Florbetapir ¹⁸F Other names: Florbetapir fluorine 18 Florbetapir (18F) Florbetapir F-18

Florbetapir F 18 binds to β-amyloid plaques and the F 18 isotope produces a positron signal that is detected by a PET scanner. In in vitro binding studies using postmortem human brain homogenates containing β-amyloid plaques, the dissociation constant (K_d) for florbetapir was 3.7 ± 0.3 nM. The binding of florbetapir F 18 to β-amyloid aggregates was demonstrated in postmortem human brain sections using autoradiographic methods, thioflavin S and traditional silver staining correlation studies as well as monoclonal antibody β-amyloid-specific correlation studies. Florbetapir binding to tau protein and a battery of neuroreceptors was not detected in in vitro studies.

Following intravenous injection, florbetapir F 18 diffuses across the human blood-brain barrier and produces a radioactivity signal detectable throughout the brain. Subsequently, cerebral perfusion decreases the brain florbetapir F 18 content, with differential retention of the drug in areas that contain β-amyloid aggregates compared to areas that lack the aggregates. The time-activity curves for florbetapir F 18 in the brain of subjects with positive scans show continual signal increases from time zero through 30 minutes post-administration, with stable values thereafter up to at least 90 minutes post-injection. Differences in the signal intensity between portions of the brain that specifically retain florbetapir F 18 and the portions of the brain with nonspecific retention of the drug forms the image interpretation methods.

Clinical studies evaluated the test-retest distribution of florbetapir F 18 within the brains of 21 subjects (11 with probable AD and 10 healthy volunteers) who underwent two injections (with PET scans), separated by a time period of 2 to 30 days. Images were shown to maintain signal distribution reproducibility when evaluated qualitatively (by a reader masked to image time points) as well as quantitatively using an automated assessment of SUV in pre-specified brain regions. A comparison of a 10-minute image acquisition time versus a 20-minute acquisition time showed no difference in the mean cortical to cerebellar SUV ratio results obtained.

Following the intravenous administration of 370 MBq (10 mCi) of florbetapir F 18 to healthy volunteers, the drug was distributed throughout the body with less than 5% of the injected F 18 radioactivity present in the blood by 20 minutes following administration, and less than 2% present by 45 minutes after administration. The residual F 18 in circulation during the 30-90 minute imaging window was principally in the form of polar F 18 metabolites. Whole body scanning following the intravenous injection showed accumulation of radioactivity in the liver within four minutes post-injection, followed by elimination of the radioactivity predominantly through the biliary/gastrointestinal tract with much lower radioactivity detected in the bladder. Essentially all radioactivity collected in the urine was present as polar metabolites of florbetapir F 18.