Quantitative imaging of 5-HT1A receptor binding in healthy volunteers with[F-18]p-MPPF

Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridin yl)-p-[F-18]fluorobenzamido]ethylpiperazine ([F-18]p-MPPF) can be used for 5-hydroxytryptamine(1A) (5-HT1A) receptor imaging. The aim of this study wa s to develop a method for the quantitative imaging of 5-HT1A receptors in h ealthy volunteers with [F-18]p-MPPF. After injection of [F-18]p-MPPF radioa ctivity was rapidly taken up in the brain, with the highest accumulation in the medial temporal cortex. Low levels of radioactivity were found in cere bellum and basal ganglia. Plasma clearance and metabolism of [F-18]p-MPPF r esulted in only about 1% of the radioactivity in plasma as parent radioliga nd after 10 min. Using a linear graphical method (Logan-Patlak), binding po tentials were calculated in several brain areas. A good correlation (r = 0. 95) was found between the obtained binding potentials and literature values for 5-HT1A receptor densities. A good correlation (r = 0.96) was also foun d between the body weight-corrected region/cerebellum ratios and the respec tive 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-C-11]WAY-100635, the binding potentia ls were four to six times lower, indicating that [F-18]p-MPPF has a lower i n vivo affinity for 5-HT1A receptors. In conclusion, [F-18]p-MPPF can be us ed for the quantitative analysis of 5-HT1A receptor distribution in human b rain. NUCL MED BIOL 27;5:473-476, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.