Meta-iodobenzylguanidine and analogues: chemistry and biology.
Meta-iodobenzylguanidine (MIBG) is a structural analogue of the neurotransmitter norepinephrine (NE) and is taken up by cells rich in sympathetic neurons by an active uptake process mediated by the NE transporter, which is referred to as uptake-1. It is a valuable agent in the diagnosis of myocardial abnormalities as well as that of several neuroendocrine tumors such as neuroblastoma, pheochromocytoma and carcinoid tumors. MIBG labeled with (131)I also is used extensively in the therapy of several neuroendocrine tumors. Over the years, a substantial amount of work has been undertaken to improve its clinical utility. Currently, radio-iodinated MIBG used in the clinic is prepared by an exchange radio-iodination method and, thus, is of low specific activity. For possible better targeting and to ward off pharmacological effects, its preparation at a no-carrier-added level both by solution-phase and solid-phase synthesis has been developed. For potential use in the treatment of micrometastatic diseases, synthesis of an analogue labeled with the a emitter (211)At was devised. Development of analogues labeled with positron emitting radionuclides such as (124)I, (18)F, and (76)Br has been reported. Further, efforts have been put in to improve its pharmacokinetic properties by structural modifications. Various aspects of these developments are reviewed herein.
Vaidyanathan
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Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. ganesan.v@duke.edu
D019797:3-Iodobenzylguanidine / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D019791:Guanidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D015282:Octreotide / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography
D007457:Iodine Radioisotopes; C520658:meta-((211)At)astatobenzylguanidine; D019797:3-Iodobenzylguanidine; D019791:Guanidine; D015282:Octreotide