Synthesis and Characterization of Rhenium and Technetium-99m Labeled Insulin

A Tc-99m-labeled insulin analogue was synthesized through a direct labeling method in which the [Tc-99m(CO)(3)](+) core was combined with a protected insulin derivative (9) bearing a M(I) chelate linked to the first amino acid of the B-chain (B1). Regioselective labeling was achieved by careful control over the pH and the reaction time. Following a TFA-anisole mediated deprotection step (decay-corrected yield of 30 +/- 11%, n = 4), the identity of the final Tc-99m-labeled product was confirmed by H PLC. Displacement of I-125-insulin from the insulin receptor (IR) by the Re analogue 6 was similar to that of native insulin (17.8 nM vs 11.7 nM, respectively). The extent of autophosphorylation and Akt activation, as indicated by production of phospho-Akt (pAkt), showed no statistical difference between 6 and native insulin in both assays. These results support the use oldie reported Tc-99m-insulin derivative as a tracer for studying insulin biochemistry in vivo.