GA68 TC-99M BIFUNCTIONAL MOABS FOR PET AND SPECT IMAGING

GA68 TC-99M 用于 PET 和 SPECT 成像的双功能 MOABS

• 批准号: 3192396
• 负责人: DAVID A GOODWIN
• 金额: $ 6.92万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3192396
• 关键词: antibody formation; antibody specificity; chemical binding; guinea pigs; haptens; human subject; immunoconjugates; injection /infusion; laboratory mouse; laboratory rabbit; metal complex; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer radionuclide diagnosis; noninvasive diagnosis; positron emission tomography; radionuclide imaging /scanning; single photon emission computed tomography; technetium; whole body radionuclide scanning

The broad long-term objectives of this project are to apply new anti-hapten monoclonal antibodies to PET and SPECT tumor imaging with Ga-68 chelates and Tc-99m pertechnetate. We will apply our novel pretargeting technology using bifunctional monoclonal antibodies with at least one target specific site and one hapten specific site. These non-radioactive conjugates will be injected and allowed to localize. After maximum target accumulation has occurred, blood levels will be rapidly lowered by injection of a suitable chase. This will be quickly followed with an injection of Ga-68 chelate or Tc-99m pertechnetate. Imaging will be carried out 1 to 3 hours following injection of the the radiolabel. For the Ga-68 experiments the use of antibodies specific for the chelates of Ga and having much larger binding constants for Ga chelates than for the other contaminating metal chelates in the generator eluant will make purification unnecessary. This will allow the Ga-68 chelates to be injected soon after elution of the generator and permit the use of small amounts af antibody. For the Tc-99m studies a monoclonal antibody binding the pertechnetate anion with high affinity will be employed in the bifunctional antibody. This will eliminate the need for reduction of pertechnetate with stannous ions, greatly simplifying its use. In addition to pretargeting with anti-Tc-99m04 antibody the 6 hr half- life of Tc-99m is long enough to allow the Tc-Ab complex to be injected, followed by a suitable chase 5 to 6 hrs later and images to be made 1-2 hrs after the chase. The methodology involves immunizing mice with specially designed antigens, screening by whole body counting of mice with radioactive antigens, organ distribution and gamma camera imaging in tumor mice and PET and SPECT images in rabbits bearing VX2 tumor. The ultimate aim is to make PET and SPECT images of tumors in humans with Ga-68 chelates and Tc-99 pertechnetate. These studies will improve tumor to background ratios, reduce patient radiation exposure, enhance the definition of tumors through PET and SPECT imaging, and provide a more accurate method for quantitation of biodistribution in humans using readily available and relatively inexpensive generator produced radionuclides.

该项目的广泛长期目标是应用新的目标 对PET和SPECT肿瘤成像的抗Hapten单克隆抗体 带有GA-68螯合物和TC-99M Pertechnetate。 我们将应用我们的 使用双功能单克隆的新型预定技术 具有至少一个目标特定部位和一个触觉的抗体 特定网站。 这些非放射活性偶联物将被注入 并允许本地化。 最大目标积累后 发生了，注射将迅速降低血液水平 合适的追逐。 这将很快进行注射 GA-68螯合物或TC-99M pertechnetate。 成像将被携带 注射放射线标记后1到3个小时。 为了 GA-68实验使用特定的抗体 GA的螯合物和GA的结合常数要大得多 螯合物比其他污染金属螯合物中的螯合物 发电机洗脱会使净化不必要。 这会 允许在洗脱后不久注入GA-68螯合物 发电机并允许使用少量AF抗体。 为了 TC-99M研究单克隆抗体结合了Pertechnetate 具有高亲和力的阴离子将在双功能中使用 抗体。 这将消除减少的需求 用尖锐的离子进行质技术，从而大大简化其使用。 在 除抗TC-99M04抗体6小时的一半 - TC-99M的寿命足够长，可以使TC-AB复合物成为 注射，然后在5至6个小时后进行合适的追逐和图像 追逐后1-2小时。 该方法涉及 用特殊设计的抗原免疫小鼠，筛查 用放射性抗原，器官对小鼠的全身计数 肿瘤小鼠和宠物的分发和伽马相机成像， 带有VX2肿瘤的兔子中的SPECT图像。 最终目标是 制作具有GA-68螯合物的人类肿瘤的PET和SPECT图像 和TC-99 Pertechnetate。 这些研究将改善肿瘤 背景比，减少患者辐射暴露，增强 通过PET和SPECT成像来定义肿瘤，并提供 更准确的定量人类生物分布的方法 使用随时可用且相对便宜的发电机 产生的放射性核素。