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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038276-03
Application #
2672539
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1996-07-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
2000-06-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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