188Re标记伊班膦酸骨转移瘤显像与靶向治疗研究

Bone metastasis is a significant clinical problem for patients with advanced malignant tumors, such as breast, prostate, and lung cancer.The early detection and targeted therapy of bone metastasis will improve the prognosis..At present, many of these patients are candidates for radionuclide therapy, including 89Sr-chloride,153Sm-ethylenediaminetetramethylenephosphonate (EDTMP). However, these treatments have limited efficacy for metastatic bone pain. Palliative care for pain remains an area that requires more effective treatment..Ibandronate is a third-generation bone-targeted bisphosphonate used for relieving severe metastatic bone pain. 188Re-Ibandronate were prepared and evaluated in vitro with regard to biodistribution and pharmacokinetics. Additionally, in vivo single-photon emission computed tomography was used to evaluate bone uptake. 188Re-Ibandronate uptake compared with 99mTc-MDP in bone metastasi was also investigated to determine its efficacy in nude mice bone metastasis model treatment. .188Re-Ibandronate should detect bone metastasis early.Combined bisphosphonate treatment with radionulide bone-targeted therapy should be beneficial for bone pain palliation. 188Re-Ibandronate will be a novel bone imaging agent and bone-targeted therapy radiopharmaceutical for bone metastasis.

骨转移常见于乳腺癌、前列腺癌、肺癌等恶性肿瘤疾病晚期，骨转移早期诊断、靶向治疗能有效改善预后。临床上常用89SrCl2、153Sm-EDTMP等放射性核素治疗缓解癌性骨痛，但疗效不够理想，迫切需求更有效的缓解骨痛治疗方法。.伊班膦酸属第三代双膦酸盐，亲骨性能高，能有效缓解转移性骨痛。本研究对伊班膦酸进行188Re标记，探索最佳标记条件，制备高放化纯的标记物；研究其在病变骨组织的摄取机理；进行正常及骨肿瘤动物体内分布、药代动力学和和体外显像研究，探讨最佳显像条件，与99mTc-MDP比较；研究188Re-伊班膦酸对骨转移瘤裸鼠疗效，与89SrCl2、伊班膦酸比较；并进行其安全性评估、量效关系、内照射吸收剂量的研究。 .188Re-伊班膦酸能早期诊断骨转移，且具有双膦酸盐治疗和放射性核素靶向治疗骨转移的双重治疗作用，能够改善肿瘤骨转移患者生存质量，有望成为一种新型骨显像剂与骨转移瘤靶向治疗剂。

骨转移常见于乳腺癌、前列腺癌、肺癌等恶性肿瘤疾病晚期，骨转移早期诊断、靶向治疗能有效改善预后。临床上常用89SrCl2、153Sm-EDTMP等放射性核素治疗缓解癌性骨痛，但疗效不够理想，迫切需求更有效的缓解骨痛治疗方法。. 伊班膦酸属第三代双膦酸盐，亲骨性能高，能有效缓解转移性骨痛。本课题进行了伊班膦酸188Re标记，探索最佳标记条件，制备高放化纯的标记物的研究；其在病变骨组织的摄取机理的研究；正常及骨肿瘤动物体内分布、药代动力学和和体外显像研究，探讨最佳显像条件，与99mTc-MDP比较；188Re-伊班膦酸对骨转移瘤裸鼠疗效的研究，与89SrCl2、伊班膦酸比较；并进行了其安全性评估、量效关系、内照射吸收剂量的研究。.188Re-伊班膦酸能早期诊断骨转移，且具有双膦酸盐治疗和放射性核素靶向骨转移治疗的双重治疗作用，能够改善肿瘤骨转移患者生存质量，有望成为一种新型骨显像剂与骨转移瘤靶向治疗剂。