Evaluation of TK1 targeting carboranyl thymidine analogs as potential delivery agents for neutron capture therapy of brain tumors.
Evaluation of TK1 targeting carboranyl thymidine analogs as potential delivery agents for neutron capture therapy of brain tumors.
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DOI：
10.1016/j.apradiso.2015.06.031
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Riley KJ
中科院分区：
文献类型：
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作者：
Barth RF;Yang W;Nakkula RJ;Byun Y;Tjarks W;Wu LC;Binns PJ;Riley KJ
在这篇报告中，我们描述了N5-2OH的研究，N5-2OH是胸腺嘧啶激酶1 （TK1）的底物，使用F98大鼠胶质瘤模型。体内BNCT研究表明，脑内（i.c）渗透泵输注N5-2OH产生的生存数据与静脉注射硼苯丙氨酸（BPA）获得的数据相当。与RG2胶质瘤模型相比，N5-2OH和BPA的结合导致F98胶质瘤大鼠MST的适度增加，这在统计学上是显著的，我们之前已经报道过。这导致我们合成了第二代cta，改善了体外酶动力学和体内肿瘤摄取。
In this report we describe studies with N5-2OH, a carboranyl thymidine analogue (CTA) that is a substrate for thymidine kinase 1 (TK1), using the F98 rat glioma model. In vivo BNCT studies have demonstrated that intracerebral (i.c.) osmotic pump infusion of N5-2OH yielded survival data equivalent to those obtained with i.v. administration of boronophenylalanine (BPA). The combination of N5-2OH and BPA resulted in a modest increase in MST of F98 glioma bearing rats compared to a statistically significant increase with the RG2 glioma model, as has been previously reported by us. This had lead us to synthesize a second generation of CTAs that have improved in vitro enzyme kinetics and in vivo tumor uptake.