This proposal will develop Tc-99m-labeled chemotactic peptides for imaging infection using standard nuclear medicine methods. The goal is to develop peptides that can be labeled in kit form with Tc-99m to yield products with high specific activity and high binding affinity. High-specific-activity peptides are needed to avoid the neutropenia that has been observed after administration of chemotactic oligopeptides. The diaminedithiol ligand system is used as a carrier of technetium; DTPA is used as a pharmacokinetic modifier. Methods of molecular modification other than DTPA will also be evaluated to optimize pharmacokinetics of the peptides. Binding of the radiolabeled peptides to the chemoattractant receptor will be studied in vitro. Biodistribution will be studied in mice and rabbits, and imaging studies in abscess-bearing rabbits will compare labeled peptides with In-111 leukocytes and Tc-99m-labeled nonspecific IgG. Metabolites of the labeled peptides will be analyzed. Effects of Tc-99m-peptide dose on leukocyte count will be studied.
|Baidoo, K E; Scheffel, U; Stathis, M et al. (1998) High-affinity no-carrier-added 99mTc-labeled chemotactic peptides for studies of inflammation in vivo. Bioconjug Chem 9:208-17|