup 68}Ga-DOTA-LAN and {sup 68}Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of {sup 68}Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for {sup 68}Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. {sup 68}Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV{sub max}) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to {sup 68}Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. {sup 68}Ga

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

    Science.gov (United States)

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

    2013-02-01

    The aim of this study was to evaluate the impact of (68)Ga-labelled DOTA(0)-lanreotide ((68)Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or (68)Ga-labelled DOTA(0),Tyr(3)-octreotide ((68)Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or (68)Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent (68)Ga-DOTA-LAN PET to evaluate a treatment option with (90)Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 ± 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. (68)Ga-DOTA-LAN and (68)Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of (68)Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for (68)Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. (68)Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV(max)) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to (68)Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. (68)Ga-DOTA-TOC revealed more tumour sites than (68)Ga

  13. Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [(11)C](+)PHNO.

    Science.gov (United States)

    Gaiser, Edward C; Gallezot, Jean-Dominique; Worhunsky, Patrick D; Jastreboff, Ania M; Pittman, Brian; Kantrovitz, Lauren; Angarita, Gustavo A; Cosgrove, Kelly P; Potenza, Marc N; Malison, Robert T; Carson, Richard E; Matuskey, David

    2016-12-01

    Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (D2/3R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D2/3Rs when compared with normal weight (NW) individuals. A D3-preferring D2/3R agonist tracer, [(11)C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D2/3R availability within striatal reward regions. To date, OB individuals have not been studied with [(11)C](+)PHNO. We assessed D2/3R availability in striatal and extrastriatal reward regions in 14 OB and 14 age- and gender-matched NW individuals with [(11)C](+)PHNO PET utilizing a high-resolution research tomograph. Additionally, in regions where group D2/3R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D2/3R availability in those respective regions. A group-by-brain region interaction effect (F7, 182=2.08, p=0.047) was observed. Post hoc analyses revealed that OB individuals exhibited higher tracer binding in D3-rich regions: the substantia nigra/ventral tegmental area (SN/VTA) (+20%; p=0.02), ventral striatum (VST) (+14%; pD2/3R availability in the SN/VTA (r=0.34, p=0.03), VST (r=0.36, p=0.02), and pallidum (r=0.30, p=0.05) across all subjects. These data suggest that individuals who are obese have higher D2/3R availability in brain reward regions densely populated with D3Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.

  14. Characterization of the radiolabeled metabolite of tau PET tracer (18)F-THK5351.

    Science.gov (United States)

    Harada, Ryuichi; Furumoto, Shozo; Tago, Tetsuro; Furukawa, Katsutoshi; Ishiki, Aiko; Tomita, Naoki; Iwata, Ren; Tashiro, Manabu; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka; Okamura, Nobuyuki

    2016-11-01

    (18)F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of (18)F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of (18)F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of (18)F-THK5351. The isolated radiometabolite of (18)F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images.

  15. Characterization of the radiolabeled metabolite of tau PET tracer {sup 18}F-THK5351

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ryuichi [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Yanai, Kazuhiko [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Okamura, Nobuyuki [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku Medical and Pharmaceutical University, Division of Pharmacology, Faculty of Medicine, Sendai (Japan)

    2016-11-15

    {sup 18}F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of {sup 18}F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of {sup 18}F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of {sup 18}F-THK5351. The isolated radiometabolite of {sup 18}F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

  16. A standardized method for the construction of tracer specific PET and SPECT rat brain templates: validation and implementation of a toolbox.

    Directory of Open Access Journals (Sweden)

    David Vállez Garcia

    Full Text Available High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain- and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195 and [11C]raclopride, and SPECT [99mTc]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion, and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70 ± 0.32 mm for [18F]FDG (n = 25, 0.23 ± 0.10mm for [11C]flumazenil (n = 13, 0.88 ± 0.20 mm for [11C]MeDAS (n = 15, 0.64 ± 0.28 mm for [11C]PK11195 (n = 19, 0.34 ± 0.15 mm for [11C]raclopride (n = 6, and 0.40 ± 0.13 mm for [99mTc]HMPAO (n = 15. These values were smallest with tracer-specific templates, when compared to the use of [18F]FDG as reference template (p<0.001. Additionally, registration errors were smallest with strain-specific templates (p<0.05, and when images and templates had the same size (p ≤ 0.001. Moreover, highest registration errors were found for the focal lesion group (p<0.005 and the diffuse lesion group (p = n.s.. In the voxel-based analysis, the reported coordinates of the focal lesion model are consistent with the stereotaxic injection procedure. The use of PET/SPECT strain- and tracer

  17. Determination of receptor occupancy in the presence of mass dose: [(11)C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746.

    Science.gov (United States)

    Gallezot, Jean-Dominique; Planeta, Beata; Nabulsi, Nabeel; Palumbo, Donna; Li, Xiaoxi; Liu, Jing; Rowinski, Carolyn; Chidsey, Kristin; Labaree, David; Ropchan, Jim; Lin, Shu-Fei; Sawant-Basak, Aarti; McCarthy, Timothy J; Schmidt, Anne W; Huang, Yiyun; Carson, Richard E

    2017-03-01

    Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds "tracer" levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [(11)C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [(11)C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%-97% and 30%-93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%-15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

  18. [{sup 11}C]FMAU and [{sup 18}F]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Erik F.J. de E-mail: e.f.j.de.vries@pet.azg.nl; Waarde, Aren van; Harmsen, Marco C.; Mulder, Nanno H.; Vaalburg, Willem; Hospers, Geke A.P

    2000-02-01

    [{sup 11}C]-2'-Fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 11}C]FMAU) and [{sup 18}F]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG), radiolabeled representatives of two classes of antiviral agents, were evaluated as tracers for measuring herpes simplex virus thymidine kinase (HSV-tk) enzyme activity after gene transfer and as tracers for localization of active human cytomegalovirus (HCMV) infections. In vitro accumulation experiments revealed that both [{sup 11}C]FMAU and [{sup 18}F]FHPG accumulated significantly more in HSV-tk expressing cells than they did in control cells. [{sup 18}F]FHPG uptake in HSV-tk expressing cells, however, was found to depend strongly on the cell line used, which might be due to cell type dependent membrane transport or cell type dependent substrate specific susceptibility of the enzyme. In vitro, both tracers exhibited a good selectivity for accumulation in HCMV-infected human umbilical vein endothelial cells over uninfected cells. In contrast to [{sup 18}F]FHPG, [{sup 11}C]FMAU uptake in control cells was relatively high due to phosphorylation of the tracer by host kinases. Therefore, [{sup 18}F]FHPG appears to be the more selective tracer not only to predict HSV-tk gene therapy outcome, but also to localize active HCMV infections with PET.

  19. Monte Carlo simulations of GeoPET experiments: 3D images of tracer distributions (18F, 124I and 58Co) in Opalinus clay, anhydrite and quartz

    Science.gov (United States)

    Zakhnini, Abdelhamid; Kulenkampff, Johannes; Sauerzapf, Sophie; Pietrzyk, Uwe; Lippmann-Pipke, Johanna

    2013-08-01

    Understanding conservative fluid flow and reactive tracer transport in soils and rock formations requires quantitative transport visualization methods in 3D+t. After a decade of research and development we established the GeoPET as a non-destructive method with unrivalled sensitivity and selectivity, with due spatial and temporal resolution by applying Positron Emission Tomography (PET), a nuclear medicine imaging method, to dense rock material. Requirements for reaching the physical limit of image resolution of nearly 1 mm are (a) a high-resolution PET-camera, like our ClearPET scanner (Raytest), and (b) appropriate correction methods for scatter and attenuation of 511 keV—photons in the dense geological material. The latter are by far more significant in dense geological material than in human and small animal body tissue (water). Here we present data from Monte Carlo simulations (MCS) reflecting selected GeoPET experiments. The MCS consider all involved nuclear physical processes of the measurement with the ClearPET-system and allow us to quantify the sensitivity of the method and the scatter fractions in geological media as function of material (quartz, Opalinus clay and anhydrite compared to water), PET isotope (18F, 58Co and 124I), and geometric system parameters. The synthetic data sets obtained by MCS are the basis for detailed performance assessment studies allowing for image quality improvements. A scatter correction method is applied exemplarily by subtracting projections of simulated scattered coincidences from experimental data sets prior to image reconstruction with an iterative reconstruction process.

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

    OpenAIRE

    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 bes...

  1. A ¹¹C-labeled 1,4-dihydroquinoline derivative as a potential PET tracer for imaging of redox status in mouse brain.

    Science.gov (United States)

    Okamura, Toshimitsu; Okada, Maki; Kikuchi, Tatsuya; Wakizaka, Hidekatsu; Zhang, Ming-Rong

    2015-12-01

    A disturbance in redox balance has been implicated in the pathogenesis of a number of diseases. This study sought to examine the feasibility of imaging brain redox status using a (11)C-labeled dihydroquinoline derivative ([(11)C]DHQ1) for positron emission tomography (PET). The lipophilic PET tracer [(11)C]DHQ1 was rapidly oxidized to its hydrophilic form in mouse brain homogenate. The redox modulators diphenyleneiodonium and apocynin significantly reduced the initial velocity of [(11)C]DHQ1 oxidation, and apocynin also caused concentration-dependent inhibition of the initial velocity. Moreover, [(11)C]DHQ1 readily entered the brain by diffusion after administration and underwent oxidation into the hydrophilic cationic form, which then slowly decreased. By contrast, apocynin treatment inhibited the in vivo oxidation of [(11)C]DHQ1 to the hydrophilic cationic form, leading to a rapid decrease of radioactivity in the brain. Thus, the difference in the [(11)C]DHQ1 kinetics reflects the alteration in redox status caused by apocynin. In conclusion, [(11)C]DHQ1 is a potential PET tracer for imaging of redox status in the living brain.

  2. Activation of P-glycoprotein (Pgp)-mediated drug efflux by extracellular acidosis: in vivo imaging with {sup 68}Ga-labelled PET tracer

    Energy Technology Data Exchange (ETDEWEB)

    Thews, Oliver; Dillenburg, Wolfgang [University Medicine Mainz, Institute of Physiology and Pathophysiology, Mainz (Germany); Fellner, Marco; Roesch, Frank [University of Mainz, Institute of Nuclear Chemistry, Mainz (Germany); Buchholz, Hans-Georg; Bausbacher, Nicole; Schreckenberger, Mathias [University Medicine Mainz, Department of Nuclear Medicine, Mainz (Germany)

    2010-10-15

    In vitro it has been shown that the functional activity of P-glycoprotein (Pgp), an important drug transporter responsible for multidrug resistance, can be strongly increased by extracellular acidosis. Here mitogen-activated protein kinases (MAPK) (p38, ERK1/2) seem to play an important role for signal transduction. However, it is unclear whether these effects are also relevant in vivo. With the newly developed PET tracer Schiff base-based {sup 68}Ga-MFL6.MZ the functional Pgp activity was visualized under acidic conditions and during inhibition of MAPKs non-invasively by means of microPET in rat tumours. Tumours were acidified either by inspiratory hypoxia (8% O{sub 2}) or by injection of lactic acid. Inhibitors of the MAPK were injected intratumourally. With increasing tumour volume the tumour pH changed from 7.0 to 6.7 and simultaneously the Pgp activity increased almost linearly. When the tumour was acidified by direct lactic acid injection the PET tracer uptake was reduced by 20% indicating a higher transport rate out of the cells. Changing the inspiratory O{sub 2} fraction to 8% dynamically led to a reduction of extracellular pH and in parallel to a decrease of tracer concentration. While inhibition of the p38 pathway reduced the Pgp transport rate, inhibition of ERK1/2 had practically no impact. An acidic extracellular environment significantly stimulates the Pgp activity. The p38 MAPK pathway plays an important role for Pgp regulation in vivo, whereas ERK1/2 is of minor importance. From these results new strategies for overcoming multidrug resistance (e.g. reducing tumour acidosis, inhibition of p38) may be developed. (orig.)

  3. Segmentation of biological target volumes on multi-tracer PET images based on information fusion for achieving dose painting in radiotherapy.

    Science.gov (United States)

    Lelandais, Benoît; Gardin, Isabelle; Mouchard, Laurent; Vera, Pierre; Ruan, Su

    2012-01-01

    Medical imaging plays an important role in radiotherapy. Dose painting consists in the application of a nonuniform dose prescription on a tumoral region, and is based on an efficient segmentation of biological target volumes (BTV). It is derived from PET images, that highlight tumoral regions of enhanced glucose metabolism (FDG), cell proliferation (FLT) and hypoxia (FMiso). In this paper, a framework based on Belief Function Theory is proposed for BTV segmentation and for creating 3D parametric images for dose painting. We propose to take advantage of neighboring voxels for BTV segmentation, and also multi-tracer PET images using information fusion to create parametric images. The performances of BTV segmentation was evaluated on an anthropomorphic phantom and compared with two other methods. Quantitative results show the good performances of our method. It has been applied to data of five patients suffering from lung cancer. Parametric images show promising results by highlighting areas where a high frequency or dose escalation could be planned.

  4. Diagnostic accuracy of {sup 18}F amyloid PET tracers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Morris, Elizabeth; Chalkidou, Anastasia [St Thomas' Hospital, King' s Technology Evaluation Centre, King' s College London, London (United Kingdom); St Thomas' Hospital, Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King' s College London, London (United Kingdom); Hammers, Alexander [St Thomas' Hospital, Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King' s College London, London (United Kingdom); Peacock, Janet; Summers, Jennifer [St Thomas' Hospital, King' s Technology Evaluation Centre, King' s College London, London (United Kingdom); King' s College London, Division of Health and Social Care Research, London (United Kingdom); King' s College London, NIHR Biomedical Research Centre at Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Keevil, Stephen [St Thomas' Hospital, King' s Technology Evaluation Centre, King' s College London, London (United Kingdom); St Thomas' Hospital, Department of Biomedical Engineering, Division of Imaging Sciences and Biomedical Engineering, King' s College London, London (United Kingdom); St Thomas' Hospital, Department of Medical Physics, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2016-02-15

    Imaging or tissue biomarker evidence has been introduced into the core diagnostic pathway for Alzheimer's disease (AD). PET using {sup 18}F-labelled beta-amyloid PET tracers has shown promise for the early diagnosis of AD. However, most studies included only small numbers of participants and no consensus has been reached as to which radiotracer has the highest diagnostic accuracy. First, we performed a systematic review of the literature published between 1990 and 2014 for studies exploring the diagnostic accuracy of florbetaben, florbetapir and flutemetamol in AD. The included studies were analysed using the QUADAS assessment of methodological quality. A meta-analysis of the sensitivity and specificity reported within each study was performed. Pooled values were calculated for each radiotracer and for visual or quantitative analysis by population included. The systematic review identified nine studies eligible for inclusion. There were limited variations in the methods between studies reporting the same radiotracer. The meta-analysis results showed that pooled sensitivity and specificity values were in general high for all tracers. This was confirmed by calculating likelihood ratios. A patient with a positive ratio is much more likely to have AD than a patient with a negative ratio, and vice versa. However, specificity was higher when only patients with AD were compared with healthy controls. This systematic review and meta-analysis found no marked differences in the diagnostic accuracy of the three beta-amyloid radiotracers. All tracers perform better when used to discriminate between patients with AD and healthy controls. The sensitivity and specificity for quantitative and visual analysis are comparable to those of other imaging or biomarker techniques used to diagnose AD. Further research is required to identify the combination of tests that provides the highest sensitivity and specificity, and to identify the most suitable position for the tracer in the

  5. WE-AB-204-07: Spatiotemporal Distribution of the FDG PET Tracer in Solid Tumors: Contributions of Diffusion and Convection Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Soltani, M [Johns Hopkins University School of Medicine, Baltimore, MD and KNT university, Tehran (Iran, Islamic Republic of); Sefidgar, M [IKI University, Qazvin (Iran, Islamic Republic of); Bazmara, H [KNT university, Tehran (Iran, Islamic Republic of); Sheikhbahaei, S; Marcus, C; Ashrafinia, S; Subramaniam, R; Rahmim, A M [Johns Hopkins University School of Medicine, Baltimore, MD (United States)

    2015-06-15

    Purpose: In this study, a mathematical model is utilized to simulate FDG distribution in tumor tissue. In contrast to conventional compartmental modeling, tracer distributions across space and time are directly linked together (i.e. moving beyond ordinary differential equations (ODEs) to utilizing partial differential equations (PDEs) coupling space and time). The diffusion and convection transport mechanisms are both incorporated to model tracer distribution. We aimed to investigate the contributions of these two mechanisms on FDG distribution for various tumor geometries obtained from PET/CT images. Methods: FDG transport was simulated via a spatiotemporal distribution model (SDM). The model is based on a 5K compartmental model. We model the fact that tracer concentration in the second compartment (extracellular space) is modulated via convection and diffusion. Data from n=45 patients with pancreatic tumors as imaged using clinical FDG PET/CT imaging were analyzed, and geometrical information from the tumors including size, shape, and aspect ratios were classified. Tumors with varying shapes and sizes were assessed in order to investigate the effects of convection and diffusion mechanisms on FDG transport. Numerical methods simulating interstitial flow and solute transport in tissue were utilized. Results: We have shown the convection mechanism to depend on the shape and size of tumors whereas diffusion mechanism is seen to exhibit low dependency on shape and size. Results show that concentration distribution of FDG is relatively similar for the considered tumors; and that the diffusion mechanism of FDG transport significantly dominates the convection mechanism. The Peclet number which shows the ratio of convection to diffusion rates was shown to be of the order of 10−{sup 3} for all considered tumors. Conclusion: We have demonstrated that even though convection leads to varying tracer distribution profiles depending on tumor shape and size, the domination of

  6. PET

    DEFF Research Database (Denmark)

    Mariager, Rasmus Mølgaard; Schmidt, Regin; Heiberg, Morten Rievers

    PET handler om den hemmelige tjenestes arbejde under den kolde krig 1945-1989. Her fortæller Regin Schmidt, Rasmus Mariager og Morten Heiberg om de mest dramatiske og interessante sager fra PET's arkiv. PET er på flere måder en udemokratisk institution, der er sat til at vogte over demokratiet....... Dens virksomhed er skjult for offentligheden, den overvåger borgernes aktiviteter, og den registrerer følsomme personoplysninger. Historien om PET rejser spørgsmålet om, hvad man skal gøre, når befolkningen i et demokrati er kritisk indstillet over for overvågningen af lovlige politiske aktiviteter......, mens myndighederne mener, at det er nødvendigt for at beskytte demokratiet. PET er på en gang en fortælling om konkrete aktioner og begivenheder i PET's arbejde og et stykke Danmarkshistorie. Det handler om overvågning, spioner, politisk ekstremisme og international terrorisme.  ...

  7. A [11C]Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced α5 benzodiazepine receptors in limbic regions.

    Science.gov (United States)

    Lingford-Hughes, Anne; Reid, Alastair G; Myers, James; Feeney, Adrian; Hammers, Alexander; Taylor, Lindsay G; Rosso, Lula; Turkheimer, Federico; Brooks, David J; Grasby, Paul; Nutt, David J

    2012-02-01

    Preclinical evidence suggests the α5 subtype of the GABA-benzodiazepine receptor is involved in some of the actions of alcohol and in memory. The positron emission tomography (PET) tracer, [(11)C]Ro15 4513 shows relative selectivity in labelling the α5 subtype over the other GABA-benzodiazepine receptor subtypes in limbic regions of the brain. We used this tracer to investigate the distribution of α5 subtype availability in human alcohol dependence and its relationship to clinical variables. Abstinent (>6 weeks) alcohol-dependent men and healthy male controls underwent an [(11)C]Ro15 4513 PET scan. We report [(11)C]Ro15 4513 brain uptake for 8 alcohol-dependent men and 11 healthy controls. We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens, parahippocampal gyri, right hippocampus and amygdala in the alcohol-dependent compared with the healthy control group. Levels of [(11)C]Ro15 4513 binding in both hippocampi were significantly and positively associated with performance on a delayed verbal memory task in the alcohol-dependent but not the control group. We speculate that the reduced limbic [(11)C]Ro15 4513 binding seen here results from the effects of alcohol, though we cannot currently distinguish whether they are compensatory in nature or evidence of brain toxicity.

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

    Science.gov (United States)

    Mathias, C J; Welch, M J; Raichle, M E; Mintun, M A; Lich, L L; McGuire, A H; Zinn, K R; John, E K; Green, M A

    1990-03-01

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

  9. Dopamine D(3) receptor antagonists: The quest for a potentially selective PET ligand. Part two: Lead optimization.

    Science.gov (United States)

    Micheli, Fabrizio; Holmes, Ian; Arista, Luca; Bonanomi, Giorgio; Braggio, Simone; Cardullo, Francesca; Di Fabio, Romano; Donati, Daniele; Gentile, Gabriella; Hamprecht, Dieter; Terreni, Silvia; Heidbreder, Christian; Savoia, Chiara; Griffante, Cristiana; Worby, Angela

    2009-08-01

    The lead optimization process to identify new selective dopamine D(3) receptor antagonists is reported. DMPK parameters and binding data suggest that selective D(3) receptor antagonists as potential PET ligands might have been identified.

  10. 68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease.

    Science.gov (United States)

    Ambrosini, Valentina; Campana, Davide; Allegri, Vincenzo; Opocher, Giuseppe; Fanti, Stefano

    2011-01-01

    A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.

  11. In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

    Directory of Open Access Journals (Sweden)

    Natascha Nebel

    2016-08-01

    Full Text Available Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled D3 subtype selective radioligand would be beneficial for this purpose; however, as yet, there is no such tracer available. The three candidates [18F]1, [18F]2a and [18F]2b were chosen for in vitro and in vivo characterization as radioligands suitable for selective PET imaging of the D3 receptor. Their evaluation included the analysis of radiometabolites and the assessment of non-specific binding by in vitro rat brain autoradiography. While [18F]1 and [18F]2a revealed high non-specific uptake in in vitro rat brain autoradiography, the D3 receptor density was successfully determined on rat brain sections (n = 4 with the candidate [18F]2b offering a Bmax of 20.38 ± 2.67 pmol/g for the islands of Calleja, 19.54 ± 1.85 pmol/g for the nucleus accumbens and 16.58 ± 1.63 pmol/g for the caudate putamen. In PET imaging studies, the carboxamide 1 revealed low signal/background ratios in the rat brain and relatively low uptake in the pituitary gland, while the azocarboxamides [18F]2a and [18F]2b showed binding that was blockable by the D3 receptor ligand BP897 in the ventricular system and the pituitary gland in PET imaging studies in living rats.

  12. Determination of tumour hypoxia with the PET tracer [{sup 18}F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Christian, Nicolas; Bol, Anne; Bast, Marc de; Labar, Daniel; Lee, John; Mahy, Pierre; Gregoire, Vincent [Universite Catholique de Louvain, Center for Molecular Imaging and Experimental Radiotherapy, Brussels (Belgium)

    2007-09-15

    The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [{sup 18}F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [{sup 18}F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). C3H mice were injected i.v. with an average of 12.95 MBq of [{sup 18}F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Ornidazole decreased the urinary excretion and increased the liver uptake of [{sup 18}F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation. (orig.)

  13. Small-Animal PET Study of Adenosine A(1) Receptors in Rat Brain : Blocking Receptors and Raising Extracellular Adenosine

    NARCIS (Netherlands)

    Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A.; Kwizera, Chantal; Sijbesma, Jurgen W. A.; Ishiwata, Kiichi; Willemsen, Antoon T. M.; Elsinga, Philip H.; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2011-01-01

    Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-C-11-methyl-3-propyl-xanthine (C-11-MPDX) and PET. This study aims to test whether C-11-MPDX

  14. Small-Animal PET Study of Adenosine A(1) Receptors in Rat Brain : Blocking Receptors and Raising Extracellular Adenosine

    NARCIS (Netherlands)

    Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A.; Kwizera, Chantal; Sijbesma, Jurgen W. A.; Ishiwata, Kiichi; Willemsen, Antoon T. M.; Elsinga, Philip H.; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2011-01-01

    Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-C-11-methyl-3-propyl-xanthine (C-11-MPDX) and PET. This study aims to test whether C-11-MPDX c

  15. Improved Estrogen Receptor Assessment by PET Using the Novel Radiotracer 4FMFES in ER+ Breast Cancer Patients: an Ongoing Phase II Clinical Trial.

    Science.gov (United States)

    Paquette, Michel; Lavallée, Éric; Phoenix, Serge; Ouellet, René; Senta, Helena; van Lier, Johan E; Guérin, Brigitte; Lecomte, Roger; Turcotte, Éric E

    2017-08-10

    Following encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) positron emission tomography (PET) radiotracer 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of 4FMFES to 16α-[(18)F]fluoroestradiol (FES) in ER positive (ER+) breast cancer patients. Methods: Patients diagnosed with ER+ breast cancer (n = 31) were recruited for this study, including six patients that undertook mastectomy and/or axillary node dissection. For each patient, FES- and 4FMFES-PET/CT scans were done sequentially (within a week) and in random order. One hour following injection of either radiotracer, a head-to-thigh static scan with 2 minutes acquisition per bed position was obtained. Blood samples were taken at different times following injection to assess each tracer metabolism by reverse-phase thin-layer chromatography (TLC). The mean standardized uptake values (SUVMean) of non-specific tissues and the maximum SUV (SUVMax) of the tumor were evaluated for each detected lesion, and tumor-to-non-specific organs ratios were calculated. Results: Blood metabolite analysis 60 minutes after injection of the tracer showed a 2.5-fold increase in metabolic stability of 4FMFES over FES. While for most foci 4FMFES-PET scored similar SUVMax values as compared to FES-PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in non-specific tissues for 4FMFES, notably a 4-fold decrease in blood pool activity as compared to FES. Consequently, image quality was considerably improved using 4FMFES, with lower overall background. As a result, 4FMFES successfully identified 9 more lesions than FES. Conclusion: This phase II study with ER+ breast cancer patients shows that 4FMFES-PET achieves lower non-specific signal and better tumor contrast than FES-PET resulting in improved diagnostic confidence and lower false negative diagnoses

  16. Neurotransmission imaging by PET

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    2001-08-01

    been developed, and serotonin transporters have recently begun to be examined. GABA has been predominantly studied by PET in epilepsy by using the GABA receptor tracer [{sup 11}C]flumazenil and there have been reports on [{sup 123}I]iomazenil SPECT in panic disorder. Abnormal GABA/benzodiazepine receptors have been hypothesized to be related to schizophrenia, although insufficient evidence has been accumulated to verify it. The acetylcholinesterase tracer [{sup 11}C]N-methyl-4-piperidyl acetate, has been used to investigate changes in acetylcholinesterase in Alzheimer's disease, and another study used [{sup 11}C]N-methyl-4-piperidylbenzilate to determine the relationship between muscarinic receptor occupancy by biperiden and its blood concentration. Because of the many disadvantages associated with [{sup 11}C]nicotine, a nicotinic acetylcholine receptor tracer, a more useful tracer needs to be developed. Glutamic acid is thought to be related to mental disorders. Two types of PET legands selective for NMDA receptor sub-units have been developed very recently. (K.H.)

  17. PET imaging for receptor occupancy: meditations on calculation and simplification.

    Science.gov (United States)

    Zhang, Yumin; Fox, Gerard B

    2012-03-01

    This invited mini-review briefly summarizes procedures and challenges of measuring receptor occupancy with positron emission tomography. Instead of describing the detailed analytic procedures of in vivo ligand-receptor imaging, the authors provide a pragmatic approach, along with personal perspectives, for conducting positron emission tomography imaging for receptor occupancy, and systematically elucidate the mathematics of receptor occupancy calculations in practical ways that can be understood with elementary algebra. The authors also share insights regarding positron emission tomography imaging for receptor occupancy to facilitate applications for the development of drugs targeting receptors in the central nervous system.

  18. Synthesis of [{sup 11}C]-S21007 a novel 5HT{sub 3} partial agonist as a potential tracer for PET studies

    Energy Technology Data Exchange (ETDEWEB)

    Guillouet, S.; Barre, L.; Gourand, F. [CEA Centre de Cyceron, 14 -Caen (France); Lasne, M.C. [Centre National de la Recherche Scientifique, 14 - Caen (France); Rault, S. [Caen Univ., 14 (France). Faculte de Pharmacie

    1996-04-01

    5HT{sub 3} receptors have been the focus of much research during the last decade. The presence of these receptors has been demonstrated in many neuronal tissues, both in periphery and in the CNS. The identification of selective agonists and antagonists for this receptor subtype has allowed the discovery of several important new therapeutic applications as the inhibition of pain, migraine, cytotoxic and radiation-induced emesis and treatment of psychoses and anxiety. The first 5HT{sub 3} antagonist labelled with a {beta}+ emitter atom was [{sup 11}C]MDL72222. The PET studies which have been performed with it in the brain of baboon (distribution, kinetics and binding) have established that it was not a good radioligand to detect a specific binding, due to its high lipophilicity. Other radioligands have been developed since, but their affinities for 5HT{sub 3} receptors PET studies have not been demonstrated. Among a series of of tricyclic piperazine derivatives synthesized, S21007 has been described as a novel selective and partial agonist which possesses a good affinity for 5HT{sub 3} receptors (IC{sub 50} = 1nM) versus other 5HT subtypes studied where IC{sub 50} > 1{mu}M. We report here the radiosynthesis of [{sup 11}C]S21007. (author).

  19. 64Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin αvβ3 Expression in Human Neuroendocrine Tumor Xenografts

    DEFF Research Database (Denmark)

    Oxbøl, Jytte; Schjøth-Eskesen, Christina; El Ali, Henrik H.

    2012-01-01

    Purpose. The purpose of this paper is to evaluate a new PET tracer (64)Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures. Nude mice with human neuroendocrine tumor xenografts (H...... human radiation-absorbed doses were estimated using OLINDA/EXM. Results. Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake, for integrin α(V) R = 0.76, integrin β(3) R = 0.75 and VEGF-A R = 0.81 (all P ... was estimated to be 0.038 and 0.029 mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion. (64)Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use....

  20. Feasibility and predictability of perioperative PET and estrogen receptor ligand in patients with invasive breast cancer.

    Science.gov (United States)

    Gemignani, Mary L; Patil, Sujata; Seshan, Venkatraman E; Sampson, Michelle; Humm, John L; Lewis, Jason S; Brogi, Edi; Larson, Steven M; Morrow, Monica; Pandit-Taskar, Neeta

    2013-10-01

    The presence of estrogen receptor (ER) in breast cancer is a prognostic indicator for both disease-free and overall survival. 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) with PET is a noninvasive test for evaluation of ER expression and has been used for predicting response to endocrine therapy in patients with ER-positive metastatic breast cancer. The purpose of this study was to correlate (18)F-FES PET and ER expression in patients with primary, operable breast cancer. Forty-eight patients were prospectively enrolled in an institutional review board-approved protocol and signed an informed consent form. All patients had undergone (18)F-FES PET preoperatively. Clinical characteristics, tumor characteristics, and treatment outcomes were recorded. Immunohistochemical analysis for ER and progesterone receptor (PgR) percentage expression (46 surgical, 2 core biopsy specimens) was performed. (18)F-FES PET standardized uptake value (SUV) of the breast lesion was correlated with percentage immunohistochemistry ER and PgR expression. (18)F-FES PET SUV was quantified, with a value of 1.5 or more considered positive, and ER and PgR was quantified, with 1% or more considered positive. Formalin-fixed paraffin-embedded tissue was available for 44 patients (42 surgical, 2 core biopsy specimens). We used a microarray platform, and estrogen-related gene expression data (ESR1, ESR2, and PGR) were compared with (18)F-FES PET SUV (Spearman rank correlation). Tumor size, ductal histology, grade, HER2-neu overexpression, PgR expression, estradiol level, body mass index (BMI), and lean BMI were compared with (18)F-FES PET uptake using univariate and multivariate analysis. Forty-eight patients completed our protocol, and 2 patients did not undergo surgery because bone metastases were identified preoperatively on (18)F-FES PET. Eighty-three percent of our patients were stage I or II, with a median tumor size of 1.9 cm. Forty-one patients underwent a sentinel node biopsy. Twenty

  1. Positron Emission Tomography (PET Quantification of GABAA Receptors in the Brain of Fragile X Patients.

    Directory of Open Access Journals (Sweden)

    Charlotte D'Hulst

    Full Text Available Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS, a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.

  2. Evaluation of 4-[18F]fluorobenzoyl-FALGEA-NH2 as a positron emission tomography tracer for epidermal growth factor receptor mutation variant III imaging in cancer

    DEFF Research Database (Denmark)

    Denholt, Charlotte Lund; Binderup, Tina; Stockhausen, Marie-Thérése;

    2011-01-01

    This study describes the radiosynthesis, in vitro and in vivo evaluation of the novel small peptide radioligand, 4-[(18)F]fluorobenzoyl-Phe-Ala-Leu-Gly-Glu-Ala-NH(2,) ([(18)F]FBA-FALGEA-NH(2)) as a positron emission tomography (PET) tracer for imaging of the cancer specific epidermal growth factor...

  3. Tracer-specific PET and SPECT templates for automatic co-registration of functional rat brain images

    NARCIS (Netherlands)

    Vállez Garcia, David; Schwarz, Adam J; Dierckx, Rudi; Koole, Michel; Doorduin, Janine

    2014-01-01

    Objectives: Template based spatial co-registration of PET and SPECT data is an important first step in its semi- automatic processing, facilitating VOI- and voxel-based analysis. Although this procedure is standard in human, using corresponding MRI images, these systems are often not accessible for

  4. Angiogenesis PET Tracer Uptake (68Ga-NODAGA-E[(cRGDyK]2 in Induced Myocardial Infarction in Minipigs

    Directory of Open Access Journals (Sweden)

    Thomas Rasmussen

    2016-06-01

    Full Text Available Angiogenesis is part of the healing process following an ischemic injury and is vital for the post-ischemic repair of the myocardium. Therefore, it is of particular interest to be able to noninvasively monitor angiogenesis. This might, not only permit risk stratification of patients following myocardial infarction, but could also facilitate development and improvement of new therapies directed towards stimulation of the angiogenic response. During angiogenesis endothelial cells must adhere to one another to form new microvessels. αvβ3 integrin has been found to be highly expressed in activated endothelial cells and has been identified as a critical modulator of angiogenesis. 68Ga-NODAGA-E[c(RGDyK]2 (RGD has recently been developed by us as an angiogenesis positron-emission-tomography (PET ligand targeted towards αvβ3 integrin. In the present study, we induced myocardial infarction in Göttingen minipigs. Successful infarction was documented by 82Rubidium-dipyridamole stress PET and computed tomography. RGD uptake was demonstrated in the infarcted myocardium one week and one month after induction of infarction by RGD-PET. In conclusion, we demonstrated angiogenesis by noninvasive imaging using RGD-PET in minipigs hearts, which resemble human hearts. The perspectives are very intriguing and might permit the evaluation of new treatment strategies targeted towards increasing the angiogenetic response, e.g., stem-cell treatment.

  5. Multiple Neoplasms Simultaneously Diagnosed by Complementary Triple-Tracer PET/CT and 123I-MIBG Scintigraphy

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Ladefoged Ebbehøj, Andreas; Poulsen, Per Løgstrup;

    2016-01-01

    A 51-year-old woman with recurrent paragangliomas and catecholamine hypersecretion underwent F-FDG PET/CT for localization and evaluation of extent of disease. This revealed multiple F-FDG avid tumors with localization pattern suggesting multiple primary neoplasms of different origin rather than...

  6. Determination of regional flow by use of intravascular PET tracers: microvascular theory and experimental validation for pig livers

    DEFF Research Database (Denmark)

    Munk, O L; Bass, L; Feng, H

    2003-01-01

    with the standard model in a pig liver study. METHODS: Eight pigs underwent a 5-min dynamic PET study after (15)O-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual...

  7. Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Gottingen minipig

    DEFF Research Database (Denmark)

    Kornum, B.R.; Lind, N.M.; Gillings, N.;

    2009-01-01

    model provides stable and precise estimates of the binding potential in all regions. The binding potentials calculated for striatum, midbrain, and cortex from the PET data were highly correlated with 5-HT(4) receptor concentrations determined in brain homogenates from the same regions, except...... for hippocampus where PET-measurements significantly underestimate the 5-HT(4) receptor binding, probably because of partial volume effects. This study validates the use of [(11)C]SB207145 as a promising PET radioligand for in vivo brain imaging of the 5-HT(4) receptor in humans Udgivelsesdato: 2009/1...

  8. Probable IgG4-related sclerosing disease presenting as a gastric submucosal tumor with an intense tracer uptake on PET/CT: a case report.

    Science.gov (United States)

    Otsuka, Ryota; Kano, Masayuki; Hayashi, Hideki; Hanari, Naoyuki; Gunji, Hisashi; Hayano, Koichi; Matsubara, Hisahiro

    2016-12-01

    A 44-year-old man consulted an internist because of abnormalities in an upper gastrointestinal series. It showed an elevated lesion with central depression in the greater curvature of the middle part of the stomach. Upper gastrointestinal endoscopy showed an elevated lesion with central depression, bridging hold, and no abnormalities of the gastric mucosa in the greater curvature of the middle part of the stomach. Endoscopic ultrasonography showed a submucosal tumor derived from the muscle layer of the stomach. Computed tomography showed a 22-mm tumor in the upper part of the stomach. Integrated position emission tomography/computed tomography (PET/CT) showed an intense tracer uptake by the tumor. Based on these findings, a gastrointestinal stromal tumor was suspected and laparoscopic endoscopic cooperative surgery was performed. A histopathological examination showed lymphoplasmacytic infiltration and fibrosis, and an immunohistochemical analysis showed the infiltration of IgG4-positive lymphoplasmacytic cells. The probable diagnosis was IgG4-related sclerosing disease of the stomach. We herein describe a rare case of probable IgG4-related sclerosing disease which presented as a gastric submucosal tumor. PET/CT is a useful imaging technique for the diagnosis and follow-up of this disease.

  9. Kinetics of the Tau PET Tracer 18F-AV-1451 (T807) in Subjects with Normal Cognitive Function, Mild Cognitive Impairment, and Alzheimer Disease.

    Science.gov (United States)

    Shcherbinin, Sergey; Schwarz, Adam J; Joshi, Abhinay; Navitsky, Michael; Flitter, Matthew; Shankle, William R; Devous, Michael D; Mintun, Mark A

    2016-10-01

    We report kinetic modeling results of dynamic acquisition data from 0 to 100 min after injection with the tau PET tracer (18)F-AV-1451 in 19 subjects. Subjects were clinically diagnosed as 4 young cognitively normal, 5 old cognitively normal, 5 mild cognitive impairment, and 5 Alzheimer disease (AD). Kinetic modeling was performed using Logan graphical analysis with the cerebellum crus as a reference region. Voxelwise binding potential ([Formula: see text]) and SUV ratio ([Formula: see text]) images were compared. In AD subjects, slower and spatially nonuniform clearance from cortical regions was observed as compared with the controls, which led to focal uptake and elevated retention in the imaging data from 80 to 100 min after injection. BP from the dynamic data from 0 to 100 min correlated strongly (R(2) > 0.86) with corresponding regional [Formula: see text] values. In the putamen, the observed kinetics (positive [Formula: see text] at the tracer delivery stage and plateauing time-SUVR curves for all diagnostic categories) may suggest either additional off-target binding or a second binding site with different kinetics. The kinetics of the (18)F-AV-1451 tracer in cortical areas, as examined in this small group of subjects, differed by diagnostic stage. A delayed 80- to 100-min scan provided a reasonable substitute for a dynamic 0- to 100-min acquisition for cortical regions although other windows (e.g., 75-105 min) may be useful to evaluate. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  10. Biokinetics and imaging with the somatostatin receptor PET radioligand {sup 68}Ga-DOTATOC: preliminary data

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, M.; Boerner, A.R.; Weckesser, E.; Oei, M.L.; Meyer, G.J.; Knapp, W.H. [Dept. of Nuclear Medicine, Hannover University Medical School (Germany); Maecke, H.; Heppeler, A. [Dept. of Radiology, Kantonspittal, Basel (Switzerland); Schoeffski, P. [Dept. of Haematology and Oncology, Hannover University Medical School (Germany); Schumacher, J.; Henze, M. [German Cancer Research Centre, Heidelberg (Germany)

    2001-12-01

    Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of {sup 68}Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to {sup 68}Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 ({+-}0.3) min and 48 ({+-}7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70{+-}20 min post injection. Kidney uptake averaged <50% compared with spleen uptake. Of 40 lesions predefined by computed tomography and/or magnetic resonance imaging, {sup 68}Ga-DOTATOC PET identified 100%, whereas {sup 111}In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ({sup 111}In-octreotide: 1.5:1) to 100:1 for CNS ({sup 111}In-octreotide: 10:1). With {sup 68}Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using {sup 68}Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with {sup 111}In-octreotide scintigraphy. (orig.)

  11. Biokinetics and imaging with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data.

    Science.gov (United States)

    Hofmann, M; Maecke, H; Börner, R; Weckesser, E; Schöffski, P; Oei, L; Schumacher, J; Henze, M; Heppeler, A; Meyer, J; Knapp, H

    2001-12-01

    Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of (68)Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to (68)Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 (+/-0.3) min and 48 (+/-7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70+/-20 min post injection. Kidney uptake averaged 68)Ga-DOTATOC PET identified 100%, whereas (111)In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ((111)In-octreotide: 1.5:1) to 100:1 for CNS ((111)In-octreotide: 10:1). With (68)Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using (68)Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with (111)In-octreotide scintigraphy.

  12. Direct reconstruction of parametric images for brain PET with event-by-event motion correction: evaluation in two tracers across count levels

    Science.gov (United States)

    Germino, Mary; Gallezot, Jean-Dominque; Yan, Jianhua; Carson, Richard E.

    2017-07-01

    Parametric images for dynamic positron emission tomography (PET) are typically generated by an indirect method, i.e. reconstructing a time series of emission images, then fitting a kinetic model to each voxel time activity curve. Alternatively, ‘direct reconstruction’, incorporates the kinetic model into the reconstruction algorithm itself, directly producing parametric images from projection data. Direct reconstruction has been shown to achieve parametric images with lower standard error than the indirect method. Here, we present direct reconstruction for brain PET using event-by-event motion correction of list-mode data, applied to two tracers. Event-by-event motion correction was implemented for direct reconstruction in the Parametric Motion-compensation OSEM List-mode Algorithm for Resolution-recovery reconstruction. The direct implementation was tested on simulated and human datasets with tracers [11C]AFM (serotonin transporter) and [11C]UCB-J (synaptic density), which follow the 1-tissue compartment model. Rigid head motion was tracked with the Vicra system. Parametric images of K 1 and distribution volume (V T  =  K 1/k 2) were compared to those generated by the indirect method by regional coefficient of variation (CoV). Performance across count levels was assessed using sub-sampled datasets. For simulated and real datasets at high counts, the two methods estimated K 1 and V T with comparable accuracy. At lower count levels, the direct method was substantially more robust to outliers than the indirect method. Compared to the indirect method, direct reconstruction reduced regional K 1 CoV by 35-48% (simulated dataset), 39-43% ([11C]AFM dataset) and 30-36% ([11C]UCB-J dataset) across count levels (averaged over regions at matched iteration); V T CoV was reduced by 51-58%, 54-60% and 30-46%, respectively. Motion correction played an important role in the dataset with larger motion: correction increased regional V T by 51% on average in the [11C

  13. Direct reconstruction of parametric images for brain PET with event-by-event motion correction: evaluation in two tracers across count levels.

