Fluoro-, bromo-, and iodopaclitaxel derivatives: synthesis and biological evaluation
Fluoro-, bromo-, and iodopaclitaxel derivatives: synthesis and biological evaluation
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DOI：
10.1016/s0969-8051(02)00351-7
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发表时间：
2003-01-01
影响因子：
3.1
通讯作者：
Eckelman, WC
中科院分区：
文献类型：
--
作者：
Kiesewetter, DO;Jagoda, EM;Eckelman, WC
紫杉醇（Taxol（R））是临床上重要的化学治疗剂。我们描述了氟-、溴-和碘代辛烷及其[F-18]氟-、[Br-76]溴-和[I-124]碘-类似物的合成。[F-18]氟尿嘧啶在大鼠组织中显示出高摄取和快速清除。紫杉醇预给药可显著增加（p < 0.005）[F-18]氟紫杉醇和[Br-76]溴紫杉醇在大鼠血液（33.0%）、心脏（32.0%）中的滞留。肺（37.6%）、肾（142.4%）和血液（33.4%）、肺（42.3%）、肾（62.4%）。[F-18]与野生型对照相比，mdr 1a/1b（-/-）小鼠脑中的荧光素摄取增加了1400%（p < 1.3e-07）。紫杉醇或XR 9576（一种调节剂）的预给药。对这些mdr 1a/1b（-/-）小鼠的生物分布几乎没有影响。结果。[F-18]氟代紫杉醇将成为研究多药耐药肿瘤的有效放射性药物。出版社：Elsevier Science Inc. All rights reserved.
Paclitaxel (Taxol(R)) is a clinically important chemotherapeutic agent. We describe the synthesis of fluoro-, bromo-, and iodopaclitaxel and their [F-18]fluoro-, [Br-76]bromo- and [I-124]iodo-analogues. [F-18]Fluoropaclitaxel shows high uptake and rapid clearance from tissues in rats. Preadministration of paclitaxel in normal rats significantly increases (p < 0.005) retention of [F-18]fluoropaclitaxel and [Br-76]bromopaclitaxel in blood (33.0%), heart (32.0%). lung (37.6%) kidney (142.4%) and blood (33.4%), lung (42.3%), kidney (62.4%), respectively. [F-18]Fluoropaclitaxel uptake in the brain of mdr1a/1b(-/-) mice is increased 1400% (p < 1.3e-07) relative to wild-type controls. Preadministration of paclitaxel or XR9576, a modulator. had little effect on the biodistribution in these mdr1a/1b(-/-) mice. As a result. [F-18]fluoropaclitaxel will be a useful radiopharmaceutical for the study of multidrug resistant tumors. Published by Elsevier Science Inc. All rights reserved.