title: Florbetapir f-18: a histopathologically validated Beta-amyloid positron emission tomography imaging agent.
abstract: 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.
authors.affiliation: Avid Radiopharmaceuticals, Philadelphia, PA. listerjames@avidrp.com
authors.forename: John
authors.initials: J
authors.lastname: Lister-James
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pontecorvo
authors.forename: Chris
authors.initials: C
authors.lastname: Clark
authors.forename: Abhinay D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Lim
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Geoff
authors.initials: G
authors.lastname: Golding
authors.forename: Seok Rye
authors.initials: SR
authors.lastname: Choi
authors.forename: Tyler E
authors.initials: TE
authors.lastname: Benedum
authors.forename: Paul
authors.initials: P
authors.lastname: Kennedy
authors.forename: Franz
authors.initials: F
authors.lastname: Hefti
authors.forename: Alan P
authors.initials: AP
authors.lastname: Carpenter
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Skovronsky
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005026:Ethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D057054:Molecular Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir