title: A receptor-specific peptide for imaging infection and inflammation.
abstract: The chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP), when radiolabelled, continues to be an attractive agent for imaging infection or inflammation. Previously, several analogues of fMLP have been prepared and radiolabelled using a bifunctional chelating agent conjugation procedure that was relatively long and complex. We have prepared a new analogue of fMLP, TP765, by the addition of 4-aminobutyric acid (4-ABA) and a group of four amino acids, Gly-Gly-d-Ala-Gly, to the carboxy terminus (i.e. to the phenylalanine) of fMLP. The adduct -(4-ABA)-Gly-Gly-d-Ala-Gly- serves as a chelating moiety for strong chelation with 99Tcm. The use of a peptide as a chelating moiety greatly simplified the synthetic procedure and rendered the analogue ready for instant chelation with 99Tcm. HPLC analysis revealed that 99Tcm-TP765 was a single chemical entity that retained biological activity and neutrophil specificity. 99Tcm-TP765 was stable when challenged with strong chelating agents in vitro and had rapid but biphasic blood clearance (alphat1/2 = 7 min, betat1/2 = 45 min). Approximately 90% of the radioactivity had cleared from circulation within 45 min post-injection and the agent had accumulated in experimental bacterial or sterile abscesses in significantly (P<0.05) higher quantities than the analogues evaluated previously. Generally, the biodistribution pattern of 99Tcm-TP765 was similar to that of other analogues examined and its abscess uptake was independent of the abscess age. In conclusion, a new analogue of fMLP, 99Tcm-TP765, was prepared by a simple procedure. This new analogue has properties similar to those of previously examined analogues used as agents for imaging infection or inflammation.
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Rao
authors.forename: V R
authors.initials: VR
authors.lastname: Pallela
authors.forename: D
authors.initials: D
authors.lastname: Vassileva-Belnikolovska
authors.forename: D
authors.initials: D
authors.lastname: Jungkind
authors.forename: M L
authors.initials: ML
authors.lastname: Thakur
mesh_terms: D000818:Animals; D015902:Gamma Cameras; D007202:Indicators and Reagents; D007239:Infections / Q000000981:diagnostic imaging*; D007249:Inflammation / Q000000981:diagnostic imaging*; D051379:Mice; D008807:Mice, Inbred BALB C; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives*; D009504:Neutrophils / Q000000981:diagnostic imaging / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011786:Quality Control; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium; D014018:Tissue Distribution
chemical_list: D007202:Indicators and Reagents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C425528:TP765; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013667:Technetium