PROSTHETIC GROUPS FOR RADIOLABELING OF FUNCTIONALIZED DRUGS AND PEPTIDES

点击翻译按钮获取中文摘要

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.