    Science.gov (United States)

    Germino, Mary; Gallezot, Jean-Dominque; Yan, Jianhua; Carson, Richard E

    2017-07-07

    Parametric images for dynamic positron emission tomography (PET) are typically generated by an indirect method, i.e. reconstructing a time series of emission images, then fitting a kinetic model to each voxel time activity curve. Alternatively, 'direct reconstruction', incorporates the kinetic model into the reconstruction algorithm itself, directly producing parametric images from projection data. Direct reconstruction has been shown to achieve parametric images with lower standard error than the indirect method. Here, we present direct reconstruction for brain PET using event-by-event motion correction of list-mode data, applied to two tracers. Event-by-event motion correction was implemented for direct reconstruction in the Parametric Motion-compensation OSEM List-mode Algorithm for Resolution-recovery reconstruction. The direct implementation was tested on simulated and human datasets with tracers [(11)C]AFM (serotonin transporter) and [(11)C]UCB-J (synaptic density), which follow the 1-tissue compartment model. Rigid head motion was tracked with the Vicra system. Parametric images of K 1 and distribution volume (V T  =  K 1/k 2) were compared to those generated by the indirect method by regional coefficient of variation (CoV). Performance across count levels was assessed using sub-sampled datasets. For simulated and real datasets at high counts, the two methods estimated K 1 and V T with comparable accuracy. At lower count levels, the direct method was substantially more robust to outliers than the indirect method. Compared to the indirect method, direct reconstruction reduced regional K 1 CoV by 35-48% (simulated dataset), 39-43% ([(11)C]AFM dataset) and 30-36% ([(11)C]UCB-J dataset) across count levels (averaged over regions at matched iteration); V T CoV was reduced by 51-58%, 54-60% and 30-46%, respectively. Motion correction played an important role in the dataset with larger motion: correction increased regional V T by 51% on average in the [(11

  14. Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT7 Receptor

    DEFF Research Database (Denmark)

    Herth, Matthias M; Andersen, Valdemar L; Hansen, Hanne D;

    2015-01-01

    We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent (11)C-labeling and in vivo...

  15. Research Progress of PET Traces for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    TANG Cai-hua1,2;HU Kong-zhen1;TANG Gang-hua1

    2014-02-01

    Full Text Available Alzheimer’s disease (AD is unknown cause progressive degenerative diseases of central nervous system. It is a serious threat to the health of the elderly people. The diagnosis is mainly based on pathological examination after death. With the wide application of positron emission tomography (PET imaging in clinic, in vivo noninvasive imaging diagnosis of AD at the early stage become possible. PET imaging mainly depends on the positron-labeled imaging agents. The PET imaging agents can be used in the early diagnosis and differential diagnosis on AD include several kinds: PET traces for glucose metabolic, PET traces combined with amyloid proteinplaques,tau protein, neurotransmitter and receptor, activation of microglia and PET traces for cell apoptosis.The research progress of various PET tracers were reviewed that can be used in the early diagnosis and differential diagnosis on AD in recent years.

  16. Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging

    DEFF Research Database (Denmark)

    Persson, Morten; El Ali, Henrik H.; Binderup, Tina

    2014-01-01

    studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of 64Cu-DOTA-AE105. MethodsFive mice received iv tail injection of 64Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung......, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22h was scaled to human value based on a difference between organ and body weights. The scaled values......Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of 64Cu-DOTA-AE105....

  17. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; McPherson, D.W.; Luo, H. [and others

    1995-06-01

    Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

  18. Evaluation of the kappa-opioid receptor-selective tracer [{sup 11}C]GR103545 in awake rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Schoultz, Bent W. [University of Oslo, Department of Chemistry, Oslo (Norway); Hjornevik, Trine; Willoch, Frode [University of Oslo, Centre for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, Oslo (Norway); Akershus University Hospital, Department of Nuclear Medicine, Loerenskog (Norway); Marton, Janos [ABX Advanced Biochemical Compounds GmbH, Radeberg (Germany); Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro [Medical and Pharmacological Research Center Foundation, Basic Research Department, Hakui City, Ishikawa (Japan); Aarstad, Erik [University College of London, Institute of Nuclear Medicine, London (United Kingdom); Drzezga, Alexander [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Matsunari, Ichiro [Medical and Pharmacological Research Center Foundation, Clinical Research Department, Hakui City, Ishikawa (Japan); Henriksen, Gjermund [University of Oslo, Department of Chemistry, Oslo (Norway); Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

    2010-06-15

    The recent development in radiosynthesis of the {sup 11}C-carbamate function increases the potential of [{sup 11}C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor ({kappa}-OR) with PET. In the present study, [{sup 11}C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [{sup 11}C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [{sup 11}C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for {kappa}-OR (K{sub i} = 0.02 {+-}0.01 nM) with excellent selectivity over {mu}-OR (6 x 10{sup 2}-fold) and {delta}-OR (2 x 10{sup 4}-fold). PET imaging revealed a volume of distribution (V{sub T}) pattern consistent with the known distribution of {kappa}-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [{sup 11}C]GR103545 is selective for {kappa}-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

  19. Design and Synthesis of an 18F-Labeled Version of Phenylethyl Orvinol ([18F]FE-PEO for PET-Imaging of Opioid Receptors

    Directory of Open Access Journals (Sweden)

    Gjermund Henriksen

    2012-09-01

    Full Text Available The semisynthetic oripavine derivative phenethyl orvinol (PEO, a full agonist at opioid receptors (OR, is an attractive structural motif for developing 18F-labeled PET tracers with a high degree of sensitivity for competition between endogenous and exogenous OR-ligands. The target cold reference compound 6-O-(2-fluoroethyl-6-O-desmethylphenylethyl orvinol (FE-PEO was obtained via two separate reaction routes. A three-step synthesis was developed for the preparation of a tosyloxyethyl precursor (TE-TDPEO, the key precursor for a direct, nucleophilic radiofluorination to yield [18F]FE-PEO. The developed radiosynthesis provides the target compound in relevantly high yield and purity, and is adaptable to routine production.

  20. Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone

    Energy Technology Data Exchange (ETDEWEB)

    Muhr, C.; Bergstroem, M.L.; Lundberg, P.O.; Bergstroem, K.H.; Hartvig, P.; Lundqvist, H.; Antoni, G.; Langstroem B2

    1986-03-01

    Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment.

  1. A Multi-tracer Dopaminergic PET Study of Young-Onset Parkinsonian Patients With and Without Parkin Gene Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, M.J. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Thobois, St.; Broussolle, E. [University of Lyon, Hospices Civils de Lyon, Neurological Hospital, Lyon (France); Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A. [INSERM, Paris (France); Lohmann, E.; Agid, Y.; Brice, A. [Department of the Nervous System Disorders, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Lohmann, E.; Lesage, S.; Dubois, B.; Agid, Y.; Brice, A. [UPMC University of Paris, Paris (France); Tezenas du Montcel, S. [Unit of de Biostatistics and Medical Information and Unit of Medical Research, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Tezenas du Montcel, S. [Modelisation in Clinical Research, UPMC University of Paris, Paris (France); Pelissolo, A. [Department of Psychiatry, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Dubois, B. [Centre de Reference sur la Maladie de Pick, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Mallet, L. [Behaviour, Emotion and Basal Ganglia, Center of Clinical Investigation, INSERM Avenir Group, Paris (France); Pollak, P. [Department of Clinical and Biological Neurosciences, University Hospital of Grenoble, Grenoble (France); Agid, Y. [Clinical Investigation Center, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Brice, A. [Department of Genetics and Cytogenetics, AP-HP, Pitie-Salpetriere Hospital, Paris (France); Remy, Ph. [CEA, I2BM, MIRCEN, URA CEA-CNRS 2210, Orsay (France); Remy, Ph. [CHU Henri Mondor, AP-HP and Faculte de Medecine Paris 12, Creteil (France)

    2009-07-01

    The impact of parkin gene mutations on nigrostriatal dopaminergic degeneration is not well established. The purpose of this study was to characterize by PET using {sup 18}F-fluoro-L-3, 4- dihydroxyphenylalanine ({sup 18}F-fluoro-L-DOPA), {sup 11}C-PE2I, and {sup 11}C-raclopride the pattern of dopaminergic lesions in young-onset Parkinson disease (YOPD) patients with or without mutations of the parkin gene and to correlate the clinical and neuro-psychologic characteristics of these patients with PET results. Methods: A total of 35 YOPD patients were enrolled (16 with parkin mutation, 19 without). The uptake constant (K{sub i}) of {sup 18}F-fluoro- L-DOPA and the binding potential (BP) of {sup 11}C-PE2I (BPDAT) and of {sup 11}C-raclopride (BPD2) were calculated in the striatum. Comparisons were made between the 2 groups of YOPD and between controls and patients. For each radiotracer, parametric images were obtained, and statistical parametric mapping (SPM) analysis using a voxel-by-voxel statistical t test was performed. Correlations between the cognitive and motor status and PET results were analyzed. Results: In YOPD patients, {sup 18}F-fluoro-L-DOPA K{sub i} values were reduced to 68% (caudate) and 40% (putamen) of normal values (P {<=} 0.0001). This decrease was symmetric and comparable for non-parkin and parkin patients. No correlation was found between the K{sub i} values and cognitive or motor status. {sup 11}C-PE2I BPDAT values in YOPD patients were decreased to 56% (caudate) and 41% (putamen) of normal values (P {<=} 0.0001) and did not differ between the 2 YOPD populations. The mean {sup 11}C-raclopride BPD2 values were reduced to 72% (caudate) and 84% (putamen) of the normal values (P {<=} 0.02) and did not differ between non-parkin and parkin patients. SPM analyses showed in patients an additional decrease of {sup 11}C-raclopride in the frontal cortex and a decrease of {sup 18}F-fluoro-L-DOPA and {sup 11}C-PE2I uptake in the substantia nigra bilaterally

  2. Preclinical evaluation of [{sup 11}C]SA4503. Radiation dosimetry, in vivo selectivity and PET imaging of sigma{sub 1} receptors in the cat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori; Ishiwata, Kiichi; Shimada, Yuhei; Kimura, Yuichi; Senda, Michio [Tokyo Metropolitan Inst. of Gerontology (Japan). Positron Medical Center; Kobayashi, Tadayuki; Matsuno, Kiyoshi; Homma, Yoshio

    2000-08-01

    Our previous in vivo study with rats has demonstrated that {sup 11}C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([{sup 11}C]SA4503) is a potential radioligand for mapping central nervous system (CNS) sigma{sub 1} receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [{sup 11}C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [{sup 11}C]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4503 and haloperidol, but not by co-injection of any of six ligands for sigma{sub 2} or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for sigma{sub 1} receptor. In the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in the cortex and cerebellum at 76 min after tracer injection. We have concluded that [{sup 11}C]SA4503 has the potential for mapping sigma{sub 1} receptor by PET. (author)

  3. Tracer kinetic modeling of [(11)C]AFM, a new PET imaging agent for the serotonin transporter.

    Science.gov (United States)

    Naganawa, Mika; Nabulsi, Nabeel; Planeta, Beata; Gallezot, Jean-Dominique; Lin, Shu-Fei; Najafzadeh, Soheila; Williams, Wendol; Ropchan, Jim; Labaree, David; Neumeister, Alexander; Huang, Yiyun; Carson, Richard E

    2013-12-01

    [(11)C]AFM, or [(11)C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine, is a new positron emission tomography (PET) radioligand with high affinity and selectivity for the serotonin transporter (SERT). The purpose of this study was to determine the most appropriate kinetic model to quantify [(11)C]AFM binding in the healthy human brain. Positron emission tomography data and arterial input functions were acquired from 10 subjects. Compartmental modeling and the multilinear analysis-1(MA1) method were tested using the arterial input functions. The one-tissue model showed a lack of fit in low-binding regions, and the two-tissue model failed to estimate parameters reliably. Regional time-activity curves were well described by MA1. The rank order of [(11)C]AFM binding potential (BPND) matched well with the known regional SERT densities. For routine use of [(11)C]AFM, several noninvasive methods for quantification of regional binding were evaluated, including simplified reference tissue models (SRTM and SRTM2), and multilinear reference tissue models (MRTM and MRTM2). The best methods for region of interest (ROI) analysis were MA1, MRTM2, and SRTM2, with fixed population kinetic values ( or b') for the reference methods. The MA1 and MRTM2 methods were best for parametric imaging. These results showed that [(11)C]AFM is a suitable PET radioligand to image and quantify SERT in humans.

  4. Comparison of semiquantitative fluorescence imaging and PET tracer uptake in mesothelioma models as a monitoring system for growth and therapeutic effects

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Yuriko [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan); Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675 (Japan); Furukawa, Takako [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Yoshida, Fukui, 910-1193 (Japan); Arano, Yasushi [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675 (Japan); Fujibayashi, Yasuhisa [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Yoshida, Fukui, 910-1193 (Japan); Saga, Tsuneo [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan)

    2008-11-15

    Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines expressing red fluorescent protein (RFP) and examined their fluorescence intensity and uptake of positron emission tomography (PET) tracer analogs to compare their characteristics and assess their usefulness in the evaluation of therapeutics. Method: A human mesothelioma cell line was stably transfected to express RFP. Fluorescence, cell number and protein amount were measured during cell growth and treatment with cytotoxic reagents. In in vivo experiments, RFP-expressing cells were injected subcutaneously or into the pleural cavity of nude mice, and fluorescence images were taken with or without pemetrexed treatment. The uptake of [{sup 3}H]3'-deoxy-3'-fluorothymidine ([{sup 3}H]FLT) and [{sup 14}C]2-fluoro-2-deoxy-D-glucose ([{sup 14}C]FDG) under treatment with the above reagents in vitro and in vivo were examined. Results: Strong correlation was observed between fluorescence intensity and total cell number with or without cytotoxic treatment. The uptake of [{sup 3}H]FLT and [{sup 14}C]FDG decreased rapidly after the initiation of treatment with actinomycin D or cycloheximide. When treated with pemetrexed, the uptake of [{sup 3}H]FLT temporarily increased. The cells formed subcutaneous and orthotopic tumors, with fluorescence intensity correlating with tumor volume. The correlation was sustained under pemetrexed treatment. The uptake of [{sup 3}H]FLT in vivo increased significantly early after pemetrexed treatment. Conclusion: Fluorescence imaging could be used to semiquantitatively monitor tumor size, whereas PET could be used to monitor tumor response to therapeutic treatments, and especially, FLT might be a good marker of the response to anti-folate chemotherapeutics.

  5. Ethnic comparison of pharmacokinetics of {sup 18}F-florbetaben, a PET tracer for beta-amyloid imaging, in healthy Caucasian and Japanese subjects

    Energy Technology Data Exchange (ETDEWEB)

    Senda, Michio; Sasaki, Masahiro; Yamane, Tomohiko; Shimizu, Keiji [Institute of Biomedical Research and Innovation, Division of Molecular Imaging, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe (Japan); Patt, Marianne; Barthel, Henryk; Sattler, Bernhard; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Nagasawa, Toshiki; Aitoku, Yasuko [Bayer Yakuhin Ltd, Osaka (Japan); Schultze-Mosgau, Marcus [Bayer HealthCare AG, Berlin (Germany); Dinkelborg, Ludger [Piramal Imaging GmbH, Berlin (Germany)

    2015-01-15

    {sup 18}F-Florbetaben is a positron emission tomography (PET) tracer indicated for imaging cerebral beta-amyloid deposition in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive decline. The present study examined ethnic comparability of the plasma pharmacokinetics, which is the input to the brain, between Caucasian and Japanese subjects. Two identical phase I trials were performed in 18 German and 18 Japanese healthy volunteers to evaluate the plasma pharmacokinetics of a single dose of 300 MBq {sup 18}F-florbetaben, either of low (≤5 μg, LD) or high (50-55 μg, HD) mass dose. Pharmacokinetic parameters were evaluated based on the total {sup 18}F radioactivity measurements in plasma followed by metabolite analysis using radio-HPLC. The pharmacokinetics of {sup 18}F-florbetaben was characterized by a rapid elimination from plasma. The dose-normalized areas under the curve of {sup 18}F-florbetaben in plasma as an indicator of the input to the brain were comparable between Germans (LD: 0.38 min/l, HD: 0.55 min/l) and Japanese (LD: 0.35 min/l, HD: 0.45 min/l) suggesting ethnic similarity, and the mass dose effect was minimal. A polar metabolite fraction was the main radiolabelled degradation product in plasma and was also similar between the doses and the ethnic groups. Absence of a difference in the pharmacokinetics of {sup 18}F-florbetaben in Germans and Japanese has warranted further global development of the PET imaging agent. (orig.)

  6. Comparison of two new angiogenesis PET tracers 68Ga-NODAGA-E[c(RGDyK)]2 and 64Cu-NODAGA-E[c(RGDyK)]2; in vivo imaging studies in human xenograft tumors

    DEFF Research Database (Denmark)

    Oxbøl, Jytte; Brandt-Larsen, Malene; Schjøth-Eskesen, Christina

    2014-01-01

    . CONCLUSION: (68)Ga-NODAGA-E[c(RGDyK)](2) and (64)Cu-NODAGA-E[c(RGDyK)](2) can be easily synthesized and are both promising candidates for PET imaging of integrin αVβ3 positive tumor cells. (68)Ga-NODAGA-E[c(RGDyK)](2) showed slightly more stable tumor retention. With the advantage of in-house commercially......INTRODUCTION: The aim of this study was to synthesize and perform a side-by-side comparison of two new tumor-angiogenesis PET tracers (68)Ga-NODAGA-E[c(RGDyK)](2) and (64)Cu-NODAGA-E[c(RGDyK)](2) in vivo using human xenograft tumors in mice. Human radiation burden was estimated to evaluate...... potential for future use as clinical PET tracers for imaging of neo-angiogenesis. METHODS: A (68)Ge/(68)Ga generator was used for the synthesis of (68)Ga-NODAGA-E[c(RGDyK)](2). (68)Ga and (64)Cu labeled NODAGA-E[c(RGDyK)](2) tracers were administrated in nude mice bearing either human glioblastoma (U87MG...

  7. The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA*CER) trial: study design and rationale.

    Science.gov (United States)

    2009-09-01

    The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA*CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. TRA*CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least 1 year. The TRA*CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. TRA*CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.

  8. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Matthias Eder

    2014-06-01

    Full Text Available The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx-HBED-CC ([68Ga]Ga-PSMA-HBED-CC represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective 68Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [68Ga]Ga-PSMA-HBED-CC.

  9. PET Imaging of the AT{sub 1} receptor with [{sup 11}C]KR31173

    Energy Technology Data Exchange (ETDEWEB)

    Zober, Tamas G. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Mathews, William B. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Seckin, Esen [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Yoo, Sung-eun [Center for Biological Modulators, Korea Research Institute of Chemical Technology, Daejeon 305-343 (Korea, Republic of); Hilton, John [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Xia Jinsong [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Sandberg, Kathryn [Department of Medicine, Georgetown University, Washington, DC 20057 (United States); Ravert, Hayden T. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Dannals, Robert F. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Szabo, Zsolt [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States)]. E-mail: zszabo@jhmi.edu

    2006-01-15

    Aim: The goal of this study was to investigate the binding characteristics of [{sup 11}C]KR31173 and its applicability for PET studies of the AT{sub 1} receptor (AT{sub 1}R). Methods: Ex vivo biodistribution and pharmacology were tested in mice. PET imaging was performed in mice, beagle dogs and a baboon. To assess nonspecific binding, PET imaging was performed both before and after pretreatment with a potent AT{sub 1}R antagonist. In the baboon, PET imaging was also performed with the previously developed radioligand [{sup 11}C]L-159,884 for comparison. Results: Ex vivo biodistribution studies in mice showed specific binding rates of 80-90% in the adrenals, kidneys, lungs and heart. Specific binding was confirmed in mice using small animal PET. In dogs, renal cortex tissue concentration at 75-95 min postinjection (pi) was 63 nCi/ml per millicurie at a specific binding rate of 95%. In the baboon renal cortex, tissue activity at 55-75 min pi was 345 nCi/ml per millicurie. In the baboon the specific binding of [{sup 11}C]KR31173 was higher (81%) than the specific binding of [{sup 11}C]L-159,884 (34%). Conclusion: [{sup 11}C]KR31173 shows accumulation and significant specific binding to the AT{sub 1}R in the kidneys of mice, dogs and baboon. These findings suggest that this radioligand is suited for imaging the renal cortical AT{sub 1}R in multiple species.

  10. Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands

    DEFF Research Database (Denmark)

    Herth, Matthias M; Petersen, Ida Nymann; Hansen, Hanne Demant

    2016-01-01

    INTRODUCTION: The serotonin 2A receptor (5-HT2AR) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins...

  11. Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Volk, Balázs; Pallagi, Katalin

    2012-01-01

    The most recently discovered serotonin (5-HT) receptor subtype, 5-HT(7), is considered to be associated with several CNS disorders. Noninvasive in vivo positron emission tomography (PET) studies of cerebral 5-HT(7) receptors could provide a significant advance in the understanding of the neurobio...

  12. Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

    Energy Technology Data Exchange (ETDEWEB)

    Kronfeld, Andrea; Müller-Forell, Wibke [Institute of Neuroradiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz 55131 (Germany); Buchholz, Hans-Georg; Maus, Stephan; Reuss, Stefan; Schreckenberger, Mathias; Miederer, Isabelle, E-mail: isabelle.miederer@unimedizin-mainz.de [Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz 55131 (Germany); Lutz, Beat [Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, Mainz 55128 (Germany)

    2015-12-15

    Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawley rats were investigated for template construction using MRI and [{sup 18}F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL

  13. Development of PET tracers for neuro inflammation imaging in neuro degenerative diseases; Developpement de radiotraceurs de la neuroinflammation pour l'imagerie des pathologies neurodegeneratives

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, F

    2007-10-15

    Inflammatory processes such as micro-glial or endothelial activation are involved in many neuro-degenerative conditions. Neuro-inflammation imaging is considered an attractive tool for fundamental research, diagnosis and therapeutic evaluation in neuro-pathologies. First, an aptamer was selected against a recombinant fragment of the endothelial target VCAM-1, but proved unable to bind the target protein in native conformation, as expressed by a cell line. Second, five radioligands of the peripheral benzodiazepine receptor (PBR), a marker of micro-glial activation, were evaluated in vivo using PET (Positron Emission Tomography) imaging in a rat model of neuro-inflammation, and were compared to [11C]PK11195. Four radiotracers displayed a better contrast than [11C]PK11195. In a competitive field of research, this work demonstrates the efficiency of in vivo screening of radiotracers for fast selection of clinically relevant molecules. (author)

  14. PET and SPECT imaging in veterinary medicine.

    Science.gov (United States)

    LeBlanc, Amy K; Peremans, Kathelijne

    2014-01-01

    Veterinarians have gained increasing access to positron emission tomography (PET and PET/CT) imaging facilities, allowing them to use this powerful molecular imaging technique for clinical and research applications. SPECT is currently being used more in Europe than in the United States and has been shown to be useful in veterinary oncology and in the evaluation of orthopedic diseases. SPECT brain perfusion and receptor imaging is used to investigate behavioral disorders in animals that have interesting similarities to human psychiatric disorders. This article provides an overview of the potential applications of PET and SPECT. The use of commercially available and investigational PET radiopharmaceuticals in the management of veterinary disease has been discussed. To date, most of the work in this field has utilized the commercially available PET tracer, (18)F-fluorodeoxyglucose for oncologic imaging. Normal biodistribution studies in several companion animal species (cats, dogs, and birds) have been published to assist in lesion detection and interpretation for veterinary radiologists and clinicians. Studies evaluating other (18)F-labeled tracers for research applications are underway at several institutions and companion animal models of human diseases are being increasingly recognized for their value in biomarker and therapy development. Although PET and SPECT technologies are in their infancy for clinical veterinary medicine, increasing access to and interest in these applications and other molecular imaging techniques has led to a greater knowledge and collective body of expertise for veterinarians worldwide. Initiation and fostering of physician-veterinarian collaborations are key components to the forward movement of this field.

  15. ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: comparison of easy-to-label recombinant proteins for [{sup 68}Ga]PET imaging of VEGF receptors in angiogenic vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Eder, Matthias [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)], E-mail: m.eder@dkfz.de; Krivoshein, Arcadius V.; Backer, Marina; Backer, Joseph M. [SibTech, Inc., Brookfield, CT 06804 (United States); Haberkorn, Uwe [Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany); Eisenhut, Michael [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)

    2010-05-15

    Introduction: VEGF receptors play a key role in angiogenesis and are important targets for several approved and many experimental drugs. Imaging of VEGF receptor expression in malignant tumors would provide important information, which can influence patient management. The aim of this study was the development of an easy-to-label positron-emitting tracer for imaging VEGF receptors. The tracer is based on engineered single-chain VEGF (scVEGF), expressed with cysteine-containing fusion tag (Cys-tag) for site-specific conjugation of PEGylated bifunctional chelating agents, HBED-CC or NOTA, suitable for labeling with {sup 68}Ga at ambient temperature. Methods: scVEGF-PEG-HBED-CC was synthesized by activating a single carboxyl group of the [Fe(HBED-CC)]{sup -} complex with N-hydroxysuccinimide. Reaction of the activated complex with NH{sub 2}-PEG-maleimide was followed by site-specific conjugation of PEGylated chelator to a thiol group in Cys-tag of scVEGF. The scVEGF-PEG-NOTA conjugate was synthesized using NHS-PEG-maleimide and p-NH{sub 2}-Bn-NOTA. {sup 68}Ga complexation was performed in HEPES buffer (pH 4.2) at room temperature. The functional activity after labeling was tested by radioligand cell binding assays. Biodistribution and PET studies in tumor-bearing mice were performed after 1, 2, 3 and 4 h postinjection. Results: The radiolabeling of scVEGF-PEG-HBED-CC proved more efficient than scVEGF-PEG-NOTA allowing to stop the reaction after 4 min (>97% radiochemical yield). Radioligand cell binding assays performed on HEK-293 cells overexpressing VEGFR-2 revealed no change in the binding properties of {sup 68}Ga-radiolabeled scVEGF relative to other scVEGF-based tracers. Both tracers showed comparable results in biodistribution, such as tumor accumulation and low liver uptake. The tracers were stable in 50% human serum for at least 72 h. Conclusions: The conjugates scVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA revealed comparable in vivo characteristics and allowed easy

  16. Frightening music triggers rapid changes in brain monoamine receptors: a pilot PET study.

    Science.gov (United States)

    Zhang, Ying; Chen, Qiaozhen; Du, Fenglei; Hu, Yanni; Chao, Fangfang; Tian, Mei; Zhang, Hong

    2012-10-01

    Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited. We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated. Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex. Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.

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

    Science.gov (United States)

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

    2015-04-01

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

  18. Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [{sup 18}F]FITM

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Tomoteru [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); Tohoku University, Graduate School of Pharmaceutical Sciences, Sendai (Japan); Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); Yoshida, Yuichiro [SHI Accelerator Service Co. Ltd., Tokyo (Japan); Zhang, Ming-Rong [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); National Institute of Radiological Sciences, Department of Molecular Probes, Molecular Imaging Centre, Chiba (Japan)

    2012-04-15

    In this study, we evaluate the utility of 4-[{sup 18}F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([{sup 18}F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [{sup 18}F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V{sub T}) was detected in the cerebellum (V{sub T} = 11.5). [{sup 18}F ]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [{sup 18}F ]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains. (orig.)

  19. Evaluation of [methyl-{sup 3}H]L655,708 and [ethyl-{sup 3}H]RY80 as putative PET ligands for central GABA{sub A} receptors containing {alpha}5 subunit

    Energy Technology Data Exchange (ETDEWEB)

    Opacka-Juffry, J. E-mail: jolanta@cu.rpms.ac.uk; Hirani, E.; Dawson, G.R.; Luthra, S.K.; Hume, S.P

    1999-10-01

    Two selective radioligands of gamma aminobutyric acid (GABA){sub A} receptors containing the {alpha}5 subunit, [{sup 3}H]L655,708 and [{sup 3}H]RY80, were evaluated in rats as potential in vivo tracers for positron emission tomography (PET). Brain uptake index (BUI), a measure of first pass extraction, was moderate for [{sup 3}H]L655,708 (BUI of 59%) and good for [{sup 3}H]RY80 (BUI of 96%). This finding was consistent with their in vitro binding to plasma proteins of {approx}76% and 50%, respectively. Following intravenous injection of either radioligand, radioactivity in plasma was measured and uptake characteristics were assessed in brain within a time period relevant to PET scanning (up to 90 min). Discrete brain regions, such as frontal cortex, striatum, hypothalamus, thalamus, hippocampus, colliculi, medulla, and cerebellum, were sampled and the temporal distribution of radioactivity analysed. Despite the reasonable delivery to the brain, neither of the radioligands had sufficient retention in the tissues rich in {alpha}5-containing GABA{sub A} receptors to achieve a good selective signal. For both radioligands, a maximal tissue:cerebellum ratio of 1.5 was seen in hippocampus at 10 min after injection. Thus, neither of the compounds studied shows potential for further development as an in vivo PET ligand.

  20. [{sup 18}F]D.P.A. 714 a new and highly promising fluorine-18-labelled tracer for imaging of neuro inflammation: evaluation in a rodent model using micro PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, F.; Van Camp, N.; Damont, M.; Hinnen, F.; Kuhnast, B.; Dolle, F.; Tavitian, B. [Service Hospitalier Frederic Joliot, CEA Institut d' Imagerie Biomedicale, Lab. d' Imagerie Moleculaire Experimentale, 91 - Orsay (France); Chauveau, F.; Van Camp, N. [Inserm, U803, 91 - Orsay (France); James, M.; Kassiou, M. [Sydney Univ., School of Medical Radiation Sciences, NSW (Australia); James, M.; Kassiou, M. [Sydney Univ., NSW (Australia). School of Chemistry; James, M.; Kassiou, M. [Sydney Univ., Ramaciotti Center for Brain Imaging, Brain and Mind Research Institute, NSW (Australia); Boutin, H. [Manchester Univ., Faculty of Life Sciences, Neurobiology Group (United Kingdom)

    2008-02-15

    We have successfully evaluated a new {sup 18}F P.B.R. (peripheral benzodiazepine receptor) tracer in an acute model of neuro inflammation. We further aim to apply this compound in clinically related models of neuro inflammation such as the experimental animal model of encephalitis for multiple sclerosis. (N.C.)

  1. Synthesis of [{sup 18}F]-labelled nebivolol as a β{sub 1}-adrenergic receptor antagonist for PET imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taek Soo; Park, Jeong Hoon; Lee, Jun Young; Yang, Seung Dae [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup (Korea, Republic of); Chang, Dong Jo [College of pharmacy, Sunchon National University, Suncheon (Korea, Republic of)

    2017-02-15

    Selective β{sub 1}-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective β{sub 1}-antagonists including nebivolol have high binding affinity on β{sub 1}-adrenergic receptor, not β{sub 2}-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective β{sub 1}-blockers in clinically used β{sub 1}- blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective β{sub 1}-blocker. Nebivolol is C{sub 2}-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of {sup 18}F. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for {sup 18}F-aromatic substitution, was synthesized in moderate yield which was readily subjected to {sup 18}F-aromatic substitution to give {sup 18}F-labelled nebivolol.

  2. [PET/CT in breast cancer: an update].

    Science.gov (United States)

    Groheux, D; Moretti, J-L; Giacchetti, S; Hindié, E; Teyton, P; Cuvier, C; Bousquet, G; Misset, J-L; Boin, C; Espié, M

    2009-11-01

    The authors discuss the various roles of 18F-FDG PET/CT in the management of breast cancer. Roles of new tracers such as F-18 fluoro-L-thymidine (a marker of cell proliferation), 18-fluoro-17-B-estradiol (marker of estrogen receptor) and sodium fluoride (marker of bone matrix) are also mentioned. There is little justification for the use of FDG-PET/CT in patient with clinically T1 (occult distant metastases, notably, early osteomedullary infiltration. Thus, for these tumors, initial PET/CT can enable better intramodality treatment planning or a change in treatment. PET/CT as a whole-body examination is also very efficient in case of suspicion of recurrence. On the other hand, many studies show that this functional imaging could be used to assess early response to neoadjuvant chemotherapy or to chemotherapy of metastatic disease. 18FDG-PET/CT could thus become an unavoidable modality to answer various clinical situations.

  3. A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl [Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Zegers, Catharina M.L.; Lieuwes, Natasja G.; Elmpt, Wouter van [Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Eriksson, Jonas; Dongen, Guus A.M.S. van [Department of Radiology and Nuclear Medicine, VU University Medical Center Amsterdam, Amsterdam (Netherlands); Dubois, Ludwig; Lambin, Philippe [Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands)

    2015-02-01

    Purpose: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [{sup 18}F]FMISO, [{sup 18}F]FAZA, and [{sup 18}F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification. Methods and Materials: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, and reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing. Results: TBR was stabilized and maximal at 2 hours p.i. for [{sup 18}F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [{sup 18}F]HX4 (7.2 ± 0.7), whereas [{sup 18}F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [{sup 18}F]FMISO (R = 0.86; Dice coefficient = 0.76) and [{sup 18}F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [{sup 18}F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [{sup 18}F]HX4 and [{sup 18}F]FAZA upon 7% oxygen breathing. Only [{sup 18}F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen. Conclusions: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put

  4. PET/CT studies of multiple myeloma using {sup 18}F-FDG and {sup 18}F-NaF: comparison of distribution patterns and tracers' pharmacokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Sachpekidis, Christos [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); German Cancer Research Center, Medical PET Group - Biological Imaging Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Goldschmidt, Hartmut; Hose, Dirk [University of Heidelberg, Medical Clinic V, Heidelberg (Germany); National Center for Tumor Diseases Heidelberg, Heidelberg (Germany); Pan, Leyun; Cheng, Caixia; Dimitrakopoulou-Strauss, Antonia [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Kopka, Klaus [German Cancer Research Center, Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); Haberkorn, Uwe [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany)

    2014-07-15

    The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) and fluorine-18 sodium fluoride ({sup 18}F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions. The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased {sup 18}F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the {sup 18}F-NaF PET/CT scans were then correlated with those detected on {sup 18}F-FDG PET/CT, which served as a reference. Moreover, the {sup 18}F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach. Whole body {sup 18}F-FDG PET/CT revealed approximately 343 focal lesions while {sup 18}F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in {sup 18}F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with {sup 18}F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal {sup 18}F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with {sup 18}F-NaF PET/CT. In three patients with multiple focal {sup 18}F-FDG-uptake, {sup 18}F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with {sup 18}F-FDG and {sup 18}F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of {sup 18}F-FDG revealed the

  5. Quantitative PET of human urokinase-type plasminogen activator receptor with 64Cu-DOTA-AE105

    DEFF Research Database (Denmark)

    Persson, Morten; Madsen, Jacob; Østergaard, Søren

    2012-01-01

    Expression levels of the urokinase-type plasminogen activator receptor (uPAR) represent an established biomarker for poor prognosis in a variety of human cancers. The objective of the present study was to explore whether noninvasive PET can be used to perform a quantitative assessment of expressi...

  6. Small Molecule PET-Radiopharmaceuticals

    NARCIS (Netherlands)

    Elsinga, Philip H.; Dierckx, Rudi A. J. O.

    2014-01-01

    This review describes several aspects required for the development of small molecule PET-tracers. Design and selection criteria are important to consider before starting to develop novel PET-tracers. Principles and latest trends in C-11 and F-18-radiochemistry are summarized. In addition an update o

  7. Gallium-68 DOTATOC PET/CT in vivo characterization of somatostatin receptor expression in the prostate.

    Science.gov (United States)

    Todorović-Tirnanić, Mila V; Gajić, Milan M; Obradović, Vladimir B; Baum, Richard P

    2014-04-01

    The aim was to investigate somatostatin receptor (sstr) expression in normal prostate by determining the maximum standardized uptake value (SUVmax) of (68)Ga-DOTATOC PET/CT in neuroendocrine tumor (NET) patients, without NET involvement of the prostate gland, for establishing the reference standard. Sixty-four NET patients underwent (68)Ga-DOTATOC PET/CT. SUVmax of the prostate gland, normal liver, testes, and gluteus muscles were evaluated. The prostate gland size was measured. Statistical analysis was performed using dedicated software (SPSS13). Mean/median (68)Ga-DOTATOC SUVmax values were as follows: normal prostate 2.6 ± 0.0, slightly enlarged prostate 4.2 ± 1.6, prostatic hypertrophy 4.9 ± 1.6, prostatic hyperplasia 5.0 ± 1.5, prostate cancer 9.5 ± 2.1, normal liver 7.3 ± 1.8, testes 1.8 ± 0.5, and gluteus 1.0 ± 0.2. The normal prostate gland had three times less sstr expression than normal liver tissue. Strong correlation was found between patient age and sstr expression in prostate/prostate size. No significant difference existed in sstr expression between prostatic hypertrophy and hyperplasia. Much higher sstr expression was found in prostatic cancer compared with normal prostate. (68)Ga-DOTATOC PET/CT defines the baseline sstr uptake in prostate not affected by NET (significantly lower than in the liver). Higher values were established in prostatic hyperplasia and hypertrophy. Only concomitant prostate cancer was associated with higher SUVmax in comparison with non-neoplastic liver.

  8. Preclinical evaluation and quantification of [{sup 18}F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Casteels, Cindy [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); University Hospital Gasthuisberg, Division of Nuclear Medicine, Leuven (Belgium); Koole, Michel; Laere, Koen van [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); Celen, Sofie; Bormans, Guy [K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); K.U. Leuven, Laboratory for Radiopharmacy, Leuven (Belgium)

    2012-09-15

    [{sup 18}F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [{sup 18}F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [{sup 18}F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V{sub T}) of [{sup 18}F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [{sup 18}F]MK-9470 in arterial plasma samples was 80 {+-} 23 % at 10 min, 38 {+-} 30 % at 40 min and 13 {+-} 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V{sub T} values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability ({<=}10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [{sup 18}F]MK-9470 V{sub T}, but was correlated. A correlation between [{sup 18}F]MK-9470 V{sub T} and SUV in the brain was also found (R {sup 2} = 0.26-0.33; p {<=} 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [{sup 18}F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  9. Metabolism of the A{sub 1} adenosine receptor PET ligand [{sup 18}F]CPFPX by CYP1A2: implications for bolus/infusion PET studies

    Energy Technology Data Exchange (ETDEWEB)

    Matusch, Andreas [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Meyer, Philipp T. [Department of Neurology, University Hospital Aachen, D-52074 Aachen (Germany); Bier, Dirk [Institute for Neuroscience and Biophysics (INB4)-Nuclear Chemistry, Research Center Juelich GmbH, D-52425 Juelich (Germany); Holschbach, Marcus H. [Institute for Neuroscience and Biophysics (INB4)-Nuclear Chemistry, Research Center Juelich GmbH, D-52425 Juelich (Germany); Woitalla, Dirk [Neurological Department, Ruhr-University Bochum, D-44791 Bochum (Germany); Elmenhorst, David [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Winz, Oliver H. [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Zilles, Karl [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Bauer, Andreas [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany)]. E-mail: an.bauer@fz-juelich.de

    2006-10-15

    The A{sub 1} adenosine receptor positron emission tomography (PET) ligand 8-cyclopentyl-3-(3-[{sup 18}F]fluoropropyl)-1-propylxanthine ([{sup 18}F]CPFPX, ) undergoes a fast hepatic metabolism. An optimal design of PET quantitation approaches (e.g., bolus/infusion studies) necessitates the knowledge of factors that influence this metabolism. Metabolites of were separated by radio thin-layer chromatography. Metabolism in vivo, in pooled human liver microsomes and in recombinant human cytochrome isoenzyme preparations was studied. Dynamic PET studies using were performed on three controls and two patients, one treated with the antidepressant and inhibitor of cytochrome CYP1A2 fluvoxamine, the other suffering from liver cirrhosis. CPFPX is metabolized by cytochrome CYP1A2 with high selectivity [K {sub M}=1.1 {mu}M (95% confidence interval, or CI, 0.6-2.0 {mu}M) and V {sub max}=243 pmol min{sup -1} mg{sup -1} (95% CI, 112-373 pmol min{sup -1} mg{sup -1}) corresponding to 2.4 pmol min{sup -1} pmol{sup -1} cytochrome P-450]. This metabolism can competitively be inhibited by fluvoxamine with K {sub I}=68 nM (95% CI, 34-138 nM). At least eight compounds found in human plasma and in the CYP1A2 in vitro preparations have an identical migration pattern and account together for >90% and >80% of the respective metabolite yield. Metabolism was considerably delayed in the two patients. In conclusion, is metabolized by cytochrome CYP1A2. Its metabolism is therefore subdued to disease-related or xenobiotic-induced changes of CYP1A2 activity. The identification of the metabolic pathway of 1 allows to optimize image quantification in A{sub 1} adenosine receptor PET studies.

  10. Quantitative measurement of histamine H{sub 1} receptors in human brains by PET and [{sup 11}C]doxepin

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Hideki; Kimura, Yuichi E-mail: ukimura@ieee.org; Ishii, Kenji; Oda, Keiichi; Sasaki, Toru; Tashiro, Manabu; Yanai, Kazuhiko; Ishiwata, Kiichi

    2004-02-01

    The aim of this study is to establish a method for quantitative measurement of histamine H{sub 1} receptor (H1R) in human brain by PET and [{sup 11}C]doxepin ([{sup 11}C]DOX). The estimated parameters with a two-compartment model were stable for the initial values for parameter estimation but those with a three-compartment model were not. This finding suggests that the H1R measured by the [{sup 11}C]DOX and PET can be evaluated with a two-compartment model.

  11. Preclinical Safety Assessment of the 5-HT(2A) Receptor Agonist PET Radioligand [ (11)C]Cimbi-36

    DEFF Research Database (Denmark)

    Ettrup, Anders; Holm, Søren; Hansen, Martin;

    2013-01-01

    PURPOSE: [(11)C]Cimbi-36 was recently developed as an agonist radioligand for brain imaging of serotonin 2A receptors (5-HT(2A)) with positron emission tomography (PET). This may be used to quantify the high-affinity state of 5-HT(2A) receptors and may have the potential to quantify changes...... in cerebral 5-HT levels in vivo. We here investigated safety aspects related to clinical use of [(11)C]Cimbi-36, including radiation dosimetry and in vivo pharmacology. PROCEDURES: [(11)C]Cimbi-36 was injected in rats or pigs, and radiation dosimetry was examined by ex vivo dissection or with PET scanning......, respectively. Based on animal data, the Organ Level INternal Dose Assessment software was used to estimate extrapolated human dosimetry for [(11)C]Cimbi-36. The 5-HT(2A) receptor agonist actions of [(11)C]Cimbi-36 in vivo pharmacological effects in mice elicited by increasing doses of Cimbi-36 were assessed...

