Study for Preparation of 99mTc-Labeled Antimicrobial Peptide and Its Application to Detect Bacterial Infection (I)

The medical community often faces the dilemma of discrimination between bacterial infection and sterile inflammation. Various radiopharmaceuticals have been developed for the scintigraphic detection of infection and inflammation in humans. However, most of them interact with host cells, and do not discriminate between infections and sterile inflammatory processes. An ideal radiopharmaceutical for infection imaging should meet the following criteria: (1) high and specific uptake at the site of infection; (2) rapid detection of infection; (3) rapid background clearance; (4) minimal accumulation in non-target tissues; (5) low toxicity and zero immune response; (6) an ability to differentiate infection from sterile inflammation. Among many antimicrobial peptides investigated, a fragment of human macrophage peptide, ubiquicidin (UBI) 29-41, has been reported to be labeled with 99mTc, the most widely used radionuclide in nuclear medicine, and shows the ability to target bacterial cells but not sterile inflammatory processes in experimental animal. The first objective of this project is to synthesize linear peptide of UBI 29-41 and to develop technique for preparation of 99mTc-labeled UBI 29-41 with a simple kit formulation. So far, 67Ga-citrate is the tracer for current practice of scintigraphic detection of inflammation/infection in vivo. The capability of 99mTc-labeled UBI 29-41 imaging to discriminate bacterial infection and sterile inflammation has to be validated in suitable animal modes and compared with the results obtained from 67Ga-citrate imaging. Accordingly, the second objective of this project is to establish animal models of bacterial infections and sterile inflammation, respectively. The specific aims of the project are as follows: The first year: 1. To develop method for synthesis of UBI 29-41 peptide, and the approach for analysis of the peptide. 2. To develop method for labeling of UBI 29-41 with 99mTc, and the approach to determine the radiochemical purity of 99mTc-UBI 29-41. 3. To establish a kit formulation that allows one-step radiolabeling of 99mTc-UBI 29-41. 4. To establish the biokinetic information of 99mTc-UBI 29-41 in healthy experimental animals. The second year: 1. To establish experimental animal model for bacterial infections. 2. To establish experimental animal models for sterile inflammation. 3. To establish the biokinetic information of 99mTc-UBI 29-41 and 67Ga-citrate in experimental animal models of bacterial infections and sterile inflammation, respectively. 4. To establish and to analyze the microSPECT imaging data of 99mTc-UBI 29-41 and 67Ga-citrate in experimental animal models of bacterial infections and sterile inflammation, respectively.

Project ID:PC9501-0031
External Project ID:NSC95-NU-7182-001