Imaging bacterial infections using [124I]FIAU as a substrate for bacterial thymidine kinase

1045 Learning Objectives To review the potential usefulness of [124I]-FIAU-PET/CT as an infectious disease imaging agent as compared to other clinically available imaging modliaties. Currently available nuclear medicine imaging modalities used in the evaluation of infectious diseases can be very useful, but suffer from a major problem which is the lack of specificity. Labeled WBC scans can demonstrate the flux of white blood cells to the region of infection. Gallium scans rely on increased vascular permeability associated with inflammation as well. However, WBC flux and increased permeability occur with both sterile and non-sterile inflammation making the differentiation between the two entities impossible. An emerging standard in the evaluation of infection is FDG/PET [1]. Differentiation between infection, sterile inflammation, and tumor however can still be very difficult. Recently, it was demonstrated that 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU) can be a substrate for the thymidine kinase (TK) enzyme of many bacteria, while it is not a substrate for the main human TK enzyme [2]. This difference in substrate specificity has been exploited to develop an imaging ligand (FIAU, labeled with [124I] or [125I]) that may be able to detect bacterial infections, in vivo. It9s believed that radiolabeled FIAU gets phosphorylated by bacterial TK, becomes trapped within the microorganism and can then be imaged using PET or SPECT [2]. The potential usefulness of radiolabeled FIAU was shown in a mouse model in which [125I]-FIAU accumulated in the wild type E.Coli infected thigh but not in the thigh infected with TK-negative E.coli [2]. This major preclinical discovery was translated shortly thereafter through successful imaging of human musculoskeletal infections using [124I]-FIAU by Diaz et al [3]. Similar human imaging studies are currently underway in multiple institutions. FIAU holds considerable promise to be the next-generation imaging agent capable of differentiating infection from sterile inflammation