Florbetapir F-18: A Histopathologically Validated Beta-Amyloid Positron Emission Tomography Imaging Agent

详细信息    查看全文

• 作者：John Lister-James ; Michael J. Pontecorvo ; Chris Clark ; Abhinay D. Joshi ; Mark A. Mintun ; Wei Zhang ; Nathaniel Lim ; Zhiping Zhuang ; Geoff Golding ; Seok Rye Choi ; Tyler E. Benedum ; Paul Kennedy ; Franz Hefti ; Alan P. Carpenter ; Hank F. Kung ; Daniel M. Skovronsky
• 刊名：Seminars in Nuclear Medicine
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：41
• 期：4
• 页码：300-304
• 全文大小：1142 K

文摘

Florbetapir F-18 is a molecular imaging agent combining high affinity for β-amyloid, pharmacokinetic properties that allow positron emission tomography (PET) imaging within a convenient time after dose administration, and the wide availability of the radionuclide fluorine-18. Florbetapir F-18 is prepared by nucleophilic radiofluorination in approximately 60 minutes with a decay-corrected yield of 20 % -40 % and with a specific activity typically exceeding 100 Ci/mmol. The florbetapir F-18 dissociation constant (K_d) for binding to β-amyloid in brain tissue from Alzheimer's disease (AD) patients was 3.7 ± 0.3 nmol/L, and the maximum binding capacity (B_max) was 8800 ± 1600 fmol/mg protein. Autoradiography studies have shown that florbetapir F-18 selectively binds to β-amyloid aggregates in AD patient brain tissue, and the binding intensity is correlated with the density of β-amyloid quantified by standard neuropathologic techniques. Studies in animals revealed no safety concerns and rapid and transient normal brain uptake (6.8 % injected dose/g at 2 minutes and 1.9 % injected dose/g at 60 minutes in the mouse). Florbetapir F-18 has been well-tolerated in studies of more than 2000 human subjects. Biodistribution studies in humans revealed predominantly hepatobiliary excretion. The whole body effective dose was 7 mSv from a dose of 370 MBq. The pharmacokinetic of florbetapir F-18 make it possible to obtain a PET image with a brief (10 minutes) acquisition time within a convenient time window of 30-90 minutes after dose administration. Clinical studies have demonstrated a clear correlation between in vivo PET imaging with florbetapir F-18 and postmortem histopathologic quantitation of β-amyloid in the brain.