The aim of this study was to compare two PET ligands, 6-[F-18]fluoro-L-dopa([F-18]FDOPA) and F-18-labeled CFT, 2 beta -carbomethoxy-3 beta-(4-[F-18]-fluorophenyl)tropane ([18F]CFT), in detecting presynaptic dopaminergic hypofunction in early Parkinson's disease (PD). These ligands reflect different aspects of presynaptic dopaminergic function, since [F-18]FDOPA mainly reflects 6-[F-18]fluorodopamine (fluorodopamine) synthesis and storage whereas [F-18]CFT uptake is related to dopamine transporter function. Eight de novo patients with PD who had never been on antiparkinsonian medication were investigated with [F-18]FDOPA and [F-18]CFT PET. Five healthy volunteers were studied as controls. In PD patients, both [F-18]FDOPA and [F-18]CFT uptakes were significantly reduced both in the contralateral and ipsilateral anterior and posterior putamen. The reduction was greatest in the contralateral posterior putamen (to 28% of control mean for [F-18]FDOPA, P < 0.0001 and to 16% for [F-18]CFT, P < 0.0001). Individually, all patients' [F-18]FDOPA and [F-18]CFT uptake values in the contralateral anterior and posterior putamen were below 3 SD of the control mean. In the caudate nucleus, the mean uptake of both tracers was significantly reduced both ipsilaterally and contralaterally, but less severely than in the putamen (to 69% of the control mean for [F-18]FDOPA, P = 0.003 and to 60% for [F-18]CFT, P = 0.001 contralaterally). Our results show that both [F-18]FDOPA as well as [F-18]CFT sensitively detect presynaptic dopaminergic hypofunction in early PD. They demonstrate a considerable reduction of tracer uptake that is greatest in the posterior putamen, followed by the anterior putamen and the caudate nucleus. Synapse 40:193-200, 2001. (C) 2001 Wiley-Liss, Inc.