  12. Radiosynthesis and in vivo evaluation of novel radioligands for PET imaging of cerebral 5-HT7 receptors

    DEFF Research Database (Denmark)

    Hansen, Hanne D; Herth, Matthias M; Ettrup, Anders;

    2014-01-01

    The serotonin (5-hydroxytryptamine [5-ΗΤ]) 7 receptor (5-HT7R) is the most recently discovered 5-HT receptor, and its physiologic and possible pathophysiologic roles are not fully elucidated. So far, no suitable 5-HT7R PET radioligand is available, thus limiting the investigation of this receptor...... in the living brain. Here, we present the radiosynthesis and in vivo evaluation of Cimbi-712 (3-{4-[4-(4-methylphenyl)piperazine-1-yl]butyl}p-1,3-dihydro-2H-indol-2-one) and Cimbi-717 (3-{4-[4-(3-methoxyphenyl)piperazine-1-yl]butyl}-1,3-dihydro-2H-indol-2-one) as selective 5-HT7R PET radioligands in the pig...... brain. The 5-HT7R distribution in the postmortem pig brain is also assessed....

  13. EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2

    DEFF Research Database (Denmark)

    Van Laere, Koen; Varrone, Andrea; Booij, Jan

    2010-01-01

    The guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2...... receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, which will increase the impact of this technique in neurological practice.The present document is an update of the first guidelines for SPECT using D2 receptor ligands labelled with (123)I [1...

  14. PET imaging in multiple sclerosis

    NARCIS (Netherlands)

    Faria, Daniele de Paula; Copray, Sjef; Buchpiguel, Carlos; Dierckx, Rudi; de Vries, Erik

    2014-01-01

    Positron emission tomography (PET) is a non-invasive technique for quantitative imaging of biochemical and physiological processes in animals and humans. PET uses probes labeled with a radioactive isotope, called PET tracers, which can bind to or be converted by a specific biological target and thus

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

    Science.gov (United States)

    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

    2014-11-01

    (11)C-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 (11)C-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 (11)C-LY2795050 distribution volume (VT) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for (11)C-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 (11)C-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 (11)C-LY2795050 to image and quantify KOR in humans.

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

    Science.gov (United States)

    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

  17. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schieferstein, Hanno

    2013-07-01

    Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new {sup 18}F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed {sup 18}F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable {sup 18}F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for {sup 18}F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K is contained in 2.2.2]{sup +}/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved. The promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were

  18. PET application in psychiatry and psychopharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-07-01

    accumulation was observed in the thalamus and striatum. The thalamus to cerebellum ratio was about 2 at 90 min after the injection of the tracer. Pretreatment with 50 mg of clomipramine resulted in 40-50% occupancy of the serotonin transporter in the thalamus. Another important potential regarding the use of PET in the psychiatric field is the investigation of the pathophysiology of brain disease and normal brain functions from in vivo neurochemistry. Brain dopamine system plays an important role in several neuropsychiatric disorders especially schizophrenia. Dopamine receptors are classified in five different classes; currently D{sub 1} and D{sub 2} receptors can be visualized with PET. Postmortem investigations have demonstrated that in the cortical region, the density of dopamine D{sub 1} receptors is approximately 10-fold that of D{sub 2} receptors. The hypothesis has been proposed that schizophrenic patients have reduced cortical dopamine activity together with increased subcortical dopamine activity. To examine both the cortical and subcortical dopamine D{sub 1} receptors in schizophrenic patients, [{sup 11}C] SCH23390 was employed in a PET study. Eighteen healthy male subjects (27.7{+-}5.6 years) and 17 male schizophrenic patients (27.4{+-}5.9 years) were included. Ten patients were neuroleptic naive and seven patients were drug free. The binding potential was obtained in the several brain regions using the cerebellum as the reference. In the striatum, there were no significant differences between the patients and normal controls. But the binding potentials in the prefrontal cortex were significantly lower in the schizophrenic patients. The binding potentials in the prefrontal cortex were negatively correlated with the BPRS negative symptom subscore. PET has many advantages over other non-invasive techniques, and PET can show us different phenomena which we can not observe with in vitro techniques. Progress in PET study will provide a whole new viewpoint for psychiatric

  19. GABAA receptor subtypes in the mouse brain: Regional mapping and diazepam receptor occupancy by in vivo [(18)F]flumazenil PET.

    Science.gov (United States)

    Müller Herde, Adrienne; Benke, Dietmar; Ralvenius, William T; Mu, Linjing; Schibli, Roger; Zeilhofer, Hanns Ulrich; Krämer, Stefanie D

    2017-02-10

    Classical benzodiazepines, which are widely used as sedatives, anxiolytics and anticonvulsants, exert their therapeutic effects through interactions with heteropentameric GABAA receptors composed of two α, two β and one γ2 subunit. Their high affinity binding site is located at the interface between the γ2 and the adjacent α subunit. The α-subunit gene family consists of six members and receptors can be homomeric or mixed with respect to the α-subunits. Previous work has suggested that benzodiazepine binding site ligands with selectivity for individual GABAA receptor subtypes, as defined by the benzodiazepine-binding α subunit, may have fewer side effects and may even be effective in diseases, such as schizophrenia, autism or chronic pain, that do not respond well to classical benzodiazepines. The distributions of the individual α subunits across the CNS have been extensively characterized. However, as GABAA receptors may contain two different α subunits, the distribution of the subunits does not necessarily reflect the distribution of receptor subtypes with respect to benzodiazepine pharmacology. In the present study, we have used in vivo [(18)F]flumazenil PET and in vitro [(3)H]flumazenil autoradiography in combination with GABAA receptor point-mutated mice to characterize the distribution of the two most prevalent GABAA receptor subtypes (α1 and α2) throughout the mouse brain. The results were in agreement with published in vitro data. High levels of α2-containing receptors were found in brain regions of the neuronal network of anxiety. The α1/α2 subunit combinations were predictable from the individual subunit levels. In additional experiments, we explored in vivo [(18)F]flumazenil PET to determine the degree of receptor occupancy at GABAA receptor subtypes following oral administration of diazepam. The dose to occupy 50% of sensitive receptors, independent of the receptor subtype(s), was 1-2mg/kg, in agreement with published data from ex vivo

  20. {sup 68}Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour

    Energy Technology Data Exchange (ETDEWEB)

    Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Guggenberg, Elisabeth von; Kendler, Dorota; Scarpa, Lorenza; Di Santo, Gianpaolo; Roig, Llanos Geraldo; Maffey-Steffan, Johanna; Virgolini, Irene Johanna [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Fritz, Josef [Medical University Innsbruck, Department of Medical Statistics, Informatics and Health Economics, Innsbruck (Austria); Horninger, Wolfgang [Medical University Innsbruck, Department of Urology, Innsbruck (Austria)

    2017-06-15

    Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by {sup 68}Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of {sup 68}Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related {sup 68}Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for {sup 68}Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUV{sub max}). The SUV{sub max} of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUV{sub max} of the primary tumour was assessed in relation to both PSA level and GS. Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUV{sub max}: 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower {sup 68}Ga-PSMA-11 uptake, with median SUV{sub max} of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUV{sub max}: 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUV{sub max}: 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUV{sub max}: 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUV{sub max}: 11.6). The GS and PSA level correlated with

  1. [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users.

    Science.gov (United States)

    Ceccarini, Jenny; Kuepper, Rebecca; Kemels, Dieter; van Os, Jim; Henquet, Cécile; Van Laere, Koen

    2015-03-01

    Δ(9) -Tetrahydrocannabinol, the main psychoactive component of cannabis, exerts its central effects through activation of the cerebral type 1 cannabinoid (CB1 ) receptor. Pre-clinical studies have provided evidence that chronic cannabis exposure is linked to decreased CB1 receptor expression and this is thought to be a component underlying drug tolerance and dependence. In this study, we make first use of the selective high-affinity positron emission tomography (PET) ligand [(18) F]MK-9470 to obtain in vivo measurements of cerebral CB1 receptor availability in 10 chronic cannabis users (age = 26.0 ± 4.1 years). Each patient underwent [(18) F]MK-9470 PET within the first week following the last cannabis consumption. A population of 10 age-matched healthy subjects (age = 23.0 ± 2.9 years) was used as control group. Parametric modified standardized uptake value images, reflecting CB1 receptor availability, were calculated. Statistical parametric mapping and volume-of-interest (VOI) analyses of CB1 receptor availability were performed. Compared with controls, cannabis users showed a global decrease in CB1 receptor availability (-11.7 percent). VOI-based analysis demonstrated that the CB1 receptor decrease was significant in the temporal lobe (-12.7 percent), anterior (-12.6 percent) and posterior cingulate cortex (-13.5 percent) and nucleus accumbens (-11.2 percent). Voxel-based analysis confirmed this decrease and regional pattern in CB1 receptor availability in cannabis users. These findings revealed that chronic cannabis use may alter specific regional CB1 receptor expression through neuroadaptive changes in CB1 receptor availability, opening the way for the examination of specific CB1 -cannabis addiction interactions which may predict future cannabis-related treatment outcome.

  2. Muscarinic Receptor Occupancy and Cognitive Impairment: A PET Study with [11C](+)3-MPB and Scopolamine in Conscious Monkeys

    OpenAIRE

    Yamamoto, Shigeyuki; Nishiyama, Shingo; Kawamata, Masahiro; Ohba, Hiroyuki; Wakuda, Tomoyasu; Takei, Nori; Tsukada, Hideo; Domino, Edward F.

    2011-01-01

    The muscarinic cholinergic receptor (mAChR) antagonist scopolamine was used to induce transient cognitive impairment in monkeys trained in a delayed matching to sample task. The temporal relationship between the occupancy level of central mAChRs and cognitive impairment was determined. Three conscious monkeys (Macaca mulatta) were subjected to positron emission tomography (PET) scans with the mAChR radioligand N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB). The scan sequence was pre-, 2,...

  3. Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET

    Science.gov (United States)

    Lanzenberger, R; Baldinger, P; Hahn, A; Ungersboeck, J; Mitterhauser, M; Winkler, D; Micskei, Z; Stein, P; Karanikas, G; Wadsak, W; Kasper, S; Frey, R

    2013-01-01

    Electroconvulsive therapy (ECT) is a potent therapy in severe treatment-refractory depression. Although commonly applied in psychiatric clinical routine since decades, the exact neurobiological mechanism regarding its efficacy remains unclear. Results from preclinical and clinical studies emphasize a crucial involvement of the serotonin-1A receptor (5-HT1A) in the mode of action of antidepressant treatment. This includes associations between treatment response and changes in 5-HT1A function and density by antidepressants. Further, alterations of the 5-HT1A receptor are consistently reported in depression. To elucidate the effect of ECT on 5-HT1A receptor binding, 12 subjects with severe treatment-resistant major depression underwent three positron emission tomography (PET) measurements using the highly selective radioligand [carbonyl-11C]WAY100635, twice before (test–retest variability) and once after 10.08±2.35 ECT sessions. Ten patients (∼83%) were responders to ECT. The voxel-wise comparison of the 5-HT1A receptor binding (BPND) before and after ECT revealed a widespread reduction in cortical and subcortical regions (P<0.05 corrected), except for the occipital cortex and the cerebellum. Strongest reductions were found in regions consistently reported to be altered in major depression and involved in emotion regulation, such as the subgenual part of the anterior cingulate cortex (−27.5%), the orbitofrontal cortex (−30.1%), the amygdala (−31.8%), the hippocampus (−30.6%) and the insula (−28.9%). No significant change was found in the raphe nuclei. There was no significant difference in receptor binding in any region comparing the first two PET scans conducted before ECT. This PET study proposes a global involvement of the postsynaptic 5-HT1A receptor binding in the effect of ECT. PMID:22751491

  4. Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    Li Zizhong [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Gifford, Andrew [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Liu Qian [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Ding Yushin [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Makriyannis, Alexandros [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Gatley, S. John [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States)]. E-mail: s.gatley@neu.edu

    2005-05-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB{sub 1} receptors that respond to {delta}{sup 9}-tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB{sub 1} receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[{sup 18}F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[{sup 18}F]fluoroaniline. The labeled precursor was synthesized from 1-[{sup 18}F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/{mu}mol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB{sub 1} receptors, absolute uptake at <0.003% injected radioactivity per cubic centimeter was lower than the previously reported uptake of the radioiodinated pyrazole AM281. Conclusions: The relatively poor brain uptake of AM5144 and other pyrazole CB{sub 1} receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB{sub 1} receptor that may require very lipophilic ligands.

  5. Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from {sup 68}Ga-RGD PET/CT and {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai-Jeon [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Ewha Womans University School of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Chun, In Kook [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kangwon National University Hospital, Department of Nuclear Medicine, Chuncheon, Kangwon-Do (Korea, Republic of); Cho, Nariya [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Im, Seock-Ah [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Jeong, Sunjoo [Dankook University, Department of Molecular Biology, Yongin (Korea, Republic of); Lee, Song [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Jung, Kyeong Cheon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Lee, Yun-Sang [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul (Korea, Republic of); Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2014-08-15

    Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes. In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6 ± 7.5 years old). {sup 68}Ga-Labeled arginine-glycine-aspartic acid (RGD) and {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}) from RGD PET/CT and SUV{sub max} and SUV{sub avg} from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered. Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88 ± 8.73 vs 10.48 ± 6.01, p = 0.02 for SUV{sub max}; 9.40 ± 5.19 vs 5.92 ± 4.09, p = 0.02 for SUV{sub avg}) and the PR-negative group (8.37 ± 4.94 vs 4.79 ± 3.93, p = 0.03 for SUV{sub avg}). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42 ± 0.59 vs 2.90 ± 0.75, p = 0.04 for SUV{sub max}; 1.60 ± 0.38 vs 1.95 ± 0.53, p = 0.04 for SUV{sub avg}) and showed a significant positive correlation with the HER2/CEP17 ratio (r = 0.38, p = 0.03 for SUV{sub max} and r = 0.46, p < 0.01 for SUV{sub avg}). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER

  6. Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI.

    Science.gov (United States)

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

    2016-04-01

    This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization.

  7. PET and PET/CT in endocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Dudczak, Robert [Department of Nuclear Medicine, Medical University of Vienna (Austria)], E-mail: robert.dudczak@meduniwien.ac.at; Traub-Weidinger, Tatjana [Department of Nuclear Medicine, Medical University of Vienna (Austria)

    2010-03-15

    Functional information provided by PET tracers together with the superior image quality and the better data quantification by PET technology had a changing effect on the significance of nuclear medicine in medical issues. Recently introduced hybrid PET/CT systems together with the introduction of novel PET radiopharmaceuticals have contributed to the fact that nuclear medicine has become a growing diagnostic impact on endocrinology. In this review imaging strategies, different radiopharmaceuticals including the basic mechanism of their cell uptake, and the diagnostic value of PET and PET/CT in endocrine tumours except differentiated thyroid carcinomas will be discussed.

  8. [C-11]FMAU and [F-18]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections

    NARCIS (Netherlands)

    de Vries, EFJ; van Waarde, A; Harmsen, MC; Mulder, NH; Vaalburg, W; Hospers, GAP

    [C-11]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ([C-11]FMAU) and [F-18]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([F-18]FHPG), radiolabeled representatives of two classes of antiviral agents, were evaluated as tracers for measuring herpes simplex virus thymidine kinase (HSV-tk)

  9. Use of micro-positron emission tomography with 18F-fallypride to measure the levels of dopamine receptor-D2 and 18F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 rats

    Science.gov (United States)

    Li, Ping; Gui, Songbai; Cao, Lei; Gao, Hua; Bai, Jiwei; Li, Chuzhong; Zhang, Yazhuo

    2016-01-01

    Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with 18F-fallypride and 18F-fluorodeoxyglucose (18F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17β-estradiol for 8 weeks. The growth of tumors was monitored by the small-animal magnetic resonance imaging and micro-PET. A series of molecular biological experiments were also performed 4 and 6 weeks after pump implantation. The micro-PET molecular imaging with 18F-fallypride revealed a decreased expression of DRD2 in F344 rat prolactinoma models, but the micro-PET molecular imaging with 18F-FDG presented an increased uptake in the prolactinoma compared with the pituitary gland. A decreasing trend of levels of DRD2 in F344 rat prolactinoma models was also detected by molecular biological experiments. From this, we can conclude that micro-PET with 18F-fallypride and 18F-FDG can be used to assess tumorigenesis of the prolactinomas in vivo and molecular imaging detection of DRD2 level in prolactinoma may be an indication of treatment effect in the animal experiment. PMID:27103832

  10. In vivo evaluation in rodents of [{sup 123}I]-3-I-CO as a potential SPECT tracer for the serotonin 5-HT{sub 2A} receptor

    Energy Technology Data Exchange (ETDEWEB)

    Blanckaert, Peter B.M. [Laboratory for Radiopharmacy, Ghent University, B-9000 Ghent (Belgium)], E-mail: peter.blanckaert@hotmail.com; Burvenich, Ingrid; Wyffels, Leonie; Bruyne, Sylvie de; Moerman, Lieselotte; Vos, Filip de [Laboratory for Radiopharmacy, Ghent University, B-9000 Ghent (Belgium)

    2008-11-15

    Introduction: [{sup 123}I]-(4-fluorophenyl)[1-(3-iodophenethyl)piperidin-4-yl]methanone ([{sup 123}I]-3-I-CO) is a potential single photon emission computed tomography tracer with high affinity for the serotonin 5-HT{sub 2A} receptor (K{sub i}=0.51 nM) and good selectivity over other receptor (sub)types. To determine the potential of the radioligand as a 5-HT{sub 2A} tracer, regional brain biodistribution and displacement studies will be performed. The influence of P-glycoprotein blocking on the brain uptake of the radioligand will also be investigated. Methods: A regional brain biodistribution study and a displacement study with ketanserin were performed with [{sup 123}I]-3-I-CO. Also, the influence of cyclosporin A (50 mg/kg) on the brain distribution of the radioligand was investigated. For the displacement study, ketanserin (1 mg/kg) was administered 30 min after injection of [{sup 123}I]-3-I-CO. Results: The initial brain uptake of [{sup 123}I]-3-I-CO was quite high, but a rapid wash-out of radioactivity was observed. Cortex-to-cerebellum binding index ratios were low (1.1 - 1.7), indicating considerable aspecific binding and a low specific 'signal' of the radioligand. Tracer uptake was reduced to the levels in cerebellum (a 60% reduction) after ketanserin displacement. Administration of cyclosporin A resulted in a doubling of the brain radioactivity concentration. Conclusions: Although [{sup 123}I]-3-I-CO showed adequate brain uptake and could be displaced by ketanserin, high aspecific binding to brain tissue was responsible for very low cortex-to-cerebellum binding index ratios, possibly limiting the potential of the radioligand as a serotonin 5-HT{sub 2A} receptor tracer. We also demonstrated that [{sup 123}I]-3-I-CO is probably a weak substrate for the P-glycoprotein efflux transporter.

  11. Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma

    DEFF Research Database (Denmark)

    Persson, Morten; Nedergaard, Mette K; Brandt-Larsen, Malene

    2016-01-01

    an orthotopic xenograft model of glioblastoma. Tumor growth was monitored using bioluminescence imaging. Five to six weeks after inoculation, all mice were scanned with small-animal PET/CT using two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and, for comparison, O-(2-(18)F...

  12. Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor

    Directory of Open Access Journals (Sweden)

    Linjing Mu

    2014-03-01

    Full Text Available Cannabinoid receptor subtype 2 (CB2 has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted.

  13. Immediate and Persistent Effects of Salvinorin A on the Kappa Opioid Receptor in Rodents, Monitored In Vivo with PET.

    Science.gov (United States)

    Placzek, Michael S; Van de Bittner, Genevieve C; Wey, Hsiao-Ying; Lukas, Scott E; Hooker, Jacob M

    2015-12-01

    Monitoring changes in opioid receptor binding with positron emission tomography (PET) could lead to a better understanding of tolerance and addiction because altered opioid receptor dynamics following agonist exposure has been linked to tolerance mechanisms. We have studied changes in kappa opioid receptor (KOR) binding availability in vivo with PET following kappa opioid agonist administration. Male Sprague-Dawley rats (n=31) were anesthetized and treated with the (KOR) agonist salvinorin A (0.01-1.8 mg/kg, i.v.) before administration of the KOR selective radiotracer [(11)C]GR103545. When salvinorin A was administered 1 min prior to injection of the radiotracer, [(11)C]GR103545 binding potential (BPND) was decreased in a dose-dependent manner, indicating receptor binding competition. In addition, the unique pharmacokinetics of salvinorin A (half-life ~8 min in non-human primates) allowed us to study the residual impact on KOR after the drug had eliminated from the brain. Salvinorin A was administered up to 5 h prior to [(11)C]GR103545, and the changes in BPND were compared with baseline, 2.5 h, 1 h, and 1 min pretreatment times. At lower doses (0.18 mg/kg and 0.32 mg/kg) we observed no prolonged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding (BPND decreased by 40-49%) which persisted up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain. These data point towards an agonist-induced adaptive response by KOR, the dynamics of which have not been previously studied in vivo with PET.

  14. Diphtheria toxin treatment of Pet-1-Cre floxed diphtheria toxin receptor mice disrupts thermoregulation without affecting respiratory chemoreception

    Science.gov (United States)

    Cerpa, Verónica; Gonzalez, Amalia; Richerson, George B.

    2014-01-01

    In genetically-modified Lmx1bf/f/p mice, selective deletion of LMX1B in Pet-1 expressing cells leads to failure of embryonic development of serotonin (5-HT) neurons. As adults, these mice have a decreased hypercapnic ventilatory response and abnormal thermoregulation. This mouse model has been valuable in defining the normal role of 5-HT neurons, but it is possible that developmental compensation reduces the severity of observed deficits. Here we studied mice genetically modified to express diphtheria toxin receptors (DTR) on Pet-1 expressing neurons (Pet-1-Cre/Floxed DTR or Pet1/DTR mice). These mice developed with a normal complement of 5-HT neurons. As adults, systemic treatment with 2 – 35 μg diphtheria toxin (DT) reduced the number of tryptophan hydroxylase immunoreactive (TpOH-ir) neurons in the raphe nuclei and ventrolateral medulla by 80%. There were no effects of DT on baseline ventilation (VE) or the ventilatory response to hypercapnia or hypoxia. At an ambient temperature (TA) of 24°C, all Pet1/DTR mice dropped their body temperature (TB) below 35°C after DT treatment, but the latency was shorter in males than females (3.0 ± 0.37 vs 4.57 ± 0.29 days, respectively; p thermoregulation, in males more than females. In comparison to models with deficient embryonic development of 5-HT neurons, acute deletion of 5-HT neurons in adults leads to a greater defect in thermoregulation, suggesting that significant developmental compensation can occur. PMID:25171790

  15. Cerebral 5-HT release correlates with [11C]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain

    DEFF Research Database (Denmark)

    Jørgensen, Louise M; Weikop, Pia; Villadsen, Jonas;

    2017-01-01

    Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [(11)C]Cimbi-36, for its...... sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [(11)C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular...... 5-HT levels with microdialysis and [(11)C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5...

  16. Tracer accumulation in radiation necrosis of the brain after thallium-201 SPECT and [{sup 11}C]methionine PET. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, Yoshiyasu; Yamanaka, Kazuhiro; Oda, Junro [Osaka City General Hospital (Japan); Tsuyuguchi, Naohiro; Ochi, Hironobu

    2001-08-01

    A 69-year-old woman was treated by local irradiation for a malignant lymphoma of the left parotid gland. Three years after the radiation therapy, magnetic resonance imaging revealed heterogeneously enhanced masses in the left temporal lobe and left cerebellum. Thallium-201 chloride single photon emission computed tomography (Tl-SPECT) revealed high uptake and [{sup 11}C]methionine positron emission tomography (Met-PET) revealed moderate uptake in both masses. Stereotactic biopsy was performed. The histological diagnosis was radiation necrosis. She was treated with steroids. Neurosurgeons should be aware of the difficulty in differentiating tumor recurrence from radiation necrosis even with Tl-SPECT and Met-PET, and the importance of obtaining a histological diagnosis for radiation necrosis. (author)

  17. Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.

    Science.gov (United States)

    Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H

    2016-10-01

    To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation.

  18. Non-FDG PET imaging of brain tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Zemin; GUAN Yihui; ZUO Chuantao; ZHANG Zhengwei; XUE Fangping; LIN Xiangtong

    2007-01-01

    Due to relatively high uptake of glucose in the brain cortex, the use of FDG PET imaging is greatly limited in brain tumor imaging, especially for low-grade gliomas and some metastatic tumours. More and more tracers with higher specificity were developed lately for brain tumor imaging. There are 3 main types of non-FDG PET tracers:amino acid tracers, choline tracers and nucleic acid tracers. These tracers are now widely applied in many aspects of brain tumor imaging. This article summarized the general use of non-FDG PET in different aspects of brain tumor imaging.

  19. PET imaging of cannabinoid type 2 receptors with [(11)C]A-836339 did not evidence changes following neuroinflammation in rats.

    Science.gov (United States)

    Pottier, Geraldine; Gómez-Vallejo, Vanessa; Padro, Daniel; Boisgard, Raphaël; Dollé, Frédéric; Llop, Jordi; Winkeler, Alexandra; Martín, Abraham

    2017-03-01

    Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using positron emission tomography (PET) imaging. In this work, we report the evaluation of the in vivo expression of CB2R with [(11)C]A-836339 PET after cerebral ischemia and in two rat models of neuroinflammation, first by intrastriatal LPS and then by AMPA injection. PET images and in vitro autoradiography showed a lack of specific [(11)C]A-836339 uptake in these animal models demonstrating the limitation of this radiotracer to image CB2 receptor under neuroinflammatory conditions. Further, using immunohistochemistry, the CB2 receptor displayed a modest expression increase after cerebral ischemia, LPS and AMPA models. Finally, [(18)F]DPA-714-PET and immunohistochemistry demonstrated decreased neuroinflammation by a selective CB2R agonist, JWH133. Taken together, these findings suggest that [(11)C]A-836339 is not a suitable radiotracer to monitor in vivo CB2R expression by using PET imaging. Future studies will have to investigate alternative radiotracers that could provide an accurate binding to CB2 receptors following brain inflammation.

  20. Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with 68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy

    OpenAIRE

    Wolfgang Luboldt; Holger Hartmann; Bärbel Wiedemann; Klaus Zöphel; Hans-Joachim Luboldt

    2010-01-01

    The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) during the course of somatostatin receptor radionuclide therapy (SRRT). In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA) and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax) of normal liver and hepatic metastases we...

  1. Radiosynthesis of (S)-[(18)F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Sarasamkan, Jiradanai; Fischer, Steffen; Deuther-Conrad, Winnie; Ludwig, Friedrich-Alexander; Scheunemann, Matthias; Arunrungvichian, Kuntarat; Vajragupta, Opa; Brust, Peter

    2017-03-18

    Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a [(18)F]-labelled analog of the highly affine and selective α3β4 ligand (S)-3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)quinuclidine ((S)-T1). (S)-[(18)F]T1 was synthesized from ethynyl-4-[(18)F]fluorobenzene ([(18)F]5) and (S)-azidoquinuclidine by click reaction. After a synthesis time of 130min (S)-[(18)F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of (S)-[(18)F]T1 in mice at 30min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of (S)-[(18)F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001. These findings make (S)-[(18)F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET.

  2. Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot.

    Science.gov (United States)

    Veronese, Mattia; Zanotti-Fregonara, Paolo; Rizzo, Gaia; Bertoldo, Alessandra; Innis, Robert B; Turkheimer, Federico E

    2016-04-15

    PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i

  3. Clinical application of PET

    Energy Technology Data Exchange (ETDEWEB)

    Lomena, Francisco [Hospital Clinico Villarroel, Barcelona (Spain). Nuclear Medicine]. E-mail: flomena@clinic.ub.es; Soler, Marina [CETIR Grup Medic. Esplkugues de Llobregat, Barcelona (Spain). PET Unit

    2005-10-15

    Positron emission tomography (PET) is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI), which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluorodeoxyglucose-F 18 (FDG) PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.(author)

  4. VII. Boettstein Colloquium: PET-Radiopharmaceuticals at PSI: achievement and future prospects

    Energy Technology Data Exchange (ETDEWEB)

    Schubiger, P.A.; Beer, H.F.; Blaeuenstein, P.; Leenders, K.E.

    1993-12-31

    The three sessions of the 1993 Boettstein colloquium dealt with the following topics: - PET-radiopharmaceuticals, - PET-scanning: significance of tracer uptake, - clinical options using PET. 22 papers were presented. figs., refs.

  5. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer

    OpenAIRE

    Matthias Eder; Oliver Neels; Miriam Müller; Ulrike Bauder-Wüst; Yvonne Remde; Martin Schäfer; Ute Hennrich; Michael Eisenhut; Ali Afshar-Oromieh; Uwe Haberkorn; Klaus Kopka

    2014-01-01

    The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical cha...

  6. Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic {beta}-cell mass

    Energy Technology Data Exchange (ETDEWEB)

    Cline, Gary W., E-mail: gary.cline@yale.edu [Yale University School of Medicine (United States); Zhao, Xiaojian [Yale University School of Medicine (United States); Jakowski, Amy B.; Soeller, Walter C.; Treadway, Judith L. [Pfizer Global Research and Development, Pfizer Inc., Groton CT (United States)

    2011-09-02

    Highlights: {yields} We screened G-protein coupled receptors for imaging pancreatic. {yields} Database mining and immunohistochemistry identified GPCRs enriched in {beta}-cells. {yields} In vitro and in vivo assays were used to determine exocrine vs endocrine specificity. {yields} GPCR candidates for imaging of {beta}-cell mass are Prokineticin-1R, mGluR5, and GLP-1R. -- Abstract: A critical unmet need exists for methods to quantitatively measure endogenous pancreatic {beta}-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity to islet {beta}-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 {approx} GLP-1R > mGluR5. Favorable islet selectivity and biodistribution

  7. Molecular imaging of neuroendocrine tumors using {sup 68}Ga-labeled peptides (Somatostatin receptor PET/CT); Molekulare Bildgebung neuroendokriner Tumoren mit {sup 68}Ga-markierten Peptiden (Somatostatinrezeptor-PET/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R.P.; Prasad, V. [Zentralklinik Bad Berka GmbH (Germany). Klinik fuer Nuklearmedizin/PET-Zentrum; Hoersch, D. [Zentralklinik Bad Berka GmbH (Germany). Klinik fuer Innere Medizin, Gastroenterologie, Onkologie, Endokrionologie

    2009-06-15

    Receptor PET/CT using {sup 68}Ga-labeled somatostatin analogues (DOTA-NOC, DOTA-TOC or DOTA-TATE) enables the highly sensitive molecular imaging of neuroendocrine tumors (NETs) based on the expression of somatostatin receptors and even the detection of receptor subtypes. Our experience after more than 3000 studies shows that receptor PET/CT has a significantly higher tumor detection rate than conventional scintigraphy (even in SPECT/CT technique), and that tumor lesions can be very accurately localized. By calculating standardized uptake values (SUV) - which are reproducible and investigator-independent - patients can be selected for peptide receptor radiotherapy and also the course after therapy can be controlled. Receptor-PET/CT is the most sensitive imaging modality for the detection of unknown primary tumors (CUP syndrome), which is especially true for the detection of neuroendocrine tumors of the pancreas and small bowel; whole-body staging (''one stop shop'') as well as restaging and selection of patients for peptide receptor radiotherapy can be performed using a patient-friendly procedure (examination finished within one hour) exposing the patient to less radiation than whole-body CT scanning. The {sup 68}Ge/{sup 68}Ga generator has proved very reliable over the years - even in a hospital environment. The effective costs for {sup 68}Ga labeled somatostatin analogues might be less than for scintigraphic agents, provided a certain number of studies per year are performed. The development of new tumor-specific peptides as well as of other DOTA- or NOTA-coupled radiopharmaceuticals opens a new avenue into the future: finally, the {sup 68}Ga generator could play a similar important role for PET/CT as did the {sup 99m}Tc-Generator for conventional gamma camera imaging over the last decades. (orig.)

  8. Angiogenesis PET Tracer Uptake (68Ga-NODAGA-E[(cRGDyK)]₂) in Induced Myocardial Infarction in Minipigs

    DEFF Research Database (Denmark)

    Rasmussen, Thomas; Follin, Bjarke; Kastrup, Jens;

    2016-01-01

    Angiogenesis is part of the healing process following an ischemic injury and is vital for the post-ischemic repair of the myocardium. Therefore, it is of particular interest to be able to noninvasively monitor angiogenesis. This might, not only permit risk stratification of patients following myo...... RGD-PET in minipigs hearts, which resemble human hearts. The perspectives are very intriguing and might permit the evaluation of new treatment strategies targeted towards increasing the angiogenetic response, e.g., stem-cell treatment....... myocardial infarction, but could also facilitate development and improvement of new therapies directed towards stimulation of the angiogenic response. During angiogenesis endothelial cells must adhere to one another to form new microvessels. αvβ₃ integrin has been found to be highly expressed in activated...... endothelial cells and has been identified as a critical modulator of angiogenesis. (68)Ga-NODAGA-E[c(RGDyK)]₂ (RGD) has recently been developed by us as an angiogenesis positron-emission-tomography (PET) ligand targeted towards αvβ₃ integrin. In the present study, we induced myocardial infarction in Göttingen...

  9. Characterization of [(11)C]Cimbi-36 as an agonist PET radioligand for the 5-HT(2A) and 5-HT(2C) receptors in the nonhuman primate brain

    DEFF Research Database (Denmark)

    Finnema, Sjoerd J; Stepanov, Vladimir; Ettrup, Anders

    2014-01-01

    a more meaningful assessment of available receptors than antagonist radioligands. In the current study we characterized [(11)C]Cimbi-36 receptor binding in the primate brain. On five experimental days, a total of 14 PET measurements were conducted in three female rhesus monkeys. On each day, PET...... agonist radioligand suitable for examination of 5-HT2A receptors in the cortical regions and of 5-HT2C receptors in the choroid plexus of the primate brain....

  10. PET/MR in oncology

    DEFF Research Database (Denmark)

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin

    2012-01-01

    of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number...... be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new...

  11. PET/MR in oncology

    DEFF Research Database (Denmark)

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin

    2012-01-01

    of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number...... be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new...

  12. Positron-emissionstomografisk kortlaegning af den levende menneskehjernes receptorer

    DEFF Research Database (Denmark)

    Gjedde, A

    2001-01-01

    tracers are used in diseases of the basal ganglia, whereas serotonin, benzodiazepine, and opiate tracers are used in lesions of the cerebral cortex. PET has revealed loss of dopaminergic terminals and dopamine synthetic capacity in Parkinson's disease, MPTP intoxication, and Lesch-Nyhan's syndrome...... receptors in Alzheimer's disease, and benzodiazepine and opiate receptors in stroke, epilepsy, and Huntington's chorea; altered opiate receptors in chronic pain and drug abuse; and release of opiates in analgesia; but changes in serotonin synthesis, transport, and binding in affective or psychotic disorders...

  13. Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Göttingen minipig

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Lind, Nanna M; Gillings, Nic;

    2009-01-01

    This study investigates 5-hydroxytryptamine 4 (5-HT(4)) receptor binding in the minipig brain with positron emission tomography (PET), tissue homogenate-binding assays, and autoradiography in vitro. The cerebral uptake and binding of the novel 5-HT(4) receptor radioligand [(11)C]SB207145 in vivo...... autoradiographic 5-HT(4) receptor distribution resembles the human 5-HT(4) receptor distribution with the highest binding in the striatum and no detectable binding in the cerebellum. We found that in the minipig brain [(11)C]SB207145 follows one-tissue compartment kinetics, and the simplified reference tissue...... model provides stable and precise estimates of the binding potential in all regions. The binding potentials calculated for striatum, midbrain, and cortex from the PET data were highly correlated with 5-HT(4) receptor concentrations determined in brain homogenates from the same regions, except...

  14. Initial investigation of three selective and potent small molecule oxytocin receptor PET ligands in New World monkeys.

    Science.gov (United States)

    Smith, Aaron L; Freeman, Sara M; Barnhart, Todd E; Abbott, David H; Ahlers, Elizabeth O; Kukis, David L; Bales, Karen L; Goodman, Mark M; Young, Larry J

    2016-07-15

    The neuropeptide oxytocin is part of a neuroendocrine system that has physiological effects ranging from ensuring uterine myometrial contractions at parturition and post-partum mammary gland milk ejection to the modulation of neural control of social relationships. This initial study was performed to investigate the potential use of positron emission tomography (PET) for localizing oxytocin receptors in two New World primates. Three biomarkers for PET (1-3) that are known to have high affinity and selectivity for the human oxytocin receptor were investigated in the common marmoset (Callithrix jacchus) via PET imaging. Brain penetration, and uptake in the salivary gland area were both observed with biomarkers 2 and 3. No brain penetration was observed with 1, but uptake was observed more specifically in several peripheral endocrine glands compared to 2 or 3. Biomarker 2, which displayed the best brain penetration of the three biomarkers in the marmoset, was then investigated in the monogamous coppery titi monkey (Callicebus cupreus) in a brain scan and a limited full body scan. No significant brain penetration of 2 was observed in the titi monkey, but significant uptake was observed in various locations throughout the periphery. Metabolism of 2 was suspected to have been significant based upon HPLC analysis of blood draws, but parent compound was still present near the end of the scan. Follow-up investigations will focus on next generation biomarkers bearing improved binding characteristics and brain penetrability as well as investigating tissue in regions where biomarker uptake was observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

    Energy Technology Data Exchange (ETDEWEB)

    Vandeputte, Caroline; Casteels, Cindy; Koole, Michel; Gerits, Anneleen [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); Struys, Tom [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Veghel, Daisy van; Evens, Nele; Bormans, Guy [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Laboratory of Radiopharmacy, Leuven (Belgium); Dresselaers, Tom; Himmelreich, Uwe [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Lambrichts, Ivo [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); Laere, Koen van [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); UZ Leuven, Division of Nuclear Medicine, Leuven (Belgium)

    2012-11-15

    Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB{sub 1} and CB{sub 2}) have been suggested. The purpose of this study was to evaluate CB{sub 1} and CB{sub 2} receptor binding over time in vivo in a rat photothrombotic stroke model using PET. CB{sub 1} and CB{sub 2} microPET imaging was performed at regular time-points up to 2 weeks after stroke using [{sup 18}F]MK-9470 and [{sup 11}C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB{sub 1} and CB{sub 2}. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68). [{sup 18}F]MK-9470 PET showed a strong increase in CB{sub 1} binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB{sub 1} immunohistochemical staining. [{sup 11}C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB{sub 2} revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB{sub 1} {sup +} and CB{sub 2} {sup +} cells showed minor immunoreactivity for CD68. Time-dependent and regionally strongly increased CB{sub 1}, but not CB{sub 2}, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB{sub 1} signalling as the role of CB{sub 2} seems minor in the acute and subacute phases of stroke. (orig.)

  16. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [{sup 18}F]ICF01006, a highly promising melanoma PET tracer

    Energy Technology Data Exchange (ETDEWEB)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Cachin, Florent [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Centre Jean Perrin, Clermont-Ferrand (France); Bonnet, Mathilde [U1071 INSERM-Universite d' Auvergne, M2USH, Clermont-Ferrand (France); Askienazy, Serge [CYCLOPHARMA Laboratories, Biopole Clermont-Limagne, Saint-Beauzire (France); Dolle, Frederic [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France)

    2012-09-15

    Here, we report a new and rapid radiosynthesis of {sup 18}F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([{sup 18}F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [{sup 18}F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [{sup 18}F]ICF01006 were evaluated at different stages of tumoural growth and compared to {sup 18}F-fluorodeoxyglucose ([{sup 18}F]FDG). The fully automated radiosynthesis of [{sup 18}F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/{mu}mol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [{sup 18}F]ICF01006 tumoural uptake of 1.64 {+-} 0.57, 3.40 {+-} 1.47 and 11.44 {+-} 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [{sup 18}F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 {+-} 2.08 %ID/g (versus 0.41 {+-} 0.90 %ID/g in control mice). In the two models, comparison with [{sup 18}F]FDG showed that both radiotracers were able to detect melanoma lesions, but [{sup 18}F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [{sup 18}F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  17. PET imaging in ectopic Cushing syndrome: a systematic review.

    Science.gov (United States)

    Santhanam, Prasanna; Taieb, David; Giovanella, Luca; Treglia, Giorgio

    2015-11-01

    Cushing syndrome due to endogenous hypercortisolism may cause significant morbidity and mortality. The source of excess cortisol may be adrenal, pituitary, or ectopic. Ectopic Cushing syndrome is sometimes difficult to localize on conventional imaging like CT and MRI. After performing a multilevel thoracoabdominal imaging with CT, the evidence regarding the use of radiotracers for PET imaging is unclear due to significant molecular and etiological heterogeneity of potential causes of ectopic Cushing's syndrome. In our systematic review of literature, it appears that GalLium-based (Ga68) somatostatin receptor analogs have better sensitivity in diagnosis of bronchial carcinoids causing Cushing syndrome and FDG PET appears superior for small-cell lung cancers and other aggressive tumors. Further large-scale studies are needed to identify the best PET tracer for this condition.

  18. Adenosine A{sub 2A} receptor imaging with [{sup 11}C]KF18446 PET in the rat brain after quinolinic acid lesion. Comparison with the dopamine receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi; Ogi, Nobuo; Hayakawa, Nobutaka [Tokyo Metropolitan Inst. of Gerontology, Tokyo (Japan). Positron Medical Center] [and others

    2002-11-01

    We proposed [{sup 11}C]KF18446 as a selective radioligand for mapping the adenosine A{sub 2A} receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [{sup 11}C]KF18446 PET can detect the change in the striatal adenosine A{sub 2A} receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [{sup 11}C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [{sup 11}C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [{sup 11}C] raclopride binding to dopamine D{sub 2} receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [{sup 11}C]SCH23390 binding to dopamine D{sub 1} receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [{sup 11}C]KF18446 PET can detect change in the adenosine A{sub 2A} receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum. (author)

  19. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna C Schacht

    2017-01-01

    approaches were used and compared: [11C]CO2 released by magnetic stirring and [11C]palmitate obtained by the solid-phase extraction (SPE) method. Finally, input functions using individual metabolite correction, was compared with population based metabolite correction to calculate myocardial fatty acid uptake...... in a patient cohort undergoing a cardiac fatty acid PET study. Results: In humans, mean effective dose was 3.2 µSv/MBq, with the liver (27.5 µSv/MBq) and heart wall (10.6 µSv/MBq) receiving the highest absorbed doses. Metabolite correction using only [11C]CO2 underestimated the fraction of metabolites compared...... ~300 MBq [11C]palmitate. [11C]CO2 underestimates the true fraction of metabolites in studies lasting more than 20 minutes. In addition, population based metabolite correction performed well compared with individual metabolite correction....

