In vivo characterization of p-[18F]MPPF, a fluoro analog of WAY-100635 for visualization of 5-HT1a receptors

The in vivo and ex vivo distributions and the pharmacological profile of the fluorinated phenylpiperazine derivative p-( 18 F)MPPF (4-(28-methoxyphenyl)-1-(28-(N- 29-pyridinyl)-p-fluorobenzamido)-ethylpiperazine) were evaluated in the cat brain as a potential selective antagonist for 5-HT1A receptors using PET. After intravenous injection of p-( 18 F)MPPF in cats, there was a rapid accumulation of radioactivity in the brain, with 4% of the total radioactivity injected present in the brain at 4 minutes postinjection. The highest uptakes of radioactivity were observed in the hippocampus and cingulate cortex, regions known to be rich in 5-HT1A receptors, whereas lower levels of radioactivity were observed in the cerebellum. The mean ratio of radioactivity in the hippocampus to the cerebellum was 4.29 (SD 5 0.21; n 5 5) from 40 to 90 minutes postinjection of p-( 18 F)MPPF. The corresponding ratio for the cingulate cortex was 3.01 (SD 5 0.16; n 5 5). Specific binding in the hippocampus and the cingulate cortex was markedly reduced following injection of unlabeled WAY-100635 and pindolol but was unaffected by treatment with a1, 5-HT2, or reuptake inhibitor agents indicating reversibility and selectivity of p-( 18 F)MPPF binding to 5-HT1A receptors. Ex vivo autoradiographic study with p-( 18 F)MPPF in cat brain sections showed labeling of areas rich in 5-HT1A receptors with a regional brain distribution that closely matched that observed using PET. These results indicate that p-( 18 F)MPPF may be a useful candidate for noninvasive PET imaging of 5-HT1A receptors in the living human brain. Synapse