Journal of Labelled Compounds and Radiopharmaceuticals 2011-09-01

Synthesis, radiosynthesis and in vivo evaluation of [I]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine as a selective tracer for imaging the dopamine transporter.

S DeBruyne, TL Boos, L Wyffels, JL Goeman, KC Rice, F DeVos

Index: J. Labelled Comp. Radiopharm. 52(8) , 304-311, (2009)

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Abstract

Dopamine transporter (DAT) neuroimaging is a useful tool in Parkinson's disease diagnosis, staging and follow-up providing information on the integrity of the dopaminergic neurotransmitter system in vivo. 4-(2-(Bis(4-fluorophenyl)-methoxy)ethyl)-1-(4-iodobenzyl)piperidine (7) has nanomolar affinity for DAT and better selectivity over the other monoamine transporters compared with the existing SPECT radioligands for DAT. The aim of this study was to synthesize and evaluate [(123)I]-7 as an in vivo tracer for DAT.The tributylstannyl precursor was synthesized with an overall yield of 25%. [(123)I]-7 was synthesized by electrophilic destannylation with a yield of 4010%. Radiochemical purity appeared to be >98%, whereas specific activity was at least 667 GBq/mol. Biodistribution studies in mice showed brain uptake of 0.960.53%ID/g at 30 s post injection (p.i.) and 0.260.02%ID/g at 3 h p.i. High blood activity was observed at all time points. Pretreatment with Cyclosporin A raised brain uptake indicating that [(123)I]-7 is transported by P-glycoprotein (P-gp) pumps. In rats, regional brain distribution of [(123)I]-7 was not in agreement with DAT distribution. These results indicate that [(123)I]-7 is not suitable for mapping DAT in vivo but could be a useful tracer for the P-gp transporter.