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

• Published in: Seminars in nuclear medicine 2011-07, Vol.41 (4), p.300-304
• Main Authors: Lister-James, John, PhD, Pontecorvo, Michael J., PhD, Clark, Chris, MD, Joshi, Abhinay D., PhD, Mintun, Mark A., MD, Zhang, Wei, PhD, Lim, Nathaniel, PhD, Zhuang, Zhiping, PhD, Golding, Geoff, PhD, Choi, Seok Rye, PhD, Benedum, Tyler E., PhD, Kennedy, Paul, PhD, Hefti, Franz, PhD, Carpenter, Alan P., PhD, Kung, Hank F., PhD, Skovronsky, Daniel M., MD, PhD
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Aniline Compounds - chemistry; Aniline Compounds - pharmacokinetics; Animals; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Dogs; Ethylene Glycols - chemistry; Ethylene Glycols - pharmacokinetics; Humans; Mice; Molecular Imaging; Positron-Emission Tomography - methods; Radiology; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Rats; Tissue Distribution
• ISSN: 0001-2998; 1558-4623
• DOI: 10.1053/j.semnuclmed.2011.03.001

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 (Kd ) 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 (Bmax ) 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.