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 bacteriophages (phages). Phages bind specifically to their host bacterium and are often highly selective in their specificity. Thus, a phage radiolabeled with an imaging radionuclide such as 99mTc may show preferential localization in sites of infection/inflammation in contrast to sites of inflammation alone. This laboratory has performed preliminary studies using the M13 bacteriophage radiolabeled with 99mTc using MAG3 as chelator. We have been able to show that the radiolabel was stable in vitro and in vivo, that the binding of the radiolabeled phage to each of three bacterial types in vitro was immediate to both live and heat killed (i.e. fragmented) bacteria, the binding was surprisingly stable to dissociation and that the percentage of phage bound varied significantly among bacterial types as an indication of preferential selection. In vivo at 3 hrs, the target thigh to normal ratio for all three phages was significantly higher (P< = 0.017) in our infection/inflammation model compared to the inflammation model to suggest increased accumulation specific to infection. We concluded that radiolabeled phages should be further 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 further investigations to help establish whether and to what degree radiolabeled phages may be used in this way. Specifically, we wish to continue with the M13 bacteriophage to confirm and expand upon our earlier studies. Thereafter, we wish to include five additional phages and seven additional host bacteria into these studies to evaluate further, binding affinity to live and lysed bacteria, specificity among bacterial hosts, label stability and biodistribution. Finally, we will compare in our infection/inflammation mouse model several of the superior phage/bacteria combinations against each other and against67 Ga citrate as an inflammation specific agent and 99mTc-UBI and Infecton as gold-standard infection specific agents. In this way, we expect to confirm our hypothesis that radiolabeled bacteriophages hold considerable promise as bacterial infection imaging agents. Relevance to public health Being able to distinguish quickly by imaging bacterial infections from inflammation and, in particular, to identify the bacterium responsible, would be of great benefit in the treatment of patients with pneumonia, prosthetic lesions and other known or suspected bacterial infections. Thus the outcome of this investigation would greatly benefit the general public. ? ?
| Rusckowski, Mary; Gupta, Suresh; Liu, Guozheng et al. (2008) Investigation of four (99m)Tc-labeled bacteriophages for infection-specific imaging. Nucl Med Biol 35:433-40 |
