Radioiodinated metaiodobenzylguanidine (MIBG): radiochemistry, biology, and pharmacology.

As an analogue of adrenergic neurotransmitter norepinephrine (NE), metaiodobenzylguanidine (MIBG) demonstrates high uptake both in normal sympathetically innervated tissues, such as the heart and salivary glands, and in tumors that express the NE transporter (NET), specifically those of neural crest and neuroendocrine origin. In 1994, (131)I-MIBG, also known as iobenguane I-131 intravenous, received Food and Drug Administration (FDA) approval as an imaging agent. In 2008, (123)I-MIBG was also approved by FDA as a tumor imaging agent. Commercial formulations of radioiodinated MIBG are prepared on the basis of radioiodide exchange reaction with unlabeled MIBG as a precursor and contain large mass amounts of unlabeled MIBG, or "cold carrier," molecules. Because the cold MIBG molecules competitively inhibit the uptake of radiolabeled MIBG molecules by adrenergic and neuroendocrine cells expressing NET, no-carrier-added (n.c.a.), high specific activity (SA) radioiodinated MIBG preparations have been developed on the basis of electrophilic radioiodination reaction and solid-phase technology by using dibutylstanyl benzylguanidine precursor linked to polymers. On the basis of n.c.a. synthetic procedures, therapeutic doses of [(131)I]MIBG can be administered with very high SA (1600 mCi/μmol or 5734 mCi/mg). The very high SA of n.c.a. [(131)I]MIBG drug would increase the specific cellular uptake of adrenergic neurons and neuroendocrine tumor cells expressing NET.