Brownell A L, Elmaleh D R, Meltzer P C, Shoup T M, Brownell G L, Fischman A J, Madras B K
Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
J Nucl Med. 1996 Jul;37(7):1186-92.
The PET imaging properties of three phenyltropane drugs with differing affinities and selectivities for the dopamine over serotonin transporter, were compared.
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).
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.
The present results clearly indicate that 11C-CFT is a useful ligand for monitoring dopamine neuronal degeneration.
比较了三种对多巴胺转运体和5-羟色胺转运体具有不同亲和力和选择性的苯基托烷类药物的正电子发射断层扫描（PET）成像特性。
使用高分辨率PET成像系统（PCR-I），对五只正常和两只经1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的食蟹猴（猕猴）中的碳-11-CFT（WIN 35,428，2β-甲氧羰基-3β-（4-氟苯基）托烷）、11C-CCT（RTI-131，2β-甲氧羰基-3β-（4-单氯苯基）托烷）和11C-CDCT（二氯托烷，2β-甲氧羰基-3β-（3,4-二氯苯基）托烷）作为多巴胺神经元的成像探针进行了评估。
对于11C-CFT，在对照动物中，60分钟时尾状核的特异性结合率（由纹状体与小脑放射性水平之比定义）为4.2±0.8，壳核为4.9±1.2；90分钟时尾状核为4.9±1.2，壳核为5.5±1.1。在经MPTP处理的猴子中，60分钟时尾状核的相应比率为1.4±0.1，壳核为1.5±0.1；90分钟时尾状核为1.3±0.1，壳核为1.4±0.3。对于CFT的单氯类似物11C-CCT，对照尾状核和壳核中的比率在60分钟时分别为2.7±0.4和3.4±0.3，在90分钟时分别为3.7±0.5和4.4±0.6。在经MPTP处理的动物中，60分钟时相应比率为1.4±0.4和1.5±0.3，90分钟时为1.4±0.4和1.6±0.4。CFT的二氯类似物CDCT对多巴胺转运体具有最高亲和力，在对照脑中产生的比率最低，60分钟时尾状核为2.3±0.4，壳核为2.4±0.5。在一只经MPTP处理的猴子中，相应比率为1.6±0.4和1.8±0.3。与11C-CFT相比，11C-CCT和11C-CDCT的选择性均较低，且丘脑摄取较高。
目前的结果清楚地表明，11C-CFT是监测多巴胺神经元变性的有用配体。
