PET Reagents for Normal and Tumor Tissue Hypoxia

正常组织和肿瘤组织缺氧的 PET 试剂

• 批准号: 6403101
• 负责人: JAMES ARTHUR RALEIGH
• 金额: $ 9.95万
• 依托单位: NATURAL PHARMACIA INTERNATIONAL, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6403101
• 关键词: bioimaging /biomedical imaging; chemical binding; chemical synthesis; contrast media; fluorine; hypoxia; imidazole; immunochemistry; positron emission tomography; radionuclides; technology /technique development

DESCRIPTION (provided by applicant): Disruption of O2 gradients in normal tissues creates major medical problems including cardiovascular disease, stroke, diabetes, liver and kidney damage and organ transplant failure. Steep O2 gradients in tumors protect tumor cells from cytotoxic therapies and create more aggressive tumors. Measurements of O2 gradients are clearly needed. This study proposes F-18 positron emission tomography (PET) reagents based on Hypoxyprobe(TM) markers for non-invasive assays of normal and malignant tissue hypoxia. Hypoxyprobe(TM) PET markers will have: high water solubility; chemical stability; universal tissue distribution; short plasma half-life; low toxicity; and, high tissue adduct stability. Hypoxyprobe(TM) kits are already marketed for studies of tissue hypoxia by flow cytometry, ELISA and immunohistology. PET reagents would be an exciting addition. The synthesis of fluorinated Hypoxyprobe(TM) analogues will be optimized and promising analogues tested in single cell suspensions and in multicellular spheroid systems for their ability to discriminate cells at different levels of hypoxia. Binding of the fluorinated analogues will be quantitated immunochemically by means of monoclonal antibodies raised against the Hypoxyprobe(TM) analogues. Analogues whose synthesis is rapid and clean with respect to fluoride incorporation and whose ability to discriminate hypoxic cells is optimal will be tested in animal PET facilities in Phase II STTR studies. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（由申请人提供）：正常中的O2梯度的破坏 组织会产生主要的医学问题，包括心血管疾病， 中风，糖尿病，肝脏和肾脏损伤以及器官移植衰竭。陡 肿瘤中的O2梯度可保护肿瘤细胞免受细胞毒性疗法的影响并创建 更具侵略性的肿瘤。显然需要测量O2梯度。这 研究提出了基于F-18正电子发射断层扫描（PET）试剂 非侵入性测定正常和恶性组织的低氧概况（TM）标记 缺氧。低氧型（TM）宠物标记将具有：高水溶性；化学 稳定;通用组织分布；短血浆半衰期；低毒性； 并且，高组织加合物的稳定性。 HypoxyProbe（TM）套件已经销售 用于通过流式细胞仪，ELISA和免疫组织学来研究组织缺氧。宠物 试剂将是一个令人兴奋的补充。氟化的合成 将优化低氧型（TM）类似物，并在 单细胞悬浮液和多细胞球体系统的能力 以不同水平的缺氧区分细胞。结合 氟化类似物将通过 针对低氧概况（TM）类似物提出的单克隆抗体。类似物 相对于氟化物的掺入，其合成既快速又干净， 在动物中将测试其区分低氧细胞的能力是最佳的 II期STTR研究中的宠物设施。 拟议的商业应用程序：不可用