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Molecular Markers for Tissue Hypoxia

组织缺氧的分子标记

基本信息

批准号：
6337080
负责人：
JAMES ARTHUR RALEIGH
金额：
$ 9.77万
依托单位：
NATURAL PHARMACIA INTERNATIONAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-05-01 至 2002-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6337080
关键词：
biomarker chemical stability enzyme linked immunosorbent assay fluorescent dye /probe hypoxia immunologic substance development /preparation monoclonal antibody tissue /cell culture water solubility

项目摘要

DESCRIPTION (PROVIDED BY APPLICANT): Hypoxia is important in cardiovascular disease and cancer, the two leading causes of death in the US. Studies of these and other diseases need a tool for following changes in tissue hypoxia. We propose the HypoxyprobeTM system of markers can meet this need. HypoxyprobeTM markers have advantages of high water solubility, chemical stability, short plasma half-life, universal tissue distribution, efficient tissue uptake, low human toxicity in single and repeated injections and high marker adduct stability in tissue. Monoclonal antibodies will be prepared against seven HypoxyprobeTM analogues using techniques already established in our laboratories. Antibody reagents will be screened in ELISA assays. Sensitivity of HypoxyprobeTM analogues to hypoxia will be determined in tissue and multicellular spheroid cultures. Promising analogues will be tested in rodent and canine tumors in a STTR Phase II study. Leading experts believe that fluctuating hypoxia is an important factor in the pathophysiology of both normal and tumor tissues. Interventions designed to offset the damaging effects of fluctuating hypoxia are under investigation and the present proposal will provide powerful tools to support studies in these important areas of medicine. PROPOSED COMMERCIAL APPLICATION: NPI, Inc has already commercialized Hypoxyprobe (TM)-1, the lead compound in the Hypoxyprobe (TM) series of markers. It is expected that Hypoxyprobe(TM) analogues and associated monoclonal antibodies will also be widely used in the study of normal and tumor tissue hypoxia.

描述（由申请人提供）：缺氧在心血管疾病中很重要疾病和癌症，美国的两大死亡原因。研究这些和其他疾病需要一种工具来跟踪组织缺氧的变化。我们提出HypoxyprobeTM标记系统可以满足这一需求。HypoxyprobeTM 标记物具有高水溶性、化学稳定性、短血浆半衰期，普遍组织分布，有效组织摄取，低单次和重复注射的人体毒性和高标记物加合物组织稳定性。将制备针对七种抗体的单克隆抗体， HypoxyprobeTM类似物使用我们已经建立的技术 laboratories.将在ELISA试验中筛选抗体试剂。灵敏度将在组织中测定HypoxyprobeTM类似物对缺氧的影响，多细胞球体培养物。有希望的类似物将在啮齿动物中进行测试和犬肿瘤的研究。权威专家认为，波动性缺氧是两者病理生理学中的重要因素，正常组织和肿瘤组织。旨在抵消破坏性影响的干预措施波动性缺氧正在调查中，目前的建议将提供强大的工具来支持这些重要医学领域的研究。拟定商业应用： NPI，Inc已经将Hypoxyprobe（TM）-1商业化，Hypoxyprobe（TM）-1是用于治疗癌症的先导化合物。 Hypoxyprobe（TM）系列标记物。预计Hypoxyprobe（TM）类似物和相关的单克隆抗体也将广泛用于研究正常和肿瘤组织缺氧。