Division of Radiological Sciences, Washington University School of Medicine, Campus Box 8225, 510 S. Kingshighway Blvd., St. Louis, MO 63110, USA.
Curr Top Med Chem. 2010;10(11):1060-95. doi: 10.2174/156802610791384261.
Carbon-11 (C-11) radiotracers are widely used for the early diagnosis of cancer, monitoring therapeutic response to cancer treatment, and pharmacokinetic investigations of anticancer drugs. PET imaging permits non-invasive monitoring of metabolic processes and molecular targets, while carbon-11 radiotracers allow a "hot-for cold" substitution of biologically active molecules. Advances in organic synthetic chemistry and radiochemistry as well as improved automated techniques for radiosynthesis have encouraged investigators in developing carbon-11 tracers for use in oncology imaging studies. The short half-life of carbon-11 (20.38 minutes) creates special challenges for the synthesis of C-11 labeled tracers; these include the challenges of synthesizing C-11 target compounds with high radiochemical yield, high radiochemical purity and high specific activity in a short time and on a very small scale. The optimization of conditions for making a carbon-11 tracer include the late introduction of the C-11 isotope, the rapid formation and purification of the target compound, and the use of automated systems to afford a high yield of the target compound in a short time. In this review paper, we first briefly introduce some basic principles of PET imaging of cancer; we then discuss principles of carbon-11 radiochemistry, focus on specific advances in radiochemistry, and describe the synthesis of C-11 radiopharmaceuticals developed for cancer imaging. The carbon-11 radiochemistry approaches described include the N,O, and S-alkylations of [(11)C]methyl iodide/[(11)C]methyl triflate and analogues of [(11)C]methyl iodide and their applications for making carbon-11 tracers; we then address recent advances in exploring a transmetallic complex mediated [(11)C]carbonyl reaction for oncologic targets.
碳-11（C-11）放射性示踪剂被广泛用于癌症的早期诊断、监测癌症治疗的疗效以及抗癌药物的药代动力学研究。正电子发射断层扫描（PET）成像允许对代谢过程和分子靶标进行非侵入性监测，而碳-11 放射性示踪剂允许对生物活性分子进行“热换冷”取代。有机合成化学和放射化学的进步以及用于放射性合成的改进自动化技术鼓励研究人员开发用于肿瘤成像研究的碳-11 示踪剂。碳-11 的半衰期短（20.38 分钟）给 C-11 标记示踪剂的合成带来了特殊挑战；这些挑战包括在短时间内以非常小的规模用高放射化学产率、高放射化学纯度和高比活度合成 C-11 靶化合物。优化制备碳-11 示踪剂的条件包括晚期引入 C-11 同位素、快速形成和纯化目标化合物以及使用自动化系统在短时间内提供目标化合物的高产率。在本文中，我们首先简要介绍了癌症正电子发射断层扫描成像的一些基本原则；然后讨论了碳-11 放射化学的原理，重点介绍了放射化学的具体进展，并描述了为癌症成像开发的 C-11 放射性药物的合成。描述的碳-11 放射化学方法包括[(11)C]甲基碘化物/[(11)C]甲基三氟甲磺酸酯及其类似物的 N,O 和 S-烷基化以及用于制备碳-11 示踪剂的方法；然后我们讨论了探索用于肿瘤靶标的过渡金属络合物介导的[(11)C]羰基反应的最新进展。
