Preparation of ^<99m>Tc radiopharmaceuticals using macroreticular Sn (II) complex

大网状Sn(II)络合物制备^<99m>Tc放射性药物

• 批准号: 04557104
• 负责人: NAKAYAMA Morio
• 金额: $ 1.86万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557104/
• 关键词: Technetium; Macromolecular Sn (II) complex; Aminophosphonic acid groups; Monoclonal anitibody; Immunoglobulin; アルブミン; キレート樹脂

Stannous chloride (SnCl_2) has the disadvantages of being easily hydrolyzed and oxidized, but it is included in most commercial kits as an appropriate reducing agent in the preparation of ^<99m>Tc radiopharmaceuticals. The replacement of SnCl_2 by the insoluble macromolecular Sn (II) (R-Sn) complex was proposed as a way to resolve some of the problems caused by a large excess of SnCl_2 Macroreticular chelating ion exchange resins having an adsorption ability for Sn (II) were investigated for the development of R-Sn complex. Among them, a chelating resin containing aminophosphonic acid groups showed a high capacity for Sn (II) , which bound strongly to the resin by chelation. The use of the R-Sn complex was expected to minimize Sn (II) comtamination of the ^<99m>Tc labeling solution and be effectively used as a reducing agent for ^<99m>Tc labeling of proteins containing sulfhydryl groups. So, the R-Sn complex was applied to the direct ^<99m>Tc labeling of human immunoglobulin (IgG) to minimize the influence of Sn (II). ^<99m>Tc labeling was achieved at greater than 90% yield simply by the short-term mixing of IgGa containing>2 -SH groups per IgG molecule, ^<99m>Tc pertechnetate, and the R-Sn complex in pH 7 solution. The ^<99m>Tc-IgGa obtained by this labeling method has high stability based on the thiol-specific binding of ^<99m>Tc without transchelation from another weakly bound ^<99m>Tc-complex.

氯化亚锡(SnCl_2)具有容易水解和氧化的缺点，但它作为制备^ 99m Tc放射性药物中合适的还原剂包含在大多数商业试剂盒中。提出用不溶性大分子Sn(II)(R-Sn)配合物代替SnCl_2来解决SnCl_2过量引起的一些问题。研究了具有Sn(II)吸附能力的大网络螯合离子交换树脂，以开发R-Sn配合物。其中，含有氨基膦酸基团的螯合树脂对Sn(II)表现出高容量，Sn(II)通过螯合与树脂牢固结合。预计R-Sn复合物的使用可最大程度地减少^ 99m Tc标记溶液的Sn(II)污染，并有效地用作含有巯基的蛋白质的^ 99m Tc标记的还原剂。因此，将R-Sn复合物应用于人免疫球蛋白(IgG)的直接^ 99m Tc标记以最小化Sn(II)的影响。简单地通过将每个IgG分子含有>2个-SH基团的IgGa、^ 99m Tc高锝酸盐和R-Sn复合物在pH 7溶液中短期混合，即可以大于90％的产率实现^ 99m > Tc标记。通过该标记方法获得的^ 99m Tc-IgGa基于^ 99m Tc的硫醇特异性结合而不与另一个弱结合的^ 99m Tc复合物发生转螯合而具有高稳定性。

项目成果

中山 守雄: "Insoluble Macromolecular Sn(II) complex for the ^<99m>Tc labeling of protein-bearing mercapto groups." J.Nucl.Biol.Med.38. 459-460 (1994)

Morio Nakayama：“用于 ^<99m>Tc 标记的蛋白质巯基基团的不溶性大分子 Sn(II) 复合物。”J.Nucl.Biol.Med.38 (1994)。

Morio Nakayama: "Insoluble Macromolecular Sn(II)complex for the ^<99m>Tc labeling of protein-bearing mercapto groups." J.Nucl.Biol.Med.38. 459-460 (1994)

Morio Nakayama：“用于对带有蛋白质的巯基进行 ^<99m>Tc 标记的不溶性大分子 Sn(II) 复合物。”

Morio Nakayama: "Development of macromolecular Sn (II) complex for reduction of ^<99m>Tc and the application to ^<99m>Tc labeling of serum protein." Radiation and Biology Reserach. 29. 349-356 (1994)

Morio Nakayama：“开发用于还原 ^<99m>Tc 的大分子 Sn (II) 复合物以及在血清蛋白的 ^<99m>Tc 标记中的应用。”

中山 守雄: "Direct ^<99m>Tc Labeling of human imunoglobulin with insoluble macromolecular Sn(II) complex." Nucl.Med.Biol.(in press). (1995)

Morio Nakayama：“用不溶性大分子 Sn(II) 复合物直接 ^<99m>Tc 标记人类免疫球蛋白。Nucl.Med.Biol.（出版中）。”

中山守雄: "Characterization of insoluble macromolecular Sn(II)complcx and its application to the 99mTc labeling of human serum albumin-bearing mercapto groups" Appl.Radiat.Isot.45. 41-47 (1994)

Morio Nakayama：“不溶性大分子 Sn(II) 络合物的表征及其在人血清白蛋白巯基基团 99mTc 标记中的应用”Appl.Radiat.Isot.41-47 (1994)。