The purpose of this research is to use specialized brain imaging techniques, Positron Emission Tomography (PET) scan and Magnetic Resonance Imaging (MRI), to learn more about the brain chemistry, e.g., how neurotransmitters and receptors in the brain function in people with schizophrenia compared to healthy controls.

开始日期2022-08-18

申办/合作机构

Washington University School of Medicine

100 项与 [18F]AZAN 相关的临床结果

登录后查看更多信息

100 项与 [18F]AZAN 相关的转化医学

登录后查看更多信息

100 项与 [18F]AZAN 相关的专利（医药）

登录后查看更多信息

项与 [18F]AZAN 相关的文献（医药）

2012-01-01·Journal of Nuclear Medicine1区 · 医学

PET Imaging of Nicotinic Acetylcholine Receptors in Baboons with ¹⁸F-AZAN, a Radioligand with Improved Brain Kinetics

1区 · 医学

Article

作者: Dannals, Robert F. ; Wong, Dean F. ; Gao, Yongjun ; Kuwabara, Hiroto ; Horti, Andrew G. ; Holt, Daniel P. ; Ravert, Hayden T. ; Valentine, Heather

There are only 2 currently available radioligands, 2-(18)F-FA and 6-(18)F-FA, for quantitative PET of the main cerebral subtype of nicotinic acetylcholine receptors (α4β2-nAChRs) in humans. Both exhibit slow distribution kinetics in the brain and require several hours for PET imaging. This makes PET of nAChRs with these radioligands logistically difficult and a serious burden for human subjects. The main purpose of this study was to preclinically evaluate (-)-2-(6-(18)F-fluoro-2,3'-bipyridin-5'-yl)-7-methyl-7-azabicyclo[2.2.1]heptane ((18)F-AZAN), our new radiolabeled antagonist of α4β2-nAChRs, that has high binding potential and rapid brain kinetics in baboons.METHODS(18)F-AZAN was synthesized using a modified (18)F-FDG synthesis module. The regional distribution of (18)F-AZAN in the brain was evaluated in baseline and cytisine-blocking studies of 4 male Papio anubis baboons. PET modeling procedures were used for calculation of regional distribution volume (V(T)), nondisplaceable binding potential (BP(ND)), and receptor occupancy.RESULTS(18)F-AZAN rapidly entered the baboon brain, reached a steady state within 90 min after injection, and specifically labeled cerebral nAChRs. The peak radioactivity in the thalamus was 540 (percentage standardized uptake value) at 18 ± 7 min (n = 4) after bolus injection. Mathematical data analysis demonstrated that scanning for only 90 min is sufficient for determination of PET outcome variables (BP(ND), 3.2 [unitless] and V(T), 32-35 mL/mL in thalamus). The dose-dependent blocking experiments with cytisine demonstrated that (18)F-AZAN binds specifically with β2-containing (predominantly α4β2) nAChRs.CONCLUSION(18)F-AZAN specifically labels nAChRs in baboon brains with a high value of BP(ND) and it requires only 90 min of PET scanning to produce estimates of V(T) and BP(ND) in the various brain regions. The blocking of nAChRs with cytisine is dose-dependent and it showed that (18)F-AZAN is suitable for application in nicotinic drug evaluation. In summary, (18)F-AZAN is superior to 2-(18)F-FA and 6-(18)F-FA for imaging cerebral β2-containing nAChRs in baboons. Further evaluations of (18)F-AZAN in the human brain are under way.

100 项与 [18F]AZAN 相关的药物交易

登录后查看更多信息