A CD4/T4 receptor peptide ligand label with technetium-99m: synthesis and biological activity.

The octapeptide D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-NH(2) ([D-Ala(1)]TNH(2)), an analog of peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH) associated with CD(4)/T(4) 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-Ala(1)]TNH(2). This was then reacted with [(99m)TcO(4)](-) and Sn(2+) to yield the monocationic complex [(99m)Tc(O)(2)(cyc-[D-Ala(1)]TNH(2))](+). 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-Ala(1)]TNH(2) were tolerated, and both cyc-[D-Ala(1)]TNH(2) and [(99m)Tc(O)(2)(cyc-[D-Ala(1)]TNH(2))](+) 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