Research on positron emitting 62-zinc and 62-copper radiopharmaceuticals for Nuclear Medicine.

核医学用正电子发射62-锌和62-铜放射性药物的研究。

• 批准号: 60870080
• 负责人: YOKOYAMA Akira
• 金额: $ 2.37万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60870080/
• 关键词: 62-zinc; 62-copper; ethylenediamine-N,N'diacetate complex; bifunctional chelate; myocardial diagnosis; functional diagnosis of pancreas; neoplastic pancreas diagnosis; ジェネレータ; 62-銅標識放射性医薬品; 62-亜鉛標識放射性医薬品; 二官能性錯体; 心筋診断薬剤; 膵臓診断薬剤; エチレンジアミン二酢酸亜鉛

The 62-zinc and 62-copper are highly applicable and suitable positron emitting radionuclides in Nuclear Medicine; manufacturing of a 62-copper generator, from its 62-zinc parent is as well plausible. In this work, making the best use of intrinsic characteristics of each of those metals, the development of positron emitting radiopharmaceuticals and 62-copper generator were carried out, as next described:1) BASIS ON 62-ZINC RADIOPHARMACEUTICAL FOR FUNCTIONAL AND NEOPLASTIC PANCREAS DIAGNOSIS. Gathered results in experimental with mouse and dog, showed a highly specific biodistribution of 62-zinc in the pancreas, if injected as a 62-zinc chelate of ethylenediamine-N,N'-diacetate; the tissue analysis revealed the presence of 62-zinc bound to carboxypeptidase A and B. Under hormonal stimulation of secretin and CCK-PZ, an increased 62-zinc excretion through the pancreatic duct was achieved; validity of this 62-zinc mobilization in the pancreas was visualyzed by pancreas imaging studies, demo … More nstrating the applicability of 62-zinc chelate as an exocrine functional diagnostic agent; moreover, a screening with tumor bearing mouse revealed its plausible use for the diagnosis of primary carcinoma.2) SEARCH FOR THE DEVELOPMENT OF 62-COPPER BIFUNCTIONAL CHELATING AGENT. Based on interesting results achieved with 99m-technetium bifunctional chelating agent of dithiosemicarbazone as the metal coordination site, various of its 62-copper chelate derivatives holding diverse active amine groups and fatty acid as parent molecules were synthesized. Their 62-copper chelate stability and biodistribution with the preserved parent molecule functionality were reflected in the specific myocardial and pancreas accumulation, an indication of their applicability in functional diagnosis. Also, valuable data were pursued with a bifunctional chelating agent of glucose, as the parent molecule.3) EXPERIMENTAL APPROACHES ON THE MANUFACTURING OF A 62-COPPER GENERATOR. Screening of the principle governing the column adsorption of 62-zinc and the condition for the separation and elution of its daughter 62-copper set the basis for the development of a new 62-copper generator. Less

62-锌和62-铜是核医学中应用性强、适用的正电子发射放射性核素；用 62 锌母体制造 62 铜发电机也是可行的。在这项工作中，充分利用每种金属的固有特性，进行了正电子发射放射性药物和62-铜发生器的开发，如下所述：1）基于62-锌放射性药物用于功能性和肿瘤性胰腺诊断。在小鼠和狗的实验中收集的结果显示，如果以乙二胺-N,N'-二乙酸盐的 62-锌螯合物形式注射，则 62-锌在胰腺中具有高度特异性的生物分布；组织分析显示存在与羧肽酶 A 和 B 结合的 62-锌。在促胰液素和 CCK-PZ 的激素刺激下，通过胰管的 62-锌排泄增加；通过胰腺成像研究可视化了这种 62-锌在胰腺中动员的有效性，演示了 62-锌螯合物作为外分泌功能诊断剂的适用性；此外，对荷瘤小鼠的筛选揭示了其在原发性癌诊断中的合理用途。2) 寻找62-铜双功能螯合剂的开发。基于以99m-锝双功能螯合剂缩氨基硫脲为金属配位点所取得的有趣结果，合成了各种含有多种活性胺基和脂肪酸的62-铜螯合物衍生物作为母体分子。它们的 62-铜螯合物稳定性和生物分布以及保留的母体分子功能性反映在特定的心肌和胰腺积聚中，这表明它们在功能诊断中的适用性。此外，还以葡萄糖双功能螯合剂作为母体分子，获得了有价值的数据。3) 62-铜发生器制造的实验方法。对62-锌的柱吸附原理及其子体62-铜的分离洗脱条件的筛选，为新型62-铜发生器的开发奠定了基础。较少的

项目成果

Akira Yokoyama.: "Development of neutral and bifunctional radiopharmaceuticals using 62-Cu-dithiosemicarbazone (DTS) chelate. Basic studies on 62-Cu chelates. (Jap)." Radioisotopes. 35. 249-255 (1986)

Akira Yokoyama.：“使用 62-Cu-二硫缩氨基脲 (DTS) 螯合物开发中性和双功能放射性药物。62-Cu 螯合物的基础研究。（日本）。”

Takeo Hosotani.: "In the procurement of a neutral and compact monomeric complex of dithiosemicarbazone (DTS) derivative: 99m-Tc-DTS." International Journal Nuclear Medicine and Biology.12. 431-437. (1986)

Takeo Hosotani.：“采购中性紧凑的缩氨基硫脲 (DTS) 衍生物单体复合物：99m-Tc-DTS。”

Yasuhisa Fujibayashi: "Zn-62-EDDA (ethylenediamine-N,N'-diacetic acid) chelate as a pancreas targetting drug: A radiopharmaceutical design for functional diagnosis." Proceedings of Interactions of Chelating Agents and Metals Relevant to Pharmacology and T

Yasuhisa Fujibayashi：“Zn-62-EDDA（乙二胺-N,N-二乙酸）螯合物作为胰腺靶向药物：用于功能诊断的放射性药物设计。”

ラジオアイソトープ. 35-5. (1986)

放射性同位素。35-5。

細谷健夫: Nuclear Medicine and Biology (International Journal of Radiation Applications and Instrumentation,Part B).13. 603-609 (1986)

Takeo Hosoya：核医学和生物学（国际辐射应用和仪器杂志，B 部分）.13.603-609（1986）