PROSTHETIC GROUPS FOR RADIOLABELING OF FUNCTIONALIZED DRUGS AND PEPTIDES

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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). Using a general scheme, we have developed a radioiodinated xanthine derivative that contains an isothiocyante group for covalent reaction with A1-adenosine receptors. Positron emission tomography (PET) has been used for imaging receptors in the brain and other organs. A prosthetic group for chemical capture of 18-F requires rapid and efficient reaction and purification; since the half life is only 110 minutes. We are utilizing this approach to image insulin receptors in vivo.