Synthesis and in vitro and in vivo evaluation of 18F-labeled positron emission tomography (PET) ligands for imaging the vesicular acetylcholine transporter.

ABSTRACT: A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized, and analogues were evaluated in vitro. (+/-)-trans-2-Hydroxy-3-(4-(4-[(18)F]fluorobenzoyl)piperidino)tetralin (9e) has K(i) values of 2.70 nM for VAChT, 191 nM for sigma(1), and 251 nM for sigma(2). The racemic precursor (9d) was resolved via chiral HPLC, and (+/-)-[(18)F]9e, (-)-[(18)F]9e, and (+)-[(18)F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [(18)F]/F(-) and Kryptofix/K(2)CO(3) in DMSO with radiochemical yields of approximately 50-60% and specific activities of >2000 mCi/micromol. (-)-[(18)F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptak

SUBMITTER: Tu Z 

PROVIDER: S-EPMC2765529 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature