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， 或在其它靶器官或组织中达到足够的水平以允许 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）。 荧光素缀合物，FITC-APEC，衍生自一系列荧光素缀合物。 作为选择性A2 α-腺苷激动剂的功能化同源物。 FITC-APEC与脑纹状体A2 a-腺苷受体的结合 通过荧光技术测量的是可饱和的并且具有高亲和力。 化学上不同的A2-腺苷受体配体的效力 通过抑制FITC-APEC结合估计的结果与 使用放射性配体结合技术测定它们的效力。 这些 研究结果证实了这种新型荧光配体的用途， 定量表征与A2-腺苷受体的结合。

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. 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 fluorescein conjugate, FITC-APEC, was derived from a series of functionalized congeners that act as selective A2a-adenosine agonists. The binding of FITC-APEC to brain striatal A2a-adenosine receptors measured by fluorescence techniques was saturable and of high affinity. The potencies of chemically diverse A2-adenosine receptor ligands estimated by inhibition of FITC-APEC binding were in good agreement with their potencies determined using radioligand binding techniques. These findings validate the use of this novel fluorescent ligand to quantitatively characterize binding to A2-adenosine receptors.