Re-186 Radiotherapeutical Agent for Bone Tumor Metastases and Bone Pain Palliation Radiotherapy

近年来，肿瘤患者骨显像缺乏对破骨细胞性骨破坏(OC)或成骨细胞性骨形成(OB)骨转移的鉴别诊断缺乏特异性。二硫代丁二酸五价多核TC-络合物(TC(V)-DMS)在骨病理学中的独特蓄积引起了人们的兴趣。本课题从细胞水平和OC、OB动物模型两个方面对其成骨特性进行了研究。在细胞水平上，TC(V)-DMS对破骨细胞有很强的亲和力。与著名的双膦(BBP)试剂TC HMDP的比较研究表明，任何OC或OB细胞都缺乏亲和力。在OC型动物模型中，通过将VX2植入兔体内，SPECT研究表明，~(18)Re(V)-DMS与转移灶有明显的亲和力，ARG(186Re(V)-DMS，186Re-HMSDP)和组织学研究证实，在OC丰富的区域有放射性聚集。TC-HMDP在OC模型中缺乏蓄积，但在骨损伤大鼠(OB模型)中蓄积10-15倍，亲和力较高，初步注射四环素，这是一种在新形成的损伤骨中蓄积的荧光剂，叠加在放射性区域。TC(V)-DMS在OC骨肿瘤中的独特蓄积表明，该制剂在OC和OB转移瘤的鉴别诊断中具有潜力，并有望用于放射治疗和骨痛缓解。

In recent years, deficiency of Tc-bone imaging in oncology patients is lack of specificity on osteoclastic (bone destruction)(OC) or osteoblastic (bone formation) (OB) bone metastases differenciation. Uniqueness of pentavalent polynuclear Tc-complex of dimercaptosuccinic acid (Tc(V)-DMS) to accumulate in bone pathologies are of interest. In this project, studies on the osteotropic character at cellular level and in OC and OB animal models were performed. At cellular level, the great affinity of Tc(V)-DMS for the osteoclastic cells was demonstrated. Comparative studies with the well known bisphosphonate (BBP) agent, Tc HMDP, showed lack of affinity in any OC or OB cells. In the OC type of animal model, by the VX2 implant in rabbit, clear affinity of Tc(V)-DMS for the metastatic area demonstrated by SPECT studies, the ARG (186Re(V)-DMS, 186Re-HMSDP) and histological studies confirmed the radioactivity accumulation in areas abundant in OC. The Tc-HMDP showed lack of accumulation in the OC model, but this agent accumulated 10-1 5 times with higher avidity in bone injured rats (OB model), demonstrated by preliminary injection of tetracycline, a fluorescent agent to accumulate in recently formed injured bone, superimposed to the radioactive region. The distinctive Tc(V)-DMS accumulation in OC bone tumor indicated the potentiality of this agent in the differentiation of OC from OB metastases and its plausible use in radiotherapy and bone pain palliation.