COCAINE CONGENERS AS PET IMAGING PROBES FOR DOPAMINE TERMINALS

PET imaging properties of three phenyltropane drugs with differing aff inities and selectivities for the dopamine over serotonin transporter, were compared. Methods: Carbon-11-CFT (WIN 35,428, 2 beta-carbomethox y-3 beta-(4-fluorophenyl)tropan), C-11-CCT (RTI-131, 2 beta-carbometho xy-3 beta-(4-monochlorophenyl)tropane), and C-11-CDCT (dichloropane, 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane) were evaluated as imaging probes for dopamine neurons in five normal and in two MPTP- treated cynomolgus monkeys (macaca fascicularis) using a high-resoluti on PET imaging system (PCR-I). Results: For C-11-CFT, the specific bin ding ratio (as defined by the ratio of radioactivity levels in striatu m versus cerebellum) was 4.2 +/- 0.8 in caudate and 4.9 +/- 1.2 in put amen at 60 min and 4.9 +/- 1.2 and 5.5 +/- 1.1 at 90 min in control an imals. In MPTP-treated monkeys the corresponding ratios were 1.4 +/- 0 .1 in caudate and 1.5 +/- 0.1 in putamen at 60 min and 1.3 +/- 0.1 in caudate and 1.4 +/- 0.3 in putamen at 90 min. For the monochloro analo g of CFT, C-11-CCT, the ratios in control caudate and putamen were 2.7 +/- 0.4 and 3.4 +/- 0.3, respectively, at 60 min and 3.7 +/- 0.5 and 4.4 +/- 0.6, respectively, at 90 min. In MPTP-treated animals, corresp onding ratios were 1.4 +/- 0.4 and 1.5 +/- 0.3 at 60 min and 1.4 +/- 0 .4 and 1.6 +/- 0.4 at 90 min. The dichloro analog of CFT, CDCT, which has the highest affinity for the dopamine transporter, generated the l owest ratios in control brains, 2.3 +/- 0.4 in caudate and 2.4 +/- 0.5 in putamen at 60 min. In one MPTP-treated monkey, the corresponding r atios were 1.6 +/- 0.4 and 1.8 +/- 0.3. In comparison with C-11-CFT, b oth C-11-CCT and C-11-CDCT were less selective and had high uptake in the thalamus. Conclusion: The present results clearly indicate that C- 11-CFT is a useful ligand for monitoring dopamine neuronal degeneratio n.