title: Cocaine congeners as PET imaging probes for dopamine terminals.
abstract: The PET imaging properties of three phenyltropane drugs with differing affinities and selectivities for the dopamine over serotonin transporter, were compared.
  
  
  METHODS
  Carbon-11-CFT (WIN 35,428, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane), 11C-CCT (RTI-131, 2 beta-carbomethoxy-3 beta-(4-monochlorophenyl)tropane), and 11C-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-resolution PET imaging system (PCR-I).
  
  
  RESULTS
  For 11C-CFT, the specific binding ratio (as defined by the ratio of radioactivity levels in striatum versus cerebellum) was 4.2 +/- 0.8 in caudate and 4.9 +/- 1.2 in putamen at 60 min and 4.9 +/- 1.2 and 5.5 +/- 1.1 at 90 min in control animals. 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 analog of CFT, 11C-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, corresponding 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 lowest 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 ratios were 1.6 +/- 0.4 and 1.8 +/- 0.3. In comparison with 11C-CFT, both 11C-CCT and 11C-CDCT were less selective and had high uptake in the thalamus.
  
  
  CONCLUSIONS
  The present results clearly indicate that 11C-CFT is a useful ligand for monitoring dopamine neuronal degeneration.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Brownell
authors.forename: D R
authors.initials: DR
authors.lastname: Elmaleh
authors.forename: P C
authors.initials: PC
authors.lastname: Meltzer
authors.forename: T M
authors.initials: TM
authors.lastname: Shoup
authors.forename: G L
authors.initials: GL
authors.lastname: Brownell
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: B K
authors.initials: BK
authors.lastname: Madras
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D003042:Cocaine / Q000031:analogs & derivatives; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D009411:Nerve Endings / Q000737:chemistry* / Q000000981:diagnostic imaging; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000000981:diagnostic imaging*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D018765:Dopamine Uptake Inhibitors; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine; D004298:Dopamine