TC-99M-F(AB)2 INSTANT KITS FOR RADIOIMMUNOSCINTIGRAPHY

TC-99M-F(AB)2 放射免疫闪烁成像即时套件

• 批准号: 3499082
• 负责人: GARY Leonard GRIFFITHS
• 金额: $ 5万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3499082
• 关键词: athymic mouse; autoradiography; immunoglobulin structure; method development; neoplasm /cancer immunodiagnosis; neoplasm /cancer radionuclide diagnosis; radioimmunoassay; technetium

The goal of this project is to develop the optimum clinical agent for radioimmunoscintigraphy. The optimum nuclide is undoubtedly technetium- 99m. Comparing IgG-SH, F(ab')2-SH and Fab'-SH, it is expected that a F(ab')2-SH fragment will have fast enough clearance from circulation to permit earlier imaging than a comparably radiolabeled IgG-SH while having less renal uptake than a comparably labeled Fab'-SH fragment. Previously, direct labeling of F(ab')2-SH was problematic in that a 50:50 mixture of Tc-99m-F(ab')2 and Tc99m-Fab' would result due to the presence of a small amount of monovalent fragment. We have a novel technique of pre.reducing intact IgG to break non-hinge region disulfide bonds prior to digestion of antibody. The resulting, pure F(ab')2-SH is capable of quantitative incorporation of technetium-99m, in the same manner as IgG-SH and Fab'-SH, are currently labeled, to yield quantitatively Tc-99m-F(ab')2. We will extend the technique to different antibodies targeted against different cancers, and ultimately use humanized F(ab')2-SH fragments. In phase l research, we will to prove the superiority of Tc99m-F(ab'), over Tc-99m- Fab' and Tc-99m-IgG as an early time-point radioimmunoimaging agent; and if successful, produce clinically usable kits at the conclusion of the phase II period.

该项目的目标是开发最佳的临床药物 放射免疫闪烁显像术。 最佳核素无疑是锝- 99米。比较 IgG-SH、F(ab')2-SH 和 Fab'-SH，预计 F(ab')2-SH 片段将有足够快的速度从循环中清除 允许比同类放射性标记 IgG-SH 更早成像，同时具有 与类似标记的 Fab'-SH 片段相比，肾脏摄取更少。之前， F(ab')2-SH 的直接标记存在问题，因为 50:50 的混合物 Tc-99m-F(ab')2 和 Tc99m-Fab' 由于存在小 单价片段的量。 我们有一种新颖的预还原技术 完整的 IgG 在消化前打破非铰链区二硫键 抗体。由此产生的纯 F(ab')2-SH 能够定量 以与 IgG-SH 和 Fab'-SH 相同的方式掺入 technetium-99m， 目前已标记，可定量产生 Tc-99m-F(ab')2。我们将 将该技术扩展到针对不同目标的不同抗体 癌症，并最终使用人源化 F(ab')2-SH 片段。 在第一阶段 研究，我们将证明Tc99m-F(ab')相对于Tc-99m-的优越性 Fab' 和 Tc-99m-IgG 作为早期时间点放射免疫显像剂；和 如果成功，在试验结束时生产临床可用的试剂盒 第二阶段时期。