Synthesis of an 18F-fluorobenzoate idarubicin derivative as new potential PET radiotracer to predict chemotherapy resistance
Synthesis of an 18F-fluorobenzoate idarubicin derivative as new potential PET radiotracer to predict chemotherapy resistance
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DOI：
10.1002/jlcr.990
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发表时间：
2005-10-15
影响因子：
1.8
通讯作者：
Silverman, DHS
中科院分区：
文献类型：
--
作者：
Seimbille, Y;Czernin, J;Silverman, DHS
蒽环类药物是目前临床实践中使用最广泛的抗肿瘤药物之一。然而，在施用蒽环类药物后经常观察到导致无法根除肿瘤的化疗耐药性，并且尚未发现能够准确预测肿瘤对这些抗肿瘤药物的耐药性的测定系统。我们试图制备一种 F-18 标记的伊达比星衍生物（一种 4-去甲氧基柔红霉素类似物），用于帮助评估体内对蒽环类药物的生理耐药性。两种不同的合成途径需要制备关键中间体[F-18]氟苯甲酸（[F-18]FBA），从而在其伯胺上用 F-18 标记伊达比星。第一种方法由 [F-18]JFBA 分两步产生所需的 [F-18] 氟苯甲酸酯伊达比星衍生物，而第二种策略包括在氰基膦酸二乙酯存在下用 [F-18]FBA 处理来直接酰化伊达比星。虽然第一种方法产生的副产物较少，但需要更多时间来获得 HPLC 纯化的放射性药物（100 分钟与 90 分钟），并导致放射化学产率较低（从起始氟化物校正的衰减为 8-25% 与 25-39%）。版权所有 (c) 2005 John Wiley & Sons, Ltd.
Anthracyclines are among the most widely used antineoplastic agents in current clinical practice. Nevertheless, chemo resistance, which results in failure to eradicate the tumor, is often observed after administration of anthracyclines, and no assay system has yet been found to accurately predict tumor resistance to those antitumor agents. We sought to prepare an F-18 labeled derivative of idarubicin, a 4-demethoxydaunorubicin analogue, to use in helping to assess physiologic resistance to anthracyclines in vivo. Two different synthetic pathways, which required the preparation of the key intermediate [F-18]fluorobenzoic acid ([F-18]FBA), are advanced to label idarubicin with F-18 on its primary amine. The first approach yielded the desired [F-18]fluorobenzoate idarubicin derivative in two steps from [F-18]JFBA, while the second strategy consisted of a direct acylation of idarubicin by treatment with [F-18]FBA in presence of diethyl cyanophosphonate. Although the first method led to fewer byproducts, it required more time to obtain the HPLC-purified radiopharmaceutical (100 min vs 90 min) and resulted in lower radiochemical yields (8-25% vs 25-39% decay corrected from starting fluoride). Copyright (c) 2005 John Wiley & Sons, Ltd.