PROSTHETIC GROUPS FOR RADIOLABELING OF FUNCTIONALIZED DRUGS AND PEPTIDES

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、心脏或其他组织中。 在其他靶器官或组织中达到足够的水平， 其成像。 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， 对于放射性同位素如18-F、123-I和125-I， 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）。 用于受体的可逆亲和标记的一般方法已经被公开。 开发 目标是进行一系列化学 修饰导致报告基团。 配体识别位点 A1-腺苷受体的牛脑膜探测， 证明了这种方法的可行性。 二硫化物或酯的用途 连接，旨在通过将标记的受体暴露于 分别考虑还原剂或羟胺。

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 ill localize in the brain, heart, or in other target organs or tissues to a sufficient level to allow for imaging thereof. 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). A general approach for reversible affinity labeling of receptors has been developed. The objective is to carry out a series of chemical modifications resulting in a reporter group. The ligand recognition site of A1-adenosine receptors in bovine brain membranes was probed to demonstrate the feasibility of this approach. Use of disulfide or ester linkages, intended for cleavage by exposure of the labeled receptor to either reducing reagents or hydroxylamine, respectively, was considered.