title: A CD(4)/T(4) receptor peptide ligand labeled with technetium-99m: synthesis and biological activity.
abstract: 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.
authors.affiliation: Laboratory of Nuclear Medicine, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Boschi
authors.forename: L
authors.initials: L
authors.lastname: Uccelli
authors.forename: C
authors.initials: C
authors.lastname: Bolzati
authors.forename: M
authors.initials: M
authors.lastname: Marastoni
authors.forename: R
authors.initials: R
authors.lastname: Tomatis
authors.forename: S
authors.initials: S
authors.lastname: Spisani
authors.forename: S
authors.initials: S
authors.lastname: Traniello
authors.forename: A
authors.initials: A
authors.lastname: Piffanelli
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D002851:Chromatography, High Pressure Liquid; D002854:Chromatography, Paper; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D009000:Monocytes / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D015704:CD4 Antigens; D008024:Ligands; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C422192:technetium Tc 99m dioxo-1-(alanyl-seryl-threonyl-theonyl-threonyl-asparaginyl-tyrosyl-threoninamide)cyclam