Department of Nuclear Medicine & PET Research, Radionuclide Centre, VU University Medical Center, P,O, box 7057, Amsterdam 1081, HV, The Netherlands.
EJNMMI Res. 2012 Jul 2;2(1):36. doi: 10.1186/2191-219X-2-36.
At present, several positron emission tomography (PET) tracers are in use for imaging P-glycoprotein (P-gp) function in man. At baseline, substrate tracers such as R-[11C]verapamil display low brain concentrations with a distribution volume of around 1. [11C]phenytoin is supposed to be a weaker P-gp substrate, which may lead to higher brain concentrations at baseline. This could facilitate assessment of P-gp function when P-gp is upregulated. The purpose of this study was to synthesize [11C]phenytoin and to characterize its properties as a P-gp tracer.
[11C]CO was used to synthesize [11C]phenytoin by rhodium-mediated carbonylation. Metabolism and, using PET, brain pharmacokinetics of [11C]phenytoin were studied in rats. Effects of P-gp function on [11C]phenytoin uptake were assessed using predosing with tariquidar.
[11C]phenytoin was synthesized via [11C]CO in an overall decay-corrected yield of 22 ± 4%. At 45 min after administration, 19% and 83% of radioactivity represented intact [11C]phenytoin in the plasma and brain, respectively. Compared with baseline, tariquidar predosing resulted in a 45% increase in the cerebral distribution volume of [11C]phenytoin.
Using [11C]CO, the radiosynthesis of [11C]phenytoin could be improved. [11C]phenytoin appeared to be a rather weak P-gp substrate.
目前，有几种正电子发射断层扫描（PET）示踪剂可用于人体 P-糖蛋白（P-gp）功能成像。在基线时，底物示踪剂如 R-[11C]维拉帕米显示低脑浓度，分布容积约为 1。[11C]苯妥英被认为是一种较弱的 P-gp 底物，这可能导致基线时脑内浓度升高。这有助于在 P-gp 上调时评估 P-gp 功能。本研究的目的是合成[11C]苯妥英，并表征其作为 P-gp 示踪剂的特性。
通过铑介导的羰基化反应，使用[11C]CO 合成[11C]苯妥英。在大鼠中研究了[11C]苯妥英的代谢和用 PET 测量的脑药代动力学。使用 tariquidar 预给药评估 P-gp 功能对[11C]苯妥英摄取的影响。
[11C]苯妥英通过[11C]CO 合成，总衰减校正产率为 22±4%。给药后 45 分钟，血浆和脑中的放射性分别有 19%和 83%代表完整的[11C]苯妥英。与基线相比，tariquidar 预给药导致[11C]苯妥英脑分布容积增加 45%。
使用[11C]CO，可改善[11C]苯妥英的放射合成。[11C]苯妥英似乎是一种较弱的 P-gp 底物。
