TWO STEP TC99M IMAGING USING BISPECIFIC ANTIBODIES

使用双特异性抗体进行两步 TC99M 成像

• 批准号: 2867151
• 负责人: William John McBride
• 金额: $ 10万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 1999-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2867151
• 关键词: antibody specificity; antitumor antibody; athymic mouse; bioimaging /biomedical imaging; carcinoembryonal antigen; contrast media; diagnostic tests; diethylenetriaminepentaacetate; image enhancement; indium; neoplasm /cancer diagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; pharmacokinetics; technetium; technology /technique development

A series of anti-CEA x anti-indium-DTPA (hMN-14 x 734) bispecific antibodies (bsAbs) will be prepared and characterized. These bsAbs will be compared for tumor uptake and clearance pattern in GW-39 tumor bearing mice. The bsAb with the highest tumor uptake and high tumor/non-tumor (T/NT) ratio will be studied further to develop into an imaging system. The tumors will be targeted with the bsAb. After allowing a sufficient time for tumor accretion and a high T/NT ratio, 99m/Tc-IMP-192, will be injected. IMP-192, a peptidyl Tc-chelator, is formulated with excess indium and lyophilized into a single vial for radiolabeling with Tc-99m. Imp-192 contains two DTPA molecules for antibody recognition and clears rapidly from circulation. The dose of the bsAb and the Tc-99m labeled peptide will be optimized for pretargeted imaging. Reduced background is expected with this pretargeted approach. This optimized pretargeted approach will then later be applicable to pretargeted radioimmunotherapy using Re-188 or Re-186 instead of Tc-99m. Re-188 radiolabeling will require reformulation of the peptide. PROPOSED COMMERCIAL APPLICATION: Final product is envisaged as a two-vial imaging kit for the diagnosis of a variety of cancers. The first vial will contain the bispecific antibody to target the tumors. The second vial will contain a lyophilized peptidyl Tc-99m chelator for instant radiolabeling with Tc-99m. For therapy, Tc-99m will be switched to Re-1898 and peptide will be reformulated.

将制备并表征一系列抗 CEA x 抗铟-DTPA (hMN-14 x 734) 双特异性抗体 (bsAb)。 将比较这些 bsAb 在 GW-39 荷瘤小鼠中的肿瘤摄取和清除模式。 具有最高肿瘤摄取和高肿瘤/非肿瘤（T/NT）比的bsAb将被进一步研究以开发成成像系统。 双特异性抗体将靶向肿瘤。 在给予肿瘤生长足够的时间和高T/NT比率后，将注射99m/Tc-IMP-192。 IMP-192 是一种肽基 Tc 螯合剂，采用过量的铟配制而成，并冻干至单个小瓶中，用于用 Tc-99m 进行放射性标记。 Imp-192 含有两个用于抗体识别的 DTPA 分子，并可快速从循环中清除。 bsAb 和 Tc-99m 标记肽的剂量将针对预靶向成像进行优化。 这种预定目标的方法预计会减少背景。这种优化的预靶向方法随后将适用于使用 Re-188 或 Re-186 代替 Tc-99m 的预靶向放射免疫治疗。 Re-188 放射性标记需要重新配制肽。拟议的商业应用：最终产品预计为两瓶成像试剂盒，用于诊断各种癌症。 第一个小瓶将含有针对肿瘤的双特异性抗体。 第二个小瓶含有冻干肽基 Tc-99m 螯合剂，用于用 Tc-99m 进行即时放射性标记。 对于治疗，Tc-99m 将改为 Re-1898，并且肽将重新配制。

项目成果

A universal pretargeting system for cancer detection and therapy using bispecific antibody.

• 发表时间: 2003-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: R. Sharkey;W. Mcbride;H. Karacay;Ken Chang;G. Griffiths;H. Hansen;D. Goldenberg