局部缓释IUdR治疗恶性星形细胞瘤实验研究(英文)

Local delivery of polymeric ^(125)I-IUdR to experimental human malignant gliomas

目的研究脑局部缓释125碘标记的5-碘脱氧尿苷(IUdR)的作用。方法为了控制释放125碘-IUdR,合成了25μCi的羧基苯氧丙烷:癸二酸(PCPPSA)(2080)125碘-IUdR聚合体。体外将合成的三聚体缓释剂(10mgPCPPSA)置于37℃磷酸盐缓冲溶液(PBS)中孵育不同时间后移出溶剂并置换为新的PBS,将移出液于放射计数器上测量数值。在体研究采用雄性裸鼠(6周)颅内接种U251人恶性星形细胞瘤及皮下接种对比研究。将颅内荷瘤鼠瘤腔内及皮下接种肿瘤组织内分别应用三聚体缓释剂及空白缓释剂,于不同时间分别测量动物头颅及皮下结节的放射活性,间接定量研究缓释状况;采血了解全身代谢情况。对于多聚磷酸酯(PPE)缓释剂研究采用皮下肿瘤结节内局部应用并测量其缓释的方法,放射自显影研究及全身不同器官缓释剂的吸收代谢研究采用接种后2、4和8d收集标本,分别行切片放射自显影和器官放射活性测定。结果体内和体外研究均显示PCPP:SA缓释剂对125碘-IUdR的控制性释放作用,尤其在体研究分别显示颅内和皮下接种的肿瘤组织对标记的IUdR的释放程度存有极大的差异,提示颅内局部应用的优越性。放射自显影定性研究显示了随距离的增加被标记的IUdR的递减趋势,为确定缓释剂施放部位和间距提供了参考数据。各主要脏器放射性测定的结果显示早期小肠内放射性较高,其次为脾脏,提示IUdR主要的代谢渠道,为处理应用其而可能引发的其他脏器损害或作用提供了线索。结论放射标记的IUdR缓释剂主要集中在接种部位且缓释作用确切。

Objective To detect the role of implantable biodegradable polymers for the local delivery of ^125I radiolabeled idoxuridine （IUdR）. Methods Para-carboxyphenoxypropane： sebacic acid （PCPP ： SA） polymers （10 nag, 25μCi of the ^125I-IUdR） and polyphosphocster （PPE） polymers （15μg ： 25μCi） were synthesized and the release of the radioactivity was counted by a calibrated scintillation counter both in vitro and in vivo. Results PCPP ： SA resuhed in controlled, protracted release of ^125I-IUdR vs. time in vitro, and the similar outcomes were obtained in vivo, The counting of the blood after implantation of the flank PCPP ： SA polymers showed the release was much faster than for the intracranial （IC） polymer. For the counting of flank tumors after ipsilateralral （IP） vs.contralateral （CL） polyphosphocster （PPE） ^125I-IUdR injection, the release speed of both sides were similar, but the IP polymer had a much higher local concentration than for the CL polymer. The release of the PPE ^125I-IUdR polymer into the blood was similar in both side implanted polymers. Autoradiographic quantification of the activity section showed decreasing activity vs. distance from the polymeric implant and decreasing activity for CL vs. IP ^125I-IUdR polymeric implantation. Organs counts showed that the highest content was for the intestine, followed by the spleen measured 2, 4, and 8 days after the polymers implantation. Conclusion The implantable and biodegradable polymers make radiolabled IUdR more concentrate in the implanted site and orotraete its release.