High-yielding, two-step 18F labeling strategy for 18F-PARP1 inhibitors.
High-yielding, two-step 18F labeling strategy for 18F-PARP1 inhibitors.
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DOI：
10.1002/cmdc.201000426
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发表时间：
2011-03-07
期刊：
影响因子：
3.4
通讯作者：
Weissleder R
中科院分区：
文献类型：
--
作者：
Keliher EJ;Reiner T;Turetsky A;Hilderbrand SA;Weissleder R
标记代谢物、药物、蛋白质和纳米材料的正电子发射断层扫描 (PET) [1-3] 正在迅速成为一种强大的成像工具，用于检测和分期疾病、研究人类生物学、研究新药的药代动力学和药效动力学，或测量临床试验中的治疗效果。[4-8] 18F 是临床成像最常用的同位素之一，因为它具有半衰期、易于生产、广泛使用以及与微流体的兼容性综合。[9]尽管标记一些小分子的方法得到了广泛的应用和完善的程序，但仍然很大程度上缺乏简便的 18F 平台型普遍适用的标记策略。对于高通量筛选中出现的小分子的快速标记或优化混合和模块化显像剂尤其如此。生物正交化学代表了开发此类通用标记平台的一种途径。迄今为止，已经描述了几种生物正交反应[10-15]，但只有少数适用于同位素标记。最流行的是叠氮化物和炔烃之间的 1, 3-偶极环加成反应，即“点击”反应。[9, 16] 这些反应被发现对于生物分子的体外 18F-氟化特别有用，现在已被广泛使用。[1, 17-20] 我们寻找替代的更快速、选择性和化学上可访问的偶联反应，无需催化剂，这促使我们研究 [4+ 2] 逆电子需求使用反式环辛烯 (TCO) 和四嗪 (Tz) 进行 Diels-Alder 环加成反应。[21,22,22] TCO/Tz 标记策略的优点包括 a) 超过 6,000 M-1s-1 的快速反应时间，b) 高选择性，c) 不需要高温或催化剂，d) 生物相容性反应条件和 e) 可活化四嗪。 [22]
Positron emission tomography (PET) of labeled metabolites, drugs, proteins and nanomaterials [1-3] is rapidly emerging as a powerful imaging tool to detect and stage disease, to study human biology, to investigate pharmacokinetics and pharmacodynamics of new drugs, or to measure treatment efficacy in clinical trials.[4-8] 18F is one of the most commonly used isotopes for clinical imaging given its half-life, ease of production, wide availability, and compatibility with microfluidics syntheses.[9] Despite extensive use and well established procedures of labeling some small molecules, facile 18F platform-type universally adaptable labeling strategies are still largely missing. This is especially true for rapid labeling of small molecules that emerge from high throughput screens or for optimizing hybrid and modular imaging agents. Bioorthogonal chemistries represent one avenue to develop such generic labeling platforms.To date, several bioorthogonal reactions have been described [10-15] but only few have been adapted for isotope labeling. The most popular ones is the 1, 3-dipolar cycloaddition,“click” reaction, between azides and alkynes.[9, 16] These reactions were found to be particularly useful for in vitro 18F-fluorination of biomolecules and are now commonly used.[1, 17-20] Our search for alternative more rapid, selective, and chemically accessible coupling reactions without need for a catalyst led us to investigate the [4+ 2] inverse electron demand Diels-Alder cycloaddition using trans-cyclooctenes (TCO) and tetrazines (Tz).[21, 22, 22] Advantages of the TCO/Tz labeling strategy include a) fast reaction times in excess of 6,000 M-1s-1, b) high selectivity, c) no need for elevated temperatures or catalysts, d) biocompatible reaction conditions and e) activatable tetrazines.[22]