Adrenal medulla imaging agents: A structure-distribution relationship study of radiolabeled aralkylguanidines

Article abstract of DOI:10.1021/jm00368a008

Fourteen ¹²⁵I-labeled aralkylguanidines were synthesized and evaluated as potential imaging agents for the adrenal medullae and tumors of adrenomedullary origin. These guanidines are radiotracer analogues of guanethidine, an antihypertensive agent thought to mediate neuron blockade by uptake into adrenergic nerves. Dog adrenal medullae were used as a model to test radiotracer affinity for catecholamine storage tissue. Tissue distribution studies revealed that a number of radioiodinated guanidines showed pronounced localization in the adrenal medullae following intravenous injection, in certain cases exceeding that of either (-)-[³H]norepinephrine or [¹⁴C]guanethidine. (m-[¹²⁵I]Iodobenzyl)guanidine (m-IBG) gave the best combination of high concentration and selectivity. The low adrenomedullary affinity observed with [¹⁴C]guanidine and m-[¹²⁵I]iodobenzylamine demonstrates the --- -------------- uniqueness of the aralkylguanidine structure. Preliminary evidence suggests that m-IBG is a storage analogue of norepinephrine. A second ¹²⁵I-aralkylguanidine is now being used clincally in imaging and radiotherapy of catecholamine tumors, such as pheochromocytoma.