1126087-96-4Relevant academic research and scientific papers
Synthesis and in vitro and in vivo evaluation of18F-labeled positron emission tomography (PET) ligands for imaging the vesicular acetylcholine transporter
Tu, Zhude,Efange, Simon M. N.,Xu, Jinbin,Li, Shihong,Jones, Lynne A.,Parsons, Stanley M.,Mach, Robert H.
, p. 1358 - 1369 (2009)
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-[18F]fluorobenzoyl)piperidino)tetralin (9e) has Ki values of 2.70 nM for VAChT, 191 nM for σ1 and 251 nM for σ2. The racemic precursor (9d) was resolved via chiral HPLC, and (±)-[18F]9e,(-)-[18F]9e, and (+)-[ 18F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [18F]/F- and Kryptofix/K 2CO3 in DMSO with radiochemical yields of ～50-60% and specific activities of >2000 mCi/μmol. (-)-[18F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum/cerebellum ratio of 1.88 at 30 min postinjection (p.i.). MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[18F]9e in putamen versus cerebellum at 2 h p.i. (-)-[18F]9e has potential to be a PET tracer for clinical imaging of the VAChT.
