أعرض في EDS

Evaluation of the Novel PET Tracer [C-11]HACH242 for Imaging the GluN2B NMDA Receptor in Non-Human Primates

التفاصيل البيبلوغرافية
العنوان: Evaluation of the Novel PET Tracer [C-11]HACH242 for Imaging the GluN2B NMDA Receptor in Non-Human Primates
المؤلفون: van der Aart, Jasper, Yaqub, Maqsood, Kooijman, Esther J M, Bakker, Jaco, Langermans, Jan A M, Schuit, Robert C, Hofman, Mark B M, Christiaans, Johannes A M, Lammertsma, Adriaan A, Windhorst, Albert D, van Berckel, Bart N M, LAS/3’R Centre ULS
المساهمون: Radiology and nuclear medicine, Amsterdam Neuroscience - Neurodegeneration, ACS - Atherosclerosis & ischemic syndromes, ACS - Heart failure & arrhythmias, LAS/3’R Centre ULS
المصدر: Molecular Imaging and Biology, 21(4), 676-685. Springer New York
Molecular Imaging and Biology, 21(4), 676. Springer New York LLC
van der Aart, J, Yaqub, M, Kooijman, E J M, Bakker, J, Langermans, J A M, Schuit, R C, Hofman, M B M, Christiaans, J A M, Lammertsma, A A, Windhorst, A D & van Berckel, B N M 2019, ' Evaluation of the Novel PET Tracer [C-11]HACH242 for Imaging the GluN2B NMDA Receptor in Non-Human Primates ', Molecular Imaging and Biology, vol. 21, no. 4, pp. 676-685 . https://doi.org/10.1007/s11307-018-1284-x
سنة النشر: 2019
مصطلحات موضوعية: Male, Cancer Research, medicine.medical_specialty, [ 11C]HACH242, N-Methyl-D-Aspartate/metabolism, Receptors, N-Methyl-D-Aspartate/metabolism, Acetamides/chemistry, Piperidines/chemistry, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Carbon Radioisotopes/blood, Internal medicine, Receptors, Radioligand, medicine, Animals, Radiopharmaceuticals/chemistry, Radiology, Nuclear Medicine and imaging, medicine.diagnostic_test, Chemistry, NR2B, Brain/diagnostic imaging, Macaca mulatta, Molecular Imaging, GluN2B, Endocrinology, PET, Oncology, Cerebral blood flow, NMDA, Positron emission tomography, Area Under Curve, Positron-Emission Tomography, NMDA receptor, Arterial blood, Radiprodil, Preclinical imaging, Ionotropic effect
الوصف: Purpose: There are currently no positron emission tomography (PET) radiotracers for the GluN2B (NR2B) binding sites of brain N-methyl-d-aspartate (NMDA) receptors. In rats, the GluN2B antagonist Ro25-6981 reduced the binding of N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamin ([11C]HACH242). This paper reports the evaluation of [11C]HACH242 PET in non-human primates at baseline and following administration of the GluN2B negative allosteric modulator radiprodil. Procedures: Eight 90-min dynamic [11C]HACH242 PET scans were acquired in three male anaesthetised rhesus monkeys, including a retest session of subject 1, at baseline and 10 min after intravenous 10 mg/kg radiprodil. Standardised uptake values (SUV) were calculated for 9 brain regions. Arterial blood samples were taken at six timepoints to characterise pharmacokinetics in blood and plasma. Reliable input functions for kinetic modelling could not be generated due to variability in the whole-blood radioactivity measurements. Results: [11C]HACH242 entered the brain and displayed fairly uniform uptake. The mean (± standard deviation, SD) Tmax was 17 ± 7 min in baseline scans and 24 ± 15 min in radiprodil scans. The rate of radioligand metabolism in plasma (primarily to polar metabolites) was high, with mean parent fractions of 26 ± 10 % at 20 min and 8 ± 5 % at 85 min. Radiprodil increased [11C]HACH242 whole-brain SUV in the last PET frame by 25 %, 1 %, 3 and 17 % for subjects 1, 2, 3 and retest of subject 1, respectively. The mean brain to plasma ratio was 5.4 ± 2.6, and increased by 39 to 110 % in the radiprodil condition, partly due to lower parent plasma radioactivity of −11 to −56 %. Conclusions: The present results show that [11C]HACH242 has a suitable kinetic profile in the brain and low accumulation of lipophilic radiometabolites. Radiprodil did not consistently change [11C]HACH242 brain uptake. These findings may be explained by variations in cerebral blood flow, a low fraction of specifically bound tracer, or interactions with endogenous NMDA receptor ligands at the binding site. Further experiments of ligand interactions are necessary to facilitate the development of radiotracers for in vivo imaging of the ionotropic NMDA receptor.
وصف الملف: image/pdf
اللغة: English
تدمد: 1536-1632
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed2dda94f11b4741ec3e41a61cbc52e2
http://www.scopus.com/inward/record.url?scp=85055269888&partnerID=8YFLogxK
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....ed2dda94f11b4741ec3e41a61cbc52e2
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15361632