BROMINE-76-METABROMOBENZYLGUANIDINE - A PET RADIOTRACER FOR MAPPING SYMPATHETIC-NERVES OF THE HEART

Iodine-123-metaiodobenzylguanidine (MIBG) is used to qualitatively ass ess heart innervation with single-photon emission computed tomography (SPECT). This approach is clinically useful in the prognostic evaluati on of congestive heart failure. To improve quantification of uptake of the tracer using positron emission tomography (PET), we studied the c haracteristics of the bromoanalog of MIBG. Bromine-76-metabromobenzylg uanidine (Br-76-MBBG) was prepared from a heteroisotopic exchange betw een radioactive bromine atoms (noncarrier-added (Br-76) BrNH4) and the cold iodine atoms of the precursor metaiodobenzylguanidine. Biodistri bution was studied in rats and PET cardiac imaging performed in dogs. Myocardial uptake was high and prolonged in both species (mean half-li fe in dogs: 580 min). In rats, myocardial uptake was inhibited by desi pramine by 64%, whereas after pretreatment with 6-hydroxydopamine upta ke was reduced by 84%. In dogs pretreated with 6-hydroxydopamine or wi th desipramine, a steep washout of the tracer occurred (mean half-life : 136 min and 118 min, respectively). The nonspecific uptake plus the passive neuronal diffusion of the tracer could be estimated at about 2 5%-30% of the total fixation. In dogs, analysis of unchanged Br-76-MBB G in plasma showed that radiotracer metabolism was slow: 60 min after injection, 80% of the radioactivity was related to unchanged Br-76-MBB G. These preliminary findings suggest that Br-76-MBBG could be used to quantitatively assess adrenergic innervation in heart disease using P ET. When combined with use of C-11-CGP 12177, cardiac adrenergic neuro transmission can be assessed.