[I-123] FP-CIT BINDS TO THE DOPAMINE TRANSPORTER AS ASSESSED BY BIODISTRIBUTION STUDIES IN RATS AND SPECT STUDIES IN MPTP-LESIONED MONKEYS

[(123)]FP-CIT (N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-[4-iodo phenyl]-tropane), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labeling of dopamine (DA) transporters by bio distribution studies in rats and by single photon emission computed to mography (SPECT) studies in unilateral 1-methy-4-phenyl-1,2,3,6-tetrah ydropyridine (MPTP)-lesioned monkeys. In rats, intravenous injection o f [I-123]FP-CIT resulted in high accumulation of radioactivity in the striatum. Less pronounced uptake was seen in brain areas with high den sities of serotonergic uptake sites. While striatal uptake of radioact ivity after injection of [I-123]FP-CIT was displaced significantly by GBR12,909 but not by fluvoxamine, the opposite was observed in brain a reas known to be rich of serotonin transporters. Monkeys which were un ilaterally treated with neurotoxic doses of MPTP showed severe loss of striatal [I-123]FP-CIT uptake at the side of treatment. The results o f this study indicate that [I-123]FP-CIT, although not being a selecti ve radioligand, binds specifically to the striatal. DA transporter in vivo and thus suggest that [I-123]FP-CIT promises to be a suitable rad ioligand for SPECT imaging of DA transporters in humans. (C) 1997 Wile y-Liss, Inc.