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-Ala(1)]TNH2), an analog of peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH) associated with CD4/T-4 receptors involved in human immunodeficiency virus infection, was c ombined with the chelating polyazamacrocycle 1,4,8,11-tetraazacyclotetradec ane (cyclam) to afford the bifunctional ligand cyc-[D-Ala(1)]TNH2, This was then reacted with [(TcO4)-Tc-99m]- and Sn2+ to yield the monocationic comp lex [Tc-99m(O)(2)(c) (cyc-[D-Ala(1)]TNH2)](+). Biological activity of both the cyclam-peptide conjugate and the resulting Tc-99m complex were evaluate d by measuring their chemotactic indexes. Results showed that N-cyclam acyl ation and subsequent labeling with Tc-99m of [D-Ala(1)]TNH2 were tolerated, and both cyc-[D-Ala(1)]TNH2 and [Tc-99m(O)(2)(cyc-[D-Ala(1)]TNH2)](+) reta ined the high chemotactic capacity of the original octapeptide. Biodistribu tion of the Tc-99m complex was carried out in rats, Fast blood clearance an d no accumulation in organs of interest were observed. NUCL MED BIOL 27;8:7 91-795, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.