RADIOSYNTHESIS AND BIODISTRIBUTION OF THE S-[F-18]FLUORETHYL ANALOG OF MCN5652

[C-11]McN5652 has been reported to exhibit favorable properties as a P ET radiotracer for studying serotonin uptake sites. However, the use o f this radiotracer may be limited by the short half life of C-11. To o btain a tracer with longer physical half life, we have synthesized the S [F-18]fluoroethyl analog of McN5652 oroethylthio)-phenyl]pyrrolo-[2 ,1-a]-isoquinoline) ([F-18]FEMcN) and evaluated as a PET radiotracer f or imaging serotonin uptake sites. The radiosynthesis was performed vi a a one-pot, two step procedure, In the first step, 1-bromo 2 [F-18]fl uoroethane was prepared from 2-bromoethyl triflate and (KF)-F-18/Krypt ofix 2.2.2. in THF at room temperature. The second step, the S-fluoroa lkylation of the normethyl McN5652, a thiol, was carried out, without isolating the 1-bromo-2-[F-18]fluoroethane, by adding the normethyl Mc N5652 to the reaction vial, which was warmed at 45 degrees C for 1 min . The fluoroalkylation reaction proceeded quickly, giving [F-18]FEMcN in an average overall radiochemical yield of 13 +/- 7%. The specific a ctivity was 1593 +/- 625 mCi/mu mol. Ex vivo autoradiographic studies revealed that [F-18]FEMcN accumulated into regions with high densities of 5 HT uptake sites such as hypothalamus, substantia nigra, and raph e nuclei. With blockade by nitroquipazine, a selective and highly pote nt 5-HT uptake blocker, the activity level in these regions was close to that in regions low in 5-HT uptake sites such as cerebellum, sugges ting that this radiotracer binds specifically to 5-HT uptake sites. Th e regional distribution of [F-18]FEMcN at 60 min postinjection correla ted with the distribution of [C-11]McN5652 reported in the literature. The specific binding of this radiotracer determined as the difference in radioactivity accumulation with and without blocking by the 5-HT u ptake blocker agreed with the distribution of the number of 5-HT uptak e sites measured in vitro, Thus, 5-HT uptake sites were visualized in vivo with [F-18]FEMcN. However, comparison with the in vivo behavior o f [C-11]McN5652 indicated less favorable properties of [F-18]FEMcN as a PET radiotracer for imaging 5-HT uptake sites, including lower blood -brain barrier penetration and lower target-to nontarget ratios.