  20. Environmental Tracers

    Directory of Open Access Journals (Sweden)

    Trevor Elliot

    2014-10-01

    Full Text Available Environmental tracers continue to provide an important tool for understanding the source, flow and mixing dynamics of water resource systems through their imprint on the system or their sensitivity to alteration within it. However, 60 years or so after the first isotopic tracer studies were applied to hydrology, the use of isotopes and other environmental tracers are still not routinely necessarily applied in hydrogeological and water resources investigations where appropriate. There is therefore a continuing need to promote their use for developing sustainable management policies for the protection of water resources and the aquatic environment. This Special Issue focuses on the robustness or fitness-for-purpose of the application and use of environmental tracers in addressing problems and opportunities scientifically, to promote their wider use and to address substantive issues of vulnerability, sustainability, and uncertainty in (groundwater resources systems and their management.

  1. Adenosine A(2A receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Masahiro Mishina

    Full Text Available Adenosine A(2A receptors (A2ARs are thought to interact negatively with the dopamine D(2 receptor (D2R, so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD. However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET with [7-methyl-(11C]-(E-8-(3,4,5-trimethoxystyryl-1,3,7-trimethylxanthine ([(11C]TMSX in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test. In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test. In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an

  2. Benzodiazepine receptor quantification in vivo in humans using [11C]flumazenil and PET

    DEFF Research Database (Denmark)

    Lassen, N A; Bartenstein, P A; Lammertsma, A A

    1995-01-01

    constant infusion of nonlabeled ("cold") flumazenil starting 2h before the bolus tracer injection and continuing until the end of scanning period. In this second study the free concentration of unmetabolized flumazenil in plasma water was measured in multiple blood samples. The observed tissue and plasma...

  3. A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Zavaleta, Cristina L

    2012-01-01

    ]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/µmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [(18)F]13 in mice showed high uptake...

  4. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform...

  5. The Impact of Somatostatin Receptor-Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Barrio, Martin; Czernin, Johannes; Fanti, Stefano; Ambrosini, Valentina; Binse, Ina; Du, Lin; Eiber, Matthias; Herrmann, Ken; Fendler, Wolfgang P

    2017-05-01

    Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. (68)Ga-DOTATATE approval by the U.S. Food and Drug Administration has triggered widespread clinical interest in SSTR PET/CT throughout the United States. Here, we performed a systematic review and meta-analysis to evaluate the impact of SSTR PET/CT on the management of patients with NETs. Methods: A comprehensive literature search was performed using The National Center for Biotechnology Information PubMed online database, applying the following key words: "management" AND "PET" AND "neuroendocrine". Fourteen of 190 studies were deemed suitable based on the following inclusion criteria: original research, cohort study, number of patients 10 or more, and reported change in management after SSTR PET/CT. Change in management across studies was determined by a random-effects model. Results: A total of 1,561 patients were included. Overall, change in management occurred in 44% (range, 16%-71%) of NET patients after SSTR PET/CT. In 4 of 14 studies, SSTR PET/CT was performed after an (111)In-Octreotide scan. In this subgroup, additional information by SSTR PET/CT led to a change in management in 39% (range, 16%-71%) of patients. Seven of 14 studies differentiated between inter- and intramodality changes, with most changes being intermodality (77%; intramodality, 23%). Conclusion: The management was changed in more than one third of patients undergoing SSTR PET/CT even when performed after an (111)In-Octreotide scan. Intermodality changes were 3 times more likely than intramodality changes, underlining the clinical impact of SSTR PET/CT. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  6. Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach

    DEFF Research Database (Denmark)

    Haugbøl, Steven; Pinborg, Lars H; Arfan, Haroon M

    2006-01-01

    PURPOSE: To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach. Further, to estimate the sample size needed to detect regional differences between two groups and, finally, to evaluate how partial volume correction affects...... reproducibility and the required sample size. METHODS: For assessment of the variability, six subjects were investigated with [18F]altanserin PET twice, at an interval of less than 2 weeks. The sample size required to detect a 20% difference was estimated from [18F]altanserin PET studies in 84 healthy subjects......% (range 5-12%), whereas in regions with a low receptor density, BP1 reproducibility was lower, with a median difference of 17% (range 11-39%). Partial volume correction reduced the variability in the sample considerably. The sample size required to detect a 20% difference in brain regions with high...

  7. Molecular imaging with {sup 68}Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kaemmerer, Daniel; Haugvik, Sven-Petter; Hommann, Merten [Zentralklinik Bad Berka GmbH, Department of General and Visceral Surgery, Bad Berka (Germany); Peter, Luisa; Lupp, Amelie; Schulz, Stefan [University of Jena, Department of Pharmacology and Toxicology, Jena (Germany); Saenger, Joerg [Laboratory of Pathology and Cytology, Bad Berka (Germany); Prasad, Vikas; Kulkarni, Harshad; Baum, Richard Paul [Zentralklinik Bad Berka, Department of Nuclear Medicine and Center for PET, Bad Berka (Germany)

    2011-09-15

    Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5. Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative {sup 68}Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV{sub max} and SUV{sub mean}) were used for PET/CT. The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV{sub max} on the PET/CT (p < 0.001; p < 0.05) and the IRS for SSTR2A with the SUV{sub mean} (p < 0.013). The level of SSTR2A score correlated significantly with chromogranin A staining and indirectly to the tumour grading. The highly significant correlation between SSTR2A and SSTR5 and the SUV{sub max} on the {sup 68}Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of {sup 68}Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using {sup 68}Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy. (orig.)

  8. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    WANG MingWei; YIN DuanZhi; LI ShiQiang; WANG YongXian

    2007-01-01

    O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [18F]FET are similar to those of [18F]FDG, but the ratios of tumor-to-brain (T/Br)are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  9. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 min. The radiochemical yield is about 40%(no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid,high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle(T/M) and tumor-to-blood(T/B) of [18F]FET are similar to those of [18F]FDG,but the ratios of tumor-to-brain(T/Br) are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  10. Gender dependent rate of metabolism of the opioid receptor-PET ligand [{sup 18}F]fluoroethyl-diprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, G.; Spilker, M.E.; Hauser, A.I.; Boecker, H.; Schwaiger, M.; Wester, H.J. [Technische Univ. Muenchen, Garching (Germany). Dept. of Nuclear Medicine; Sprenger, T.; Platzer, S.; Toelle, T.R. [Technische Univ. Muenchen, Garching (Germany). Klinikum rechts der Isar, Neurology

    2006-07-01

    Aim: The morphinane-derivate 6-O-(2-[{sup 18}F]fluoroethyl)-6-O-desmethyldiprenorphine ([{sup 18}F]FDPN) is a non-selective opioid receptor ligand currently used in positron emission tomography (PET). Correction for plasma metabolites of the arterial input function is necessary for quantitative measurements of [{sup 18}]FDPN binding. A study was undertaken to investigate if there are gender dependent differences in the rate of metabolism of [{sup 18}F]FDPN. Methods: The rate of metabolism of [{sup 18}F]FDPN was mathematically quantified by fitting a bi-exponential function to each individual's dynamic metabolite data. Results: No statistically significant gender differences were found for age, weight, body mass index or dose. However, significant differences (p<0.01) in two of the four kinetic parameters describing the rate of metabolism were found between the two groups, with women metabolizing [{sup 18}F]FDPN faster than men. These differences were found in the contribution of the fast and slow kinetic components of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of [{sup 18}F]FDPN in women than in men. Conclusion: The findings reinforce the need for individualized metabolite correction during [{sup 18}F]FDPN-PET scans and also indicate that in certain cases, grouping according to gender could be performed in order to minimize methodological errors of the input function prior to kinetic analyses. (orig.)

  11. Verbal memory and 5-HT1A receptors in healthy volunteers--A PET study with [carbonyl-(11)C]WAY-100635.

    Science.gov (United States)

    Penttilä, Jani; Hirvonen, Jussi; Tuominen, Lauri; Lumme, Ville; Ilonen, Tuula; Någren, Kjell; Hietala, Jarmo

    2016-03-01

    The serotonin 5-HT1A receptor is a putative drug development target in disorders with cognitive and in particular memory deficits. However, previous human positron emission tomography (PET) studies on 5-HT1A receptor binding and memory functions have yielded discrepant results. We explored the association between verbal memory and 5-HT1A receptor binding in 24 healthy subjects (14 male, 10 female, aged 18-41 years). The cognitive tests included the Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Wisconsin Card Sorting Test (WCST). 5-HT1A receptor binding was measured with PET and the radioligand [carbonyl-(11)C]WAY-100635, which was quantified with the gold standard method based on kinetic modeling using arterial blood samples. We found that global 5-HT1A receptor binding was positively correlated with measures of verbal memory, such that subjects who had higher receptor binding tended to have better verbal memory than subjects who had lower receptor binding. Regional analyses suggested significant correlations in multiple neocortical brain regions and the raphe nuclei. We did not find significant correlations between 5-HT1A receptor binding and executive functions as measured with WCST. We conclude that neocortical as well as raphe 5-HT1A receptors are involved in verbal memory function in man.

  12. Synthesis of carbon-11 labelled SCH 39166, a new selective dopamine D-1 receptor ligand, and preliminary PET investigations

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Farde, Lars; Sedvall, Goeran (Karolinska Hospital, Stockholm (Sweden). Dept. of Psychiatry and Psychology); Barnett, Allen (Schering-Plough Corp., Bloomfield, NJ (USA))

    1991-01-01

    SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo(d)naphtho-(2,1-b)azepine ) is a new more selective dopamine D-1 receptor antagonist than the widely used SCH 23390. ({sup 11}C)SCH 39166 was prepared by N-methylation of the desmethyl compound SCH 40853 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-5H-benzo(d)naphtho -(2,1-b)azepine) with ({sup 11}C)methyl iodide. Reaction in acetone with subsequent straight-phase semi-preparative HPLC resulted in 20-30% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 35-40 min and a radiochemical purity >99%. The specific activity obtained at EOS was about 1500 Ci/mmol (55 GBq/{mu}mol). ({sup 11}C)SCH 39166 was injected into a Cynomolgus monkey. PET-analysis demonstrated accumulation in the striatum, a region known to have a high density of dopamine D-1 receptors. In a displacement experiment, radioactivity in the striatum was markedly reduced after injection of 6 mg unlabelled SCH 23390, thus demonstrating the specificity and reversibility of ({sup 11}C)SCH 39166 binding to dopamine D-1 receptors. (author).

  13. In vitro and in vivo evaluation of [{sup 11}C]MPEPy as a potential PET ligand for mGlu{sub 5} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Severance, Alin J. [Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States); Parsey, Ramin V. [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States)]. E-mail: rparsey@neuron.cpmc.columbia.edu; Kumar, J.S. Dileep [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States); Underwood, Mark D.; Arango, Victoria [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States); Majo, Vattoly J.; Prabhakaran, Jaya [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States); Simpson, Norman R.; Heertum, Ronald L. van [Dept. of Radiology, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States); Mann, J. John [New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States)

    2006-11-15

    Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR{sub 5}) has been implicated in depression, neuropathic pain and other psychiatric, neurological and neurodegenerative diseases. A mGluR{sub 5} radioligand for in vivo quantification by positron emission tomography (PET) would facilitate studies of the role of this receptor in disease and treatment. 3-Methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity antagonist at the mGluR{sub 5} receptor was selected as a candidate ligand; a recent publication by Yu et al. [Nucl Med Biol 32 (2005) 631-640] presented initial micro-PET results for [{sup 11}C]MPEPy with enthusiasm. Building on their efforts, we report as unique contributions (1) an improved chemical synthesis method, (2) the first data using human tissue, (3) phosphor images for rat brain preparations, (4) a novel comparison of anesthetic agents and (5) in vivo data in baboon. In vitro phosphor imaging studies of this ligand using human and rat brain tissue demonstrated high specific binding in the hippocampus, striatum and cortex with minimal specific binding in the cerebellum. In contrast, in vivo micro-PET studies in rats using urethane anesthesia, PET studies in baboons using isoflurane anesthesia and ex vivo micro-PET studies in unanesthetized rats each showed little specific binding in the brain. Despite the promising in vitro results, the low signal-to-noise ratio found in vivo does not justify the use of [{sup 11}C]MPEPy as a PET radiotracer in humans.

  14. PET studies in epilepsy

    OpenAIRE

    Sarikaya, Ismet

    2015-01-01

    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. 18Fluoro-2-deoxyglucose (18F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients...

  15. {sup 68}Ga-DOTA-affibody molecule for in vivo assessment of HER2/neu expression with PET

    Energy Technology Data Exchange (ETDEWEB)

    Kramer-Marek, Gabriela; Capala, Jacek [National Institutes of Health, National Cancer Institute, Bethesda, MD (United States); Shenoy, Nalini; Griffiths, Gary L. [National Institutes of Health, Imaging Probe Development Center, National Heart, Lung, and Blood Institute, Rockville, MD (United States); Seidel, Jurgen; Choyke, Peter [National Institutes of Health, Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD (United States)

    2011-11-15

    Overexpression of HER2/neu in breast cancer is correlated with a poor prognosis. It may vary between primary tumors and metastatic lesions and change during the treatment. Therefore, there is a need for a new means to assess HER2/neu expression in vivo. In this work, we used {sup 68}Ga-labeled DOTA-Z{sub HER2:2891}-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts. DOTA-Z{sub HER2:2891}-Affibody molecules were labeled with {sup 68}Ga. In vitro binding was characterized by a receptor saturation assay. Biodistribution and PET imaging studies were conducted in athymic nude mice bearing subcutaneous human breast cancer tumors with three different levels of HER2/neu expression. Nonspecific uptake was analyzed using non-HER2-specific Affibody molecules. Signal detected by PET was compared with ex vivo assessment of the tracer uptake and HER2/neu expression. The {sup 68}Ga-DOTA-Z{sub HER2:2891}-Affibody probe showed high binding affinity to MDA-MB-361 cells (K{sub D} = 1.4 {+-} 0.19 nM). In vivo biodistribution and PET imaging studies demonstrated high radioactivity uptake in HER2/neu-positive tumors. Tracer was eliminated quickly from the blood and normal tissues, resulting in high tumor-to-blood ratios. The highest concentration of radioactivity in normal tissue was seen in the kidneys (227 {+-} 14%ID/g). High-contrast PET images of HER2/neu-overexpressing tumors were recorded as soon as 1 h after tracer injection. A good correlation was observed between PET imaging, biodistribution estimates of tumor tracer concentration, and the receptor expression. These results suggest that PET imaging using {sup 68}Ga-DOTA-Z{sub HER2:2891}-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo. (orig.)

  16. Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D{sub 2} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer E-mail: christer.halldin@neuro.ks.se; Dolle, Frederic; Swahn, Carl-Gunnar; Olsson, Hans; Lundkvist, Per Karlsson; Hall, Haakan; Sandell, Johan; Vaufrey, Camilla; Loc' h, Christian; Franzoise; Crouzel, Christian; Maziere, Bernard; Farde, Lars

    1999-07-01

    Epidepride {l_brace}(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide= {r_brace} binds with a picomolar affinity (K{sub i}=24 pM) to the dopamine D{sub 2} receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D{sub 2} receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [{sup 11}C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/{mu}mol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [{sup 11}C]epidepride binding. The fraction of unchanged [{sup 11}C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [{sup 11}C]epidepride. The availability of [{sup 11}C]epidepride allows the PET-verification of the data obtained from quantitation studies with

  17. Synthesis and evaluation of 1'-[[sup 18]F]fluorometoprolol as a potential tracer for the visualization of [beta]-adrenoceptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Groot, T.J. de; Waarde, A. van; Elsinga, P.H.; Visser, G.M.; Vaalburg, Willem (Groningen Univ. Hospital (Netherlands)); Brodde, O.-E. (Essen Univ. (Germany). Biochemisches Forschungslabor)

    1993-07-01

    ([+-])-1'[[sup 18]F]Fluorometoprol 4 was prepared from desisopropylmetoprolol and [[sup 18]F]fluoroisopropyl tosylate 2 with a radiochemical yield of 2% [corrected for decay to end of bombardment (EOB), synthesis time 90 min]. Synthon 2 was prepared from (S)-1,2-propanediol di(p-toluenesulfonate) in 45% radiochemical yield. Compound 4 shows in two in vitro assays a similar affinity at [beta]-adrenoceptors (about 0.3 [mu]M) as metroprolol 5, but with a slightly higher [beta][sub 1]/[beta][sub 2]-adrenoceptor selectivity ratio (48.6 vs 30.7). In vivo experiments with 4 showed almost no receptor-mediated uptake in the heart probably because the affinity of (fluoro)metoprolol for the [beta][sub 1]-adrenoceptors is too low for successful imaging. However, the in vitro experiments suggest that the fluoroisopropyl group is suitable for the synthesis of [[sup 18]F]fluorinated [beta][sub 1]-adrenergic receptor binding ligands. (Author).

  18. Respiratory gating in cardiac PET

    DEFF Research Database (Denmark)

    Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E

    2017-01-01

    BACKGROUND: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim...... stress (82)RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4.......7) min(-1), P PET...

  19. Synthesis, radiolabeling and evaluation of novel amine guanidine derivatives as potential positron emission tomography tracers for the ion channel of the N-methyl-d-aspartate receptor.

    Science.gov (United States)

    Klein, Pieter J; Chomet, Marion; Metaxas, Athanasios; Christiaans, Johannes A M; Kooijman, Esther; Schuit, Robert C; Lammertsma, Adriaan A; van Berckel, Bart N M; Windhorst, Albert D

    2016-08-08

    The N-Methyl-d-Aspartate receptor (NMDAR) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. The aim of this study was to develop a positron emission tomography (PET) ligand to assess the bio-availability of the NMDAR ion channel in vivo. A series of tri-N-substituted diarylguanidines was synthesized and their in vitro binding affinities for the NMDAR ion channel assessed in rat forebrain membrane fractions. Compounds 21, 23 and 26 were radiolabeled with either carbon-11 or fluorine-18 and ex vivo biodistribution and metabolite studies were performed in Wistar rats. Biodistribution studies showed high uptake especially in prefrontal cortex and lowest uptake in cerebellum. Pre-treatment with MK-801, however, did not decrease uptake of the radiolabeled ligands. In addition, all three ligands showed fast metabolism.

  20. Synthesis of (R)- and (S)-[C-11]L-365,260 for PET studies of brain cholecystokinin (CCK) receptors

    Energy Technology Data Exchange (ETDEWEB)

    Haradahira, T. [Research Development Corporation of Japan, Tokyo (Japan); Suzuki, K.; Inoue, O. [National Institute of Radiological Sciences, Chiba (Japan)

    1994-05-01

    Cholecystokinin (CCK) is a recognized peptide hormone in the gut and proposed as a neurotransmitter or neuromodulator in the central nervous system. Two distinct CCK receptors termed CCK-A and CCK-B have been characterized. CCK-A receptor is primarily distributed in the peripheral tissues including pancreas and gallbladder and also known to be distributed in a few brain regions. CCK-B receptor is widely distributed in the brain and has been proposed to be involved in anxiety, satiety and nociception. To investigate the functional roles of the CCK receptors in the brain by positron emission tomography, we have synthesized an enantiomeric pair of C-11 labeled non-peptide antagonists against the CCK receptors. L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl)-N`-(3-methylpheny lurea)] is a potent CCK-B selective non-peptide antagonist (CCK-A/CCK-B ratio of IC50, 140), whereas its (S)-enantiomer is selective toward CCK-A receptor (CCK-A/CCK-B ratio of IC50, 0.02). We have synthesized the (R)- and (S)-enantiomers of [C-11]-365,260 by N-methylation (50{degrees}C for 5 min) of the racemic desmethyl precursor with [C-11]iodomethane using sodium hydride as a base and subsequent optical resolution with HPLC (column: ChiraSpher, 250 x 10 mm, Merck; eluent: n-hexane / 1,4-dioxane / 2-propanol / triethylamine = 70 / 25 / 5 / 0.1). Radiochemical yields (decay corrected) and optical purities were 34%, 99% for R-enantiomer and 36%, 99% for S-enantiomer, respectively. The total synthesis time was 40 min and specific activity was about 37 GBq/{mu}mol. In PET studies on rhesus monkey (R)-enantiomer showed a high uptake of radioactivity in the cerebral cortex, region known to have a high concentration of CCK-B receptor.

  1. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

    DEFF Research Database (Denmark)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian;

    2013-01-01

    responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide...

  2. In vivo evaluation of [{sup 11}C]N-(2-chloro-5-thiomethylphenyl)-N'- (3-methoxy-phenyl)-N'-methylguanidine ([{sup 11}C]GMOM) as a potential PET radiotracer for the PCP/NMDA receptor

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. E-mail: rnw7@columbia.edu; Slifstein, Mark; Dumont, Filip; Zhao Jun; Chang, Raymond C.; Sudo, Yasuhiko; Sultana, Abida; Balter, Andrew; Laruelle, Marc

    2004-10-01

    The development of imaging methods to measure changes in NMDA ion channel activation would provide a powerful means to probe the mechanisms of drugs and device based treatments (e.g., ECT) thought to alter glutamate neurotransmission. To provide a potential NMDA/PCP receptor PET tracer, we synthesized the radioligand [{sup 11}C]GMOM (K{sub i} = 5.2 {+-}0.3 nM; log P = 2.34) and evaluated this ligand in vivo in awake male rats and isoflurane anesthetized baboons. In rats, the regional brain uptake of [{sup 11}C]GMOM ranged from 0.75{+-}0.13% ID/g in the medulla and pons to 1.15{+-}0.17% ID/g in the occipital cortex. MK801 (1 mg/kg i.v.) significantly reduced (24-28%) [{sup 11}C]GMOM uptake in all regions. D-serine (10 mg/kg i.v.) increased [{sup 11}C]GMOM %ID/g values in all regions (10-24%) reaching significance in the frontal cortex and cerebellum only. The NR2B ligand RO 25-6981 (10 mg/kg i.v.) reduced [{sup 11}C]GMOM uptake significantly (24-38%) in all regions except for the cerebellum and striatum. Blood activity was 0.11{+-}0.03 %ID/g in the controls group and did not vary significantly across groups. PET imaging in isoflurane-anesthetized baboons with high specific activity [{sup 11}C]GMOM provided fairly uniform regional brain distribution volume (V{sub T}) values (12.8-17.1 ml g{sup -1}). MK801 (0.5 mg/kg, i.v., n = 1, and 1.0 mg/kg, i.v., n = 1) did not significantly alter regional V{sub T} values, indicating a lack of saturable binding. However, the potential confounding effects associated with ketamine induction of anesthesia along with isoflurane maintenance must be considered because both agents are known to reduce NMDA ion channel activation. Future and carefully designed studies, presumably utilizing an optimized NMDA/PCP site tracer, will be carried out to further explore these hypotheses. We conclude that, even though [{sup 11}C]GMOM is not an optimized PCP site radiotracer, its binding is altered in vivo in awake rats as expected by modulation of

  3. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Tatsuro [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)]. E-mail: tsucchy@fmsrsa.fukui-med.ac.jp; Okazawa, Hidehiko [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Kobayashi, Masato [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Yoshida, Yoshio [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Itoh, Harumi [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)

    2007-02-15

    Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16{alpha}-[{sup 18}F]fluoro-17{beta}-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03{+-}1.05 vs. 3.97{+-}1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration.

  4. Test-retest measurements of dopamine D{sub 1}-type receptors using simultaneous PET/MRI imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kaller, Simon; Patt, Marianne; Becker, Georg-Alexander; Luthardt, Julia; Meyer, Philipp M.; Werner, Peter; Barthel, Henryk; Bresch, Anke; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Girbardt, Johanna [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Fritz, Thomas H. [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); University of Gent, Institute for Psychoacoustics and Electronic Music (IPEM), Ghent (Belgium); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Integrated Research and Treatment Centre (IFB) Adiposity Diseases, Leipzig (Germany)

    2017-06-15

    The role of dopamine D{sub 1}-type receptor (D{sub 1}R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D{sub 1}-mediated neuronal network regulation using simultaneous PET/MRI and D{sub 1}R-selective [{sup 11}C]SCH23390, this study investigated the stability of central D{sub 1}R measurements between two independent PET/MRI sessions under baseline conditions. Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [{sup 11}C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of D{sub 1}R distribution volume ratio (DVR) and binding potential (BP{sub ND}) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D{sub 1}R density. The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D{sub 1}R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D{sub 1}R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BP{sub ND} values. Accordingly, the absolute variability of BP{sub ND} ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D{sub 1}R content, such as the occipital cortex, with higher mean variability. The test-retest reliability of D{sub 1}R measurements in this study was very high. This was the case not only for D{sub 1}R-rich brain areas, but

  5. Test-retest variability of high resolution positron emission tomography (PET imaging of cortical serotonin (5HT2A receptors in older, healthy adults

    Directory of Open Access Journals (Sweden)

    Graff-Guerrero Ariel

    2009-07-01

    Full Text Available Abstract Background Position emission tomography (PET imaging using [18F]-setoperone to quantify cortical 5-HT2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT2A receptor (5HT2AR binding potential. The purpose of this study was to assess the test-retest variability of [18F]-setoperone PET with a high resolution scanner (HRRT for measuring 5HT2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65–78 years completed two [18F]-setoperone PET scans on two separate occasions 5–16 weeks apart. Results The average difference in the binding potential (BPND as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. Conclusion We conclude that the test-retest variability of [18F]-setoperone PET in elderly subjects is comparable to that of [18F]-setoperone and other 5HT2AR radiotracers in younger subject samples.

  6. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Jakobsen, Annika Loft

    2010-01-01

    Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In-diethylenetriamin......Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In......-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with (123)I-metaiodobenzylguanidine (MIBG), and (18)F-FDG PET. METHODS: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET on average within 40 d. The functional images were fused with low......-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. RESULTS: The overall sensitivity of SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were (18)F-FDG PET...

  7. PET and SPECT in medically non-refractory complex partial seizures. Temporal asymmetries of glucose consumption, Benzodiazepine receptor density

    Energy Technology Data Exchange (ETDEWEB)

    Matheja, P.; Kuwert, T.; Wolf, K.; Schober, O. [Muenster Univ. (Germany). Kliniken und Polikliniken fuer Nuklearmedizin; Stodieck, S.R.G.; Diehl, B.; Ringelstein, E.B. [Muenster Univ. (Germany). Klinik fuer Neurologie; Schuierer, G. [Muenster Univ. (Germany). Inst. fuer Klinische Radiologie

    1998-12-31

    Aim: In contrast to medically refractory complex partial seizures (CPS), only limited knowledge exists on cerebral perfusion and metabolism in medically non-refractory CPS. The aim of this study was to investigate the frequency of temporal asymmetries in regional cerebral glucose consumption (rCMRGlc), regional cerebral blood flow (rCBF), and regional cerebral benzodiazepine receptor density (BRD) in this group of patients. Methods: The study included 49 patients with medically non-refractory cryptogenic CPS (age: 36.0{+-}16.1 years). rCMRGlc was studied with F-18-FDG-PET (FDG), rCBF with Tc-99m-ECD-SPECT (ECD), and BRD with I-123-iomazenil-SPECT (IMZ). All studies were performed interictally and within four weeks in each patient. Duration of epilepsy ranged from 0.1 to 42 years (median 4.0 years). SPECT was performed with the triple-headed SPECT camera Multispect 3, PET with the PET camera ECAT EXACT 47. Using linear profiles, glucose consumption, as well as uptake of ECD and IMZ, were measured in four temporal regions of interest (ROIs), and asymmetry indices were calculated (ASY). The results were compared to 95% confidence intervals determined in control subjects. Results: Thirty-five of the 49 (71%) patients had at least one significantly elevated ASY; temporal rCMRGlc was asymmetrical in 41% of the patients, temporal BRD in 29%, and temporal rCBF in 24%. One patient had an asymmetry of all three variables, two of temporal rCMRGlc and BRD, three of temporal rCMRGlc and rCBF, and another four of rCBF and BRD. Fourteen patients had an isolated temporal asymmetry in rCMRGlc, seven in BRD, and four in rCBF. A discrepancy in lateralization between the three modalities was not observed. Conclusion: The majority of patients with medically non-refractory CPS have focal abnormalities of blood flow and metabolism in their temporal lobe. In this group of patients, FDG-PET demonstrates abnormalities with the highest frequency of the three modalities studied, followed by

  8. Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

    Energy Technology Data Exchange (ETDEWEB)

    Zouakia, A. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Chalon, S. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Kung, H.F. (Hospital of the Univ. of Pennsylvania, Dept. of Radiology, Philadelphia, PA (United States)); Dognon, A.M. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Saliba, E. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Besnard, J.C. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France)); Guilloteau, D. (INSERM U316, Lab. de Biophysique Medicale et Pharmaceutique, 37 - Tours (France))

    1994-06-01

    In order to evaluate in vivo SPET for assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D[sub 1] and D[sub 2] dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O[sub 2]. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [[sup 125]I]TISCH and [[sup 125]I]IBZM for the D[sub 1] and D[sub 2] dopamine receptors, respectively. Using [[sup 125]I]TISCH, we observed no modifications of D[sub 1] receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [[sup 125]I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D[sub 2] dopamine receptor ligand usable for SPET imaging. (orig./MG)

  9. The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-{sup 11}C]WAY-100635

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Patrycja; Savli, Markus; Fink, Martin; Spindelegger, Christoph; Moser, Ulrike; Kasper, Siegfried; Lanzenberger, Rupert [Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna (Austria); Wadsak, Wolfgang; Dudczak, Robert; Kletter, Kurt [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Mitterhauser, Markus; Mien, Leonhard-Key [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); University of Vienna, Department of Pharmaceutical Technology, Vienna (Austria)

    2008-12-15

    The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT{sub 1A}) receptor. Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl-{sup 11}C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT{sub 1A} receptor BP{sub ND} was quantified using (1) the 'gold standard' manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling. The 5-HT{sub 1A} receptor BP{sub ND} was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP{sub ND} values in every region investigated, with a borderline significant sex difference in the hypothalamus (p=0.012, uncorrected). There was a high intersubject variability of the 5-HT{sub 1A} receptor BP{sub ND} within both sexes compared to the small mean differences between men and women. To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT{sub 1A} receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT{sub 1A} receptor expression. (orig.)

  10. Biological evaluation of 2'-[{sup 18}F]fluoroflumazenil ([{sup 18}F]FFMZ), a potential GABA receptor ligand for PET

    Energy Technology Data Exchange (ETDEWEB)

    Mitterhauser, Markus E-mail: markus.mitterhauser@akh-wien.ac.at; Wadsak, Wolfgang; Wabnegger, Leila; Mien, Leonhard-Key; Toegel, Stefan; Langer, Oliver; Sieghart, Werner; Viernstein, Helmut; Kletter, Kurt; Dudczak, Robert

    2004-02-01

    [{sup 11}C]Flumazenil, a highly selective benzodiazepine antagonist is the most extensively used GABA{sub A} ligand for PET so far. To overcome half life disadvantages of {sup 11}C a [{sup 18}F]-labeled flumazenil derivative, 2'-[{sup 18}F]fluoroflumazenil (FFMZ) was developed and biologically evaluated with respect to the GABA{sub A} receptor. Organ with the highest uptake was the pituitary gland. Brain uptake was high and followed the order cortex>thalamus>cerebellum>rest brain. Fluoroflumazenil displaced [{sup 3}H]flumazenil binding from membrane GABA{sub A} receptors with an IC{sub 50}value (3.5 nM) comparable to that of Flumazenil (2.8 nM). The presented data confirm the potential of [{sup 18}F]FFMZ for PET imaging of the GABA-ergic system.

  11. PET applications in pediatrics

    Energy Technology Data Exchange (ETDEWEB)

    Shulkin, B. L. [Ann Arbor, Univ. of Michigan Medical Center (United States). Pediatric Nuclear Medicine Section

    1997-12-01

    This article summarizes the major PET studies which have been performed in pediatric patients to elucidate and characterize diseases and normal development. Issues special for the application of the technique in children, such as dosimetry, patient preparation, and image acquisition are discussed. Studies of central nervous system (CNS) development and pathology, including epilepsy, intraventricular hemorrhage, neonatal asphyxia, tumors, and effects on the CNS from treatment of other tumors are reviewed. These have contributed information fundamental to their understanding of CNS development and pathology. PET investigations into the pathophysiology of congenital heart disease have begun and hold great promise to aid their understanding of these conditions. The second major area in which PET has been applied is the study of non CNS neoplasms. Neuroblastoma has been investigated with tracers which explore basic biochemical features which characterize this tumor, as well as with tracers which explore biochemical events relatively specific for this malignancy. Other common and uncommon tumors of childhood are discussed. The PET technique has been shown useful for answering questions of clinical relevance for the management of these uncommon neoplasms. PET is likely to continue to aid their understanding of many pediatric diseases and may gain more widespread clinical acceptance as the technology continues to disseminate rapidly.

  12. Design, synthesis and validation of integrin {alpha}{sub 2}{beta}{sub 1}-targeted probe for microPET imaging of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chiun-Wei; Li, Zibo; Cai, Hancheng; Chen, Kai; Shahinian, Tony; Conti, Peter S. [University of Southern California, Department of Radiology, Los Angeles, CA (United States)

    2011-07-15

    The ability of PET to aid in the diagnosis and management of recurrent and/or disseminated metastatic prostate cancer may be enhanced by the development of novel prognostic imaging probes. Accumulating experimental evidence indicates that overexpression of integrin {alpha}{sub 2}{beta}{sub 1} may correlate with progression in human prostate cancer. In this study, {sup 64}Cu-labeled integrin {alpha}{sub 2}{beta}{sub 1}-targeted PET probes were designed and evaluated for the imaging of prostate cancer. DGEA peptides conjugated with a bifunctional chelator (BFC) were developed to image integrin {alpha}{sub 2}{beta}{sub 1} expression with PET in a subcutaneous PC-3 xenograft model. The microPET images were reconstructed by a two-dimensional ordered subsets expectation maximum algorithm. The average radioactivity accumulation within a tumor or an organ was quantified from the multiple region of interest volumes. The PET tracer demonstrated prominent tumor uptake in the PC-3 xenograft (integrin {alpha}{sub 2}{beta}{sub 1}-positive). The receptor specificity was confirmed in a blocking experiment. Moreover, the low tracer uptake in a CWR-22 tumor model (negative control) further confirmed the receptor specificity. The sarcophagine-conjugated DGEA peptide allows noninvasive imaging of tumor-associated {alpha}{sub 2}{beta}{sub 1} expression, which may be a useful PET probe for evaluating the metastatic potential of prostate cancer. (orig.)

  13. Synthesis and in vivo evaluation of [O-methyl-{sup 11}C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT{sub 2A} receptor PET ligand

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, J.S. Dileep [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: dk2038@columbia.edu; Prabhakaran, Jaya [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Erlandsson, Kjell [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Majo, Vattoly J. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Simpson, Norman R. [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Pratap, Mali [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Heertum, Ronald L. van [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Mann, J. John [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Parsey, Ramin V. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-05-15

    The serotonin{sub 2A} (5-HT{sub 2A}) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT{sub 2A} antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K {sub i}=0.79 nM) 5HT{sub 2A} antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [{sup 11}C]methyltriflate in order to determine the suitability of [{sup 11}C]MPM to quantify 5-HT{sub 2A} in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40{+-}5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [{sup 11}C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT{sub 2A} receptors. The time-activity curves for the high-binding regions peaked at {approx}45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT{sub 2A} receptors but also 38% blocking in cerebellum, which has a low 5-HT{sub 2A} receptor concentration. Although [{sup 11}C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT{sub 2A} receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT{sub 2A} receptors with PET.

  14. Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ikuko, E-mail: nakamuri@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Cardiovascular Medicine, Saga University, Saga (Japan); Hasegawa, Koki [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Pathology and Experimental Medicine, Kumamoto University, Kumamoto (Japan); Wada, Yasuhiro [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Hirase, Tetsuaki; Node, Koichi [Department of Cardiovascular Medicine, Saga University, Saga (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan)

    2013-03-29

    Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectin mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin m

  15. Test-retest reliability of {sup 11}C-ORM-13070 in PET imaging of α{sub 2C}-adrenoceptors in vivo in the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Lehto, Jussi; Peltonen, Juha M.; Volanen, Iina; Scheinin, Mika [University of Turku, Clinical Research Services Turku CRST, Turku (Finland); TYKSLAB, Unit of Clinical Pharmacology, Turku (Finland); Virta, Jere R. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); Oikonen, Vesa; Roivainen, Anne; Luoto, Pauliina; Arponen, Eveliina; Helin, Semi; Virtanen, Kirsi [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Hietamaeki, Johanna; Holopainen, Aila; Rouru, Juha; Sallinen, Jukka [Orion Pharma, Turku (Finland); Kailajaervi, Marita [Turku Imanet, GE Healthcare, Turku (Finland); Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); University of Turku, Clinical Research Services Turku CRST, Turku (Finland)

    2015-01-15

    α{sub 2C}-Adrenoceptors share inhibitory presynaptic functions with the more abundant α{sub 2A}-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α{sub 2}-adrenoceptor subtypes. PET imaging with the specific α{sub 2C}-adrenoceptor antagonist tracer [{sup 11}C]ORM-13070 was performed twice in six healthy male subjects to investigate the test-retest reliability of tracer binding. The bound/free ratio of tracer uptake relative to nonspecific uptake into the cerebellum during the time interval of 5 - 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test-retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [{sup 11}C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autoradiography. PET data analysis results obtained with a compartmental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method. The results of this study support the use of [{sup 11}C]ORM-13070 PET in the quantitative assessment of α{sub 2C}-adrenoceptors in the human brain in vivo. Reliable assessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios. (orig.)

  16. Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Foged, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm (Sweden)]|[Novo Nordisk A/S, Health Care Discovery and Development, Maaloev (Denmark); Halldin, C.; Pauli, S.; Suhara, T.; Swahn, C.G.; Karlsson, P.; Farde, L. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm (Sweden); Loc`h, C.; Maziere, B.; Maziere, M. [Service Hospitalier Frederic Joliot, CEA, Orsay (France); Hansen, H.C. [Novo Nordisk A/S, Health Care Discovery and Development, Maaloev (Denmark)

    1997-10-01

    NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared {sup 76}Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [{sup 11}C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [{sup 76}Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [{sup 76}Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. (orig.) With 8 figs., 28 refs.

  17. AZD5213: a novel histamine H3 receptor antagonist permitting high daytime and low nocturnal H3 receptor occupancy, a PET study in human subjects.

    Science.gov (United States)

    Jucaite, Aurelija; Takano, Akihiro; Boström, Emma; Jostell, Karl-Gustav; Stenkrona, Per; Halldin, Christer; Segerdahl, Märta; Nyberg, Svante

    2013-07-01

    The histamine H3 receptor represents an appealing central nervous system drug target due to its important role in the neurobiology of cognition and wake-sleep regulation. The therapeutic benefit of H3 antagonists/inverse agonists may be hampered by disruption of sleep that has been observed in humans with prolonged high H3 receptor occupancy (H3RO), extending into night-time. AZD5213 is a highly selective H3 antagonist (in vitro inverse agonist) developed to achieve a pharmacokinetic profile permitting circadian fluctuations of H3RO. Its efficacy has been demonstrated in rodent behavioural models of cognition. In human subjects, AZD5213 was safe and well tolerated following repeated doses (1-14 mg/d) and demonstrated a short (∼5 h) half-life. In this PET study H3RO was measured using the radioligand [11C]GSK189254 ([11C]AZ12807110) in seven young male volunteers following single doses of AZD5213 (0.05-30 mg). H3RO was calculated using the Lassen plot method. The plasma concentrations and the affinity constant (K i,pl 1.14 nmol/l, corresponding to the plasma concentration required to occupy 50% of available receptors) were used to estimate the H3RO time-course. AZD5213 showed dose and concentration dependent H3RO ranging from 16 to 90%. These binding characteristics and the pharmacokinetic profile of AZD5213 indicate that high daytime and low night-time H3RO could be achieved following once daily oral dosing of AZD5213. Fluctuations of H3RO following circadian rhythm of the histamine system may be expected to reduce the risk of sleep disruption while maintaining daytime efficacy. AZD5213 may thus be an optimal compound to evaluate the clinical benefit of selective H3 antagonism in cognitive disorders.

  18. Suitability of the retrograde tracer Dil for electrophysiological studies of brainstem neurons: adverse ramifications for G-protein coupled receptor agonists.

    Science.gov (United States)

    Zhang, Liang; Jongeling, Amy C; Hammond, Donna L

    2007-02-15

    Despite the acknowledged advantages of studying identified populations of neurons, few studies have convincingly established that fluorescent retrograde tracers do not alter the passive membrane properties, action potential characteristics, or effects of drugs on the labeled neurons. Whole-cell patch clamp recordings were made from spinally-projecting serotonergic neurons in the rostral ventromedial medulla (RVM) and spinally-projecting noradrenergic neurons in the locus coeruleus (LC) that were retrogradely labeled with 1,1'-dioactadecyl-3,3,3',3'-tetramethylindocarbodyanine perchlorate (Dil). The passive membrane and the action potential properties of Dil-labeled (0.2%) and non-labeled serotonergic neurons in the RVM did not differ. Similarly, the passive membrane and action potential properties of non-labeled noradrenergic LC neurons did not differ from neurons labeled with 0.2% or 5% Dil. Although the mu opioid receptor agonist [D-Ala(2)-NMePhe(4)-Gly-ol(5)]enkephalin (DAMGO) produced equivalent outward currents in non-labeled noradrenergic LC neurons and those labeled with 0.2% Dil, significantly smaller currents were recorded in LC neurons labeled with 5% Dil. Baclofen, a gamma-aminobutryic acid(B) receptor agonist, also produced smaller currents in RVM neurons labeled with 5% Dil compared to 0.2% Dil. These results indicate that 0.2% Dil is suitable for retrograde labeling of brainstem neurons in vivo for subsequent in vitro electrophysiological study. However, 5% Dil is likely to confound studies of the postsynaptic actions of G-protein coupled receptor ligands.

  19. Radionuclide Tracers for Myocardial Perfusion Imaging and Blood Flow Quantification.

    Science.gov (United States)

    deKemp, Robert A; Renaud, Jennifer M; Klein, Ran; Beanlands, Rob S B

    2016-02-01

    Myocardial perfusion imaging is performed most commonly using Tc-99m-sestamibi or tetrofosmin SPECT as well as Rb-82-rubidium or N-13-ammonia PET. Diseased-to-normal tissue contrast is determined by the tracer retention fraction, which decreases nonlinearly with flow. Reduced tissue perfusion results in reduced tracer retention, but the severity of perfusion defects is typically underestimated by 20% to 40%. Compared to SPECT, retention of the PET tracers is more linearly related to flow, and therefore, the perfusion defects are measured more accurately using N-13-ammonia or Rb-82.

