Isomers of 4-[18F] fluoro-proline: Radiosynthesis, Biological Evaluation and Results in Humans Using PET
Isomers of 4-[18F] fluoro-proline: Radiosynthesis, Biological Evaluation and Results in Humans Using PET
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DOI：
10.2174/1874471007666140902152916
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发表时间：
2014-01-01
影响因子：
2.3
通讯作者：
Langen, Karl-Josef
中科院分区：
文献类型：
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作者：
Geisler, Stefanie;Ermert, Johannes;Langen, Karl-Josef
脯氨酸和羟脯氨酸代表哺乳动物结构蛋白，特别是胶原蛋白的主要成分。二十年前开发了F-18标记的脯氨酸衍生物顺式/反式-4-[F-18]氟-L-脯氨酸的有效放射合成，目的是使用正电子发射断层扫描（PET）研究具有改变的胶原合成的各种疾病。许多研究已经探索了顺式-4-[F-18]氟-L-脯氨酸在与胶原形成增加相关的各种病理和肿瘤性病变中的摄取，但到目前为止，结果并不十分乐观。反式-4-[F-18]氟-L-脯氨酸尚未进行详细研究，但与其顺式对映体相比，该化合物在代谢行为和生物分布方面表现出相当大的差异。近年来，顺式/反式-4-[F-18]氟-脯氨酸的D-异构体也被认为是PET示踪剂，并且观察到与其L-异构体相比，两者都表现出优先摄取到脑中。令人惊讶的是，在表现出继发性神经变性的脑区域以及脑肿瘤治疗后放射性坏死的区域中发现顺式-4-[18F]氟-D-脯氨酸的高摄取。本文综述了顺/反-4-[F-18]氟-D/L-脯氨酸的生物学和生理学特性及其在各种病理学中的研究结果，包括本实验室以前未发表的一些结果。
Proline and hydroxyproline represent major constituents of mammalian structural proteins, especially of collagen. An efficient radiosynthesis of the F-18-labeled proline derivatives cis-/trans-4-[F-18] fluoro-L-proline was developed two decades ago with the aim to investigate various diseases with altered collagen synthesis using Positron-Emission-Tomography (PET). A number of studies have explored cis-4-[F-18] fluoro-L-proline uptake in various pathologies associated with increased collagen formation and in neoplastic lesions, but so far the results have not been very promising. Trans-4-[F-18] fluoro-L-proline has not yet been investigated in detail, however the compound exhibits considerable differences in metabolic behavior and biodistribution compared with its cis-enantiomer. In recent years, the D-isomers of cis/trans-4-[F-18] fluoro-proline have been considered as PET tracers as well, and it was observed that both exhibit a preferred uptake into the brain compared with their L-isomers. Surprisingly, a high uptake of cis-4-[18F] fluoro-D-proline was found in brain areas exhibiting secondary neurodegeneration as well as in areas of radionecrosis after treatment of brain tumors. In this article, the present knowledge on the biological and physiological properties of cis-/trans-4-[F-18] fluoro-D/L-proline and the results in various pathologies are reviewed, including some previously unpublished results from our laboratory.