Molecular Imaging by Affinity Enhancement PET

通过亲和力增强 PET 进行分子成像

• 批准号: 6690054
• 负责人: GARY Leonard GRIFFITHS
• 金额: $ 11.92万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6690054
• 关键词: affinity labeling; athymic mouse; bioimaging /biomedical imaging; carcinoembryonal antigen; colorectal neoplasms; diagnosis design /evaluation; gallium; haptens; molecular oncology; positron emission tomography; radionuclide imaging /scanning; reagent /indicator; affinity labeling; athymic mouse; bioimaging /biomedical imaging; carcinoembryonal antigen; colorectal neoplasms; diagnosis design /evaluation; gallium; haptens; molecular oncology; positron emission tomography; radionuclide imaging /scanning; reagent /indicator

DESCRIPTION (provided by applicant): The objective of this work is to develop a set of reagents that together comprise a new imaging system for detection of cancer, in its early, its metastatic, and its recurrent stages. Early detection, better treatment choices and new information that save uneccessary surgeries and treatments are long-term aim of this work. The reagents in this project will be developed for the colo-rectal cancer indication, but the same targeting and detection principles will be broadly applicable, and can be extended later to any cancer type. Use of molecularly targeted reagents will be combined with the most senstitive imaging modality, positron emission tomography. This SBIR Phase I application will explore the feasibility of using a bispecific antibody construct, targeted against the carcinoembryonic antigen, and up-regulated in many cancers, as an agent to selectively place a secondary binding arm specifically at sites of disease. Once circulating bispecific antibody has cleared normal tissue and maximized at tumor sites, a secondary recognition hapten recognized by tumor-localized bispecific antibody will be administered. This secondary recognition hapten will be radiolabeled with gallium-68, a positron-emitting radionuclide, and will be molecularly designed to rapidly flush from the living system if not bound at the sites of disease. Such an approach is expected to result in very high tumor to background ratios with regard to all major internal organs, and combined with the exceptional sensitivity of positron emission tomographic imaging of the tumor-localized gallium-68 radionuclide, comprizes a unique opportunity to significantly enhance specifc imaging of this disease. In this Phase I work feasibility will be shown by preparation and combination of the various components of the imaging system, together with demonstration of the method through the stage of preclincal testing in an appropriate animal model of human colon cancer. SBIR Phase II will support the effort to extend the system into a human clincial trial, to expedite the methodology into clincial application as soon as possible. With success, SBIR Phase II will concentrate on the effort to obtain Food and Drug Administration approval of the imaging methodology and to commercialize the agents to improve diagnosis and therapy of CEA positive tumors.

描述（由申请人提供）： 这项工作的目的是开发一组试剂，共同构成了一种新的成像系统，以便在其早期，转移性和复发阶段进行癌症的检测。这项工作的长期目的是早期发现，更好的治疗选择和新信息，以节省不塞手术和治疗。该项目中的试剂将用于Colo直肠癌指示，但是相同的靶向和检测原理将广泛适用，并且可以在以后扩展到任何癌症类型。分子靶向试剂的使用将与最剂量成像形式（正电子发射断层扫描）结合使用。该SBIR I期应用将探讨使用双特异性抗体构建体的可行性，该抗体构建体针对癌胚抗原，并在许多癌症中上调，作为一种药剂，可以选择性地将次级结合组定位在疾病部位。一旦循环双特异性抗体清除了正常的组织并在肿瘤部位最大化，将施用由肿瘤定位的双特异性抗体识别的继发识别触发。这种二次识别触觉将以镀甘特（Gallium-68）的放射性标记，这是一种发射正电子的放射性核素，如果不在疾病部位结合，则将其分子设计为从生活系统中迅速冲洗。预计这种方法将导致所有主要内部器官的肿瘤与背景比非常高，并与正电子发射层造影成像的非凡灵敏度相结合，构成了一种独特的机会，可以显着增强该疾病的指定成像。在这一阶段，I的工作可行性将通过成像系统的各个组成部分的制备和组合以及通过在适当的人类结肠癌的适当动物模型中的linc骨测试阶段进行准备和组合。 SBIR第二阶段将支持将系统扩展到人类斜角试验中的努力，以尽快将方法加快到斜度应用中。随着成功，SBIR II期将集中精力，以获得成像方法的食品和药物管理批准，并将其商业化，以改善CEA阳性肿瘤的诊断和治疗。