title: Imaging inflammation with 99Tcm-labeled chemotactic peptides: analogues with reduced neutropenia.
abstract: Two 99Tcm-labelled analogues of the chemotactic peptide ForMLF were evaluated as potential agents for imaging inflammation and infection, in the hope that they would be simple to use and would give diagnostically useful images shortly after injection. The peptides differed in the chelation site for 99Tcm and the presence of a hydrophilic spacer. The sequences of RP050 and RP056 were ForNleLFNleYK(G)G-C(Acm)-GPic and ForNleLFNleYKK(DG)GC(Acm)SPic respectively, where Pic is picolinic acid. In in vitro tests of binding to the ForMLF receptor on polymorphonuclear neutrophils and potency for release of myeloperoxidase, RP056 was similar in potency to ForMLF, whereas RP050 was 10 times more potent. When administered in 5-nmol doses to rats, RP050 produced less extensive neutropenia than ForMLF, whereas RP056 produced very little neutropenia. Following labelling by ligand exchange from tartrate or glucoheptonate at 100 degrees C and purification using a C-18 solid-phase extraction cartridge, 4-MBq doses were administered to rats bearing infectious (Escherichia coli) or sterile (zymosan) inflammation sites in the thigh. The inflammation-to-normal muscle ratios at 30 min after injection were 3.9 +/- 0.4 for RP050 and 4.7 +/- 0.3 for RP056 (mean +/- S.E.M., n = 4), and the ratios were maintained for up to 3 h. These peptides are promising agents for imaging inflammation and infection.
authors.affiliation: Resolution Pharmaceuticals Inc., Mississauga, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Pollak
authors.forename: A E
authors.initials: AE
authors.lastname: Goodbody
authors.forename: J R
authors.initials: JR
authors.lastname: Ballinger
authors.forename: G S
authors.initials: GS
authors.lastname: Duncan
authors.forename: L L
authors.initials: LL
authors.lastname: Tran
authors.forename: R
authors.initials: R
authors.lastname: Dunn-Dufault
authors.forename: K
authors.initials: K
authors.lastname: Meghji
authors.forename: F
authors.initials: F
authors.lastname: Lau
authors.forename: T W
authors.initials: TW
authors.lastname: Andrey
authors.forename: I
authors.initials: I
authors.lastname: Boxen
authors.forename: M
authors.initials: M
authors.lastname: Sumner-Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002614:Chelating Agents / Q000009:adverse effects / Q000737:chemistry; D002630:Chemotactic Factors / Q000009:adverse effects / Q000737:chemistry; D066298:In Vitro Techniques; D007249:Inflammation / Q000000981:diagnostic imaging*; D008297:Male; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D009503:Neutropenia / Q000209:etiology / Q000517:prevention & control; D009842:Oligopeptides / Q000009:adverse effects / Q000737:chemistry; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D013667:Technetium / Q000009:adverse effects
chemical_list: D002614:Chelating Agents; D002630:Chemotactic Factors; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013667:Technetium