The integrity of the disulfide bond in a cyclic somatostatin analog duringTc-99m complexation reactions

Recent development of a variety of thiol free chelating agents has facilita ted the design of Tc-99m-labered somatostatin analogs suitable for receptor imaging of somatostatin-positive tumors. However, it remains ambiguous whe ther the disulfide bonds in cyclic peptides are stable during Tc-99m comple xation reactions, and contradictory results have been reported regarding th e integrity of disulfide bonds in cyclic somatostatin analogs. To estimate the stability of the disulfide bond in a synthetic somatostatin analog at l ow peptide concentrations, [I-125]I-RC 160, in which radioiodine was incorp orated into the 3-Tyr residue, was synthesized and the integrity of the dis ulfide bond of the peptide was investigated in the presence of reducing age nts such as ascorbic acid, dithionite, and stannous ions. The disulfide bon d in [I-125]I-RC-160 remained stable in the presence of ascorbic acid in bo iling water. The disulfide bond was also stable when treated with stannous ions at concentrations sufficient to reduce Tc-99m for complexation with a thiol free chelating agent, bis(hydroxamamide) analog when the Tc-99m compl exation reaction was performed at room temperature. However, the disulfide bond of [I-125]I-RC-160 was slightly cleaved in the presence of a small amo unt of stannous ions when the reaction was performed in boiling water. Trea tment of [I-125]I-RC-160 with dithionite in boiling water markedly reduced the disulfide bond of the parental peptide. These findings indicated that s ynthetic somatostatin analogs may be labeled with Tc-99m with stannous ions as the reducing agent without impairing their structure after conjugation of thiol free chelating agents that provide Tc-99m chelates under mild reac tion conditions. (C) 2000 Elsevier Science Tnc, All rights reserved.