Bioavailability and toxicity after oral administration of m-iodobenzylguanidine (MIBG)

meta-iodobenzylguanidine (MIBG) radiolabelled with iodine-131 is used for d iagnosis and treatment of neuroadrenergic neoplasms such as phaeochromocyto ma and neuroblastoma. In addition, non-radiolabelled MIBG, administered i.v ., is used in several clinical studies. These include palliation of the car cinoid syndrome, in which MIBG proved to be effective in 60% of the patient s. Oral MIBG administration might be convenient to maintain palliation and possibly improve the percentage of responders. We have. therefore, investig ated the feasibility of oral administration of MIBG in an animal model. Ora lly administered MIBG demonstrated a bioavailability of 59%, with a maximal tolerated dose of 60 mg kg(-1). The first and only toxicity encountered wa s a decrease in renal function. measured by a reduced clearance of [Cr-51]E DTA and accompanied by histological tubular damage. Repeated MIBG administr ation of 40 mg kg(-1) for 5 sequential days or of 20 mg kg(-1) for two cour ses of 5 sequential days with a 2-day interval did not affect renal clearan ce and was not accompanied by histological abnormalities in kidney, stomach , intestines, liver, heart, lungs, thymus, salivary glands and testes. Beca use of a sufficient bioavailability in absence of gastrointestinal toxicity , MIBG is considered suitable for further clinical investigation of repeate d oral administration in patients.