  20. PET Imaging of Steroid Receptor Expression in Breast and Prostate Cancer

    NARCIS (Netherlands)

    Hospers, G. A. P.; Helmond, F. A.; Dierckx, R. A.; de Vries, Emma; de Vries, Erik

    2008-01-01

    The vast majority of breast and prostate cancers express specific receptors for steroid hormones, which play a pivotal role in tumor progression. Because of the efficacy of endocrine therapy combined with its relatively mild side-effects, this intervention has nowadays become the treatment of choice

  1. PET Imaging of Steroid Receptor Expression in Breast and Prostate Cancer

    NARCIS (Netherlands)

    Hospers, G. A. P.; Helmond, F. A.; Dierckx, R. A.; de Vries, Emma; de Vries, Erik

    2008-01-01

    The vast majority of breast and prostate cancers express specific receptors for steroid hormones, which play a pivotal role in tumor progression. Because of the efficacy of endocrine therapy combined with its relatively mild side-effects, this intervention has nowadays become the treatment of choice

  2. Kinetic modeling in PET imaging of hypoxia

    DEFF Research Database (Denmark)

    Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas

    2014-01-01

    Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can...... be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET...... analysis for PET imaging of hypoxia....

  3. A small-animal pharmacokinetic/pharmacodynamic PET study of central serotonin 1A receptor occupancy by a potential therapeutic agent for overactive bladder.

    Directory of Open Access Journals (Sweden)

    Yosuke Nakatani

    Full Text Available Serotonin 1A (5-HT1A receptors have been mechanistically implicated in micturition control, and there has been a need for an appropriate biomarker surrogating the potency of a provisional drug acting on this receptor system for developing a new therapeutic approach to overactive bladder (OAB. Here, we analyzed the occupancy of 5-HT1A receptors in living Sprague-Dawley rat brains by a novel candidate drug for OAB, E2110, using positron emission tomography (PET imaging, and assessed the utility of a receptor occupancy (RO assay to establish a pharmacodynamic index translatable between animals and humans. The plasma concentrations inducing 50% RO (EC50 estimated by both direct and effect compartment models were in good agreement. Dose-dependent therapeutic effects of E2110 on dysregulated micturition in different rat models of pollakiuria were also consistently explained by achievement of 5-HT1A RO by E2110 in a certain range (≥ 60%. Plasma drug concentrations inducing this RO range and EC50 would accordingly be objective indices in comparing pharmacokinetics-RO relationships between rats and humans. These findings support the utility of PET RO and plasma pharmacokinetic assays with the aid of adequate mathematical models in determining the in vivo characteristics of a drug acting on 5-HT1A receptors and thereby counteracting OAB.

  4. The GABA-A benzodiazepine receptor complex: Role of pet and spect in neurology and psychiatry; Der GABA-A-benzodiazepinrezeptorkomplex: Rolle von PET und SPECT in Neurologie und Psychiatrie

    Energy Technology Data Exchange (ETDEWEB)

    Juengling, F.D. [Abt. fuer Nuklearmedizin, Radiologie III, Universitaetsklinik Ulm (Germany); Schaefer, M.; Heinz, A. [Klinik fuer Psychiatrie und Psychotherapie, Charite, Humboldt-Univ. zu Berlin (Germany)

    2002-09-01

    Nuclear medicine imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) for selective depiction of GABA-A-benzodiazepine receptor (GBZR) binding are complementary investigations in the diagnostic process of neurological and psychiatric disorders. This review summarizes the current knowledge about options and limitations of PET and SPECT for in vivo diagnostics in neurology and psychiatry. The growing importance of GBZR-imaging for the understanding of pathophysiology and pharmacological treatment in different psychiatric syndromes is discussed. (orig.) [German] Mit der Entwicklung selektiver Liganden fuer den GABA-A-Benzodiazepinrezeptorkomplex (GBZR) hat die nuklearmedizinische Bildgebung mittels positronen-emissionstomographie (PET) und single-photon-emissionscomputertomographie (SPECT) einen festen Stellenwert fuer Klinik und Forschung in der Neurologie und Psychiatrie erlangt. Die vorliegende Ueberblicksarbeit fasst den aktuellen Wissensstand von Anwendungsmoeglichkeiten und -grenzen der nuklearmedizinischen Bildgebung der GBZR in vivo zusammen und beleuchtet ihren klinischen Nutzen. Die wachsende Bedeutung fuer das Verstaendnis der Pathophysiologie und pharmakotherapeutischer Konzepte unterschiedlicher psychiatrischer Erkrankungen wird herausgestellt. (orig.)

  5. Quantitative Techniques in PET-CT Imaging

    NARCIS (Netherlands)

    Basu, Sandip; Zaidi, Habib; Holm, Soren; Alavi, Abass

    2011-01-01

    The appearance of hybrid PET/CT scanners has made quantitative whole body scanning of radioactive tracers feasible. This paper deals with the novel concepts for assessing global organ function and disease activity based on combined functional (PET) and structural (CT or MR) imaging techniques, their

  6. (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M;

    2015-01-01

    Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C......]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs....... However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs....

  7. MicroPET imaging of 5-HT{sub 1A} receptors in rat brain: a test-retest [{sup 18}F]MPPF study

    Energy Technology Data Exchange (ETDEWEB)

    Aznavour, Nicolas [McGill University, Department of Psychiatry, Montreal, QC (Canada)]|[Laboratory of Neuroenergetics and Cellular Dynamics, EPFL, SV, BMI, Lausanne (Switzerland); Benkelfat, Chawki; Gravel, Paul [McGill University, Department of Psychiatry, Montreal, QC (Canada)]|[McGill University, Department of Neurology and Neurosurgery, Montreal, QC (Canada); Aliaga, Antonio [McGill University, Department of Small Animal Imaging Laboratory, Montreal, QC (Canada); Rosa-Neto, Pedro [Douglas Hospital, Molecular NeuroImaging Laboratory, Montreal, QC (Canada); Bedell, Barry [McGill University, Department of Neurology and Neurosurgery, Montreal, QC (Canada)]|[McGill University, Department of Small Animal Imaging Laboratory, Montreal, QC (Canada); Zimmer, Luc [CERMEP, ANIMAGE Department, Lyon (France)]|[Universite Lyon 1 and CNRS, Lyon (France); Descarries, Laurent [Universite de Montreal, Department of Pathology and Cell Biology, Montreal, QC (Canada)]|[Universite de Montreal, Department of Physiology, Montreal, QC (Canada)]|[Universite de Montreal, GRSNC, Montreal, QC (Canada)

    2009-01-15

    Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [{sup 18}F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptors in different regions of animal and human brain, including that of 5-HT{sub 1A} autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems). Scans from isoflurane-anaesthetised rats (n = 18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model. Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei. MicroPET brain imaging of 5-HT{sub 1A} receptors with [{sup 18}F]MPPF thus represents a promising avenue for investigating 5-HT{sub 1A} receptor function in rat. (orig.)

  8. A bolus/infusion paradigm for the novel NMDA receptor SPET tracer [{sup 123}i]CNS 1261

    Energy Technology Data Exchange (ETDEWEB)

    Bressan, Rodrigo A; Erlandsson, Kjell E-mail: k.erlandsson@nucmed.ucl.ac.uk; Mulligan, Rachel S; Gunn, Roger N.; Cunningham, Vincent J.; Owens, Jonathan; Cullum, Ian D.; Ell, Peter J.; Pilowsky, Lyn S

    2004-02-01

    We have previously performed quantitative kinetic modeling of [{sup 123}I]CNS 1261, a new SPET ligand for the MK801 intrachannel site of the NMDA receptor. We now report a bolus-infusion protocol, which eliminates the need for arterial blood sampling. Dynamic SPET scanning and venous blood sampling were performed in 7 healthy volunteers. Good agreement was obtained between kinetic and equilibrium analysis. SPET scanning with a bolus-infusion protocol is a valid method to estimate the total volume of distribution for [{sup 123}I]CNS 1261 in clinical populations.

  9. 胰腺癌:PET诊断学%Pancreatic cancer-Diagnostics:PET

    Institute of Scientific and Technical Information of China (English)

    Uwe Haberkorn

    2007-01-01

    Important challenges for imaging of pancreatic cancer are the late presentation of the disease and the fact that therapeutic management is of limited success. Surgery continues to be the only treatment that offers potential cure. Therefore,defining whether the patient has an operable tumor remains the ultimate aim of imaging in pancreatic cancer. PET and PET/CT with fluorodeoxyglucose (FDG) are of value in differential diagnosis between pancreatitis and carcinoma and for the detection of remote metastases, but relatively inefficient in the detection of nodal disease. The detection of recurrent disease is of little clinical consequence. FDG-PET may be considered as a prognostic marker for patient survival or therapy response, but evidence for these applications is lacking. Future applications will broaden the spectrum of tracers applied using molecules for the assessment of proliferation and detection of receptors.

  10. 99mTc-YIGSR as a Receptor Tracer in Imaging the Ehrlich Ascites Tumor-bearing Mice as Compared with 99mTc-MIBI

    Institute of Scientific and Technical Information of China (English)

    HU Jia; QIN Guangming; ZHANG Yongxue; AN Rui; LAN Xiaoli

    2007-01-01

    The validity of 99mTc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with 99mTc by using a bifunctional chelator S-Acetly-NH3-MAG3. The MIBI was labeled with 99mTc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of 99mTc-YIGSR or 99mTc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C18 chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH3-MAG3. The conjugated YIGSR could be radio-labeled successfully with 99mTc at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH3-MAG3, the YIGSR was labeled with 99mTc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of 99mTc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio (T/M) of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the 99mTc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group (P<0.001). In the 99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with 99mTc-YIGSR (P<0.001).It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH3-MAG3.99mTc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization

  11. Imaging neuronal pathways with 52Mn PET

    DEFF Research Database (Denmark)

    Napieczynska, Hanna; Severin, Gregory; Fonslet, Jesper

    2017-01-01

    tomography (PET) neuronal tract tracer. We used 52Mn for imaging dopaminergic pathways after a unilateral injection into the ventral tegmental area (VTA), as well as the striatonigral pathway after an injection into the dorsal striatum (STR) in rats. Furthermore, we tested potentially noxious effects...... of the radioactivity dose with a behavioral test and histological staining. 24 h after 52Mn administration, the neuronal tracts were clearly visible in PET images and statistical analysis confirmed the observed distribution of the tracer. We noticed a behavioral impairment in some animals treated with 170 kBq of 52Mn...... for PET imaging....

  12. Effects of dopamine D2 receptor partial agonist antipsychotic aripiprazole on dopamine synthesis in human brain measured by PET with L-[β-11C]DOPA.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ito

    Full Text Available Dopamine D(2 receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2 receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11C]raclopride and L-[β-(11C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2 receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2 receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

  13. Development of a PET radioligand for the central 5-HT{sub 1B} receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Jan D., E-mail: j.d.andersson@ki.s [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Pierson, M. Edward [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Finnema, Sjoerd J.; Gulyas, Balazs [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Heys, Richard; Elmore, Charles S. [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Farde, Lars [AstraZeneca Pharmaceuticals, Neuroscience Clinical, SE-15185 Soedertaelje (Sweden); Halldin, Christer [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden)

    2011-02-15

    Introduction: The serotonin 1B (5-HT{sub 1B}) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT{sub 1B} receptor in the primate brain in vivo. Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [{sup 11}C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography. Results: In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/{mu}mol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [{sup 11}C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT{sub 1B} receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics. Conclusion: Candidate [{sup 11}C]6, i.e., [{sup 11}C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT{sub 1B} receptors and was nominated for further preclinical characterization and PET examination in human subjects.

  14. [{sup 18}F]F15599, a novel 5-HT{sub 1A} receptor agonist, as a radioligand for PET neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemoine, Laetitia; Verdurand, Mathieu [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian [Centre de Recherches Pierre Fabre, Castres (France); Le Bars, Didier [CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Zimmer, Luc [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); CERMEP - Imagerie du Vivant, ANIMAGE Department, Lyon (France)

    2010-03-15

    The serotonin-1A (5-HT{sub 1A}) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT{sub 1A} receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT{sub 1A} receptors. Since all clinical PET 5-HT{sub 1A} radiopharmaceuticals are antagonists, it is of great interest to develop a{sup 18}F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{l_brace}[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl{r_brace}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT{sub 1A} receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT{sub 1A} receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [{sup 18}F]MPPF, a validated 5-HT{sub 1A} antagonist radiopharmaceutical. The chemical and radiochemical purities of [{sup 18}F]F15599 were >98%. In vitro [{sup 18}F ]F15599 binding was consistent with the known 5-HT{sub 1A} receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [{sup 18}F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [{sup 18}F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT{sub 1A} antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer

  15. 18FDG, [18F]FLT, [18F]FAZA, and 11C-Methionine Are Suitable Tracers for the Diagnosis and In Vivo Follow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    György Trencsényi

    2014-01-01

    Full Text Available Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1 in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb and cyclosporine A (CSA is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG, 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT, and [18F]fluoroazomycin-arabinofuranoside (18FAZA for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+ and negative (Pgp− human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET.

  16. 5-HTT and 5-HT(1A) receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects.

    Science.gov (United States)

    Stenkrona, Per; Halldin, Christer; Lundberg, Johan

    2013-10-01

    Vortioxetine (Lu AA21004) is a new potential substance for the treatment of anxiety and mood disorders. It has high affinity for the 5-HT transporter (5-HTT) and moderate affinity for the 5-HT1A receptor in vitro. Positron emission tomography (PET) has commonly been used to examine the relation between dose/plasma concentration and occupancy to predict relevant dose intervals in a clinical setting. In this study 11 control subjects were examined with PET and [¹¹C]MADAM at baseline, after a single dose and after 9 days of dosing with Lu AA21004 (2.5, 10 or 60 mg) for quantification of 5-HTT occupancy. Four subjects were examined with PET and [¹¹C]WAY 100635 at baseline, after a single dose and after 9 days of dosing of Lu AA21004 (30 mg) for quantification of 5-HT(1A) occupancy. To allow for quantification of binding in the raphe nuclei, PET data were analyzed using wavelet aided parametric imaging. 5-HTT occupancy ranged from 2 (mean, 2.5 mg day 1) to 97% (60 mg day 9). The apparent affinity of Lu AA21004 binding to 5-HTT (KD(ND)) was calculated to 16.7 nM (R=0.95), and the corresponding oral dose (KD(ND)-dose) to 8.5 mg (R=0.91). No significant occupancy of 5-HT(1A) receptors was found after dosing of 30 mg Lu AA21004. Based on the literature and the present [¹¹C]MADAM binding data, a dose of 20-30 mg Lu AA21004 is suggested to give clinically relevant occupancy of the 5-HTT.

  17. In vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States) and Department of Radiology, Columbia University, New York, NY 10032 (United States) and Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: rnw7@columbia.edu; Chang, Raymond C. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Zhao, Jun [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Carambot, Patty E. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-02-15

    Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K {sub D}=0.5{+-}0.2 nM, log P=2.9) sigma-1 receptor radiotracer [{sup 18}F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [{sup 18}F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [{sup 18}F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [{sup 18}F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([{sup 18}F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([{sup 18}F]SFE) (K {sub D}=5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [{sup 18}F]SFE was synthesized (n=4) as previously described in good yield (54{+-}6% EOB), high specific activity (2.1{+-}0.6 Ci/{mu}mol EOS) and radiochemical purity (98{+-}1%) and evaluated in awake adult male rats. Results: Similar to [{sup 18}F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [{sup 18}F]SFE were highest in occipital cortex (1.86{+-}0.06 %ID/g) and frontal cortex (1.76{+-}0.38 %ID/g), and lowest in the hippocampus (1.01{+-}0.02%ID/g). Unlike [{sup 18}F]FPS, [{sup 18}F]SFE cleared from the brain with {approx}40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [{sup 18}F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [{sup 18}F]SFE in discrete brain regions. Conclusions

  18. SPECT og PET i neurobiologien

    DEFF Research Database (Denmark)

    Paulson, O.B.; Lassen, N.A.

    1997-01-01

    PET (positron emission tomography) and SPECT (single photon emission computed tomography) are isotopic methods in which the distribution is registered of radiolabelled tracers given in such small amounts that they are without effect on the organism or the organism's disposal of them. Thus, a series...

  19. SPECT og PET i neurobiologien

    DEFF Research Database (Denmark)

    Paulson, O B; Lassen, N A

    1997-01-01

    PET (positron emission tomography) and SPECT (single photon emission computed tomography) are isotopic methods in which the distribution is registered of radiolabelled tracers given in such small amounts that they are without effect on the organism or the organism's disposal of them. Thus, a series...

  20. Evaluation in vitro and in animals of a new {sup 11}C-labeled PET radioligand for metabotropic glutamate receptors 1 in brain

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Clark, David T.; Morse, Cheryl; Pike, Victor W. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); Barth, Vanessa N.; Rhoads, Emily; Siuda, Edward; Heinz, Beverly A.; Nisenbaum, Eric; Dressman, Bruce; Joshi, Elizabeth; Luffer-Atlas, Debra; Fisher, Matthew J.; Masters, John J.; Goebl, Nancy; Kuklish, Steven L.; Tauscher, Johannes [Eli Lilly and Co., Indianapolis, IN (United States); Innis, Robert B. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States)

    2013-02-15

    Two allosteric modulators of the group I metabotropic glutamate receptors (mGluR1 and mGluR5) were evaluated as positron emission tomography (PET) radioligands for mGluR1. LY2428703, a full mGluR1 antagonist (IC{sub 50} 8.9 nM) and partial mGluR5 antagonist (IC{sub 50} 118 nM), and LSN2606428, a full mGluR1 and mGluR5 antagonist (IC{sub 50} 35.3 nM and 10.2 nM, respectively) were successfully labeled with {sup 11}C and evaluated as radioligands for mGluR1. The pharmacology of LY2428703 was comprehensively assessed in vitro and in vivo, and its biodistribution was investigated by liquid chromatography-mass spectrometry/mass spectrometry, and by PET imaging in the rat. In contrast, LSN2606428 was only evaluated in vitro; further evaluation was stopped due to its unfavorable pharmacological properties and binding affinity. {sup 11}C-LY2428703 showed promising characteristics, including: (1) high potency for binding to human mGluR1 (IC{sub 50} 8.9 nM) with no significant affinity for other human mGlu receptors (mGluR2 through mGluR8); (2) binding to brain displaceable by administration of an mGluR1 antagonist; (3) only one major radiometabolite in both plasma and brain, with a negligible brain concentration (with 3.5 % of the total radioactivity in cerebellum) and no receptor affinity; (4) a large specific and displaceable signal in the mGluR1-rich cerebellum with no significant in vivo affinity for mGluR5, as shown by PET studies in rats; and (5) lack of substrate behavior for efflux transporters at the blood-brain barrier, as shown by PET studies conducted in wild-type and knockout mice. {sup 11}C-LY2428703, a new PET radioligand for mGluR1 quantification, displayed promising characteristics both in vitro and in vivo in rodents. (orig.)

  1. PET studies in epilepsy.

    Science.gov (United States)

    Sarikaya, Ismet

    2015-01-01

    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. (18)Fluoro-2-deoxyglucose ((18)F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced (11)C-flumazenil (GABAA-cBDZ) and (18)F-MPPF (5-HT1A serotonin) and increased (11)C-cerfentanil (mu opiate) and (11)C-MeNTI (delta opiate) bindings in the area of seizure. (11)C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that (11)C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous

  2. N1'-fluoroethyl-naltrindole (BU97001) and N1'-fluoroethyl-(14-formylamino)-naltrindole (BU97018) potential {delta}-opioid receptor PET ligands

    Energy Technology Data Exchange (ETDEWEB)

    Tyacke, Robin J.; Robinson, Emma S.J.; Schnabel, Rebecca; Lewis, John W.; Husbands, Stephen M.; Nutt, David J.; Hudson, Alan L. E-mail: a.l.hudson@bristol.ac.uk

    2002-05-01

    The properties of two prospective positron emission tomography (PET) ligands for the {delta}-opioid receptor, N1'-fluoroethyl-naltrindole (BU97001) and N1'-fluoroethyl-(14-formylamino)-naltrindole (BU97018) were investigated. Both were antagonists in the mouse vas deferens, and showed high affinity and selectivity, 1.81 nM and 3.09 nM respectively. [{sup 3}H]BU97001 binding to rat whole brain was also of high affinity, K{sub D} of 0.42 nM of and B{sub MAX} of 59.95 fmol mg of protein{sup -1}. In autoradiographic studies, it was found to bind to brain areas previously shown to be associated with the {delta}-opioid receptor and good correlations were found to exist with naltrindole and DPDPE. BU97018 and especially BU97001 appear to show good potential as {delta}-opioid receptor PET ligands with the incorporation of {sup 18}F.

  3. PET/Computed Tomography in Renal, Bladder, and Testicular Cancer.

    Science.gov (United States)

    Bouchelouche, Kirsten; Choyke, Peter L

    2015-07-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/computed tomography (CT) is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in urooncology. In both bladder and renal cancers, there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with limited renal excretion. Thus, new tracers are being introduced. This review focuses on the clinical role of FDG and other PET agents in renal, bladder, and testicular cancers.

  4. PET/CT in renal, bladder and testicular cancer

    Science.gov (United States)

    Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

    2015-01-01

    Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

  5. PET radiopharmaceuticals for neuroreceptor imaging

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Routine clinical PET radiopharmaceuticals for the noninvasive imaging of brain receptors, transporters,and enzymes are commonly labeled with positron emitting nuclides such as carbon-11 or fluorine-18. Certain minimal conditions need to be fulfilled for these PET ligands to be used as imaging agents in vivo. Some of these prerequisites are discussed and examples of the most useful clinical PET radiopharmaceuticals that have found application in the central nervous system are reviewed.

  6. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Ianniello, Annarita; Sansovini, Maddalena; Severi, Stefano; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Unit, Meldola (Italy); Grana, Chiara Maria [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy); Massri, Katrin [Ospedale San Luca, Nuclear Medicine, Department of Radiology, Lucca (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Antonuzzo, Lorenzo [AOU Careggi, SC Oncologia Medica 1, Firenze (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela; Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2016-06-15

    Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and {sup 18}F-FDG PET as prognostic factors in patients with advanced TC or AC. A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients. The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group. Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of

  7. Clinical Translation of a Dual Integrin αvβ3- and Gastrin-Releasing Peptide Receptor-Targeting PET Radiotracer, 68Ga-BBN-RGD.

    Science.gov (United States)

    Zhang, Jingjing; Niu, Gang; Lang, Lixin; Li, Fang; Fan, Xinrong; Yan, Xuefeng; Yao, Shaobo; Yan, Weigang; Huo, Li; Chen, Libo; Li, Zhiyuan; Zhu, Zhaohui; Chen, Xiaoyuan

    2017-02-01

    This study aimed to document the first-in-human application of a (68)Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin αvβ3 and gastrin-releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnostic value of (68)Ga-BBN-RGD PET/CT in prostate cancer patients in comparison with (68)Ga-BBN. Five healthy volunteers (4 men and 1 woman; age range, 28-53 y) were enrolled to validate the safety of (68)Ga-BBN-RGD. Dosimetry was calculated using the OLINDA/EXM software. Thirteen patients with prostate cancer (4 newly diagnosed and 9 posttherapy) were enrolled. All the patients underwent PET/CT scans 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of (68)Ga-BBN-RGD and also accepted (68)Ga-BBN PET/CT within 2 wk for comparison. With a mean injected dose of 107.3 ± 14.8 MBq per patient, no side effect was found during the whole procedure and 2 wk follow-up, demonstrating the safety of (68)Ga-BBN-RGD. A patient would be exposed to a radiation dose of 2.90 mSv with an injected dose of 129.5 MBq (3.5 mCi), which is much lower than the dose limit set by the Food and Drug Administration. In 13 patients with prostate cancer diagnosed by biopsy, (68)Ga-BBN-RGD PET/CT detected 3 of 4 primary tumors, 14 metastatic lymph nodes, and 20 bone lesions with an SUVmax of 4.46 ± 0.50, 6.26 ± 2.95, and 4.84 ± 1.57, respectively. Only 2 of 4 primary tumors, 5 lymph nodes, and 12 bone lesions were positive on (68)Ga-BBN PET/CT, with the SUVmax of 2.98 ± 1.24, 4.17 ± 1.89, and 3.61 ± 1.85, respectively. This study indicates the safety and efficiency of a new type of dual integrin αvβ3- and GRPR-targeting PET radiotracer in prostate cancer diagnosis and staging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  8. Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies.

    Science.gov (United States)

    Eriksson, B; Bergström, M; Orlefors, H; Sundin, A; Oberg, K; Långström, B

    2000-03-01

    to visualize small lesions in the pancreas and thorax (e.g. ACTH-producing bronchial carcinoids) not detectable by any other method including octreotide scintigraphy, MRI and CT. Several other tracers have been investigated, e.g. the monoamineoxidase (MAO-A) inhibitor harmine with promising results in non-functioning EPTs. We are currently exploring a wide range of biochemical systems, including enzymes and receptors, both for neurotransmitters and for peptides and proteins in in vitro assays with the potential to use some of the developed tracers for in vivo visualization and tumor biological studies. In conclusion, PET is a valuable tool in the diagnosis of neuroendocrine tumors. It can detect small lesions in the thorax and abdomen not detected by other methods, which has been of great value preoperatively in several cases. It detects more lesions in the liver and lymph nodes than other methods and furthermore, it can be used to monitor treatment effects.

  9. Treatment with enalapril and not diltiazem ameliorated progression of chronic kidney disease in rats, and normalized renal AT1 receptor expression as measured with PET imaging.

    Science.gov (United States)

    Ismail, Basma; deKemp, Rob A; Croteau, Etienne; Hadizad, Tayebeh; Burns, Kevin D; Beanlands, Rob S; DaSilva, Jean N

    2017-01-01

    ACE inhibitors are considered first line of treatment in patients with many forms of chronic kidney disease (CKD). Other antihypertensives such as calcium channel blockers achieve similar therapeutic effectiveness in attenuating hypertension-related renal damage progression. Our objective was to explore the value of positron emission tomography (PET) imaging of renal AT1 receptor (AT1R) to guide therapy in the 5/6 subtotal-nephrectomy (Nx) rat model of CKD. Ten weeks after Nx, Sprague-Dawley rats were administered 10mg/kg/d enalapril (NxE), 30mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional 8-10 weeks. Kidney AT1R expression was assessed using in vivo [18F]fluoropyridine-losartan PET and in vitro autoradiography. Compared to shams, Nx rats exhibited higher systolic blood pressure that was reduced by both enalapril and diltiazem. At 18-20 weeks, plasma creatinine and albuminuria were significantly increased in Nx, reduced to sham levels in NxE, but enhanced in NxD rats. Enalapril treatment decreased kidney angiotensin II whereas diltiazem induced significant elevations in plasma and kidney levels. Reduced PET renal AT1R levels in Nx were normalized by enalapril but not diltiazem, and results were supported by autoradiography. Reduction of renal blood flow in Nx was restored by enalapril, while no difference was observed in myocardial blood flow amongst groups. Enhanced left ventricle mass in Nx was not reversed by enalapril but was augmented with diltiazem. Stroke volume was diminished in untreated Nx compared to shams and restored with both therapies. [18F]Fluoropyridine-Losartan PET allowed in vivo quantification of kidney AT1R changes associated with progression of CKD and with various pharmacotherapies.

  10. Drug action at the 5-HT{sub 1A} receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-{sup 11}C]WAY-100635

    Energy Technology Data Exchange (ETDEWEB)

    Rabiner, Eugenii A. E-mail: ilan@cu.rpms.ac.uk; Gunn, Roger N.; Wilkins, Martin R.; Sargent, Peter A.; Mocaer, Elizabeth; Sedman, Ewen; Cowen, Philip J.; Grasby, Paul M

    2000-07-01

    Serotonin{sub 1A} (5-HT{sub 1A}) receptors have been implicated in the pathophysiology and treatment of anxiety and depression and are a target for novel drug development. In this qualitative study, positron emission tomography (PET) and [carbonyl-{sup 11}C]WAY-100635 were used to assess 5-HT{sub 1A} autoreceptor and postsynaptic receptor occupancy in man in vivo by five different compounds with nanomolar affinity for this site. Occupancy by pindolol, penbutolol, buspirone, EMD 68843, and S 15535 was compared to test-retest data from 10 healthy volunteers. All drugs, apart from buspirone, displayed occupancy at the 5-HT{sub 1A} receptor site. Pindolol demonstrated a preferential occupancy at the autoreceptor compared to the postsynaptic receptor over a plasma range of about 10-20 ng/mL. Differential occupancy may be an important component of novel drug action. The level of autoreceptor or postsynaptic occupancy needed to achieve significant physiological effects is not known, although it is of note that none of the drugs in this study achieved occupancies beyond 60%. Overall this study demonstrates the utility of PET in aiding novel drug development.

  11. Clinical application of pet

    Directory of Open Access Journals (Sweden)

    Francisco Lomeña

    2005-10-01

    Full Text Available Positron emission tomography (PET is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT and magnetic resonance imaging (MRI, which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluordeoxyglucose-F18 (FDG PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.A tomografia por emissão de pósitrons (PET é uma técnica de diagnóstico por imagem que fornece informação sobre o metabolismo e funcionamento dos tecidos, diferente de outras técnicas de imagens como tomografia computadorizada (TC e ressonância magnética (RM, as quais fornecem informações estruturais ou anatômicas. O PET alcançou seu desenvolvimento em investigação biomédica devido à sua capacidade de usar traçadores análogos a muitas substâncias endógenas e de medir in vivo e de forma não invasiva seu consumo em diferentes órgãos e tecidos dos mamíferos 18Fluordesoxiglicose (FDG PET tem provado ser uma exploração de uso clínico com excelente relação custo benefício em oncologia e em muitas doenças neurológicas. Os atuais tomógrafos por PET-CT podem chegar a ser a melhor ferramenta de diagnóstico nos pacientes que sofrem de câncer.

  12. Methoxyphenylethynyl, methoxypyridylethynyl and phenylethynyl derivatives of pyridine: synthesis, radiolabeling and evaluation of new PET ligands for metabotropic glutamate subtype 5 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Yu Meixiang [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States)]. E-mail: myu@utmck.edu; Tueckmantel, Werner [Acenta Discovery Inc., Tucson, AZ 85747 (United States); Wang, Xukui [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States); Zhu Aijun [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States); Kozikowski, Alan P. [Acenta Discovery Inc., Tucson, AZ 85747 (United States); [Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612 (United States); Brownell, Anna-Liisa [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States)]. E-mail: abrownell@partners.org

    2005-08-01

    We have synthesized three different PET ligands to investigate the physiological function of metabotropic glutamate subtype 5 receptors (mGluR5) in vivo: 2-[{sup 11}C]methyl-6-(2-phenylethynyl)pyridine ([{sup 11}C]MPEP), 2-(2-(3-[{sup 11}C]methoxyphenyl)ethynyl)pyridine ([{sup 11}C]M-MPEP) and 2-(2-(5-[{sup 11}C]methoxypyridin-3-yl)ethynyl)pyridine ([{sup 11}C]M-PEPy). [{sup 11}C]Methyl iodide was used to label the compounds under basic conditions, and a Pd(0) catalyst was applied to label [{sup 11}C]MPEP in a Stille coupling reaction. In vivo microPET imaging studies of the functional accumulation of radiolabeled ligands were conducted in 35 rats (Sprague-Dawley, 8 weeks old male, weight of 300 g). Specific binding was tested using pre-administration of unlabeled mGluR5 antagonist 2-methyl-6-(2-phenylethynyl)pyridine (MPEP) (10 mg/kg iv 5 min before radioactivity injection). In the radiolabeling of [{sup 11}C]MPEP, [{sup 11}C]M-MPEP and [{sup 11}C]M-PEPy, a specific radioactivity of 700-1200 mCi/{mu}mol and over 97% radiochemical purity were obtained. The microPET studies showed these three radiolabeled mGluR5 antagonists having the highest binding in the olfactory bulb followed by striatum, hippocampus and cortex. Pre-administration of the mGluR5 antagonist MPEP induced a 45.1% decrease in [{sup 11}C]MPEP binding, a 59.7% decrease in [{sup 11}C]M-MPEP binding and an 84.6% decrease in [{sup 11}C]M-PEPy binding in the olfactory bulb at 5 min. The feasibility of synthesizing high-affinity and high-selectivity ligands for mGluR5 receptors and their suitability as PET imaging ligands for mGluR5 receptors in vivo are demonstrated.

  13. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    Science.gov (United States)

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M

    2007-12-01

    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  14. Measuring α4β2* nicotinic acetylcholine receptor density in vivo with [(18)F]nifene PET in the nonhuman primate.

    Science.gov (United States)

    Hillmer, Ansel T; Wooten, Dustin W; Slesarev, Maxim S; Ahlers, Elizabeth O; Barnhart, Todd E; Schneider, Mary L; Mukherjee, Jogeshwar; Christian, Bradley T

    2013-11-01

    [(18)F]Nifene is an agonist PET radioligand developed to image α4β2* nicotinic acetylcholine receptors (nAChRs). This work aims to quantify the receptor density (Bmax) of α4β2* nAChRs and the in vivo (apparent) dissociation constant (KDapp) of [(18)F]nifene. Multiple-injection [(18)F]nifene experiments with varying cold nifene masses were conducted on four rhesus monkeys with a microPET P4 scanner. Compartment modeling techniques were used to estimate regional Bmax values and a global value of KDapp. The fast kinetic properties of [(18)F]nifene also permitted alternative estimates of Bmax and KDapp at transient equilibrium with the same experimental data using Scatchard-like methodologies. Averaged across subjects, the compartment modeling analysis yielded Bmax values of 4.8±1.4, 4.3±1.0, 1.2±0.4, and 1.2±0.3 pmol/mL in the regions of antereoventral thalamus, lateral geniculate, frontal cortex, and subiculum, respectively. The KDapp of nifene was 2.4±0.3 pmol/mL. The Scatchard analysis based on graphical evaluation of the data after transient equilibrium yielded Bmax estimations comparable to the modeling results with a positive bias of 28%. These findings show the utility of [(18)F]nifene for measuring α4β2* nAChR Bmax in vivo in the rhesus monkey with a single PET experiment.

  15. Measurement of central {mu}-opioid receptor binding in vivo with PET and [{sup 11}C]carfentanil: a test-retest study in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Hirvonen, Jussi [Turku PET Centre, University of Turku and Turku University Central Hospital, Turku (Finland)]|[Turku PET Centre, Turku (Finland); Aalto, Sargo; Maksimow, Anu; Oikonen, Vesa; Naagren, Kjell [Turku PET Centre, University of Turku and Turku University Central Hospital, Turku (Finland); Hagelberg, Nora; Scheinin, Harry [Turku PET Centre, University of Turku and Turku University Central Hospital, Turku (Finland)]|[Turku University Central Hospital, Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku (Finland); Ingman, Kimmo [University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Virkkala, Jussi [Pirkanmaa Hospital District, Department of Clinical Neurophysiology, Medical Imaging Centre, Tampere (Finland)

    2009-02-15

    [{sup 11}C]Carfentanil has been widely used in positron emission tomography (PET) studies for measuring {mu}-opioid receptor binding in humans, but the reproducibility of the binding parameter estimates is unknown. Eight healthy volunteers were scanned twice during the same day with [{sup 11}C]carfentanil PET, and binding to receptors was assessed with both reference tissue and arterial plasma input-based models using region of interest (ROI) and voxel-based quantification. The two-tissue compartmental model distribution volume (V{sub T}) was highly reproducible as indicated by low variability (VAR < 6%) and high intraclass correlation coefficients (ICC > 0.93). BP{sub ND} (BP relative to the nondisplaceable tissue compartment) was also highly reproducible (VAR < 10%, ICC > 0.90) both at ROI- and voxel-level, and reference tissue-based models provided stable estimates after 40 min. The reproducibility of [{sup 11}C]carfentanil binding parameter estimates is excellent with outcome measures based on both arterial plasma and reference tissue input, and a scanning time of 40 min appears sufficient. (orig.)

  16. Regional distribution and behavioral correlates of 5-HT(2A) receptors in Alzheimer's disease with [(18)F]deuteroaltanserin and PET.

    Science.gov (United States)

    Santhosh, Lekshmi; Estok, Kristina M; Vogel, Rebecca S; Tamagnan, Gilles D; Baldwin, Ronald M; Mitsis, Effie M; Macavoy, Martha G; Staley, Julie K; van Dyck, Christopher H

    2009-09-30

    Postmortem studies show reductions in brain serotonin 2A (5-HT(2A)) receptors in Alzheimer's disease (AD). Converging evidence also suggests that serotonergic dysregulation may contribute to behavioral symptoms that frequently occur in AD. This study aimed to define regional reductions in 5-HT(2A) binding in AD patients and to examine their behavioral correlates. Nine patients with probable AD and eight elderly controls were studied using a constant infusion paradigm for equilibrium modeling of [(18)F]deuteroaltanserin with positron emission tomography (PET). Region of interest analyses were performed on PET images coregistered to MRI scans. The outcome measures BP(P) (ratio of specific brain uptake to total plasma parent concentration) and BP(ND) (ratio of specific to nondisplaceable uptake) were obtained for pertinent cortical and subcortical regions. AD patients showed a statistically significant decrease in the anterior cingulate in both BP(P) and BP(ND), but in no other region. Within the AD patient sample, no significant correlations were observed between regional 5-HT(2A) binding and behavioral measures, including depressive and psychotic symptoms. These results confirm a reduction in cortical 5-HT(2A) receptors in AD, specifically in the anterior cingulate. However, in a limited AD patient sample, they fail to demonstrate a relationship between regional 5-HT(2A) binding and major behavioral symptoms.

  17. Evaluation of C.L.I.N.D.E. as potent peripheral-type benzodiazepine receptor tracer in a rat model of micro-glial activation

    Energy Technology Data Exchange (ETDEWEB)

    Arlicot, N.; Guilloteau, D.; Chalon, S. [Institut National de la Sante et de la Recherche Medicale (INSERM), U619, 37 - Tours (France); Universite Francois Rabelais de Tours, 37 (France); Katsifis, A.; Mattner, F. [ANSTO, Sydney (Australia)

    2008-02-15

    The peripheral-type benzodiazepine receptors (P.B.R.) are localized in mitochondria of glial cells and are very low expressed in normal brain. Their expression rises after micro-glial activation consecutive to brain injury. Accordingly, P.B.R. are potential targets to evaluate neuro inflammatory changes in a variety of C.N.S. disorders. To date no effective tool is available to explore P.B.R. by SPECT. We characterized here 6-chloro-2-(4 iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine- 3-acetamide, C.L.I.N.D.E., in a rat model of excitotoxic lesion. Excitotoxicity was induced in male Wistar rats by unilateral intra striatal injection of different amounts of quinolinic acid (Q.A.: 75, 150 or 300 nmol). One week later, 2 groups of rats (n = 5-6/group) were i.v. injected with [{sup 125}I]-C.L.I.N.D.E. (0.4 MBq), one group being pre-injected with P.K.11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography and immunohistochemical studies using O.X.-42 were performed on brain sections In the control group, [{sup 125}I]-C.L.I.N.D.E. binding was significantly higher ( p < 0.001) in lesioned than that in intact side (striatum: 0.552 {+-} 0.109 vs. 0.123 {+-} 0.012% I.D./g tissue; cortex: 0.385 {+-} 0.126 vs. 0.131 {+-} 0.007% with 300 nmol Q.A.). This binding disappeared in rats pretreated with P.K.11195 ( p < 0.001), showing specific binding of C.L.I.N.D.E. to P.B.R.. Ex vivo autoradiography and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated micro-glia. Regression analysis yielded a significant correlation ( p < 0.001) between the ligand binding and the dose of Q.A.. These results demonstrate that C.L.I.N.D.E. is suitable for P.B.R. in vivo SPECT imaging to explore their involvement in neuro degenerative disorders associated with micro-glial activation. (authors)

  18. 18F-FET-PET in Primary Hyperparathyroidism

    DEFF Research Database (Denmark)

    Krakauer, Martin; Kjær, Andreas; Bennedbæk, Finn Noe

    2016-01-01

    Preoperative localisation of the diseased parathyroid gland(s) in primary hyperparathyroidism (PHP) is a prerequisite for subsequent minimally invasive surgery. Recently, as alternatives to conventional sestamibi parathyroid scintigraphy, the (11)C-based positron emission tomography (PET) tracers...

  19. Radiosynthesis and evaluation of [{sup 11}C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1

    Energy Technology Data Exchange (ETDEWEB)

    Yanamoto, Kazuhiko; Konno, Fujiko; Odawara, Chika; Yamasaki, Tomoteru; Kawamura, Kazunori; Hatori, Akiko; Yui, Joji; Wakizaka, Hidekatsu [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Nengaki, Nobuki [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan); Takei, Makoto [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan); Zhang Mingrong, E-mail: zhang@nirs.go.j [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)

    2010-07-15

    Introduction: Developing positron emission tomography (PET) ligands for imaging metabotropic glutamate receptor type 1 (mGluR1) is important for studying its role in the central nervous system. N-cyclohexyl-6-{l_brace}[N-(2-methoxyethyl)-N-methylamino]methyl{r_brace} -N-methylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-202074) exhibited high binding affinity for mGluR1 (K{sub i}=4.8 nM), and selectivity over other mGluRs in vitro. The purpose of this study was to label YM-202074 with carbon-11 and to evaluate in vitro and in vivo characteristics of [{sup 11}C]YM-202074 as a PET ligand for mGluR1 in rodents. Methods: [{sup 11}C]YM-202074 was synthesized by N-[{sup 11}C]methylation of its desmethyl precursor with [{sup 11}C]methyl iodide. The in vitro and in vivo brain regional distributions were determined in rats using autoradiography and PET, respectively. Results: [{sup 11}C]YM-202074 (262-630 MBq, n=5) was obtained with radiochemical purity of >98% and specific activity of 27-52 GBq/{mu}mol at the end of synthesis, starting from [{sup 11}C]CO{sub 2} of 19.3-21.5 GBq. In vitro autoradiographic results showed that the high specific binding of [{sup 11}C]YM-202074 for mGluR1 was presented in the cerebellum, thalamus and hippocampus, which are known as mGluR1-rich regions. In ex vivo autoradiography and PET studies, the radioligand was specifically distributed in the cerebellum, although the uptake was low. Furthermore, the regional distribution was fairly uniform in the whole brain by pretreatment with JNJ16259685 (a mGluR1 antagonist). However, radiometabolite(s) was detected in the brain. Conclusions: From these results, especially considering the low brain uptake and the influx of radiometabolite(s) into brain, [{sup 11}C]YM-202074 may not be a useful PET ligand for in vivo imaging of mGluR1 in the brain.

  20. The effects of lorazepam on extrastriatal dopamine D(2/3)-receptors-A double-blind randomized placebo-controlled PET study.

