摘要
基于卟啉类仿生分子有亲多种肿瘤性和辐射增敏性,本文作者以亚锡还原法研究了无载体188Re标记中位-四(4-磺酸苯基)卟啉(TPPS4)制备条件对188Re-TPPS4合成的影响,以荷肝癌及黑色素瘤裸鼠为模型探索了188Re-TPPS4在健康鼠及裸瘤鼠体内靶向行为。结果表明,以Sn(II)-Tart为还原剂,在pH为1~5,沸水浴氮气氛中反应30m in,可获得产率大于95%的188Re-TPPS4,其放射性比活度可达11.2 GBq(mol.TPPS4)-1;Vc可增强产物在靶器官肝的摄取以及提高188Re-TPPS4的体内稳定性,有助于防止其标记物氧化分解为ReO4-,188Re-TPPS4在瘤裸鼠体内行为实验表明肝癌或黑色素瘤对其有较高摄取,注射后8h时瘤摄取(%ID.g-1)分别为5.7和4.4,且非瘤靶组织摄取相对较低,这提示188Re-卟啉配合物可望作为潜在肿瘤治疗剂。
Porphyrin or metalloporphyrin derivatives are important biological compounds for targeting cancer treatment due to special affinity in tumors.The development of 188Re radiopharmaceuticals with radiosensitivity for treatment of tumors is valuable since such nuclide agents may increase therapeutic effects.In this paper,we present studies on synthesis and biological behaviors of meso-tetrakis（4-sulfophenyl）porphyrin（TPPS4）labeled with 188Re.The results showed that using Sn（II） reduction method,188Re-TPPS4 could be prepared at pH1~5,in boiling water bath for more than 30 min,and the labeling yield was more than 95% with radioactive special activity 11.2 GBq（mol.TPPS4）-1.The results from bio-distribution of 188Re-TPPS4 with or without Vitamin C（Vc,10mg.mL-1） in normal mice indicated that Vc could help to increase in vivo stability of the labeled compound.The biological behaviors of 188Re-TPPS4 in tumor mice shown the higher uptake（%ID.g-1） of 188Re-TPPS4 up to 5.7 and 4.4 in liver tumor and melanoma respectively at post-injection 8h than that in other tissues,and demonstrated that 188Re-TPPS4 could be used as a potential therapeutic agent for the tumors.
出处
《化学研究与应用》
CAS
CSCD
北大核心
2010年第12期1531-1536,共6页
Chemical Research and Application
基金
中国工程物理研究院基金资助(2008B0301022)
国家自然科学基金资助项目(30900378)
