Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs

J Nucl Med. 1991 Mar;32(3):483-91.

Abstract

Four DTPA-derivatized chemotactic peptide analogs: ForNleLFNleYK-DTPA (P1), ForMLFNH(CH2)6NH-DTPA (P2), ForNleLFK(NH2)-DTPA (P3), and ForNleLFK-DTPA (P4), were synthesized and evaluated for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 111In by transchelation and their biodistribution determined in rats at 5, 30, 60 and 120 min after injection. Localization at sites of infection was determined by scintillation camera imaging in animals with deep-thigh infection due to Escherichia coli. Images were recorded from 5 min to 2 hr after injection. All peptides maintained biologic activity (EC50 for O2-production by human PMN's: 3-150 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMN's (EC50 for binding: 7.5-50 nM); biologic activity and receptor binding were highly correlated (r = 0.99). For all the peptides, blood clearance was rapid (half-lives: 21.5, 33.1, 31.6, and 28.7 min for P1, P2, P3, and P4, respectively). Biodistributions of the individual peptides were similar with low levels of accumulation in the heart, lung, liver, spleen, and gastrointestinal tract. In the kidney, P1 had much greater accumulation than other organs. All peptides yielded high quality images of the infection sites within 1 hr of injection. This study demonstrates that 111In-labeled chemotactic peptide analogs were effective agents for the external imaging of focal sites of infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacterial Infections / diagnostic imaging*
  • Bacterial Infections / metabolism
  • Chemotactic Factors* / pharmacokinetics
  • Escherichia coli Infections / diagnostic imaging
  • Indium Radioisotopes*
  • Isotope Labeling
  • Leukocyte Count / drug effects
  • Male
  • Oligopeptides* / pharmacokinetics
  • Pentetic Acid* / pharmacokinetics
  • Radionuclide Imaging
  • Rats
  • Rats, Inbred Strains
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / drug effects
  • Receptors, Peptide / drug effects
  • Tissue Distribution

Substances

  • Chemotactic Factors
  • Indium Radioisotopes
  • Oligopeptides
  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Peptide
  • Pentetic Acid