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.
Subject(s)
Chemotactic Factors , Inflammation/diagnostic imaging , Oligopeptides , Technetium , Amino Acid Sequence , Animals , Chelating Agents/adverse effects , Chelating Agents/chemistry , Chemotactic Factors/adverse effects , Chemotactic Factors/chemistry , In Vitro Techniques , Male , Molecular Sequence Data , N-Formylmethionine Leucyl-Phenylalanine/analogs & derivatives , N-Formylmethionine Leucyl-Phenylalanine/chemistry , Neutropenia/etiology , Neutropenia/prevention & control , Oligopeptides/adverse effects , Oligopeptides/chemistry , Radionuclide Imaging , Rats , Rats, Sprague-Dawley , Receptors, Formyl Peptide , Receptors, Immunologic/metabolism , Receptors, Peptide/metabolism , Technetium/adverse effectsABSTRACT
Static imaging of lung ventilation in multiple views or with SPECT requires a 99mTc aerosol which does not wash out during imaging. Commercially available 99mTc colloids have suitable physical properties but are inefficiently delivered from jet nebulizers. An in vitro system was used to compare the delivery of various 99mTc radiopharmaceuticals from nebulizer solutions. Delivery of noncolloidal agents (pertechnetate, pentetate, imidodiphosphate, albumin) was much greater than that of colloids. However, addition of phosphate buffer to an in-house 99mTc-tin colloid produced an agent that was delivered as efficiently as the noncolloidal tracers and which shows promise for clinical use.
