Tc-99m-labeled MIBG derivatives: Novel Tc-99m complexes as myocardial imaging agents for sympathetic neurons

Radioactive-iodine-labeled meta-iodobenzylguanidine (MIBG) is currently bei ng used as an in vivo imaging agent to evaluate neuroendocrine tumors as we ll as the myocardial sympathetic nervous system in patients with myocardial infarct and cardiomyopathy. It is generally accepted that MIBC; is an anal ogue of norepinephrine and its uptake in the heart corresponds to the distr ibution of norepinephrine and the density of sympathetic neurons. A series of MIBG derivatives containing suitable chelating functional groups N2S2 fo r the formation of [(TcO)-O-v]3+N2S2 complex was successfully synthesized, and the Tc-99m-labeled complexes were prepared and tested in rats. One of t he compounds, [Tc-99m]2, tested showed significant, albeit lower, heart upt akes post iv injection in rats (0.21% dose/g at 4 h) as compared to [I-125] MIBG (1.7% dose/g at 4 h). The heart uptake of the Tc-99m-labeled complex a ppears to be specific and can be reduced by co-injection with nonradioactiv e MIBG or by pretreatment with desipramine, a selective norepinephrine tran sporter inhibitor. Further evaluation of the in vitro uptake of [Tc-99m]2 i n cultured neuroblastoma cells displayed consistently lower, but measurable uptake (approximately 10% of that for [I-125]MIBG). These preliminary resu lts suggested that the mechanisms of heart uptake of [Tc-99m]2 may be relat ed to those for [I-125]MIBG uptake. If suitable Tc-99m-labeled MIBG derivat ives can be further developed, the prevalent availability of Tc-99m in nucl ear medicine clinics will allow them to be readily available for widespread application.