Production of ィイD1105ィエD1Rh and application of this nuclide to therapeutic radiopharmaceuticals

D1105D1Rh的生产及其在治疗放射性药物中的应用

• 批准号: 10670833
• 负责人: ANDO Atsushi
• 金额: $ 1.28万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670833/
• 关键词: Radiotherapeutic nuclide; Rhodium-105; EDTMP; Rh-105-EDTMP; Bone metastases; 疼痛緩和剤; 治療用放射性医薬品; ^<105>Rh; ブレオマイシン; ^<105>Rh-ブレオマイシン

Rhodium-105(ィイD1105ィエD1Rh) has favorable physical characteristics as a radiotherapeutic nuclide. Carrier-free ィイD1105ィエD1Rh can be produced by the neutron activation of ィイD1104ィエD1Ru followed by beta decay of ィイD1105ィエD1Ru. It was clarified that carrier-free ィイD1105ィエD1Rh can be produced in quantities and the purity necessary for chemical and clinical investigations of its use as a nuclide for radiotherapy.ィイD157ィエD1Co-bleomycin is selectively accumulated in some cancer. However, the long half-life of ィイD157ィエD1Co(270 days) poses contamination problems which preclude its widespread clinical use. Kono suggested from the similarity of chemical property between cobalt and rhodium and from the in vitro study that Rh-bleomycin would have tumor affinity. Bleomycin-hydrochloride was added the solution of ィイD1105ィエD1Rh(II) and heated for 5 min in boiling water. ィイD1105ィエD1Rh-bleomycin(BLM) was separated from the reaction mixture by thin-layer chromatography on silica gel plate using the solvent system, MeOH : 10% CHィイD23ィエD2COONHィイD24ィエD2 in HィイD22ィエD20(1:1). Tumor affinity of ィイD1105ィエD1Rh-BLM was examined with Ehrlich tumor-bearing mice. In this experiment, ィイD1105ィエD1Rh-BLM did not accumulated in tumor tissue.On the other hand, we produced ィイD1105ィエD1Rh-EDTMP for therapeutic bone agent. ィイD1105ィエD1Rh-EDTMP was simply obtained from ィイD1105ィエD1RhィイD13+ィエD1 and EDTMP by heating for 30 min in boiling water, giving a radiochemical yield of > 99 %. Dissociation of radioactivity assessed by paperchromatography was negligible for up to 5 days after its preparation. In animals, ィイD1105ィエD1Rh-EDTMP showed rapid blood clearance and selective uptake in the bone.Hence, ィイD1105ィエD1Rh-EDTMP is thought to be a promising therapeutic agent for the treatment of pain due to bone metastases.

铑-105（Rhodium D1105）是一种具有良好物理特性的放射性核素。无载流子的氘代D1105氘代D1 Rh可以通过氘代D1104氘代D1 Ru的中子活化，然后由氘代D1105氘代D1 Ru的β衰变产生。它澄清了无载体的D1105-D1 Rh可以生产的数量和纯度所需的化学和临床研究，它作为放射治疗的核素。然而，由于D157的半衰期较长（270天），造成了污染问题，妨碍了其广泛的临床应用。Kono从钴和铑化学性质的相似性以及体外研究中提出Rh-博来霉素具有肿瘤亲和力。将盐酸博莱霉素加入到盐酸博莱霉素D1105的溶液中，并在沸水中加热5分钟。通过硅胶板上的薄层色谱法，使用溶剂系统MeOH：10%CH2Cl2 D23水溶液D2COONH水溶液D24水溶液D2的水溶液D22水溶液D20（1：1），从反应混合物中分离BLM-博来霉素（BLM）。用荷埃利希瘤小鼠检测了紫杉醇D1105紫杉醇D1 Rh-BLM的肿瘤亲和性。在本实验中，イD1105 D1 Rh-BLM在肿瘤组织中没有积累。另一方面，我们生产了治疗性骨剂イD1105 D1 Rh-EDTMP。由D1105铑D1铑D13+铑D1和EDTMP在沸水中加热30分钟，简单地得到D1105铑D1铑EDTMP，放射化学产率> 99%。通过纸色谱法评估的放射性解离在制备后长达5天内可忽略不计。在动物实验中，顺铂D1105顺铂D1 Rh-EDTMP具有快速的血液清除和骨选择性摄取，因此，顺铂D1105顺铂D1 Rh-EDTMP被认为是一种有前途的治疗骨转移疼痛的药物。

项目成果

Atsushi Ando: "Production of ^<105>Rh-EDTMP and its bone accumulation"Applied Radiation and Isotopes. 52. 211-215 (2000)

Atsushi Ando：“^<105>Rh-EDTMP 的生产及其骨积累”应用辐射和同位素。

Atsushi Ando: "Production of ィイD1105ィエD1Rh-EDTMP and its bone accumulation"Applied Radiation and Isotopes. Vol. 52. 211-215 (2000)

Atsushi Ando：“D1105D1Rh-EDTMP 的生产及其骨积累”应用辐射和同位素，第 52 卷，211-215（2000）。