Quantitative imaging of 5-HT(1A) receptor binding in healthy volunteers with [(18)f]p-MPPF

Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido+ ++] ethylpiperazine ([(18)F]p-MPPF) can be used for 5-hydroxytryptamine(1A) (5-HT(1A)) receptor imaging. The aim of this study was to develop a method for the quantitative imaging of 5-HT(1A) receptors in healthy volunteers with [(18)F]p-MPPF. After injection of [(18)F]p-MPPF radioactivity was rapidly taken up in the brain, with the highest accumulation in the medial temporal cortex. Low levels of radioactivity were found in cerebellum and basal ganglia. Plasma clearance and metabolism of [(18)F]p-MPPF resulted in only about 1% of the radioactivity in plasma as parent radioligand after 10 min. Using a linear graphical method (Logan-Patlak), binding potentials were calculated in several brain areas. A good correlation (r = 0.95) was found between the obtained binding potentials and literature values for 5-HT(1A) receptor densities. A good correlation (r = 0.96) was also found between the body weight-corrected region/cerebellum ratios and the respective binding potentials. Moreover, a blocking experiment with pindolol (n = 3) showed a decrease of 40% in the region/cerebellum ratios of the target areas. Compared to those of [carbonyl-(11)C]WAY-100635, the binding potentials were four to six times lower, indicating that [(18)F]p-MPPF has a lower in vivo affinity for 5-HT(1A) receptors. In conclusion, [(18)F]p-MPPF can be used for the quantitative analysis of 5-HT(1A) receptor distribution in human brain.