Synthesis and biodistribution of [11C]adenosine 5′-monophosphate ([11C]AMP)
Synthesis and biodistribution of [11C]adenosine 5′-monophosphate ([11C]AMP)
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DOI：
10.1007/s11307-005-4118-6
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Wahl, RL
中科院分区：
文献类型：
--
作者：
Mathews, WB;Nakamoto, Y;Wahl, RL
目的：嘌呤受体和腺苷酸在体内的生物分布成像不仅对正常腺苷酸代谢的研究具有临床意义，而且对某些组织和器官的腺苷酸摄取和/或释放可能改变的病理状态（如某些类型的癌症）也具有重要意义。为了开发一种不会损失其放射性同位素的正电子发射断层扫描（PET）示踪剂，用碳-11在C-8位置对腺苷5'-单磷酸腺苷（AMP）进行了本质标记。步骤：用[C-11]甲醛与5-氨基-1- β - d -核呋喃酰基咪唑-4-羧脒-5'-磷酸反应合成[C-11]AMP。体外测定了在双嘧达莫存在和不存在的情况下，[C-11]AMP在人血液中的代谢。测定了[C-11]AMP在正常小鼠体内的生物分布和体内剂量。测定了双嘧达莫对小鼠体内[C-11]AMP分布的影响。结果：[C-11]AMP在34分钟（n = 7）内可靠合成，平均放射学产率为2.4%，合成结束时平均比活性为90.10 GBq/mu mol （2435 mCi/mu mol）。在正常小鼠中，肺、血液和心脏对[11C]AMP的摄取最高。小鼠离体实验表明，注射后60分钟，服用双吡达摩的动物肺部对C-11放射性示踪剂的摄取明显低于对照组。剂量学结果表明，肾和膀胱是造成辐射剂量负担的关键器官。结论：双嘧达莫阻断了红细胞对细胞外腺苷的摄取，从而阻断了其随后在细胞内向ATP的转化。生物分布研究表明示踪剂在肾脏、肺、心脏和血液中有大量积累。[C-11]AMP作为一种pet显像剂有望在体内追踪腺苷酸生物学。
Purpose: Imaging purine receptors and adenylate biodistribution in vivo may be of clinical importance not only for the investigation of normal adenylate metabolism but also in pathological conditions where adenylate uptake and/or release from certain tissues and organs may be altered, such as some types of cancer. In order to develop a tracer for positron emission tomography (PET) that would not be subject to loss of its radioisotope, adenosine 5'-mono-phosphate (AMP) was intrinsically labeled at the C-8 position with carbon-11.Procedures: [C-11]AMP was synthesized by reacting 5-amino-1-beta-D-ribofuranosylimidazole-4-carboxamidine-5'-phosphate with [C-11]formaldehyde. The metabolism of [C-11]AMP in human blood was determined in vitro both in the presence and absence of dipyridamole. The ex vivo biodistribution of [C-11]AMP and its in vivo dosimetry were determined in normal mice. The effect of dipyridamole on the distribution of [C-11]AMP in mice was also determined.Results: [C-11]AMP was reliably synthesized in 34 minutes (n = 7) with an average radiochernical yield of 2.4% and an average specific activity of 90.10 GBq/mu mol (2435 mCi/mu mol) at end of synthesis. In normal mice, the highest uptake of [11C]AMP was in the lungs, blood, and heart. The ex vivo mouse experiments showed that the uptake of C-11 radiotracer in the lungs at 60 minutes postinjection was significantly lower for dipyridamole-treated animals than controls. Dosimetry showed that the critical organs for radiation dose burden are kidneys and bladder.Conclusions: Treatment with dipyridamole blocked the red blood cell uptake of extracellular adenosine and therefore its subsequent intracellular conversion to ATP. The biodistribution studies indicate that the tracer has substantial accumulation in the kidneys, lungs, heart, and blood. [C-11]AMP is promising as a PET-imaging agent to trace adenylate biology in vivo.