PROSTHETIC GROUPS FOR RADIOLABELING OF FUNCTIONALIZED DRUGS AND PEPTIDES

用于功能化药物和肽的放射性标记的辅基

• 批准号: 3776297
• 负责人: K JACOBSON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3776297
• 关键词: adenosine; blood brain barrier; brain imaging /visualization /scanning; chemical conjugate; chemical group; drug receptors; fluorine; iodine; molecular site; neurotransmitter receptor; nuclear medicine; peptides; positron emission tomography; radionuclides; radiopharmacology; radiotracer; receptor binding; theophylline

The use of radioisotopes to label organic compounds for use in diagnostic nuclear medicine is well documented in the literature. It has been found that certain radiolabeled compounds will localize in the brain, heart, or in other target organs or tissues to a sufficient level to allow for imaging thereof. There has been increasing interest in finding compounds which will more effectively cross the blood-brain barrier, thus facilitating more efficacious imaging of the brain. Binding sites for certain drugs in an animal or organ may be localized as a result of the synthesis of high specific activity radiolabeled analogs which have high affinity for that binding site. Prosthetic groups may be attached to a drug or other receptor ligand for the purpose of efficient and selective chemical capture of a particular radioisotope. Having developed functionalized congeners of theophylline and other drugs acting at adenosine receptors, we are now developing prosthetic groups for radioisotopes such as 18-F, 123-I, and 125-I, to be coupled to these functionalized drug molecules. The prosthetic groups contain amino or carboxylic groups which are to be condensed covalently to functionalized drugs to give conjugates of high affinity at a particular receptor, or drugs that bind the label irreversibly (trifunctional reagents). We have developed a radioiodinated derivative that contains an azido group for covalent reaction with A2-adenosine receptors.

使用放射性同位素标记有机化合物用于诊断 核医学在文献中有很好的记载。 已经发现 某些放射性标记的化合物会定位在大脑，心脏， 或在其它靶器官或组织中达到足够的水平以允许 其成像。 人们对寻找化合物的兴趣越来越大 它将更有效地穿过血脑屏障， 促进对大脑的更有效成像。 某些药物在动物或器官中的结合位点可能是局部的 作为合成高比活度放射性标记的 对该结合位点具有高亲和力的类似物。 假体 基团可以连接到药物或其它受体配体上 有效和有选择性的化学捕获特定的放射性同位素。 开发了茶碱和其他药物的功能化同类物 作用于腺苷受体，我们现在正在开发辅基， 对于18-F、123-I和125-I等放射性同位素，将与这些物质偶联 功能化药物分子。 辅基含有氨基或 待共价缩合至官能化的羧基， 在特定受体上产生高亲和力缀合物的药物，或 不可逆地结合标签的药物（三功能试剂）。 我们有 开发了一种含有叠氮基的放射性碘化衍生物， 与A2-腺苷受体的共价反应。