Bacterial Specific Oligomers for Infection Detection Through Imaging

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): There is a need for a bacteria-specific infection imaging agent in diagnostic nuclear medicine. At least two agents (Infecton and UBI) are currently under development to meet this need. We feel that one alternative approach to specific bacterial infection imaging has been overlooked-the use of radiolabeled oligomers with specificity to bacterial ribosomal RNA. It has been shown by others that DNA oligomers bind in vitro to their species-specific bacterium. Thus, an oligomer analogue radiolabeled with an imaging radionuclide such as 99m Tc may show preferential localization in sites of infection/inflammation in contrast to sites of inflammation alone. We concluded that radiolabeled species specific oligomers should be investigated as potential agents for specific imaging of infection especially since these agents may be useful in antibiotic treated patients. The objective of this proposed research is to conduct these investigations to identify the oligomer analogues that can be used with bacteria to show specific binding, and that is also compatible within vivo conditions. Then once the correct chemistry is established we will evaluate to what degree radiolabeled oligomers may be useful in vivo for infection detection. This laboratory has experience with infection detection mouse models and an extensive background in radiolabeled oligomer analogues for in vivo applications. We wish to continue our studies of infection specific agents and complement it with our experience with radiolabeled oligomers to expand upon our other studies. Beginning with species specific oligomer sequences already in the literature, we will evaluate their chemical forms in vitro using phosphorothioate, peptide nucleic acid (PNA) and morpholino analogues. Once the chemistry is established, the selected chemistry will be tested on six bacterial specific oligomer sequence and their respective bacteria to evaluate specificity. As controls we will use a universal bacterial binding oligomer and a known non-binding oligomer as negative control. Thereafter, we will test in vivo only those oligomers showing specificity in a mouse infection model. Finally, we will compare in our infection mouse model several of the best oligomers/bacteria combinations against each other and against 67 Ga citrate as an inflammation specific agent and 99m Tc-UBI, and Infecton as gold-standard infection specific agents. In this way, we expect to confirm our hypothesis that radiolabeled oligomers hold considerable promise as bacterial infection imaging agents. Statement The relevance of this work to public health is that it would enable the physician to quickly and effectively distinguish by imaging bacterial infections from inflammation and, most importantly, to identify the bacterium responsible. This is an unmet need in medicine and accomplishing this would be of great benefit in the treatment of patients with suspected bacterial infections such as pneumonia and prosthetic lesions. Thus, the outcome of this investigation would greatly benefit the general public. [unreadable] [unreadable] [unreadable]