    Science.gov (United States)

    Vilkman, Harry; Kajander, Jaana; Aalto, Sargo; Vahlberg, Tero; Någren, Kjell; Allonen, Topias; Syvälahti, Erkka; Hietala, Jarmo

    2009-11-30

    Lorazepam is a widely used anxiolytic drug of the benzodiazepine class. The clinical actions of benzodiazepines are thought to be mediated via specific allosteric benzodiazepine binding sites and enhancement of GABAergic neurotransmission in the brain. However, the indirect effects of benzodiazepines on other neurotransmitter systems have not been extensively studied. Previous experimental evidence suggests that benzodiazepines inhibit striatal dopamine release by enhancing the GABAergic inhibitory effect on dopamine neurons whereas very little is known about cortical or thalamic gamma-amino-butyric (GABA)-dopamine interactions during benzodiazepine administration. We explored the effects of lorazepam (a single 2.5 mg dose) on cortical and thalamic D(2/3) receptor binding using Positron-Emission Tomography (PET) and the high-affinity D(2/3)-receptor ligand [(11)C]FLB 457 in 12 healthy male volunteers. We used a randomized, double-blind and placebo-controlled study design. Dopamine D(2)/D(3) receptor binding potential was measured with the reference tissue method in several extrastriatal D(2)-receptor areas including frontal, parietal, temporal cortices and thalamus. The main subjective effect of lorazepam was sedation. Lorazepam induced a statistically significant decrease of D(2)/D(3) receptor BP(ND) in medial temporal and dorsolateral prefrontal cortex (DLPFC) that was also confirmed by a voxel-level analysis. The sedative effect of lorazepam was associated with a decrease in D(2)/D(3) receptor BP(ND) in the DLPFC. In conclusion, lorazepam decreased [(11)C]FLB 457 binding in frontal and temporal cortex, suggesting that cortical GABA-dopamine interaction may be involved in the central actions of lorazepam in healthy volunteers. The correlation between lorazepam-induced sedation and D(2)/D(3) receptor binding potential (BP) change further supports this hypothesis.

  1. Giardia & Pets

    Science.gov (United States)

    ... body of water Young pets, like puppies and kittens, have a higher risk of illness than adult ... If your pet has persistent diarrhea, seek veterinary care. Diarrhea has different causes and could result in ...

  2. Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Nielsen, Carsten Haagen

    2014-01-01

    and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation. METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid...

  3. Incidental detection of breast cancer by {sup 68}Ga-DOTATOC-PET/CT in women suffering from neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Elgeti, F.; Denecke, T.; Steffen, I.; Stelter, L.; Ruf, J. [Campus Virchow-Klinikum, Berlin (Germany). Klinik fuer Strahlenheilkunde; Amthauer, H. [Universitaetsklinikum Magdeburg (Germany). Klinik fuer Radilogie und Nuklearmedizin; Heuck, F. [Campus Virchow-Klinikum, Berlin (Germany). Medizinische Klinik m. S. Hepatologie und Gastroenterologie

    2008-07-01

    Aim: Somatostatin receptor (sstr) imaging using 68Ga- DOTATOC-PET/CT in neuroendocrine tumors (NET) is promising, suggesting a more sensitive detection of lesions with a low sstr-expression. This is also important for other sstr positive tumors, especially breast cancer whose incidence and age-range is similar to that of NET. Patients, methods: The PET/CT data of 33 consecutive women with NET (age: 33-78 years, mean 59) who underwent whole-body staging with {sup 6}8Ga-DOTATOC was retrospectively analyzed for breast lesions. The data was read separately, side-byside and as fused images. Focal tracer uptake in the breast was semiquantitatively analyzed by comparing the lesional SUV{sub max} to normal breast tissue using Wilcoxon's rank sum test. Breast cancer lesions were compared visually to concomitant NET- lesions. Results: In six of 33 patients (18%) breast lesions were observed on the CT-scans and classified in four patients (12%) as suspicious. The same lesions also showed a pathological tracer uptake on the corresponding PET-scan, visually and semiquantitatively (p<0.01). Histological reevaluation of the suspicious lesions revealed two patients with NET metastases. Two patients had primary breast cancer with lower tracer uptake than concomitant abdominal NET-lesions. Breast cancer diagnosis resulted in a change of the therapeutic regimen. Conclusion: {sup 68}Ga- DOTATOC-PET/CT not only improves the staging of NET-patients, but also increases the chance to detect sstr-positive breast cancer. Although these lesions may show a lower tracer uptake than NET, they must not be overlooked or misinterpreted as metastases. Further imaging and clarification by histopathology is warranted, as the confirmation of a secondary malignoma has great impact on further therapeutic proceedings. (orig.)

  4. 5-HT(1A) receptor and 5-HTT binding during the menstrual cycle in healthy women examined with [(11)C] WAY100635 and [(11)C] MADAM PET.

    Science.gov (United States)

    Jovanovic, Hristina; Karlsson, Per; Cerin, Asta; Halldin, Christer; Nordström, Anna-Lena

    2009-04-30

    The aim of the present study was to explore the effects of the menstrual cycle phases on 5-HT(1A) receptor and 5-HTT binding potentials (BPs) in healthy women by using positron emission tomography (PET). Women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [(11)C]WAY10035 (n=13) and [(11)C]MADAM (n=8) to study 5-HT(1A) and 5-HTT BPs. The BPs values were quantified using the simplified reference tissue model. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TSV) and plasma levels of hormones estradiol (E(2)), progesterone (P(4)), follicle stimulating hormone (FSH) and luteinizing hormone (LH).The 5-HT(1A) receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between the change in E(2) or P(4) values with the change in 5-HT(1A) receptor or 5-HTT BPs. The results provide principally a new in vivo finding in human female biology, suggesting the absence of influence of menstrual cycle phase on 5-HT(1A) receptors or 5-HTT. The finding however does not preclude that gonadal hormones differentially influence central serotonin system inwomen and men, which might contribute to gender differences in serotonin-associated disorders.

  5. Pet Health

    Science.gov (United States)

    Pets can add fun, companionship and a feeling of safety to your life. Before getting a pet, think carefully about which animal is best for ... is each family member looking for in a pet? Who will take care of it? Does anyone ...

  6. Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor

    DEFF Research Database (Denmark)

    Hansen, Hanne Demant; Lacivita, Enza; Di Pilato, Pantaleo

    2014-01-01

    In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best com...

  7. Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with 68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Wolfgang Luboldt

    2010-11-01

    Full Text Available The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs during the course of somatostatin receptor radionuclide therapy (SRRT. In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax of normal liver and hepatic metastases were calculated. In addition, the volumes of hepatic metastases (volume of interest [VOI] were measured using four cut-offs to separate normal liver tissue from metastases (SUVmax of the normal liver plus 10% [VOIliver+10%], 20% [VOIliver+20%], 30% [VOIliver+30%] and SUV = 10 [VOI10SUV]. The SUVmaxof the normal liver was below 10 (7.2 ± 1.3 in all patients and without significant changes. Overall therapy changes (Δ per patient (mean [95% CI] were statistically significant with p < .01 for ΔCgA = −43 (−69 to −17, ΔSUVmax = −22 (−29 to −14, and ΔVOI10SUV = −53 (−68 to −38% and significant with p < .05 for ΔVOIliver+10% = −29 (−55 to −3%, ΔVOIliver+20% = −32 (−62 to −2 and ΔVOIliver+30% = −37 (−66 to −8. Correlations were found only between ΔCgA and ΔVOI10SUV (r = .595; p < .01, ΔSUVmax and ΔVOI10SUV (0.629, p < .01, and SUVmax and ΔSUVmax (r = .446; p < .05. 68Ga-DOTATOC PET/CT allows volumetric therapy monitoring via an SUV-based cut-off separating hepatic metastases from normal liver tissue (10 SUV recommended.

  8. Metastatic neuroendocrine tumour in a renal transplant recipient: Dual-tracer PET-CT with {sup 18}F-FDG nd {sup 68}Ga-DOTANOC in this rare setting

    Energy Technology Data Exchange (ETDEWEB)

    Karunaithi, Sellam; Roy, Shambo Guha; Shama, Punit; Bal, Chandrasejhar; Kumar, Rakesh [Dept. of Nuclear Medicine, All India Institute of Medical Sciences, E-81, Ansari Nagar (East) AIIMS Campus, New Delhi (India); Yadav, Rajni [Dept. of Pathology, All India Institute of Medical Sciences, New Delhi (India)

    2015-03-15

    Recipients of renal transplant are at increased risk of developing various malignancies, especially post-transplant lymphoproliferative disorder (PTLD) and skin cancers. Neuroendocrine tumours (NET) of the gastrointestinal tract have not been reported in this setting. Here we describe the case of a 75-year-old male who had undergone renal transplant 8 years back and now presented with significant weight loss and backache, clinically suspected as PTLD. {sup 18}F-Fluordeoxyglucose ({sup 18}F-FDG) positron emission tomography-computed tomography (PET-CT) showed hypermetabolic lesions in the liver and rectum, raising the suspicion of PTLD. However, biopsy from the liver lesion showed poorly differentiated NET. {sup 68}Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI{sup 3}-octreotide ({sup 68}Ga-DOTANOC) PET-CT was then done, which confirmed the primary lesion in the rectum with liver metastases.

  9. Temporal Heterogeneity of Estrogen Receptor Expression in Bone-Dominant Breast Cancer: 18F-Fluoroestradiol PET Imaging Shows Return of ER Expression.

    Science.gov (United States)

    Currin, Erin; Peterson, Lanell M; Schubert, Erin K; Link, Jeanne M; Krohn, Kenneth A; Livingston, Robert B; Mankoff, David A; Linden, Hannah M

    2016-02-01

    Changes in estrogen receptor (ER) expression over the course of therapy may affect response to endocrine therapy. However, measuring temporal changes in ER expression requires serial biopsies, which are impractical and poorly tolerated by most patients. Functional ER imaging using (18)F-fluoroestradiol (FES)-PET provides a noninvasive measure of regional ER expression and is ideally suited to serial studies. Additionally, lack of measurable FES uptake in metastatic sites of disease predict tumor progression in patients with ER-positive primary tumors treated with endocrine therapy. This report presents a case of restored sensitivity to endocrine therapy in a patient with bone-dominant breast cancer who underwent serial observational FES-PET imaging over the course of several treatments at our center, demonstrating the temporal heterogeneity of regional ER expression. Although loss and restoration of endocrine sensitivity in patients who have undergone prior hormonal and cytotoxic treatments has been reported, this is, to our knowledge, the first time the accompanying changes in ER expression have been documented by molecular imaging.

  10. MicroPET Outperforms Beta-Microprobes in Determining Neuroreceptor Availability under Pharmacological Restriction for Cold Mass Occupancy.

    Science.gov (United States)

    Glorie, Dorien; Servaes, Stijn; Verhaeghe, Jeroen; Wyckhuys, Tine; Wyffels, Leonie; Vanderveken, Olivier; Stroobants, Sigrid; Staelens, Steven

    2017-01-01

    Both non-invasive micro-positron emission tomography (μPET) and in situ beta-microprobes have the ability to determine radiotracer kinetics and neuroreceptor availability in vivo. Beta-microprobes were proposed as a cost-effective alternative to μPET, but literature revealed conflicting results most likely due to methodological differences and inflicted tissue damage. The current study has three main objectives: (i) evaluate the theoretical advantages of beta-microprobes; (ii) perform μPET imaging to assess the impact of (beta-micro)probe implantation on relative tracer delivery (R1) and receptor occupancy (non-displaceable binding potential, BPND) in the rat brain; and (iii) investigate whether beta-microprobe recordings produce robust results when a pharmacological restriction for cold mass dose (tracer dose condition) is imposed. We performed acquisitions (n = 61) in naive animals, dummy probe implanted animals (outer diameter: 0.75 and 1.00 mm) and beta-microprobe implanted animals (outer diameter: 0.75 mm) using two different radiotracers with high affinity for the striatum: [(11)C]raclopride (n = 29) and [(11)C]ABP688 (n = 32). In addition, acquisitions were completed with or without an imposed restriction for cold mass occupancy. We estimated BPND and R1 values using the simplified reference tissue method (SRTM). [(11)C]raclopride dummy μPET BPND (0.75 mm: -13.01 ± 0.94%; 1.00 mm: -13.89 ± 1.20%) and R1 values (0.75 mm: -29.67 ± 4.94%; 1.00 mm: -39.07 ± 3.17%) significantly decreased at the implant side vs. the contralateral intact side. A similar comparison for [(11)C]ABP688 dummy μPET, demonstrated significantly (p probe insertion. We advise to use tracer dose μPET to obtain accurate results concerning receptor availability and tracer delivery, keeping in mind associated partial volume effects for which it is possible to correct.

  11. Dopamine D{sub 2} receptor occupancy in normal humans treated with a novel antipsychotic drug YKP1358 measured by PET and [11c]raclopride

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. S.; Kim, S. J.; Lee, K. J.; Kim, E.; Yu, K. S.; Jang, I. J.; Kwon, J. S.; Kang, W. J.; Jeong, J. M.; Lee, D. S.; Chung, J. K.; Lee, M. C. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    YKP1358 is a novel serotonin (5-HT{sub 2A}) and dopamine (D{sub 2}) antagonist, and fitted the general profile of an atypical neuroleptic agent in preclinical studies. The time course of D{sub 2} receptor occupancy in the brain of living human after a single oral dose of YKP1358 was measured using PET and related to the plasma drug levels. A single oral dose, dose escalation (100 mg, 200 mg, and 250 mg), open-label study was performed in 9 healthy male volunteers (3 per each dose) using the [{sup 11}C]raclopried PET. After the baseline scan, each subject was studied at 2, 5, and 10 hours after the single administration of YKP1358. Blood samples for evaluation of plasma concentration of YKP1358 were also taken at various time points (0-32 hours post-dose). Binding potential (BP) of [{sup 11}C]raclopride in the putamen was estimated with simplified reference tissue model and percent reduction of the BP was calculated to obtain the D{sub 2} receptor occupancy. BP parametric image was generated using a pixel-wise Logan noninvasive plot. T{sub max} of plasma concentration-time profiles was 0.67 hours, and elimination half-life was 5.71, 7.46, and 8.58 hours in 100 mg, 200 mg, and 250 mg dosing groups, respectively. D{sub 2} receptor occupancy of YKP1358 was 60 to 80% at 2 hours, 40 to 60% at 5 hours, and 20 to 50% at 10 hours. The relationship of plasma concentration and D{sub 2} receptor occupancy of YKP1358 was well predicted by Emax model, and Emax was 100 %, EC50 was 8.9 (=1.1) ng/mI, and Hills coefficient was 0.525. PK profile of YKP1358 showed individual variation, but the D{sub 2} receptor occupancy was less variable and well predicted by an Emax model. Since D{sub 2} antagonists show therapeutic effects at 50 to 80% D{sub 2} occupancy and the EC50 of YKP1358 is less than 10 ng/ml, doses of YKP1358 which maintain plasma concentrations above 10 ng/ml are expected to show therapeutic effects.

  12. Contourlet-based active contour model for PET image segmentation

    NARCIS (Netherlands)

    Abdoli, M.; Dierckx, R. A. J. O.; Zaidi, H.

    Purpose: PET-guided radiation therapy treatment planning, clinical diagnosis, assessment of tumor growth, and therapy response rely on the accurate delineation of the tumor volume and quantification of tracer uptake. Most PET image segmentation techniques proposed thus far are suboptimal in the

  13. PET imaging of the myocardial innervation system : CME

    NARCIS (Netherlands)

    Slart, Riemer

    2014-01-01

    PET imaging of the cardiac autonomic nervous system has advanced in recent years, and multiple pre- and postsynaptic tracers have been introduced. The high spatial and temporal resolution of PET enables noninvasive quantification of neurophysiologic processes at the tissue level. Ligands for

  14. Contourlet-based active contour model for PET image segmentation

    NARCIS (Netherlands)

    Abdoli, M.; Dierckx, R. A. J. O.; Zaidi, H.

    2013-01-01

    Purpose: PET-guided radiation therapy treatment planning, clinical diagnosis, assessment of tumor growth, and therapy response rely on the accurate delineation of the tumor volume and quantification of tracer uptake. Most PET image segmentation techniques proposed thus far are suboptimal in the pres

  15. Value of C-11-methionine PET in imaging brain tumours and metastases

    NARCIS (Netherlands)

    Glaudemans, Andor W J M; Enting, Roeline; Heesters, Martinus; Dierckx, Rudi A J O; van Rheenen, Ronald W J; Walenkamp, Annemiek M E; Slart, Riemer H J A

    2013-01-01

    C-11-methionine (MET) is the most popular amino acid tracer used in PET imaging of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses on the role of MET PET in imaging cerebral gliomas. The Introduct

  16. Synthesis and evaluation of [11C]Cimbi-806 as a potential PET ligand for 5-HT7 receptor imaging

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Hansen, Hanne Demant; Ettrup, Anders Janusz;

    2012-01-01

    2-(2',6'-Dimethoxy-[1,1'-biphenyl]-3-yl)-N,N-dimethylethanamine has been identified as a potent ligand for the serotonin 7 (5-HT(7)) receptor. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]2-(2',6'-dimethoxy-[1,1'-biphenyl]-3-yl......)-N,N-dimethylethanamine ([(11)C]Cimbi-806) as a radioligand for imaging brain 5-HT(7) receptors with positron emission tomography (PET). Precursor and reference compound was synthesized and subsequent (11)C-labelling with [(11)C]methyltriflate produced [(11)C]Cimbi-806 in specific activities ranging from 50 to 300 GBq......L/cm(3) in the cerebellum to 12 mL/cm(3) in the thalamus. Pretreatment with the 5-HT(7) receptor antagonist SB-269970 did not result in any significant changes in [(11)C]Cimbi-806 binding in any of the analyzed regions. Despite the high brain uptake and relevant distribution pattern, the absence...

  17. Molecular cardiac PET besides FDG viability imaging; Molekulare Kardiale PET jenseits der FDG-Vitalitaetsdiagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Lindner, O.; Burchert, W. [Universitaetsklinik der Ruhr-Univ. Bochum (Germany). Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung, Herz- und Diabetszentrum NRW

    2009-06-15

    Molecular cardiac non F-18-FDG PET is currently based on perfusion imaging. It is of excellent diagnostic accuracy to detect coronary artery disease (CAD) and superior to perfusion SPECT. There is also evidence for its incremental prognostic value. The unique feature of PET to measure myocardial perfusion in absolute terms and in short time periods define its impact on cardiac imaging enabling both the evaluation of early changes in CAD and the accurate characterization of multivessel disease. Currently, all available PET perfusion tracers in Europe are cyclotron products. Rb-82, a generator product, is the most frequently employed perfusion tracer in the United States and cyclotron independent. This tracer has the potential to become an alternative in Europe soon. Nowadays, PET systems are manufactured as hybrid PET-CT scanners. In oncology, hybrid imaging revealed, that the combination of functional and morphological imaging is superior to the single components. In cardiology, the integration of perfusion PET imaging with CT calcium scoring and CT anatomy of the coronary arteries represents a similar constellation. Atherosclerotic plaque evaluation by combined PET-CT technique will be one of the most promising future applications with a potential immense impact on prophylaxis, diagnosis and therapy of CAD in the future. (orig.)

  18. The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction:Combining preclinical evidence with human Positron Emission Tomography (PET studies

    Directory of Open Access Journals (Sweden)

    Sylvia eTerbeck

    2015-03-01

    Full Text Available In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5 activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET and combined the findings with preclinical animal research. This combined view of different methodological approaches — from basic neurobiological approaches to human studies — might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC. Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays in important role in systems for social functioning and the response to social stress. Finally, mGluR5’s important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC’s arousal and modulatory systems domain. Glutamate was previously mostly investigate in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

  19. Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism.

    Science.gov (United States)

    Lingford-Hughes, Anne; Myers, James; Watson, Ben; Reid, Alastair G; Kalk, Nicola; Feeney, Adrian; Hammers, Alexander; Riaño-Barros, Daniela A; McGinnity, Colm J; Taylor, Lindsay G; Rosso, Lula; Brooks, David J; Turkheimer, Federico; Nutt, David J

    2016-05-15

    The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.

  20. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

    Science.gov (United States)

    Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

  1. PET imaging evaluation of [{sup 18}F]DBT-10, a novel radioligand specific to α{sub 7} nicotinic acetylcholine receptors, in nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Hillmer, Ansel T.; Zheng, Ming-Qiang; Li, Songye; Lin, Shu-fei; Holden, Daniel; Labaree, David; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun [Yale University, PET Center, 801 Howard Ave, PO Box 208048, New Haven, CT (United States); Scheunemann, Matthias; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig (Germany)

    2016-03-15

    Positron emission tomography (PET) radioligands specific to α{sub 7} nicotinic acetylcholine receptors (nAChRs) afford in vivo imaging of this receptor for neuropathologies such as Alzheimer's disease, schizophrenia, and substance abuse. This work aims to characterize the kinetic properties of an α{sub 7}-nAChR-specific radioligand, 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-[{sup 18}F]-fluorodibenzo[b,d]thiophene 5,5-dioxide ([{sup 18}F]DBT-10), in nonhuman primates. [{sup 18}F]DBT-10 was produced via nucleophilic substitution of the nitro-precursor. Four Macaca mulatta subjects were imaged with [{sup 18}F]DBT-10 PET, with measurement of [{sup 18}F]DBT-10 parent concentrations and metabolism in arterial plasma. Baseline PET scans were acquired for all subjects. Following one scan, ex vivo analysis of brain tissue was performed to inspect for radiolabeled metabolites in brain. Three blocking scans with 0.69 and 1.24 mg/kg of the α{sub 7}-nAChR-specific ligand ASEM were also acquired to assess dose-dependent blockade of [{sup 18}F]DBT-10 binding. Kinetic analysis of PET data was performed using the metabolite-corrected input function to calculate the parent fraction corrected total distribution volume (V{sub T}/f{sub P}). [{sup 18}F]DBT-10 was produced within 90 min at high specific activities of 428 ± 436 GBq/μmol at end of synthesis. Metabolism of [{sup 18}F]DBT-10 varied across subjects, stabilizing by 120 min post-injection at parent fractions of 15-55 %. Uptake of [{sup 18}F]DBT-10 in brain occurred rapidly, reaching peak standardized uptake values (SUVs) of 2.9-3.7 within 30 min. The plasma-free fraction was 18.8 ± 3.4 %. No evidence for radiolabeled [{sup 18}F]DBT-10 metabolites was found in ex vivo brain tissue samples. Kinetic analysis of PET data was best described by the two-tissue compartment model. Estimated V{sub T}/f{sub P} values were 193-376 ml/cm{sup 3} across regions, with regional rank order of thalamus > frontal cortex > striatum

  2. Evaluation of two novel {sup 64}Cu-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin α{sub v}β{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Reinier; Graves, Stephen A.; Nickles, Robert J. [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); Czerwinski, Andrzej; Valenzuela, Francisco [Peptides International, Inc., Louisville, KY (United States); Chakravarty, Rubel; Yang, Yunan; England, Christopher G. [University of Wisconsin, Department of Radiology, Madison, WI (United States); Cai, Weibo [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2015-11-15

    Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin α{sub v}β{sub 3}, may offer advantages in image contrast, time for imaging, and low uptake in nontarget tissues. Two cyclic RGDfK derivatives, (PEG){sub 2}-c(RGDfK) and PEG{sub 4}-SAA{sub 4}-c(RGDfK), were constructed and conjugated to NOTA for {sup 64}Cu labeling. Their integrin α{sub v}β{sub 3}-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the {sup 64}Cu-labeled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h after injection. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers. The IC{sub 50} values of NOTA-(PEG){sub 2}-c(RGDfK) and NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) were 444 ± 41 nM and 288 ± 66 nM, respectively. Dynamic PET data of {sup 64}Cu-NOTA-(PEG){sub 2}-c(RGDfK) and {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) showed similar circulation t{sub 1/2} and peak tumor uptake of about 4 %ID/g for both tracers. Due to its marked hydrophilicity, {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintained excellent tumor-to-background ratios. Static PET scans at later time-points corroborated the enhanced excretion of the tracer, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the integrin α{sub v}β{sub 3}-specificity of the peptides. Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed fast, high-contrast PET imaging of tumor-associated integrin α{sub v}β{sub 3}. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake. (orig.)

  3. Sigma-1 Receptor Imaging in the Brain : Cerebral sigma-1 receptors and cognition: Small-animal PET studies using 11C-SA4503

    NARCIS (Netherlands)

    Kuzhuppilly Ramakrishnan, Nisha

    2014-01-01

    The sigma-1 receptor is a unique orphan receptor, strongly expressed in neurons and glia. Sigma-1 receptors are involved in several central nervous system (CNS) disorders like depression, anxiety, psychosis, schizophrenia, Parkinson’s disease, Alzheimer’s disease, addiction and neuropathic pain. Sev

  4. Test-retest reliability of the novel 5-HT{sub 1B} receptor PET radioligand [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Saricicek, Aybala [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Izmir Katip Celebi University, Department of Psychiatry, Izmir (Turkey); Chen, Jason; Ruf, Barbara [Yale University, Department of Psychiatry, New Haven, CT (United States); Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun [Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Subramanyam, Kalyani; Maloney, Kathleen [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Matuskey, David [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Deserno, Lorenz [Charite - Universitaetsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin (Germany); Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Berlin (Germany); Neumeister, Alexander [Yale University, Department of Psychiatry, New Haven, CT (United States); Mount Sinai School of Medicine, Department of Psychiatry, New York, NY (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Krystal, John H. [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Carson, Richard E. [Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bhagwagar, Zubin [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bristol-Myers Squibb, Wallingford, CT (United States)

    2014-11-27

    [{sup 11}C]P943 is a novel, highly selective 5-HT{sub 1B} PET radioligand. The aim of this study was to determine the test-retest reliability of [{sup 11}C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP{sub ND} was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP{sub ND}, 0.5 % and 11.5 % for MA1 BP{sub P}, 16.7 % and 28.3 % for MA1 BP{sub F}, and between 0.2 % and 5.4 % for MRTM2 BP{sub ND}. The power analyses showed a greater number of subjects were required using MA1 BP{sub F} compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP{sub ND} and the lowest with MA1 BP{sub F} in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT{sub 1B} receptor binding can be obtained using the novel PET radioligand [{sup 11}C]P943. Quantification of 5-HT{sub 1B} receptor binding with MRTM2 BP{sub ND} and with MA1 BP{sub P

  5. Imaging with {sup 124}I in differentiated thyroid carcinoma: is PET/MRI superior to PET/CT?

    Energy Technology Data Exchange (ETDEWEB)

    Binse, I.; Poeppel, T.D.; Ruhlmann, M.; Gomez, B.; Bockisch, A.; Rosenbaum-Krumme, S.J. [University of Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Essen (Germany); Umutlu, L. [University of Duisburg-Essen, Medical Faculty, Department of Radiology, Essen (Germany)

    2016-06-15

    The aim of this study was to compare integrated PET/CT and PET/MRI for their usefulness in detecting and categorizing cervical iodine-positive lesions in patients with differentiated thyroid cancer using {sup 124}I as tracer. The study group comprised 65 patients at high risk of iodine-positive metastasis who underwent PET/CT (low-dose CT scan, PET acquisition time 2 min; PET/CT{sub 2}) followed by PET/MRI of the neck 24 h after {sup 124}I administration. PET images from both modalities were analysed for the numbers of tracer-positive lesions. Two different acquisition times were used for the comparisons, one matching the PET/CT{sub 2} acquisition time (2 min, PET/MRI{sub 2}) and the other covering the whole MRI scan time (30 min, PET/MRI{sub 30}). Iodine-positive lesions were categorized as metastasis, thyroid remnant or inconclusive according to their location on the PET/CT images. Morphological information provided by MRI was considered for evaluation of lesions on PET/MRI and for volume information. PET/MRI{sub 2} detected significantly more iodine-positive metastases and thyroid remnants than PET/CT{sub 2} (72 vs. 60, p = 0.002, and 100 vs. 80, p = 0.001, respectively), but the numbers of patients with at least one tumour lesion identified were not significantly different (21/65 vs. 17/65 patients). PET/MRI{sub 30} tended to detect more PET-positive metastases than PET/MRI{sub 2} (88 vs. 72), but the difference was not significant (p = 0.07). Of 21 lesions classified as inconclusive on PET/CT, 5 were assigned to metastasis or thyroid remnant when evaluated by PET/MRI. Volume information was available in 34 % of iodine-positive metastases and 2 % of thyroid remnants on PET/MRI. PET/MRI of the neck was found to be superior to PET/CT in detecting iodine-positive lesions. This was attributed to the higher sensitivity of the PET component, Although helpful in some cases, we found no substantial advantage of PET/MRI over PET/CT in categorizing iodine

  6. Kinetic analysis of dynamic PET data

    Energy Technology Data Exchange (ETDEWEB)

    Knittel, B.

    1983-12-01

    Our goal is to quantify regional physiological processes such as blood flow and metabolism by means of tracer kinetic modeling and positron emission tomography (PET). Compartmental models are one way of characterizing the behavior of tracers in physiological systems. This paper describes a general method of estimating compartmental model rate constants from measurements of the concentration of tracers in blood and tissue, taken at multiple time intervals. A computer program which applies the method is described, and examples are shown for simulated and actual data acquired from the Donner 280-Crystal Positron Tomograph.

  7. TSPO PET for glioma imaging using the novel ligand (18)F-GE-180: first results in patients with glioblastoma.

    Science.gov (United States)

    Albert, Nathalie L; Unterrainer, M; Fleischmann, D F; Lindner, S; Vettermann, F; Brunegraf, A; Vomacka, L; Brendel, M; Wenter, V; Wetzel, C; Rupprecht, R; Tonn, J-C; Belka, C; Bartenstein, P; Niyazi, M

    2017-08-19

    The 18-kDa mitochondrial translocator protein (TSPO) was reported to be upregulated in gliomas. (18)F-GE-180 is a novel 3rd generation TSPO receptor ligand with improved target-to-background contrast compared to previous tracers. In this pilot study, we compared PET imaging with (18)F-GE-180 and MRI of patients with untreated and recurrent pretreated glioblastoma. Eleven patients with histologically confirmed IDH wildtype gliomas (10 glioblastomas, 1 anaplastic astrocytoma) underwent (18)F-GE-180 PET at initial diagnosis or recurrence. The PET parameters mean background uptake (SUVBG), maximal tumour-to-background ratio (TBRmax) and PET volume using different thresholds (SUVBG × 1.6, 1.8 and 2.0) were evaluated in the 60-80 min p.i. summation images. The different PET volumes were compared to the contrast-enhancing tumour volume on MRI. All gliomas were positive on (18)F-GE-180 PET and were depicted with extraordinarily high tumour-to-background contrast (median SUVBG 0.47 (0.37-0.93), TBRmax 6.61 (3.88-9.07)). (18)F-GE-180 uptake could be found even in areas without contrast enhancement on MRI, leading to significantly larger PET volumes than MRI-based volumes (median 90.5, 74.5, and 63.8 mL vs. 31.0 mL; p = 0.003, 0.004, 0.013). In percentage difference, the PET volumes were on average 179%, 135%, and 90% larger than the respective MRI volumes. The median spatial volumetric correlation (Sørensen-Dice coefficient) of PET volumes and MRI volumes prior to radiotherapy was 0.48, 0.54, and 0.58. (18)F-GE-180 PET provides a remarkably high tumour-to-background contrast in untreated and pretreated glioblastoma and shows tracer uptake even beyond contrast enhancement on MRI. To what extent (18)F-GE-180 uptake reflects the tumour extent of human gliomas and inflammatory cells remains to be evaluated in future prospective studies with guided stereotactic biopsies and correlation of histopathological results.

  8. PET and PET/CT in clinical cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Won, Kyoung Sook [Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2005-02-15

    Cardiac PET emerged as a powerful tool that allowed in vivo quantification of physiologic processes including myocardial perfusion and metabolism, as well as neuronal and receptor function for more than 25 years. Now PET imaging has been playing an important role in the clinical evaluation of patients with known or suspected ischemic heart disease. This important clinical role is expected to grow with the availability of PET/CT scanner that allow a true integration of structure and function. The objective of this review is to provide and update on the current and future role of PET in clinical cardiology with a special eye on the great opportunities now offered by PET/CT.

  9. In vivo imaging of insulin receptors by PET: preclinical evaluation of iodine-125 and iodine-124 labelled human insulin

    Energy Technology Data Exchange (ETDEWEB)

    Iozzo, P.; Osman, S.; Glaser, M.; Knickmeier, M.; Ferrannini, E.; Pike, V.W.; Camici, P.G.; Law, M.P. E-mail: marilyn.law@csc.mrc.ac.uk

    2002-01-01

    [A{sub 14}-*I]iodoinsulin was prepared for studies to assess the suitability of labeled iodoinsulin for positron emission tomography (PET). Iodine-125 was used to establish the methods and for preliminary studies in rats. Further studies and PET scanning in rats were carried out using iodine-124. Tissue and plasma radioactivity was measured as the uptake index (UI={l_brace}cpm{center_dot}(g tissue){sup -1}{r_brace}/{l_brace}cpm injected{center_dot}(g body weight){sup -1}{r_brace}) at 1 to 40 min after intravenous injection of either [A{sub 14}-{sup 125}I]iodoinsulin or [A{sub 14}-{sup 124}I]iodoinsulin. For both radiotracers, initial clearance of radioactivity from plasma was rapid (T{sub 1/2} {approx} 1 min), reaching a plateau (UI = 2.8) at {approx} 5 min which was maintained for 35 min. Tissue biodistributions of the two radiotracers were comparable; at 10 min after injection, UI for myocardium was 2.4, liver, 4.0, pancreas, 5.4, brain, 0.17, kidney, 22, lung, 2.3, muscle, 0.54 and fat, 0.28. Predosing rats with unlabelled insulin reduced the UI for myocardium (0.95), liver (1.8), pancreas (1.2) and brain (0.08), increased that for kidney (61) but had no effect on that for lung (2.5), muscle (0.50) or fat (0.34). Analysis of radioactivity in plasma demonstrated a decrease of [{sup 125}I]iodoinsulin associated with the appearance of labeled metabolites; the percentage of plasma radioactivity due to [{sup 125}I]iodoinsulin was 40% at 5 min and 10% at 10 min. The heart, liver and kidneys were visualized using [{sup 124}I]iodoinsulin with PET.

  10. Practical use and implementation of PET in children in a hospital PET centre

    Energy Technology Data Exchange (ETDEWEB)

    Borgwardt, Lise; Larsen, Helle Jung; Pedersen, Kate; Hoejgaard, Liselotte [Department of Clinical Physiology, Nuclear Medicine and PET, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen (Denmark)

    2003-10-01

    Children are not just small adults - they differ in their psychology, normal physiology and pathophysiology, and various aspects should be considered when planning a positron emission tomography (PET) scan in a child. PET in children is a growing area, and this article describes the practical use and implementation of PET in children in a hospital PET centre. It is intended to be of use to nuclear medicine departments implementing or starting to implement PET scans in children. Topics covered are: dealing with children, dosimetry, organisation within the department and relations with other departments, preparation of the child (provision of information to the child and parents and the fasting procedure), the imaging procedure (resting, tracer injection, positioning, sedation and bladder emptying) and pitfalls in the interpretation of PET scans in children, including experiences with telemedicine. (orig.)

  11. Practical use and implementation of PET in children in a hospital PET centre

    DEFF Research Database (Denmark)

    Borgwardt, Lise; Larsen, Helle Jung; Pedersen, Kate

    2003-01-01

    Children are not just small adults-they differ in their psychology, normal physiology and pathophysiology, and various aspects should be considered when planning a positron emission tomography (PET) scan in a child. PET in children is a growing area, and this article describes the practical use...... and implementation of PET in children in a hospital PET centre. It is intended to be of use to nuclear medicine departments implementing or starting to implement PET scans in children. Topics covered are: dealing with children, dosimetry, organisation within the department and relations with other departments......, preparation of the child (provision of information to the child and parents and the fasting procedure), the imaging procedure (resting, tracer injection, positioning, sedation and bladder emptying) and pitfalls in the interpretation of PET scans in children, including experiences with telemedicine....

  12. Basics and principles of radiopharmaceuticals for PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Wadsak, W. [Department of Nuclear Medicine, Medical University of Vienna (Austria); Mitterhauser, M. [Department of Nuclear Medicine, Medical University of Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

    2010-03-15

    The presented review provides general background on PET radiopharmaceuticals for oncological applications. Special emphasis is put on radiopharmacological, radiochemical and regulatory aspects. This review is not meant to give details on all different PET tracers in depth but to provide insights into the general principles coming along with their preparation and use. The PET tracer plays a pivotal role because it provides the basis both for image quality and clinical interpretation. It is composed of the radionuclide (signaller) and the molecular vehicle which determines the (bio-)chemical properties (e.g. binding characteristics, metabolism, elimination rate)

  13. Comparison of benzodiazepine receptor and regional cerebral blood flow imagings of epileptiform foci in hippocampal kindled rabbits; A study with a double tracer autoradiography using [sup 125]I-Ro 16-0154 and [sup 99m]Tc-HMPAO

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Kenzo (Kanazawa Univ. (Japan). School of Medicine)

    1993-10-01

    To compare the benzodiazepine (Bz) receptor imaging and regional cerebral blood flow (rCBF) imaging in the detection of epileptic foci, the distribution pattern of the Bz receptor and rCBF in hippocampal kindled rabbits was examined by a double tracer autoradiography using ethyl 7-[[sup 125]I]-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1, 5-a][1,4] benzodiazepine-3-carboxylate ([sup 125]I-Ro 16-0154) and [sup 99m]Tc-hexamethyl-propyleneamine oxime ([sup 99m]Tc-HMPAO). In visual and quantitative analyses, [sup 125]I-Ro 16-0154 accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled CA1 region mimicking a primary epileptic focus. [sup 125]I-Ro 16-0154 accumulation was moderately decreased in the ipsilateral temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. [sup 99m]Tc-HMPAO accumulation was found to be decreased in the ipsilateral CA1, frontal, temporal and dentate gyri. However, the decrease was much more slight and less extensive than that in [sup 125]I-Ro 16-0154 accumulation. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy. (author).

  14. Synthesis and biological evaluation of carbon-11- and fluorine-18-labeled 2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Evens, Nele [Laboratory for Radiopharmacy, K.U. Leuven, 3000 Leuven (Belgium); Muccioli, Giulio G. [Unite de Chimie Pharmaceutique et de Radiopharmacie, U.C. Louvain, 1200 Bruxelles (Belgium); Houbrechts, Nele [Laboratory for Radiopharmacy, K.U. Leuven, 3000 Leuven (Belgium); Lambert, Didier M. [Unite de Chimie Pharmaceutique et de Radiopharmacie, U.C. Louvain, 1200 Bruxelles (Belgium); Verbruggen, Alfons M. [Laboratory for Radiopharmacy, K.U. Leuven, 3000 Leuven (Belgium); Van Laere, Koen [Division of Nuclear Medicine, K.U. Leuven, 3000 Leuven (Belgium); Bormans, Guy M. [Laboratory for Radiopharmacy, K.U. Leuven, 3000 Leuven (Belgium)], E-mail: guy.bormans@pharm.kuleuven.be

    2009-05-15

    Introduction: The type 2 cannabinoid (CB{sub 2}) receptor is part of the endocannabinoid system and has been suggested as a mediator of several central and peripheral inflammatory processes. Imaging of the CB{sub 2} receptor has been unsuccessful so far. We synthesized and evaluated a carbon-11- and a fluorine-18-labeled 2-oxoquinoline derivative as new PET tracers with high specificity and affinity for the CB{sub 2} receptor. Methods: Two 2-oxoquinoline derivatives were synthesized and radiolabeled with either carbon-11 or fluorine-18. Their affinity and selectivity for the human CB{sub 2} receptor were determined. Biological evaluation was done by biodistribution, radiometabolite and autoradiography studies in mice. Results: In vitro studies showed that both compounds are high affinity CB{sub 2}-specific inverse agonists. Biodistribution study of the tracers in mice showed a high in vivo initial brain uptake and fast brain washout, in accordance with the low CB{sub 2} receptor expression levels in normal brain. A persistently high in vivo binding to the spleen was observed, which was inhibited by pretreatment with two structurally unrelated CB{sub 2} selective inverse agonists. In vitro autoradiography studies with the radioligands confirmed CB{sub 2}-specific binding to the mouse spleen. Conclusion: We synthesized two novel CB{sub 2} receptor PET tracers that show high affinity/selectivity for CB{sub 2} receptors. Both tracers show favourable characteristics as radioligands for central and peripheral in vivo visualization of the CB{sub 2} receptor and are promising candidates for primate and human CB{sub 2} PET imaging.

  15. Packet Tracer network simulator

    CERN Document Server

    Jesin, A

    2014-01-01

    A practical, fast-paced guide that gives you all the information you need to successfully create networks and simulate them using Packet Tracer.Packet Tracer Network Simulator is aimed at students, instructors, and network administrators who wish to use this simulator to learn how to perform networking instead of investing in expensive, specialized hardware. This book assumes that you have a good amount of Cisco networking knowledge, and it will focus more on Packet Tracer rather than networking.

  16. Longitudinal assessment of cerebral 5-HT{sub 2A} receptors in healthy elderly volunteers: an [{sup 18}F]-altanserin PET study

    Energy Technology Data Exchange (ETDEWEB)

    Marner, Lisbeth; Knudsen, Gitte M.; Haugboel, Steven [University Hospital Rigshospitalet, Neurobiology Research Unit, N9201, Copenhagen O (Denmark); Holm, Soeren [Rigshospitalet, PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen (Denmark); Baare, William [Hvidovre Hospital, Danish Research Center for Magnetic Resonance, Copenhagen (Denmark); Hasselbalch, Steen G. [University Hospital Rigshospitalet, Neurobiology Research Unit, N9201, Copenhagen O (Denmark)]|[Memory Disorders Research Unit, The Neuroscience Center, Copenhagen (Denmark)

    2009-02-15

    The serotonin 2A (5-HT{sub 2A}) receptor is of interest in several psychiatric and neurological diseases. In the present study we investigated the longitudinal stability of 5-HT{sub 2A} receptors and the stability of the quantification procedure in the elderly in order to be able to study elderly patients with neuropsychiatric diseases on a longitudinal basis. [{sup 18}F]-Altanserin PET was used to quantify 5-HT{sub 2A} receptors in 12 healthy elderly individuals at baseline and at 2 years in six volumes of interest. A bolus/infusion protocol was used to achieve the binding potential, BP{sub P}. The reproducibility as assessed in terms of variability and the reliability as assessed in terms of intraclass correlation coefficient (ICC) were used to compare inter- and intraobserver stability and to evaluate the effects of increasing complexity of partial volume (PV) corrections. We also compared the stability of our measurements over 2 years with the stability of data from an earlier study with 2-week test-retest measurements. BP{sub P} was unaltered at follow-up without the use of PV correction and when applying two-tissue PV correction, test-retest reproducibility was 12-15% and reliability 0.45-0.67 in the large bilateral regions such as the parietal, temporal, occipital and frontal cortices, while orbitofrontal and anterior cingulate cortical regions were less stable. The use of PV correction decreased the variability but also decreased the between-subject variation, thereby worsening the reliability. In healthy elderly individuals, brain 5-HT{sub 2A} receptor binding remains stable over 2 years, and acceptable reproducibility and reliability in larger regions and high intra- and interobserver stability allow the use of [{sup 18}F]-altanserin in longitudinal studies of patients with neuropsychiatric disorders. (orig.)

