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.

一系列抗CEA X抗Intium-DTPA（HMN-14 X 734）双特异性抗体（BSABS）将被制备和表征。 这些BSAB将在GW-39肿瘤轴承小鼠中的肿瘤摄取和清除模式进行比较。 将进一步研究具有最高肿瘤摄取和高肿瘤/非肿瘤（T/NT）比的BSAB，以进一步发展为成像系统。 肿瘤将以BSAB为目标。 在允许足够的时间进行肿瘤积聚和高T/NT比，即99m/tc-Imp-192。 Imp-192是一种肽基TC螯合剂，用过量的依赖剂配制，并冻干成单个小瓶，用于带有TC-99M的放射性标记。 IMP-192包含两个用于抗体识别的DTPA分子，并迅速清除了循环。 BSAB的剂量和TC-99M标记的肽的剂量将被优化用于预定的成像。 通过这种有限的方法，预计背景会减少。这种优化的预定方法将随后适用于使用RE-188或RE-186而不是TC-99M的预先设定的放射免疫疗法。 RE-188放射性标记将需要对肽进行重新制定。拟议的商业应用：将最终产品设想为诊断各种癌症的两腔成像套件。 第一个小瓶将包含靶向肿瘤的双特异性抗体。 第二个小瓶将含有冻干的肽基TC-99M螯合剂，用于用TC-99M即时标记。 对于治疗，TC-99M将转移到RE-1898，并将重新构建肽。

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