chapter  10
26 Pages

Imaging Infection Based on Expression of Thymidine Kinase

ByChetan Bettegowda, Youngjoo Byun, Catherine A. Foss, George Sgouros, Richard F. Ambinder, and Martin G. Pomper

One technique worthy of more detailed mention is FDG-PET, which is undergoing trials in a variety of different infectious and inammatory processes (de Winter et al., 2001; Meller et al., 2002, 2007; El-Haddad et al., 2004; Makinen et al., 2005; Goebel et al., 2007; Keidar et al., 2007). e keyword of the previous sentence is “inammatory,” underscoring the lack of speci-city of FDG-PET, the premier metabolic imaging technique for oncology, for imaging infection. As a molecular imaging technique, FDG-PET enables detection of physiological processes, such as infection or inammation, at a much earlier stage than the standard, anatomic techniques. Furthermore, PET is not aected by metallic implants and does not show the same limitations, for example, in bone infections, for which the three-phase bone scan and tagged WBC studies tend to be limited within the axial skeleton. PET studies can also be performed fairly readily aer administration of isotope, in about 2h. Nevertheless, because FDG uptake is due to an increase in glycolysis in tissues, it can be seen in inammatory, granulomatous, or frankly infectious processes. In one animal study, 29% of FDG uptake within tumor was actually within associated macrophages and granulation tissue (Beckers et al., 2004). FDG uptake is somewhat dependent on serum glucose level (Meller et al., 2007). FDGPET has proved utility in chronic osteomyelitis, vasculitis, and in a variety of other infectious and inammatory entities in the references noted above; however, it is also sequestered by healing infections, particularly within bone (Lankinen et  al., 2008). e timing of FDG infection imaging is critical, such that it cannot be performed until several weeks aer surgery, aer which most of the inammation should have subsided. Despite those drawbacks, FDG-PET is considered the method of choice for chronic osteomyelitis, particularly of the axial skeleton, and is likely to become the clinical standard (Meller et  al., 2007). One may argue that FDG-PET imaging for infection and inammation is on the right track. It emphasizes use of a lowmolecular-weight agent that does not have signicant blood pool circulation and localizes to the infectious or

the inammatory foci in a mechanism-based fashion. e FIAU-based method that we discuss can be considered analogous to FDG-PET; however, in part because of the dierences in substrate specicity of human versus bacterial TK, FIAU is not as signicantly sequestered by mammalian cells and will therefore not be seen in inammation and will be detected only in the presence of an organism that possesses the appropriate bacterial (or viral or possibly fungal) TK.