  17. PET and paediatrics; La tomographie par emission de positons (ou PET scan) en pediatrie

    Energy Technology Data Exchange (ETDEWEB)

    Boddaert, N. [Necker Enfants Malades, AP-HP, Serv Radiol Pediat, Paris (France); Ribeiro, M.J. [CEA, DSV, I2BM, Serv Hosp Frederic Joliot, F-91406 Orsay (France)

    2008-07-01

    Positon emission tomography (PET scan) is a functional imagery technique.As in scintigraphy, a radioactive tracer is administrated to the patient and its distribution into the organism is detected by a tomograph or a PET scanner. The nuclear medicine techniques which use radioactive tracers allow to obtain an imagery of the regional metabolism of glucose, blood flow or of different neurotransmitters. The PET-TDM (tomodensitometry) is an hybrid imagery system which associates a PET to a multi-bars scanner (4 to 64 bars). The use of hybrid imagery systems allows an anatomic register of the metabolic anomalies or others, as well as the adjustment of the attenuation of the emitted particles. (O.M.)

  18. Type 1 cannabinoid receptor mapping with [{sup 18}F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Casteels, Cindy [KU Leuven and University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); University Hospital Gasthuisberg, Division of Nuclear Medicine, Leuven (Belgium); Martinez, Emili; Camon, Lluisa; Vera, Nuria de; Planas, Anna M. [IDIBAPS, Institute for Biomedical Research (IIBB-CSIC), Barcelona (Spain); Bormans, Guy [KU Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); KU Leuven, Laboratory for Radiopharmacy, Leuven (Belgium); Baekelandt, Veerle [KU Leuven, Laboratory for Neurobiology and Gene Therapy, Leuven (Belgium); Laere, Koen van [KU Leuven and University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium)

    2010-12-15

    Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [{sup 18}F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB{sub 1}) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D{sub 2} receptor availability and amphetamine-induced turning behaviour. Twenty-one Wistar rats (11 QA and 10 shams) were investigated. Small animal PET acquisitions were conducted on a Focus 220 with approximately 18 MBq of [{sup 18}F]MK-9470, [{sup 18}F]FDG and [{sup 11}C]raclopride. Relative glucose metabolism and parametric CB{sub 1} receptor and D{sub 2} binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2). In the QA model, [{sup 18}F]MK-9470 uptake, glucose metabolism and D{sub 2} receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p < 2.10{sup -5}), while an increase for these markers was observed on the contralateral side (>5%, all p < 7.10{sup -4}). [{sup 18}F]MK-9470 binding was also increased in the cerebellum (p = 2.10{sup -5}), where it was inversely correlated to the number of ipsiversive turnings (p = 7.10{sup -6}), suggesting that CB{sub 1} receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p = 1.10{sup -6}). These data point to in vivo changes in endocannabinoid transmission, specifically for CB{sub 1} receptors in the QA model, with involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D{sub 2} and CB{sub 1} neurotransmission in the contralateral hemisphere. (orig.)

  19. PET Imaging of Tau Deposition in the Aging Human Brain.

    Science.gov (United States)

    Schöll, Michael; Lockhart, Samuel N; Schonhaut, Daniel R; O'Neil, James P; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L; Vogel, Jacob W; Faria, Jamie; Schwimmer, Henry D; Rabinovici, Gil D; Jagust, William J

    2016-03-02

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

  20. Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems.

    Science.gov (United States)

    Tuominen, Lauri; Nummenmaa, Lauri; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Hietala, Jarmo

    2014-05-01

    All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of "system level" connectivity in the brain is increasing rapidly, we lack "molecular level" information on brain networks and connectivity patterns. We introduce novel voxel-based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ-opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty-one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ-opioid receptor tracer. First, voxel-by-voxel "intracorrelations" (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel-level opioid-serotonin intercorrelations (between neurotransmitters) were computed. Regional μ-opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain-striatum-thalamus-amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker-based rationale for targeted

  1. Evaluation of unusual neuroendocrine tumours by means of 68Ga-DOTA-NOC PET.

    Science.gov (United States)

    Fanti, Stefano; Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Montini, Giancarlo; Allegri, Vincenzo; Grassetto, Gaia; Rubello, Domenico; Nanni, Cristina; Franchi, Roberto

    2008-12-01

    (18)F-FDG PET value for the assessment of neuroendocrine tumours (NET) is limited. Preliminary studies indicate that somatostatin receptor PET using (68)Ga-DOTA-peptides is more accurate for disease assessment and provide additional data on receptor status, that are crucial for targeted radionuclide therapy. At present, however, few papers investigated the role of (68)Ga-DOTA-NOC PET in NET, especially in unusual situations. The purpose of the present study was to evaluate (68)Ga-DOTA-NOC for the evaluation of NET of uncommon presentation. Patients with biopsy-proven NET were scheduled for (68)Ga-DOTA-NOC PET; we excluded from further evaluation cases with most common NET tumours (gastro-entero-pancreatic and pulmonary localization of primary lesion, MEN syndromes, medullary thyroid carcinoma, pheochromocytomas). PET results were compared with findings of conventional imaging, including CT, ultrasonography, MR and somatostatin receptor scintigraphy; finally PET results were compared with follow-up data with respect to the impact on patient management. Fourteen patients were finally enrolled; primary tumours were located at uterine level (3 cases), prostate (3 cases), ovary (1 case), kidney (1 case), breast (1 case), ear (1 case); also 3 cases of paraganglioma (at neck, abdominal and mediastinum level) and 1 case of lymphoma were included. (68)Ga-DOTA-NOC PET was positive, showing at least 1 lesion, in 6/14 cases while 5 cases turned out negative and 2 inconclusive. On a clinical basis, (68)Ga-DOTA-NOC provided additional information in comparison to conventional imaging procedures in 7/14 cases, and was considered useful in 12/14 patients, with 8 patients in which (68)Ga-DOTA-NOC PET was determinant for patient's management. Although the number of patients studied is limited, our data show that (68)Ga-DOTA-NOC can be usefully applied for the evaluation of NET of uncommon presentation; in particular very promising results were obtained in paraganglioma. On the other

  2. Diagnostic performances of the S.R.S. (scintigraphy of somatostatin receptors) and of the PET-F.D.G. in the extension situation of the well differentiated endocrine carcinomas at high Ki67; Performances diagnostiques de la SRS et de la TEP-FDG dans le bilan d'extension des carcinomes endocrines bien differencies a Ki67 eleve ({>=} 10%)

    Energy Technology Data Exchange (ETDEWEB)

    Abgrala, R.; Leboulleux, S.; Deandreis, D.; Lumbroso, J.; Schlumberger, M.; Baudin, E. [Medecine nucleaire, institut Gustave-Roussy, Villejuif, (France); Auperin, A. [Biostatistiques, Institut Gustave-Roussy, Villejuif, (France); Dromain, C. [radiologie, institut Gustave-Roussy, Villejuif, (France); Guigay, J. [pneumologie, institut Gustave-Roussy, Villejuif, (France); Ducreux, M. [hepato-gastroenterologie, Institut Gustave-Roussy, Villejuif, (France)

    2009-05-15

    The results suggest that among 90% of patients with well differentiated endocrine carcinomas at high Ki, the PET-F.D.G. is more noticeable or equivalent to the scintigraphy of somatostatin receptors (S.R.S.). (N.C.)

  3. A novel electrophilic synthesis and evaluation of medium specific radioactivity (1R,2S)-4-[{sup 18}F]fluorometaraminol, a tracer for the assessment of cardiac sympathetic nerve integrity with PET

    Energy Technology Data Exchange (ETDEWEB)

    Eskola, Olli E-mail: olesko@utu.fi; Groenroos, Tove; Bergman, Joergen; Haaparanta, Merja; Marjamaeki, Paeivi; Lehikoinen, Pertti; Forsback, Sarita; Langer, Oliver; Hinnen, Francoise; Dolle, Frederic; Halldin, Christer; Solin, Olof

    2004-01-01

    (1R,2S)-4-[{sup 18}F]fluorometaraminol (4-[{sup 18}F]FMR), a tracer for cardiac sympathetic innervation, was synthesized by electrophilic aromatic substitution. A trimethylstannyl precursor, protected with tert-butoxycarbonyl protecting groups, was radiofluorinated with high specific radioactivity [{sup 18}F]F{sub 2}. Specific radioactivity of 4-[{sup 18}F]FMR, in average 11.8 {+-}3.3 GBq/{mu}mol, was improved 40-800-fold in comparison to the previous electrophilic fluorinations. The biodistribution of 4-[{sup 18}F]FMR in rat was in accordance with the known distribution of sympathetic innervation. 4-[{sup 18}F]FMR showed no metabolic degradation in left ventricle of rat heart, where the uptake was high, rapid and specific.

  4. Value of {sup 18}F-FDG uptake on PET/CT and CEA level to predict epidermal growth factor receptor mutations in pulmonary adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kai-Hsiung; Hsu, Hsian-He; Chang, Wei-Chou; Hsu, Yi-Chih; Chang, Tsun-Hou [Tri-Service General Hospital and National Defense Medical Center, Department of Radiology, Taipei 114 (China); Huang, Tsai-Wang; Chang, Hung [Tri-Service General Hospital and National Defense Medical Center, Department of Thoracic Surgery, Taipei (China); Gao, Hong-Wei [Tri-Service General Hospital and National Defense Medical Center, Department of Pathology, Taipei (China); Shen, Daniel H.Y. [Tri-Service General Hospital and National Defense Medical Center, Department of Nuclear medicine, Taipei (China); Chu, Chi-Ming [Institute of Public Health, National Defense Medical Center and University, Section of Health Informatics, Taipei (China); Ho, Ching-Liang [Tri-Service General Hospital and National Defense Medical Center, Division of Hematology-Oncology, Department of Internal Medicine, Taipei (China)

    2014-10-15

    The identification of the mutation status of the epidermal growth factor receptor (EGFR) is important for the optimization of treatment in patients with pulmonary adenocarcinoma. The acquisition of adequate tissues for EGFR mutational analysis is sometimes not feasible, especially in advanced-stage patients. The aim of this study was to predict EGFR mutation status in patients with pulmonary adenocarcinoma based on {sup 18}F-fluorodeoxyglucose (FDG) uptake and imaging features in positron emission tomography/computed tomography (PET/CT), as well as on the serum carcinoembryonic antigen (CEA) level. We retrospectively reviewed 132 pulmonary adenocarcinoma patients who underwent EGFR mutation testing, pretreatment FDG PET/CT and serum CEA analysis. The associations between EGFR mutations and patient characteristics, maximal standard uptake value (SUVmax) of primary tumors, serum CEA level and CT imaging features were analyzed. Receiver-operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. EGFR mutations were identified in 69 patients (52.2 %). Patients with SUVmax ≥6 (p = 0.002) and CEA level ≥5 (p = 0.013) were more likely to have EGFR mutations. The CT characteristics of larger tumors (≥3 cm) (p = 0.023) and tumors with a nonspiculated margin (p = 0.026) were also associated with EGFR mutations. Multivariate analysis showed that higher SUVmax and CEA level, never smoking and a nonspiculated tumor margin were the most significant predictors of EGFR mutation. The combined use of these four criteria yielded a higher area under the ROC curve (0.82), suggesting a good discrimination. The combined evaluation of FDG uptake, CEA level, smoking status and tumor margins may be helpful in predicting EGFR mutation status in patients with pulmonary adenocarcinoma, especially when the tumor sample is inadequate for genetic analysis or genetic testing is not available. Further large-scale prospective studies are

  5. Biodistribution and radiation dosimetry of the A{sub 1} adenosine receptor ligand {sup 18}F-CPFPX determined from human whole-body PET

    Energy Technology Data Exchange (ETDEWEB)

    Herzog, Hans; Elmenhorst, David; Winz, Oliver [Forschungszentrum Juelich GmbH, Institute of Neuroscience and Biophysics - Medicine, Juelich (Germany); Bauer, Andreas [Forschungszentrum Juelich GmbH, Institute of Neuroscience and Biophysics - Medicine, Juelich (Germany); University Hospital Duesseldorf, Department of Neurology, Duesseldorf (Germany)

    2008-08-15

    {sup 18}F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ({sup 18}F-CPFPX) is a potent radioligand to study human cerebral A{sub 1} adenosine receptors and their neuromodulatory and neuroprotective functions with positron emission tomography (PET). The purpose of this study was to determine the biodistribution and the radiation dose of {sup 18}F-CPFPX by whole-body scans in humans. Six normal volunteers were examined with 12 whole-body PET scans from 1.5 min to 4.5 h after injection. Volumes of interest were defined over all visually identifiable organs, i.e. liver, gallbladder, kidneys, small intestines, heart, and brain to obtain the organs' volumes and time-activity curves (TACs). TACs were fitted with exponential functions, extrapolated, multiplied with the physical decay and normalized to injected activities so that the residence times could be computed as area under the curve. Radiation doses were calculated using the OLINDA/EXM software for internal dose assessment in nuclear medicine. The liver uptake shows peak values (decay-corrected) of up to 35% of the injected radioactivity. About 30% is eliminated by bladder voiding. The highest radiation dose is received by the gallbladder (136.2 {+-} 66.1 {mu}Sv/MBq), followed by the liver (84.4 {+-} 10.6 {mu}Sv/MBq) and the urinary bladder (78.3 {+-} 7.1 {mu}Sv/MBq). The effective dose was 17.6 {+-} 0.5 {mu}Sv/MBq. With 300 MBq of injected {sup 18}F-CPFPX a subject receives an effective dose (ICRP 60) of 5.3 mSv. Thus the effective dose of an {sup 18}F-CPFPX study is comparable to that of other {sup 18}F-labelled neuroreceptor ligands. (orig.)

  6. The need for clinical quantification of combined PET/MRI data in pediatric epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Muzik, Otto, E-mail: otto@pet.wayne.edu [Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI (United States); Department of Radiology, Wayne State University School of Medicine, Detroit, MI (United States); Pai, Darshan [Department of Computer Science, Wayne State University School of Medicine, Detroit, MI (United States); Juhasz, Csaba [Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI (United States); Hua, Jing [Department of Computer Science, Wayne State University School of Medicine, Detroit, MI (United States)

    2013-02-21

    In the past, multimodality integrative analysis of image data has been used to obtain a better understanding of underlying mechanisms of seizure generation and propagation in children with extratemporal lobe epilepsy. However, despite important advances in the combined analysis of PET, MRI, DTI and EEG data, successful surgical outcome is only achieved in about 2/3 of patients undergoing resective surgery. The advent of simultaneous PET/MR data acquisition promises an important advance in neuroimaging through clinical quantification, which will finally translate the strength of PET (which is the ability to absolutely quantify physiological parameters such as metabolic rates and receptor densities) into clinical work. Taking advantage of recently developed integrated PET/MR devices, absolute physiological values will be available in clinical routine, replacing currently used visual assessment of relative tissue tracer uptake. This will allow assessment of global increases/decreases of brain function during critical phases of development and is likely to have a significant impact on patient management in pediatric epilepsy.

  7. Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

    Directory of Open Access Journals (Sweden)

    Vadim Bernard-Gauthier

    2015-12-01

    Full Text Available Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed.

  8. Evaluation of Positron Emission Tomographic Tracers for Imaging of Papillomavirus-Induced Tumors in Rabbits

    Directory of Open Access Journals (Sweden)

    Sonja Probst

    2014-01-01

    Full Text Available In this study, simultaneous positron emission tomography (PET/magnetic resonance (MR imaging was employed to evaluate the feasibility of the PET tracers 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG, 11C-choline, and 18F-fluorothymidine (18F-FLT to detect papillomavirus-induced tumors in an established rabbit model system. The combined PET/MR allowed the analysis of tracer uptake of the tumors using the morphologic information acquired by MR. New Zealand White rabbits were infected with cottontail rabbit papillomavirus genomes and were imaged for up to 10 months with a simultaneous PET/MR system during the course of infection. The uptake characteristics of the PET tracers 11C-choline and 18F-FLT of tumors and reference tissues were examined relative to the clinical standard, 18F-FDG. Tracer biodistribution of various organs was measured by gamma-counting after the last PET scan and compared to the in vivo PET/MR 18F-FDG uptake. Increased tracer uptake was found 2 months postinfection in primary tumors with 18F-FDG and 11C-choline, whereas 18F-FLT failed to detect the tumors at all measured time points. Our data show that the PET tracer 18F-FDG is superior for imaging papillomavirus-induced tumors in rabbits compared to 11C-choline and 18F-FLT. However, 11C-choline imaging, which has previously been applied to detect various tumor entities in patients, appears to be an alternative to 18F-FDG.

  9. PET Image Reconstruction Using Information Theoretic Anatomical Priors

    Science.gov (United States)

    Somayajula, Sangeetha; Panagiotou, Christos; Rangarajan, Anand; Li, Quanzheng; Arridge, Simon R.

    2011-01-01

    We describe a nonparametric framework for incorporating information from co-registered anatomical images into positron emission tomographic (PET) image reconstruction through priors based on information theoretic similarity measures. We compare and evaluate the use of mutual information (MI) and joint entropy (JE) between feature vectors extracted from the anatomical and PET images as priors in PET reconstruction. Scale-space theory provides a framework for the analysis of images at different levels of detail, and we use this approach to define feature vectors that emphasize prominent boundaries in the anatomical and functional images, and attach less importance to detail and noise that is less likely to be correlated in the two images. Through simulations that model the best case scenario of perfect agreement between the anatomical and functional images, and a more realistic situation with a real magnetic resonance image and a PET phantom that has partial volumes and a smooth variation of intensities, we evaluate the performance of MI and JE based priors in comparison to a Gaussian quadratic prior, which does not use any anatomical information. We also apply this method to clinical brain scan data using F18 Fallypride, a tracer that binds to dopamine receptors and therefore localizes mainly in the striatum. We present an efficient method of computing these priors and their derivatives based on fast Fourier transforms that reduce the complexity of their convolution-like expressions. Our results indicate that while sensitive to initialization and choice of hyperparameters, information theoretic priors can reconstruct images with higher contrast and superior quantitation than quadratic priors. PMID:20851790

  10. The antipsychotic sultopride is overdosed--a PET study of drug-induced receptor occupancy in comparison with sulpiride.

    Science.gov (United States)

    Takano, Akihiro; Suhara, Tetsuya; Yasuno, Fumihiko; Suzuki, Kazutoshi; Takahashi, Hidehiko; Morimoto, Takuya; Lee, Young-Joo; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Okubo, Yoshiro

    2006-10-01

    Conventional antipsychotics tend to elicit extrapyramidal symptoms at clinical doses, but dose optimization could reduce the risk of such side-effects. In-vivo receptor-binding studies have suggested that 70-80% of dopamine D2 receptor occupancy provides the desired antipsychotic effects without extrapyramidal symptoms. In terms of dose optimization based on the occupancy, there has not been enough supporting data regarding the clinical doses of the respective antipsychotics. In this study, we measured dopamine D2 receptor occupancy of two conventional benzamide antipsychotics, sulpiride and sultopride, using positron emission tomography, to investigate the rationale of their clinical dose. Although they are prescribed at similar doses (300-1200 mg), the doses required to obtain similar receptor occupancy (70-80%) were quite different: 1010-1730 mg for sulpiride but 20-35 mg for sultopride. In terms of dose, sultopride has about 50 times greater potency than sulpiride based on dopamine D2 receptor occupancy. Evidence for the optimal doses of conventional antipsychotics based on dopamine D2 receptor occupancy would be helpful for rational antipsychotic therapy.

  11. Benzodiazepine receptor equilibrium constants for flumazenil and midazolam determined in humans with the single photon emission computer tomography tracer [123I]iomazenil

    DEFF Research Database (Denmark)

    Videbaek, C; Friberg, L; Holm, S

    1993-01-01

    twice, once without receptor blockade and once with a constant degree of partial blockade of the benzodiazepine receptors by infusion of nonradioactive flumazenil (Lanexat) or midazolam (Dormicum). Single photon emission computer tomography and blood sampling were performed intermittently for 6 h after...

  12. Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.

    Science.gov (United States)

    Tateno, Amane; Arakawa, Ryosuke; Okumura, Masaki; Fukuta, Hajime; Honjo, Kazuyoshi; Ishihara, Keiichi; Nakamura, Hiroshi; Kumita, Shin-ichiro; Okubo, Yoshiro

    2013-04-01

    Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

  13. Quantitative PET of EGFR expression in xenograft-bearing mice using {sup 64}Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Weibo; Chen, Kai; He, Lina; Cao, Qizhen; Chen, Xiaoyuan [Stanford University School of Medicine, The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford, CA (United States); Koong, Albert [Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA (United States)

    2007-06-15

    Cetuximab, a chimeric monoclonal antibody targeting epidermal growth factor receptor (EGFR) on the surface of cancer cells, was approved by the FDA to treat patients with metastatic colorectal cancer. It is currently also in advanced-stage development for the treatment of several other solid tumors. Here we report for the first time the quantitative positron emission tomography (PET) imaging of EGFR expression in xenograft-bearing mice using {sup 64}Cu-labeled cetuximab. We conjugated cetuximab with macrocyclic chelating agent 1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA), labeled with {sup 64}Cu, and tested the resulting {sup 64}Cu-DOTA-cetuximab in seven xenograft tumor models. The tracer uptake measured by PET was correlated with the EGFR expression quantified by western blotting. The estimated human dosimetry based on the PET data in Sprague-Dawley rats was also calculated. MicroPET imaging showed that {sup 64}Cu-DOTA-cetuximab had increasing tumor activity accumulation over time in EGFR-positive tumors but relatively low uptake in EGFR-negative tumors at all times examined (<5%ID/g). There was a good correlation (R {sup 2} = 0.80) between the tracer uptake (measured by PET) and the EGFR expression level (measured by western blotting). Human dosimetry estimation indicated that the tracer may be safely administered to human patients for tumor diagnosis, with the dose-limiting organ being the liver. The success of EGFR-positive tumor imaging using {sup 64}Cu-DOTA-cetuximab can be translated into the clinic to characterize the pharmacokinetics, to select the right population of patients for EGFR-targeted therapy, to monitor the therapeutic efficacy of anti-EGFR treatment, and to optimize the dosage of either cetuximab alone or cetuximab in combination with other therapeutic agents. (orig.)

  14. Advance in studies of the tracer of N-methyl-D-aspartate receptor%N-甲基-D-天冬氨酸受体显像剂研究进展

    Institute of Scientific and Technical Information of China (English)

    颜成龙; 周杏琴; 曹国宪

    2009-01-01

    N-methyl-D-aspartate receptors have recently been a novel target of drug development related to neurodegenerative diseases such as Parkinson diseases, Alzheimer disease, schizophrenia, epilepsy and Huntingtons disease. NMDA receptor imaging agents can provide a sensitive molecular prob and a powerful diagnostic tool for the early diagnosis and therapy of neurodegenerative diseases. Because of inadequate lipophilicity and affinity, many NMDA receptor imaging agents couldn't be used in clinical. 123I-N-(1-napthyl) -N'-(3-iodophenyl)-N-methylguanidine (123I-CNS1261)has the potential to be a NMDA receptor imaging agent. Basing on the researches which has accomplished in the abroad at present, this review concluded the progresses of the tracer of NMDA receptor.%N-甲基-D-天冬氨酸(NMDA)受体已成为发展帕金森病、阿尔茨海默病、精神分裂症、癫痫、亨廷顿舞蹈症等神经变性疾病药物的新靶点.NMDA受体显像剂的研制将为神经变性疾病的早期诊断和治疗提供灵敏的分子探针和特异的诊断方法.多数NMDA受体显像剂因脂溶性和亲和力欠佳而不宜用于临床,有希望成为NMDA受体显像剂的是123I-CNS1261.该文综述了近年来关于NMDA受体显像剂的研究进展.

  15. Adenosine A{sub 1} receptors in human sleep regulation studied by electroencephalography (EEG) and positron emission tomography (PET)[Dissertation 17227

    Energy Technology Data Exchange (ETDEWEB)

    Geissler, E

    2007-07-01

    Sleep is an essential physiological process. However, the functions of sleep and the endogenous mechanisms involved in sleep regulation are only partially understood. Convergent lines of evidence support the hypothesis that the build-up of sleep propensity during wakefulness and its decline during sleep are associated with alterations in brain adenosine levels and adenosine receptor concentrations. The non-selective A{sub 1} and A{sub 2A} adenosine receptor antagonist caffeine stimulates alertness and is known to attenuate changes in the waking and sleep electroencephalogram (EEG) typically observed after prolonged waking. Several findings point to an important function of the adenosine A{sub 1} receptor (A{sub 1}AR) in the modulation of vigilance states. The A{sub 1}AR is densely expressed in brain regions involved in sleep regulation, and pharmacological manipulations affecting the A{sub 1}AR were shown to influence sleep propensity and sleep depth. However, an involvement of the A{sub 2A} adenosine receptor (A{sub 2A}AR) is also assumed. The distinct functions of the A{sub 1} and A{sub 2A} receptor subtypes in sleep-wake regulation and in mediating the effects of caffeine have not been identified so far. The selective adenosine A{sub 1} receptor antagonist, 8-cyclopentyl-3-(3-{sup 18}Ffluoropropyl)- 1-propylxanthine ({sup 18}F-CPFPX), offers the opportunity to get further insights into adenosinergic mechanisms by in vivo imaging of the A{sub 1}AR subtype with positron emission tomography (PET). The aim of this thesis was to elucidate the role of adenosine A{sub 1} receptors in human sleep regulation, combining {sup 18}F-CPFPX PET brain imaging and EEG recordings, the gold standard in sleep research. It was hypothesized that sleep deprivation would induce adenosine accumulation and/or changes in A{sub 1}AR density. Thus, the question was addressed whether these effects of prolonged wakefulness can be visualized by altered {sup 18}F-CPFPX binding. Moreover, it was

  16. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET.

    Science.gov (United States)

    Jovanovic, Hristina; Lundberg, Johan; Karlsson, Per; Cerin, Asta; Saijo, Tomoyuki; Varrone, Andrea; Halldin, Christer; Nordström, Anna-Lena

    2008-02-01

    Women and men differ in serotonin associated psychiatric conditions, such as depression, anxiety and suicide. Despite this, very few studies focus on sex differences in the serotonin system. Of the biomarkers in the serotonin system, serotonin(1A) (5-HT(1A)) receptor is implicated in depression, and anxiety and serotonin transporter (5-HTT) is a target for selective serotonin reuptake inhibitors, psychotropic drugs used in the treatment of these disorders. The objective of the present study was to study sex related differences in the 5-HT(1A) receptor and 5-HTT binding potentials (BP(ND)s) in healthy humans, in vivo. Positron emission tomography and selective radioligands [(11)C]WAY100635 and [(11)C]MADAM were used to evaluate binding potentials for 5-HT(1A) receptors (14 women and 14 men) and 5-HTT (8 women and 10 men). The binding potentials were estimated both on the level of anatomical regions and voxel wise, derived by the simplified reference tissue model and wavelet/Logan plot parametric image techniques respectively. Compared to men, women had significantly higher 5-HT(1A) receptor and lower 5-HTT binding potentials in a wide array of cortical and subcortical brain regions. In women, there was a positive correlation between 5-HT(1A) receptor and 5-HTT binding potentials for the region of hippocampus. Sex differences in 5-HT(1A) receptor and 5-HTT BP(ND) may reflect biological distinctions in the serotonin system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result of the present study may help in understanding sex differences in drug treatment responses to drugs affecting the serotonin system.

  17. Qualitative and quantitative comparison of PET/CT and PET/MR imaging in clinical practice.

    Science.gov (United States)

    Al-Nabhani, Khalsa Z; Syed, Rizwan; Michopoulou, Sofia; Alkalbani, Jokha; Afaq, Asim; Panagiotidis, Emmanouil; O'Meara, Celia; Groves, Ashley; Ell, Peter; Bomanji, Jamshed

    2014-01-01

    The aim of this study was to prospectively compare whole-body PET/MR imaging and PET/CT, qualitatively and quantitatively, in oncologic patients and assess the confidence and degree of inter- and intraobserver agreement in anatomic lesion localization. Fifty patients referred for staging with known cancers underwent PET/CT with low-dose CT for attenuation correction immediately followed by PET/MR imaging with 2-point Dixon attenuation correction. PET/CT scans were obtained according to standard protocols (56 ± 20 min after injection of an average 367 MBq of (18)F-FDG, 150 MBq of (68)Ga-DOTATATE, or 333.8 MBq of (18)F-fluoro-ethyl-choline; 2.5 min/bed position). PET/MR was performed with 5 min/bed position. Three dual-accredited nuclear medicine physicians/radiologists identified the lesions and assigned each to an exact anatomic location. The image quality, alignment, and confidence in anatomic localization of lesions were scored on a scale of 1-3 for PET/CT and PET/MR imaging. Quantitative analysis was performed by comparing the standardized uptake values. Intraclass correlation coefficients and the Wilcoxon signed-rank test were used to assess intra- and interobserver agreement in image quality, alignment, and confidence in lesion localization for the 2 modalities. Two hundred twenty-seven tracer-avid lesions were identified in 50 patients. Of these, 225 were correctly identified on PET/CT and 227 on PET/MR imaging by all 3 observers. The confidence in anatomic localization improved by 5.1% when using PET/MR imaging, compared with PET/CT. The mean percentage interobserver agreement was 96% for PET/CT and 99% for PET/MR imaging, and intraobserver agreement in lesion localization across the 2 modalities was 93%. There was 10% (5/50 patients) improvement in local staging with PET/MR imaging, compared with PET/CT. In this first study, we show the effectiveness of whole-body PET/MR imaging in oncology. There is no statistically significant difference between PET

  18. Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [{sup 68}Ga]SB3 and PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Maina, Theodosia; Charalambidis, David; Nock, Berthold A. [INRASTES, NCSR ' ' Demokritos' ' , Molecular Radiopharmacy, Athens (Greece); Bergsma, Hendrik; Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Kulkarni, Harshad R.; Mueller, Dirk; Baum, Richard P. [Zentralklinik, Molecular Radiotherapy and Molecular Imaging, Bad Berka (Germany); Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Radiology, Rotterdam (Netherlands)

    2016-05-15

    Gastrin-releasing peptide receptors (GRPR) represent attractive targets for tumor diagnosis and therapy because of their overexpression in major human cancers. Internalizing GRPR agonists were initially proposed for prolonged lesion retention, but a shift of paradigm to GRPR antagonists has recently been made. Surprisingly, radioantagonists, such as [{sup 99m}Tc]DB1 ({sup 99m}Tc-N{sub 4}'-DPhe{sup 6},Leu-NHEt{sup 13}BBN(6-13)), displayed better pharmacokinetics than radioagonists, in addition to their higher inherent biosafety. We introduce here [{sup 68}Ga]SB3, a [{sup 99m}Tc]DB1 mimic-carrying, instead of the {sup 99m}Tc-binding tetraamine, the chelator DOTA for labeling with the PET radiometal {sup 68}Ga. Competition binding assays of SB3 and [{sup nat}Ga]SB3 were conducted against [{sup 125}I-Tyr{sup 4}]BBN in PC-3 cell membranes. Blood samples collected 5 min postinjection (pi) of the [{sup 67}Ga]SB3 surrogate in mice were analyzed using high-performance liquid chromatography (HPLC) for degradation products. Likewise, biodistribution was performed after injection of [{sup 67}Ga]SB3 (37 kBq, 100 μL, 10 pmol peptide) in severe combined immunodeficiency (SCID) mice bearing PC-3 xenografts. Eventually, [{sup 68}Ga]SB3 (283 ± 91 MBq, 23 ± 7 nmol) was injected into 17 patients with breast (8) and prostate (9) cancer. All patients had disseminated disease and had received previous therapies. PET/CT fusion images were acquired 60-115 min pi. SB3 and [{sup nat}Ga]SB3 bound to the human GRPR with high affinity (IC{sub 50}: 4.6 ± 0.5 nM and 1.5 ± 0.3 nM, respectively). [{sup 67}Ga]SB3 displayed good in vivo stability (>85 % intact at 5 min pi). [{sup 67}Ga]SB3 showed high, GRPR-specific and prolonged retention in PC-3 xenografts (33.1 ± 3.9%ID/g at 1 h pi - 27.0 ± 0.9%ID/g at 24 h pi), but much faster clearance from the GRPR-rich pancreas (∼160%ID/g at 1 h pi to <17%ID/g at 24 h pi) in mice. In patients, [{sup 68}Ga]SB3 elicited no adverse effects and

  19. Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Tao; Tsui, Benjamin M. W.; Li, Xin; Vranesic, Melin; Lodge, Martin A.; Gulaldi, Nedim C. M.; Szabo, Zsolt, E-mail: zszabo@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287 (United States)

    2015-11-15

    Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method in pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent

  20. (64)Cu- and (68)Ga-Based PET Imaging of Folate Receptor-Positive Tumors: Development and Evaluation of an Albumin-Binding NODAGA-Folate.

    Science.gov (United States)

    Farkas, Renáta; Siwowska, Klaudia; Ametamey, Simon M; Schibli, Roger; van der Meulen, Nicholas P; Müller, Cristina

    2016-06-06

    A number of folate-based radioconjugates have been synthesized and evaluated for nuclear imaging purposes of folate receptor (FR)-positive tumors and potential therapeutic application. A common shortcoming of radiofolates is, however, a significant accumulation of radioactivity in the kidneys. This situation has been faced by modifying the folate conjugate with an albumin-binding entity to increase the circulation time of the radiofolate, which led to significantly improved tumor-to-kidney ratios. The aim of this study was to develop an albumin-binding folate conjugate with a NODAGA-chelator (rf42) for labeling with (64)Cu and (68)Ga, allowing application for PET imaging. The folate conjugate rf42 was synthesized in 8 steps, with an overall yield of 5%. Radiolabeling with (64)Cu and (68)Ga was carried out at room temperature within 10 min resulting in (64)Cu-rf42 and (68)Ga-rf42 with >95% radiochemical purity. (64)Cu-rf42 and (68)Ga-rf42 were stable (>95% intact) in phosphate-buffered saline over more than 4 half-lives of the corresponding radionuclide. In vitro, the plasma protein-bound fraction of (64)Cu-rf42 and (68)Ga-rf42 was determined to be >96%. Cell experiments proved FR-specific uptake of both radiofolates, as it was reduced to 68)Ga-rf42 was found in KB tumors of mice (14.52 ± 0.99% IA/g and 11.92 ± 1.68% IA/g, respectively) at 4 h after injection. The tumor-to-kidney ratios were in the range of 0.43-0.55 over the first 4 h of investigation. At later time points (up to 72 h p.i. of (64)Cu-rf42) the tumor-to-kidney ratio increased to 0.73. High-quality PET/CT images were obtained 2 h after injection of (64)Cu-rf42 and (68)Ga-rf42, respectively, allowing distinct visualization of tumors and kidneys. Comparison of PET/CT images obtained with (64)Cu-rf42 and a (64)Cu-labeled DOTA-folate conjugate (cm10) clearly proved the superiority of NODAGA for stable coordination of (64)Cu. (64)Cu-cm10 showed high liver uptake, most probably as a consequence of

  1. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  2. Modification of dopamine D2 receptor activity by pergolide in Parkinson's disease : An in vivo study by PET

    NARCIS (Netherlands)

    Linazasoro, G; Obeso, JA; Gomez, JC; Martinez, M; Antonini, A; Leenders, KL

    1999-01-01

    It is well known that chronic administration of pergolide and other dopamine agonists may induce a downregulation of dopamine D2 receptors in the rat model of Parkinson's disease (PD). To our knowledge, this effect has not been demonstrated in vivo in patients with PD. At present, the status of

  3. Automated preparation of the dopamine D{sub 2/3} receptor agonist ligand [{sup 11}C]-(+)-PHNO for human PET imaging studies

    Energy Technology Data Exchange (ETDEWEB)

    Plisson, Christophe, E-mail: Christophe.2.plisson@gsk.com [GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London W12 0NN (United Kingdom); Huiban, Mickael; Pampols-Maso, Sabina; Singleton, Goerkem; Hill, Samuel P.; Passchier, Jan [GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London W12 0NN (United Kingdom)

    2012-02-15

    Carbon-11 labelled (+)-4-Propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([{sup 11}C]-(+)-PHNO) is used as a high-affinity state, dopamine D{sub 2/3} receptor ligand in clinical PET studies. To facilitate its use, robust, rapid, efficient and GMP compliant methods are required for the manufacturing and QC testing processes. Additionally, to allow for full quantification of the resulting signal in the CNS, a reliable method is required to establish the parent plasma concentration over the course of the scan. This paper provides high-quality methods to support clinical application of [{sup 11}C]-(+)-PHNO. - Highlights: Black-Right-Pointing-Pointer Fully automated synthesis of [{sup 11}C]-(+)-PHNO. Black-Right-Pointing-Pointer Rapid multi-step synthesis and QC analysis. Black-Right-Pointing-Pointer Reproducible synthesis process typically yielding more than 3 GBq of [{sup 11}C]-(+)-PHNO. Black-Right-Pointing-Pointer Very low failure rate.

  4. Cross sectional PET study of cerebral adenosine A{sub 1} receptors in premanifest and manifest Huntington's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matusch, Andreas; Elmenhorst, David [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Saft, Carsten; Kraus, Peter H.; Gold, Ralf [St. Josef Hospital, Ruhr University Bochum, Department of Neurology, Huntington Centre NRW, Bochum (Germany); Hartung, Hans-Peter [Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany); Bauer, Andreas [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany)

    2014-06-15

    To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). We quantified the cerebral binding potential (BP{sub ND}) of the A{sub 1}AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [{sup 18} F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36). Cerebral A{sub 1}AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p <.01, in the thalamus on average). Across stages a successive reduction of A{sub 1}AR BP{sub ND} was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p <.01, in the caudatus and amygdala. There was a strong correlation between A{sub 1}AR BP{sub ND} and years to onset. Before onset of HD, the assumed annual rates of change of A{sub 1}AR density were -1.2 % in the caudatus, -1.7 % in the thalamus and -3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively. Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism. (orig.)

  5. Comparison of F-18-FLT PET and F-18-FDG PET in esophageal cancer

    NARCIS (Netherlands)

    van Westreenen, HL; Cobben, DCP; Jager, PL; van Dullemen, HM; Wesseling, J; Elsinga, PH; Plukker, JT

    F-18-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer F-18-fluoro-3'-deoxy-3'-L-fluorothymidine (F-18-FLT) might not have these drawbacks. The aim of this study

  6. Quantitative imaging of protein targets in the human brain with PET

    Science.gov (United States)

    Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

    2015-11-01

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

  7. Development of radio tracers for the radiopharmaceutical characterization of Eph receptors; Entwicklung von Radiotracern fuer die radiopharmakologische Charakterisierung von Eph-Rezeptoren

    Energy Technology Data Exchange (ETDEWEB)

    Pretze, Marc

    2014-06-17

    In the frame of the thesis fundamental work was performed for two F-18 fluorination agents including a trial to use small molecules as radiotracers. Peptide and small molecules ware labeled with F-18 that are based on selective extra and intra cellular inhibitors foe Eph receptors. Eph receptors are supposed to be an adequate target for tumor diagnostics and therapy. The new potential radiotracer shows high in vitro stability (rat plasma) and was tested with melanoma cell lines. The used peptide sequences are discussed in detail.

  8. Pet Allergy Quiz

    Science.gov (United States)

    ... Treatments ▸ Allergies ▸ Pet Allergy ▸ Pet Allergy Quiz Share | Pet Allergy Quiz More than half of U.S. households ... cat family. Yet, millions of people suffer from pet allergies. Take this quiz to test your knowledge ...

  9. Utility of (18)F-fluoroestradiol ((18)F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.

    Science.gov (United States)

    Lin, Frank I; Gonzalez, E M; Kummar, S; Do, K; Shih, J; Adler, S; Kurdziel, K A; Ton, A; Turkbey, B; Jacobs, P M; Bhattacharyya, S; Chen, A P; Collins, J M; Doroshow, J H; Choyke, P L; Lindenberg, M L

    2017-03-01

    Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. (18)F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes (18)F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with (18)F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with (18)F-FES 1-5 days post administration of Z-endoxifen. Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

  10. Utility of {sup 18}F-fluoroestradiol ({sup 18}F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Frank I. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Gonzalez, E.M.; Kurdziel, K.A.; Ton, A.; Turkbey, B.; Choyke, P.L.; Lindenberg, M.L. [National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Kummar, S.; Do, K.; Collins, J.M.; Doroshow, J.H. [National Cancer Institute, Division of Cancer Treatment and Diagnosis and Center for Cancer Research, Bethesda, MD (United States); Shih, J. [National Cancer Institute, NIH, Biometric Research Program, Bethesda, MD (United States); Adler, S. [Leidos Biomedical Research, Inc., Clinical Research Directorate/Clinical Monitoring Research Program, Frederick, MD (United States); Jacobs, P.M. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); Bhattacharyya, S. [Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States); Chen, A.P. [National Cancer Institute, Early Clinical Trials Development Program, DCTD, Bethesda, MD (United States)

    2017-03-15

    Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. {sup 18}F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes {sup 18}F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with {sup 18}F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with {sup 18}F-FES 1-5 days post administration of Z-endoxifen. Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy. (orig.)

  11. Automatic extraction of forward stroke volume using dynamic PET/CT

    DEFF Research Database (Denmark)

    Harms, Hans; Tolbod, Lars Poulsen; Hansson, Nils Henrik;

    Background: Dynamic PET can be used to extract forward stroke volume (FSV) by the indicator dilution principle. The technique employed can be automated and is in theory independent on the tracer used and may therefore be added to any dynamic cardiac PET protocol. The aim of this study was to vali......Background: Dynamic PET can be used to extract forward stroke volume (FSV) by the indicator dilution principle. The technique employed can be automated and is in theory independent on the tracer used and may therefore be added to any dynamic cardiac PET protocol. The aim of this study...... was to validate automated methods for extracting FSV directly from dynamic PET studies for two different tracers and to examine potential scanner hardware bias. Methods: 21 subjects underwent a dynamic 27 min 11C-acetate PET scan on a Siemens Biograph TruePoint 64 PET/CT scanner (scanner I). In addition, 8...... subjects underwent a dynamic 6 min 15O-water PET scan followed by a 27 min 11C-acetate PET scan on a GE Discovery ST PET/CT scanner (scanner II). The LV-aortic time-activity curve (TAC) was extracted automatically from dynamic PET data using cluster analysis. The first-pass peak was isolated by automatic...

