Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Hospital, Stockholm, Sweden.
J Nucl Med. 2011 Jan;52(1):132-9. doi: 10.2967/jnumed.110.077651.
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.
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).
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).
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.
在非人类灵长类动物中，使用放射性配体 11C-N-(3-碘丙-2E-烯基)-2β- 碳甲氧基-3β-(4-甲基苯基)去甲托烷（11C-PE2I）和 18F-FE-PE2I，通过使用母体和放射性代谢物的输入函数的动力学和图形分析，来评估放射性代谢物的潜在贡献，比较多巴胺转运体（DAT）的定量与 11C-PE2I 和 18F-FE-PE2I。
使用高分辨率灵长类动物放射断层扫描仪（HRRT）系统，对 3 只恒河猴进行 11C-PE2I 和 18F-FE-PE2I 检测。测量了母体和放射性代谢物 M1 的动脉输入函数。使用母体输入（方法 1 和 3）或母体加放射性代谢物输入（方法 2 和 4）进行了动力学和图形分析。测量指标为分布容积（VT 和 VND）、平衡时特异性与非特异性组织放射性比值（BPND；母体输入）和存在代谢物时特异性与非特异性组织放射性比值（RT；母体加放射性代谢物输入）。
与方法 1 和 3 相比，方法 2 和 4 计算的 11C-PE2I 的分布容积更高（纹状体 VT，约 300%；小脑 VND，约 30%）。对于每种放射性配体，11C-PE2I 的纹状体 VT 用方法 2 和 4 计算大约高 60%，而小脑 VND 没有差异。用方法 1 和 3 估计的 BPND 比用方法 2 和 4 估计的 RT 更倾向于升高，但与 RT 相比，11C-PE2I 的 BPND 偏差（纹状体的 40%-60%）比 18F-FE-PE2I（纹状体的 <10%）大得多。
放射性配体的直接比较证实，18F-FE-PE2I 比 11C-PE2I 显示出更快的动力学和更有利的代谢。母体和放射性代谢物输入函数的动力学和图形分析表明，18F-FE-PE2I 的 BPND 偏差比 11C-PE2I 低得多，这表明放射性代谢物 M1 的产生较低会使 18F-FE-PE2I 更适合 DAT 的定量。有必要在人类中进一步研究以确认这些发现。
