A CD4/T-4 receptor peptide ligand labeled with technetium-99m: Synthesis and biological activity

The octapeptide D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-NH2 ([D-Ala1]TNH2), an analog of peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH) associated with CD4/T4 receptors involved in human immunodeficiency virus infection, was combined with the chelating polyazamacrocycle 1,4,8,11-tetraazacyclotetradecane (cyclam) to afford the bifunctional ligand cyc-[D-Ala1]TNH2. This was then reacted with [99mTcO4]- and Sn2+ to yield the monocationic complex [99mTc(O)2(cyc-[D-Ala1]TNH2)]+. Biological activity of both the cyclam-peptide conjugate and the resulting Tc-99m complex were evaluated by measuring their chemotactic indexes. Results showed that N-cyclam acylation and subsequent labeling with Tc-99m of [D-Ala1]TNH2 were tolerated, and both cyc-[D-Ala1]TNH2 and [99mTc(O)2(cyc-[D-Ala1]TNH2)]+ retained the high chemotactic capacity of the original octapeptide. Biodistribution of the Tc-99m complex was carried out in rats. Fast blood clearance and no accumulation in organs of interest were observed