Kinetic analysis and quantification of the dopamine transporter in the nonhuman primate brain with 11C-PE2I and 18F-FE-PE2I.

UNLABELLED: 18F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β- (4'-methyl-phenyl)nortropane (18F-FE-PE2I) is a novel radioligand for dopamine transporter (DAT) PET. As compared with 11C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (11C-PE2I), 18F-FE-PE2I shows faster kinetics and more favorable metabolism, with less production of a radiometabolite with intermediate lipophilicity (M1), which-in the case of 11C-PE2I-has been shown to enter the rat brain. In this study, we compared DAT quantification with 11C-PE2I and 18F-FE-PE2I in nonhuman primates, using kinetic and graphical analysis with the input function of both the parent and the radiometabolite, to assess the potential contribution of the radiometabolite.
METHODS: Three rhesus monkeys were examined with 11C-PE2I and 18F-FE-PE2I using the HRRT system. Arterial input functions of the parent and radiometabolite M1 were measured. Kinetic and graphical analyses were applied using either the parent input (methods 1 and 3) or the parent plus radiometabolite input (methods 2 and 4). Outcome measures were distribution volumes (VT and VND), specific-to-nondisplaceable tissue radioactivity ratio at equilibrium (BPND; parent input), and specific-to-nondisplaceable tissue radioactivity ratio at equilibrium in the presence of metabolites (RT; parent plus radiometabolite input).
RESULTS: 11C-PE2I showed higher distribution volumes than 18F-FE-PE2I calculated with methods 1 and 3 (striatal VT, ∼300%; VND in cerebellum, ∼30%). With methods 2 and 4, VT in the striatum was approximately 60% higher in the case of 11C-PE2I, whereas no difference in VND was found in the cerebellum. For each radioligand, BPND estimated with methods 1 and 3 tended to be higher than RT estimated with methods 2 and 4. However, the bias of BPND, compared with RT, was much larger for 11C-PE2I (40%-60% in the caudate and putamen) than for 18F-FE-PE2I (<10% in the caudate and putamen).
CONCLUSION: The direct comparison between the radioligands confirmed that 18F-FE-PE2I shows faster kinetics and more favorable metabolism than 11C-PE2I. The kinetic and graphical analyses with the input function of the parent and radiometabolite showed that the bias in BPND was much lower for 18F-FE-PE2I than for 11C-PE2I and suggested that the lower production of the radiometabolite M1 would make 18F-FE-PE2I more suitable for the DAT quantification. Further studies in humans are necessary to confirm these findings.