  12. Positron Emission Tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1990-01-01

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

  13. Positron Emission Tomography (PET)

    Science.gov (United States)

    Welch, M. J.

    1990-01-01

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

  14. Synthesis of a [2-pyridinyl-18F]-labelled fluoro derivative of (-)-cytisine as a candidate radioligand for brain nicotinic alpha4beta2 receptor imaging with PET.

    Science.gov (United States)

    Roger, Gaëlle; Lagnel, Béatrice; Rouden, Jacques; Besret, Laurent; Valette, Héric; Demphel, Stéphane; Gopisetti, JaganMohan; Coulon, Christine; Ottaviani, Michele; Wrenn, Lori A; Letchworth, Sharon R; Bohme, Georg A; Benavides, Jesus; Lasne, Marie-Claire; Bottlaender, Michel; Dollé, Frédéric

    2003-12-01

    In recent years, there has been considerable effort to design and synthesize radiotracers suitable for use in Positron Emission Tomography (PET) imaging of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) subtype. A new fluoropyridinyl derivative of (-)-cytisine (1), namely (-)-9-(2-fluoropyridinyl)cytisine (3, K(i) values of 24 and 3462 nM for the alpha4beta2 and alpha7 nAChRs subtypes, respectively) has been synthesized in four chemical steps from (-)-cytisine and labelled with fluorine-18 (T(1/2): 119.8 min) using an efficient two-step radiochemical process [(a). nucleophilic heteroaromatic ortho-radiofluorination using the corresponding N-Boc-protected nitro-derivative, (b). TFA removal of the Boc protective group]. Typically, 20-45 mCi (0.74-1.67 GBq) of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3, 2-3 Ci/micromol or 74-111 GBq/micromol) were easily obtained in 70-75 min starting from a 100 mCi (3.7 GBq) aliquot of a cyclotron-produced [18F]fluoride production batch (20-45% non decay-corrected yield based on the starting [18F]fluoride). The in vivo pharmacological profile of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) was evaluated in rats with biodistribution studies and brain radioactivity monitoring using intracerebral radiosensitive beta-microprobes. The observed in vivo distribution of the radiotracer in brain was rather uniform, and did not match with the known regional densities of nAChRs. It was also significantly different from that of the parent compound (-)-[3H]cytisine. Moreover, competition studies with (-)-nicotine (5 mg/kg, 5 min before the radiotracer injection) did not reduce brain uptake of the radiotracer. These experiments clearly indicate that (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) does not have the required properties for imaging nAChRs using PET.

  15. Facile labelling of an anti-epidermal growth factor receptor nanobody with {sup 68}Ga via a novel bifunctional desferal chelate for immuno-PET

    Energy Technology Data Exchange (ETDEWEB)

    Vosjan, Maria J.W.D.; Perk, Lars R.; Stigter van Walsum, Marijke [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); Roovers, Rob C.; Bergen en Henegouwen, Paul M.P. van [Utrecht University, Cellular Dynamics, Science Faculty, Utrecht (Netherlands); Visser, Gerard W.M. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Dongen, Guus A.M.S. van [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands)

    2011-04-15

    The {proportional_to}15 kDa variable domains of camelid heavy-chain-only antibodies (called Nanobodies {sup registered}) have the flexibility to be formatted as monovalent, monospecific, multivalent or multispecific single chain proteins with either fast or slow pharmacokinetics. We report the evaluation of the fast kinetic anti-epidermal growth factor receptor (EGFR) Nanobody 7D12, labelled with {sup 68}Ga via the novel bifunctional chelate (BFC) p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS). Df-Bz-NCS has recently been introduced as the chelate of choice for {sup 89}Zr immuno-positron emission tomography (PET). Nanobody 7D12 was premodified with Df-Bz-NCS at pH 9. Radiolabelling with purified {sup 68}Ga was performed at pH 5.0-6.5 for 5 min at room temperature. For in vitro stability measurements in storage buffer (0.25 M NaOAc with 5 mg ml{sup -1} gentisic acid, pH 5.5) at 4 C or in human serum at 37 C, a mixture of {sup 67}Ga and {sup 68}Ga was used. Biodistribution and immuno-PET studies of {sup 68}Ga-Df-Bz-NCS-7D12 were performed in nude mice bearing A431 xenografts using {sup 89}Zr-Df-Bz-NCS-7D12 as the reference conjugate. The Df-Bz-NCS chelate was conjugated to Nanobody 7D12 with a chelate to Nanobody molar substitution ratio of 0.2:1. The overall {sup 68}Ga radiochemical yield was 55-70% (not corrected for decay); specific activity was 100-500 MBq/mg. Radiochemical purity of the conjugate was >96%, while the integrity and immunoreactivity were preserved. {sup 68/67}Ga-Df-Bz-NCS-7D12 was stable in storage buffer as well as in human serum during a 5-h incubation period (<2% radioactivity loss). In biodistribution studies the {sup 68}Ga-labelled Nanobody 7D12 showed high uptake in A431 tumours (ranging from 6.1 {+-} 1.3 to 7.2 {+-} 1.5%ID/g at 1-3 h after injection) and high tumour to blood ratios, which increased from 8.2 to 14.4 and 25.7 at 1, 2 and 3 h after injection, respectively. High uptake was also observed in the kidneys. Biodistribution was

  16. 5HT{sub 2} receptors in cerebral cortex of migraineurs studied using PET and {sup 18}F-fluorosetoperoene

    Energy Technology Data Exchange (ETDEWEB)

    Chabriat, H.; Tehindrazanarivelo, A.; Vera, P.; Samson, Y.; Pappata, S.; Boullais, N.; Bousser, M.G. [Hospital Saint Antoine, Paris (France)

    1995-04-01

    Since the brain 5HT{sub 2} might be implicated in migraine pathogenesis, the authors have used positron emission tomography and {sup 18}F-fluorosetoperone, a 5HT{sub 2} specific radioligand, to investigate in vivo the cortical 5HT{sub 2} receptors in migraine subjects. Nine migraineurs who had either migraine with and without aura or only migraine without aura were studied between attacks. 12 unmedicated healthy subjects of similar mean age were used as controls. Brain radioactivity was measured after {sup 18}F-setoperone IV injection for 90 min. A decrease of the regional specific distribution volumes (SDV) of the ligand was observed both in migraineurs and in controls. The age adjusted group means of SDV did not differ between patients and controls for the whole and for the right or left frontal, temporal, parietal and occipital cortex. These results suggest that cortical 5HT{sub 2} receptors may be unaltered between attacks in migraine sufferers. 30 refs., 4 figs., 2 tabs.

  17. [Non-invasive evaluation of the cardiac autonomic nervous system by PET]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-01

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

  18. [Non-invasive evaluation of the cardiac autonomic nervous system by PET

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-01

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

  19. Simplified PET measurement for evaluating histamine H{sub 1} receptors in human brains using [{sup 11}C]doxepin

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Hideki [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Kimura, Yuichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)]. E-mail: ukimura@ieee.org; Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Sasaki, Toru [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Tashiro, Manabu [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Yanai, Kazuhiko [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)

    2004-11-01

    The aim of this study was to develop simplified positron emission tomography measurement using [{sup 11}C]doxepin ([{sup 11}C]DOX) to evaluate histamine H{sub 1} receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [{sup 11}C]DOX, estimated quantitatively with a two-compartment model, and the [{sup 11}C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [{sup 11}C]DOX-H1R binding.

  20. Particle Accelerators for PET radionuclides

    DEFF Research Database (Denmark)

    Jensen, Mikael

    2012-01-01

    The requirements set for particle accelerators for production of radioactive isotopes for PET can easily be derived from first principles. The simple general need is for proton beams with energy in the region 10–20 MeV and current 20–100 microAmps. This is most reliably and cost-effectively achie......The requirements set for particle accelerators for production of radioactive isotopes for PET can easily be derived from first principles. The simple general need is for proton beams with energy in the region 10–20 MeV and current 20–100 microAmps. This is most reliably and cost...... different manufacturers will be discussed the light of what is actually needed for a given PET site operation. Alternatives to the conventional cyclotron have been proposed and tested but have at present very limited use. These alternatives will be discussed, as well as the future possibilities of supplying...... point of demand tracer production with very small cyclotrons of energy well below 10 MeV. The authors best advice at present for new PET sites is to negotiate for conventional cyclotron solutions from experienced manufacturers. It is the combined performance of cyclotron and target in terms of available...

  1. Imaging of I{sub 2}-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-{sup 11}C]tolyl)-4,5-dihydro-1H-imidazole ([{sup 11}C]FTIMD)

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori, E-mail: kawamur@nirs.go.j [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Naganawa, Mika [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Konno, Fujiko; Yui, Joji [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Wakizaka, Hidekatsu [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Yamasaki, Tomoteru; Yanamoto, Kazuhiko; Hatori, Akiko [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Takei, Makoto [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Tokyo Nuclear Services Co., Ltd., Tokyo 110-0016 (Japan); Yoshida, Yuichiro [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); SHI Accelerator Service Ltd., Tokyo 141-0032 (Japan); Sakaguchi, Kazuya [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Fukumura, Toshimitsu [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Kimura, Yuichi [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Zhang, Ming-Rong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2010-07-15

    Introduction: Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I{sub 1}R and I{sub 2}R). I{sub 2}Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I{sub 2}Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I{sub 2}Rs by PET. We labeled a selective I{sub 2}R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole (FTIMD) with {sup 11}C and performed the first imaging of I{sub 2}Rs by PET using 2-(3-fluoro-[4-{sup 11}C]tolyl)-4,5-dihydro-1H-imidazole ([{sup 11}C]FTIMD). Methods: [{sup 11}C]FTIMD was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [{sup 11}C]methyl iodide in the presence of tris(dibenzylideneacetone)dipalladium(0) and tri(o-tol)phosphine. Biodistribution was investigated in rats by tissue dissection. [{sup 11}C]FTIMD metabolites were measured in brain tissues and plasma. Dynamic PET scans were acquired in rats, and the kinetic parameters estimated. Results: [{sup 11}C]FTIMD was successfully synthesized with a suitable radioactivity for the injection. Co-injection with 0.1 mg/kg of cold FTIMD and BU224 induced a significant reduction in the brain-to-blood ratio 15 and 30 min after the injection. In metabolite analysis, unchanged [{sup 11}C]FTIMD in the brain was high (98%) 30 min after the injection. In PET studies, high radioactivity levels were observed in regions with a high density of I{sub 2}R. The radioactivity levels and V{sub T} values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control. Conclusion: [{sup 11}C]FTIMD showed specific binding to I{sub 2}Rs in rat brains with a high density of I{sub 2}R.

  2. PARAMETRIC IMAGING AND TEST-RETEST VARIABILITY OF 11C-(+)-PHNO BINDING TO D2/D3 DOPAMINE RECEPTORS IN HUMANS ON THE HRRT PET SCANNER

    Science.gov (United States)

    Gallezot, Jean-Dominique; Zheng, Ming-Qiang; Lim, Keunpoong; Lin, Shu-fei; Labaree, David; Matuskey, David; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E.; Malison, Robert T.

    2014-01-01

    11C-(+)-PHNO is an agonist radioligand for imaging dopamine D2 and D3 receptors in the human brain with PET. In this study we evaluated the reproducibility of 11C-(+)-PHNO binding parameters using a within-day design and assessed parametric imaging methods. Methods Repeated studies were performed in eight subjects, with simultaneous measurement of the arterial input function and plasma free fraction. Two 11C-(+)-PHNO scans on the same subject were separated by 5.4±0.7 h. After evaluating compartment models, 11C-(+)-PHNO volumes of distribution VT and VT/fP and binding potentials BPND, BPP and BPF were quantified using the multilinear analysis MA1, with the cerebellum as reference region. Parametric images of BPND were also computed using SRTM and SRTM2. Results The test-retest variability of 11C-(+)-PHNO BPND was 9% in D2-rich regions (caudate and putamen). Among D3-rich regions, variability was low in pallidum (6%), but higher in substantia nigra (19%), thalamus (14%) and hypothalamus (21%). No significant mass carry-over effect was observed in D3-rich regions, although a trend in BPND was present in substantia nigra (−14±15%). Due to the relatively fast kinetics, low noise BPND parametric images were obtained with both SRTM and SRTM2 without spatial smoothing. Conclusion 11C-(+)-PHNO can be used to compute low noise parametric images in both D2 and D3 rich regions in humans. PMID:24732151

  3. Association between cerebral cannabinoid 1 receptor availability and body mass index in patients with food intake disorders and healthy subjects: a [(18)F]MK-9470 PET study.

    Science.gov (United States)

    Ceccarini, J; Weltens, N; Ly, H G; Tack, J; Van Oudenhove, L; Van Laere, K

    2016-07-12

    Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12.5-40.6 kg/m(2)) and 26 age-, gender- and average BMI-matched healthy subjects (BMI range=18.5-26.6 kg/m(2)). The association between regional CB1R availability and BMI was assessed within predefined homeostatic and reward-related regions of interest using voxel-based linear regression analyses. CB1R availability was inversely associated with BMI in homeostatic brain regions such as the hypothalamus and brainstem areas in both patients with FID and healthy subjects. However, in FID patients, CB1R availability was also negatively correlated with BMI throughout the mesolimbic reward system (midbrain, striatum, insula, amygdala and orbitofrontal cortex), which constitutes the key circuit implicated in processing appetitive motivation and hedonic value of perceived food rewards. Our results indicate that the cerebral homeostatic CB1R system is inextricably linked to BMI, with additional involvement of reward areas under conditions of disordered body weight.

  4. In Vivo Stabilization of a Gastrin-Releasing Peptide Receptor Antagonist Enhances PET Imaging and Radionuclide Therapy of Prostate Cancer in Preclinical Studies.

    Science.gov (United States)

    Chatalic, Kristell L S; Konijnenberg, Mark; Nonnekens, Julie; de Blois, Erik; Hoeben, Sander; de Ridder, Corrina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; van Gent, Dik C; Nock, Berthold A; Maina, Theodosia; van Weerden, Wytske M; de Jong, Marion

    2016-01-01

    A single tool for early detection, accurate staging, and personalized treatment of prostate cancer (PCa) would be a major breakthrough in the field of PCa. Gastrin-releasing peptide receptor (GRPR) targeting peptides are promising probes for a theranostic approach for PCa overexpressing GRPR. However, the successful application of small peptides in a theranostic approach is often hampered by their fast in vivo degradation by proteolytic enzymes, such as neutral endopeptidase (NEP). Here we show for the first time that co-injection of a NEP inhibitor (phosphoramidon (PA)) can lead to an impressive enhancement of diagnostic sensitivity and therapeutic efficacy of the theranostic (68)Ga-/(177)Lu-JMV4168 GRPR-antagonist. Co-injection of PA (300 µg) led to stabilization of (177)Lu-JMV4168 in murine peripheral blood. In PC-3 tumor-bearing mice, PA co-injection led to a two-fold increase in tumor uptake of (68)Ga-/(177)Lu-JMV4168, 1 h after injection. In positron emission tomography (PET) imaging with (68)Ga-JMV4168, PA co-injection substantially enhanced PC-3 tumor signal intensity. Radionuclide therapy with (177)Lu-JMV4168 resulted in significant regression of PC-3 tumor size. Radionuclide therapy efficacy was confirmed by production of DNA double strand breaks, decreased cell proliferation and increased apoptosis. Increased survival rates were observed in mice treated with (177)Lu-JMV4168 plus PA as compared to those without PA. This data shows that co-injection of the enzyme inhibitor PA greatly enhances the theranostic potential of GRPR-radioantagonists for future application in PCa patients.

  5. Radiosynthesis and biological evaluation of a promising {sigma}{sub 2}-receptor ligand radiolabeled with fluorine-18 or iodine-125 as a PET/SPECT probe for imaging breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tu Zhude; Xu Jinbin; Jones, Lynne A.; Li Shihong; Zeng Dexing [Division of Radiological Sciences, Washington University School of Medicine, Campus Box 8225, 510 South Kingshighway Blvd., St. Louis, MO 63110 (United States); Kung Meiping; Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Mach, Robert H., E-mail: rhmach@mir.wustl.ed [Division of Radiological Sciences, Washington University School of Medicine, Campus Box 8225, 510 South Kingshighway Blvd., St. Louis, MO 63110 (United States)

    2010-12-15

    Sigma-2 receptors represent an endogenous marker for proliferation in solid tumors. The high affinity, high selectivity {sigma}{sub 2} receptor ligand N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl) -2-(2-fluoroethoxy)-5-iodo-3-methoxybenzamide (3) was separately radiolabeled with F-18 and I-125. The radiolabeling yield was 30% and 70% for [{sup 18}F]3 and [{sup 125}I]3, respectively. Studies of [{sup 125}I]3 using murine 66 breast tumor membrane homogenates and evaluation of [{sup 18}F]3 and [{sup 125}I]3 in 66 tumor-bearing mice indicate that this ligand has potential as a PET or a SPECT probe for imaging {sigma}{sub 2} receptors in breast cancer.

  6. Imaging corn plants with PhytoPET, a modular PET system for plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.; Kross, B.; McKisson, J.; McKisson, J. E.; Weisenberger, A. G.; Xi, W.; Zorn, C.; Bonito, G.; Howell, C. R.; Reid, C. D.; Crowell, A.; Cumberbatch, L. C.; Topp, C.; Smith, M. F.

    2013-11-01

    PhytoPET is a modular positron emission tomography (PET) system designed specifically for plant imaging. The PhytoPET design allows flexible arrangements of PET detectors based on individual standalone detector modules built from single Hamamatsu H8500 position sensitive photomultiplier tubes and pixelated LYSO arrays. We have used the PhytoPET system to perform preliminary corn plant imaging studies at the Duke University Biology Department Phytotron. Initial evaluation of the PhytoPET system to image the biodistribution of the positron emitting tracer {sup 11}C in corn plants is presented. {sup 11}CO{sub 2} is loaded into corn seedlings by a leaf-labeling cuvette and translocation of {sup 11}C-sugars is imaged by a flexible arrangement of PhytoPET modules on each side. The PhytoPET system successfully images {sup 11}C within corn plants and allows for the dynamic measurement of {sup 11}C-sugar translocation from the leaf to the roots.

  7. [{sup 18}F]p-MPPF: A Radiolabeled Antagonist for the Study of 5-HT{sub 1A} Receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Plenevaux, A. E-mail: Alain.Plenevaux@ulg.ac.be; Lemaire, C.; Aerts, J.; Lacan, G.; Rubins, D.; Melega, W.P.; Brihaye, C.; Degueldre, C.; Fuchs, S.; Salmon, E.; Maquet, P.; Laureys, S.; Damhaut, P.; Weissmann, D.; Le Bars, D.; Pujol, J.-F.; Luxen, A

    2000-07-01

    This paper summarizes the present status of the researches conducted with [{sup 18}F]4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluoro benzamido]ethyl] -piperazine known as [{sup 18}F]p-MPPF, a new 5-HT{sub 1A} antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism.

  8. Development of a New Folate-Derived Ga-68-Based PET Imaging Agent.

    Science.gov (United States)

    Brand, Christian; Longo, Valerie A; Groaning, Mike; Weber, Wolfgang A; Reiner, Thomas

    2017-02-13

    The folate receptor (FR) has emerged as an interesting diagnostic and therapeutic drug target with many potential applications in oncologic and inflammatory disorders. It was therefore the aim of this study to develop a folate-derived Ga-68-based positron emission tomography (PET) imaging tracer that is straightforward to radiolabel and could be broadly used in clinical studies. We validated its target binding affinity and specificity and compared it to [(99m)Tc]EC20, the folate single-photon emission computed tomography (SPECT) imaging tracer that has been most extensively studied clinically so far. The new folic acid-derived PET imaging agent is linked via a polyethyleneglycol linker to the chelator 1,4,7-triazacyclononane-1,4,7-trisacetic acid (NOTA). This new compound, NOTA-folate, was labeled with gallium-68. We tested the probe's stability in human plasma and its selectivity in vitro, using the FR-positive KB cell line as well as the FR-negative A549 cell line. The pharmacokinetic profile of [(68)Ga]NOTA-folate was evaluated in FR-positive KB mouse xenografts. Following intravenous injection of [(68)Ga]NOTA-folate (383 ± 53 μCi), PET/computed tomography (CT) imaging studies as well as biodistribution studies were performed using KB tumor-bearing mice (n = 3). In vitro as well as in vivo studies were performed in parallel with the SPECT imaging tracer [(99m)Tc]EC20. In comparison to [(99m)Tc]EC20 (radiochemical yield (RCY) = 82.0 ± 2.9 %, 91.8 ± 2.0 % purity), similar radiochemical yield (87.2 ± 6.9 %) and radiochemical purity (95.6 ± 1.8 %) could be achieved for [(68)Ga]NOTA-folate. For both tracers, we observed high affinity for FR-positive cells in vitro and high plasma stability. In PET/CT and biodistribution studies, [(68)Ga]NOTA-folate appeared to display slightly superior in vivo performance in comparison to [(99m)Tc]EC20. In detail, (68)Ga-NOTA-folate showed very good tumor uptake and retention (6.6 ± 1.1 %ID/g), relatively

  9. Visualization of micro glial activation in the L.A.S. by PET molecular imaging: use of a tracer specific of T.S.P.O, the [{sup 18}F]-D.P.A.-714; Visualisation de l'activation microgliale dans la SLA par l'imagerie moleculaire TEP: utilisation d'un traceur specifique des TSPO, le [{sup 18}F]-DPA-714

    Energy Technology Data Exchange (ETDEWEB)

    Tauber, C.; Vercouillie, J.; Le Borgne, A.; Guilloteau, D.; Venel, Y.; Le Pogam, A.; Aesch-Prunier, C.; Corcia, P.; Baulieu, J.L. [CHU de Tours, Inserm U930, medecine nucleaire, 37 (France); Kassiou, M. [Brain and Mind Research Institute, Sydney (Australia)

    2010-07-01

    The [{sup 18}F]-D.P.A.-714 (N, N-diethyl-2-[2-(4-(2-fluoro-ethoxy)phenyl)-5,7-dimethyl-pyrazolo1,5-a] pyrimidine-3-yl]-acetamide) is a new ligand of high affinity of T.S.P.O. (trans-locator proteins [18kDa], current name of Peripheral-type benzodiazepine receptor) expressed during micro glial activation. The aim of this work was to explore the feasibility of the cerebral PET with [{sup 18}F]-D.P.A.-714 and to evaluate the micro glial activation in the lateral amyotrophic scleroses (L.A.S.). PET with this new ligand is feasible in man. The preliminary results do not provide ant argument for a specific micro glial activation in the brain of patients suffering of L.A.S.. (N.C.)

  10. Senior Pets

    Science.gov (United States)

    ... by Animal/Species Browse by Topic Browse by Discipline Resources Tools for K-12 Educators You are here: Home | Public Resources | Pet ... to 6 years of age. Contrary to popular belief, dogs do not age at a rate of 7 human years for each year in dog years. Age ...

  11. Pet Therapy.

    Science.gov (United States)

    Kavanagh, Kim

    1994-01-01

    This resource guide presents information on a variety of ways that animals can be used as a therapeutic modality with people having disabilities. Aspects addressed include: pet ownership and selection criteria; dogs (including service dogs, hearing/signal dogs, seeing leader dogs, and social/specialty dogs); horseriding for both therapy and fun;…

  12. Radiosynthesis and initial evaluation of [{sup 18}F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Alan A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: alan.wilson@camhpet.ca; Garcia, Armando; Parkes, Jun [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); McCormick, Patrick [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Houle, Sylvain; Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)

    2008-04-15

    Introduction: A novel [{sup 18}F]-radiolabelled phenoxyanilide, [{sup 18}F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [{sup 18}F]-FEPPA and two other radiotracers for imaging PBR, namely [{sup 11}C]-PBR28 and [{sup 11}C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [{sup 18}F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [{sup 18}F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a K{sub i} of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [{sup 18}F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [{sup 18}F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [{sup 18}F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [{sup 18}F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models.

  13. The effects of d-amphetamine on extrastriatal dopamine D{sub 2}/D{sub 3} receptors: a randomized, double-blind, placebo-controlled PET study with [{sup 11}C]FLB 457 in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, Sargo [University of Turku, Turku PET Centre, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Hirvonen, Jussi; Kajander, Jaana; Naagren, Kjell; Rinne, Juha O. [University of Turku, Turku PET Centre, Turku (Finland); Kaasinen, Valtteri [University of Turku, Department of Neurology, P.O. Box 52, Turku (Finland); Hagelberg, Nora [University of Turku, Turku PET Centre, Turku (Finland); Turku University Central Hospital, Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku (Finland); Seppaelae, Timo [Drug Research Unit, National Public Health Institute, Helsinki (Finland); Scheinin, Harry [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Hietala, Jarmo [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Psychiatry, Turku (Finland)

    2009-03-15

    The dopamine D{sub 2}/D{sub 3} receptor ligand [{sup 11}C]FLB 457 and PET enable quantification of low-density extrastriatal D{sub 2}/D{sub 3} receptors, but it is uncertain whether [{sup 11}C]FLB 457 can be used for measuring extrastriatal dopamine release. We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [{sup 11}C]FLB 457 binding potential (BP{sub ND}) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. The effects of d-amphetamine on [{sup 11}C]FLB 457 BP{sub ND} and distribution volume (V{sub T}) in the frontal cortex were not different from those of placebo. Small decreases in [{sup 11}C]FLB 457 BP{sub ND} were observed only in the posterior cingulate and hippocampus. The regional changes in [{sup 11}C]FLB 457 BP{sub ND} did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria. This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D{sub 2}/D{sub 3} receptor binding. Our results indicate that [{sup 11}C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans. (orig.)

  14. Positron emission tomography in presurgical diagnosis of partial epilepsies. Praeoperative Lokalisationsdiagnostik bei fokaler Epilepsie durch PET

    Energy Technology Data Exchange (ETDEWEB)

    Hajek, M.; Leenders, K.L. (Universitaetsspital Zurich (Switzerland). Neurologische Klinik Paul Scherrer Institut, Villigen (Switzerland)); Wieser, H.G. (Universitaetsspital Zurich (Switzerland). Neurologische Klinik)

    1992-06-01

    We present results of studies in which positron emission tomography was applied to the presurgical evaluation of epileptics. Emphasis is placed on results of PET studies with various tracers in partial epilepsies and on the use of PET in age-related epileptic syndromes in children. (orig.).

  15. Silicon Photomultipliers and Monolithic Scintillators for Time-of-Flight PET

    NARCIS (Netherlands)

    Seifert, S.

    2012-01-01

    Positron emission tomography (PET) is a nuclear medical imaging modality. Its aim is to visualize the 3-dimensional distribution of a radiopharmaceutical (also called the tracer) within a patient (clinical PET) or test-animal (in case of preclinical investigations). The information that can be obtai

  16. Silicon Photomultipliers and Monolithic Scintillators for Time-of-Flight PET

    NARCIS (Netherlands)

    Seifert, S.

    2012-01-01

    Positron emission tomography (PET) is a nuclear medical imaging modality. Its aim is to visualize the 3-dimensional distribution of a radiopharmaceutical (also called the tracer) within a patient (clinical PET) or test-animal (in case of preclinical investigations). The information that can be obtai

  17. Silicon Photomultipliers and Monolithic Scintillators for Time-of-Flight PET

    NARCIS (Netherlands)

    Seifert, S.

    2012-01-01

    Positron emission tomography (PET) is a nuclear medical imaging modality. Its aim is to visualize the 3-dimensional distribution of a radiopharmaceutical (also called the tracer) within a patient (clinical PET) or test-animal (in case of preclinical investigations). The information that can be

  18. 68Ga-NOTA-Aca-BBN(7–14) PET/CT in Healthy Volunteers and Glioma Patients

    Science.gov (United States)

    Zhang, Jingjing; Li, Deling; Lang, Lixin; Zhu, Zhaohui; Wang, Ling; Wu, Peilin; Niu, Gang; Li, Fang; Chen, Xiaoyuan

    2017-01-01

    This work was designed to study the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR)– targeting, 68Ga-labeled bombesin (BBN) peptide derivative PET tracer, NOTA-Aca-BBN(7–14) (denoted as 68Ga-BBN) in healthy volunteers and to assess the level of receptor expression in glioma patients. Methods Four healthy volunteers (2 male and 2 female) underwent whole-body PET/CT at multiple time points after a bolus injection of 68Ga-BBN (111 ± 148 MBq). Regions of interest were drawn manually over major organs, and time–activity curves were obtained. Dosimetry was calculated using the OLINDA/EXM software. Twelve patients with glioma diagnosed by contrast-enhanced MRI underwent PET/CT at 30–45 min after 68Ga-BBN injection. Within 1 wk afterward, the tumor was surgically removed and immunohistochemical staining of tumor samples against GRPR was performed and correlated with the PET/CT results. Results 68Ga-BBN was well tolerated in all healthy volunteers, with no adverse symptoms being noticed or reported. 68Ga-BBN cleared rapidly from the circulation and was excreted mainly through the kidneys and urinary tract. The total effective dose equivalent and effective dose were 0.0335 ± 0.0079 and 0.0276 ± 0.0066 mSv/MBq, respectively. In glioma patients, all MRI-identified lesions showed high signal intensity on 68Ga-BBN PET/CT. SUVmax and SUVmean were 2.08 ± 0.58 and 1.32 ± 0.37, respectively. With normal brain tissue as background, tumor-to-background ratios were 24.0 ± 8.85 and 13.4 ± 4.54 based on SUVmax and SUVmean, respectively. The immunohistochemical staining confirmed a positive correlation between SUV and GRPR expression level (r2 = 0.71, P < 0.001). Conclusion 68Ga-BBN is a PET tracer with favorable pharmacokinetics and a favorable dosimetry profile. It has the potential to evaluate GRPR expression in glioma patients and guide GRPR-targeted therapy of glioma. PMID:26449838

  19. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas

    DEFF Research Database (Denmark)

    Albert, Nathalie L.; Weller, Michael; Suchorska, Bogdana

    2016-01-01

    This guideline provides recommendations for the use of PET imaging in gliomas. The review examines established clinical benefit in glioma patients of PET using glucose (18F-FDG) and amino acid tracers (11C-MET, 18F-FET, and 18F-FDOPA). An increasing number of studies have been published on PET im...

  20. Automated radiosynthesis of [{sup 18}F]PBR111 and [{sup 18}F]PBR102 using the Tracerlab FX{sub FN} and Tracerlab MX{sub FDG} module for imaging the peripheral benzodiazepine receptor with PET

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, Thomas, E-mail: thomas@nucmed.rpa.cs.nsw.gov.au [PET and Nuclear Medicine Department, Royal Prince Alfred Hospital, Missenden road, Camperdown NSW 2050, Sydney (Australia); Pham, Tien Q. [LifeSciences, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Sydney (Australia); Henderson, David [PET and Nuclear Medicine Department, Royal Prince Alfred Hospital, Missenden road, Camperdown NSW 2050, Sydney (Australia); Jackson, Timothy [LifeSciences, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Sydney (Australia); Lam, Peter [PET and Nuclear Medicine Department, Royal Prince Alfred Hospital, Missenden road, Camperdown NSW 2050, Sydney (Australia); Izard, Michael; Katsifis, Andrew [LifeSciences, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Sydney (Australia)

    2012-01-15

    [{sup 18}F]PBR111 and [{sup 18}F]PBR102 are selective radioligands for imaging of the Peripheral Benzodiazepine Receptor (PBR). We have developed a fully automated method for the radiosynthesis of [{sup 18}F]PBR111 and [{sup 18}F]PBR102 in the Tracerlab FX{sub FN} (30{+-}2% radiochemical yield non-decay-corrected for both tracers) and Tracerlab MX{sub FDG} (25{+-}2% radiochemical yield non-decay-corrected for both tracers) from the corresponding p-toluenesulfonyl precursors. For all tracers, radiochemical purity was >99% and specific activity was >150 GBq/{mu}mol after less than 60 min of preparation time. - Highlights: Black-Right-Pointing-Pointer Radiosynthesis of novel ligands PBR111 and PBR102 with fluorine-18. Black-Right-Pointing-Pointer Fully automated synthesis undertaken using the GE Tracerlab FX{sub FN} and MX{sub FDG} modules. Black-Right-Pointing-Pointer Reproducible high yields suitable for clinical applications. Black-Right-Pointing-Pointer Radiosynthesis and formulation achieved in less than 60 mins. Black-Right-Pointing-Pointer PBR111 and PBR102 prepared in high radiochemical yield and specific activity.

  1. Development of a Ga-68 labeled triptorelin analog for GnRH receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zoghi, Masoumeh; Niazi, Ali [Islamic Azad Univ., Arak (Iran, Islamic Republic of). Dept. of Chemistry; Jalilian, Amir R.; Johari-daha, Fariba; Alirezapour, Behrouz [Nuclear Science and Technology Research Institute (NSTRI) (Iran, Islamic Republic of). Radiation Application Research School; Ramezanpour, Sorour [K.N. Toosi Univ. of Technology, Tehran (Iran, Islamic Republic of). Peptide Chemistry Research Center

    2016-08-01

    Optimized total synthesis, radiolabeling and quality control of [{sup 68}Ga]-DOTA-Hyd-TRP as an efficient and possible PET radiotracer for GnRH receptor imaging in various tumors is of great interest. DOTA-Hyd-TRP was synthesized using solid phase peptide synthesis followed by conjugation to DOTA using pSCN-Bn-DOTA. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared using generator-based [{sup 68}Ga]GaCl{sub 3} and DOTA-Hyd-TRP under optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting up to 120 min. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared at optimized conditions in 5-7 min at 95 C followed by separation using C{sub 18} cartridge (radiochemical purity ∼99 ± 0.88% ITLC, > 99% HPLC, specific activity: 300 ± 15 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min as well as significant testicular uptake consistent with reported GnRH receptor mappings. Block test studies by triptorelin pretreatment of the animals prior to tracer administration demonstrated significant specific uptake in receptor rich organs including testes and stomach.

  2. Development of an Optimum Tracer Set for Apportioning Emissions of Individual Power Plants Using Highly Time-Resolved Measurements and Advanced Receptor Modeling

    Energy Technology Data Exchange (ETDEWEB)

    John Ondov; Gregory Beachley

    2007-07-05

    In previous studies, 11 elements (Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Se, and Zn) were determined in 30-minute aerosol samples collected with the University of Maryland Semicontinuous Elements in Aerosol Sampler (SEAS; Kidwell and Ondov, 2001, 2004; SEAS-II) in several locations in which air quality is influenced by emissions from coal- or oil-fired power plants. At this time resolution, plumes from stationary high temperature combustion sources are readily detected as large excursions in ambient concentrations of elements emitted by these sources (Pancras et al. ). Moreover, the time-series data contain intrinsic information on the lateral diffusion of the plume (e.g., {sigma}{sub y}), which Park et al. (2005 and 2006) have exploited in their Pseudo-Deterministic Receptor Model (PDRM), to calculate emission rates of SO{sub 2} and 11 elements (mentioned above) from four individual coal- and oil-fired power plants in the Tampa Bay area. In the current project, we proposed that the resolving power of source apportionment methods might be improved by expanding the set of maker species and that there exist some optimum set of marker species that could be used. The ultimate goal was to determine the utility of using additional elements to better identify and isolate contributions of individual power plants to ambient levels of PM and its constituents. And, having achieved better resolution, achieve, also, better emission rate estimates. In this study, we optimized sample preparation and instrumental protocols for simultaneous analysis of 28 elements in dilute slurry samples collected with the SEAS with a new state-of-the-art Thermo-Systems, Inc., X-series II, Inductively Coupled Plasma Mass Spectroscopy (ICP-MS), and reanalyzed the samples previously collected in Tampa during the modeling period studied by Park et al. (2005) in which emission rates from four coal- and oil-fired power plants affected air quality at the sampling site. In the original model, Park et al

  3. Rapid and efficient radiosynthesis of [{sup 123}I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pimlott, Sally L. [Department of Clinical Physics, West of Scotland Radionuclide Dispensary, Western Infirmary, G11 6NT Glasgow (United Kingdom)], E-mail: s.pimlott@clinmed.gla.ac.uk; Stevenson, Louise [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom); Wyper, David J. [Institute of Neurological Sciences, Southern General Hospital, G51 4TF Glasgow (United Kingdom); Sutherland, Andrew [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom)

    2008-07-15

    Introduction: [{sup 123}I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [{sup 123}I]I-PK11195 in order to develop a rapid and efficient method that obtains [{sup 123}I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [{sup 123}I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [{sup 123}I]I-PK11195. Conclusions: [{sup 123}I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved.

  4. Does the pretherapeutic tumor SUV in 68Ga DOTATOC PET predict the absorbed dose of 177Lu octreotate?

    Science.gov (United States)

    Ezziddin, Samer; Lohmar, Jonas; Yong-Hing, Charlotte J; Sabet, Amir; Ahmadzadehfar, Hojjat; Kukuk, Guido; Biersack, Hans-Jürgen; Guhlke, Stefan; Reichmann, Karl

    2012-06-01

    Selection of candidates for peptide receptor radionuclide therapy (PRRT) is increasingly based on receptor positron emission tomography (PET) imaging, including the common tracer 68Ga DOTATOC. However, no studies have yet compared standardized uptake values (SUVs) and absorbed doses in this field. We retrospectively analyzed a consecutive cohort of 21 patients with 61 evaluable tumor lesions undergoing both pretherapeutic 68Ga DOTATOC-PET/CT (Biograph Duo [Siemens Medical Solutions, Erlangen, Germany]; PET acquisition, 75.3 ± 15.4 minutes postinjection; 117.3 ± 33.9 MBq 68Ga DOTATOC) and PRRT with Lu octreotate (7.47 ± 1.39 GBq; intratherapeutic tumor dosimetry with serial whole-body scans; 1, 2, and 4 days postinjection) at our institution. SUVs were compared with the tumor-absorbed doses per injected activity (D/A0) of the subsequent first treatment cycle. The correlation of SUV and D/A0 was r = 0.72 (SUVmean) and r = 0.71 (SUVmax), both P 15; SUVmax >25) resulted in high D/A0 (>10 Gy/GBq) in 66.7% to 70.8% and low D/A0 (<5 Gy/GBq) in only 8.3% to 12.5% on subsequent PRRT. The mentioned low D/A0 range, on the other hand, was achieved by all lesions with SUVmean <7 or SUVmax <9. Somatostatin receptor PET imaging may predict tumor-absorbed doses. The ability to indicate insufficient target irradiation by a low SUV could aid in selection of appropriate candidates for PRRT. However, larger series are needed to confirm and validate these initial findings.

  5. In vitro and in vivo targeting of different folate receptor-positive cancer cell lines with a novel {sup 99m}Tc-radiofolate tracer

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Cristina [Paul Scherrer Institute, Center for Radiopharmaceutical Science ETH-PSI-USZ, Villigen-PSI (Switzerland); Schubiger, P.A.; Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Science ETH-PSI-USZ, Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich (Switzerland)

    2006-10-15

    For the assessment of folate-based radiopharmaceuticals, human nasopharyngeal KB carcinoma cells are traditionally used although nasopharyngeal cancer is rare. On the other hand, the folate receptor (FR) is frequently overexpressed on diverse cancer types, the highest frequency (>90%) being on ovarian carcinomas. The goal of our study was the in vitro and in vivo assessment of different FR-positive human carcinoma cells. In addition, a murine sarcoma cell line was assessed as a pre-clinical alternative to human xenograft models. FR-positive human nasopharyngeal, cervical, ovarian and colorectal cancer cell lines and the transgenic mouse sarcoma (24JK-FBP) cell line were targeted with a novel {sup 99m}Tc-tricarbonyl folate derivative 2. Comparative in vitro cell binding studies were carried out under standardised folate-deficient conditions. In vivo studies were performed in nude mice and C6 black mice. The in vitro cell experiments revealed only FR-specific binding (unspecific <0.02%), ranging from 3.5% to 52% of complex 2 owing to variable levels of FR expression of the cell lines. In vivo tumour uptake of radiotracer 2 varied less than in vitro. It ranged from 0.66{+-}0.17% ID/g (LoVo) through 1.16{+-}0.64% ID/g (IGROV-1) and 1.55{+-}0.43% ID/g (24JK-FBP) to 2.33{+-}0.36% ID/g (KB) 4 h p.i. These pre-clinical studies indicate that in vitro data obtained in FR-positive cancer cells do not necessarily correspond with or predict in vivo radiofolate uptake in corresponding (xeno)grafts. In addition, the murine 24JK-FBP cell line proved to be a valuable pre-clinical alternative to human tumour models. (orig.)

  6. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with {sup 18}F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Groheux, David [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France); Martineau, Antoine; Vercellino, Laetitia; Merlet, Pascal [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Teixeira, Luis; Espie, Marc [Saint-Louis Hospital, Breast Diseases Unit, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France)

    2017-07-15

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an {sup 18}F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV{sub max} and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV{sub max} and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV{sub max} and TLG were able to predict response to NAC, TFs failed. (orig.)

  7. Comparison of PET/CT and PET/MRI hybrid systems using a {sup 68}Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Afshar-Oromieh, A. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Department of Radiology, Heidelberg (Germany); Haberkorn, U. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit of Nuclear Medicine, Heidelberg (Germany); Schlemmer, H.P.; Fenchel, M.; Roethke, M. [German Cancer Research Center (DKFZ), Department of Radiology, Heidelberg (Germany); Eder, M.; Eisenhut, M. [German Cancer Research Center (DKFZ), Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Hadaschik, B.A. [University Hospital Heidelberg, Department of Urology, Heidelberg (Germany); Kopp-Schneider, A. [German Cancer Research Center (DKFZ), Department of Biostatistics, Heidelberg (Germany)

    2014-05-15

    {sup 68}Ga-labelled HBED-CC-PSMA is a highly promising tracer for imaging recurrent prostate cancer (PCa). The intention of this study was to evaluate the feasibility of PET/MRI with this tracer. Twenty patients underwent PET/CT 1 h after injection of the {sup 68}Ga-PSMA ligand followed by PET/MRI 3 h after injection. Data from the two investigations were first analysed separately and then compared with respect to tumour detection rate and radiotracer uptake in various tissues. To evaluate the quantification accuracy of the PET/MRI system, differences in SUVs between PET/CT and corresponding PET/MRI were compared with differences in SUVs between PET/CT 1 h and 3 h after injection in another patient cohort. This cohort was investigated using the same PET/CT system. With PET/MRI, different diagnostic sequences, higher contrast of lesions and higher resolution of MRI enabled a subjectively easier evaluation of the images. In addition, four unclear findings on PET/CT could be clarified as characteristic of PCa metastases by PET/MRI. However, in PET images of the PET/MRI, a reduced signal was observed at the level of the kidneys (in 11 patients) and around the urinary bladder (in 15 patients). This led to reduced SUVs in six lesions. SUV{sub mean} values provided by the PET/MRI system were different in muscles, blood pool, liver and spleen. PCa was detected more easily and more accurately with Ga-PSMA PET/MRI than with PET