**5. Infection-specific agents**

#### **5.1 Iodine-124 fialuridine**

The radioiodinated thymidine analog fialuridine (FIAU) was developed for reporter genes, for cells that were transfected with herpes simplex virus thymidine kinase (TK). This enzyme transfers a phosphate group from ATP to pyrimidine deoxynucleoside. The lipophilic agent diffuses into the cell where it is trapped with the TK activity [82]. FIAU is also phosphorylated by endogenous bacterial TK. In a pilot investigation, 124I-FIAU PET/CT successfully detected musculoskeletal infection in seven patients and was negative in one healthy control [83]. Results of subsequent investigations of 124I-FIAU for diagnosing musculoskeletal infection were less satisfactory. In 19 subjects with suspected lower extremity PJI, image quality was suboptimal because of metal artifact and high nonspecific muscle uptake [84]. In an investigation of 124I FIAU for diagnosing foot osteomyelitis in diabetics the study was terminated because of a lack of correlation between 124I FIAU uptake and bone biopsy results [85].

#### **5.2 Fluorine-18 fluorodeoxysorbitol**

Sorbitol, a sugar alcohol, is a metabolic substrate for Enterobacteriaceae, the largest group of Gram-negative bacterial pathogens in humans. Sorbitol is selectively taken up by bacteria *via* surface transporters, phosphorylated, and further metabolized [86]. The radiolabeled sorbitol analog, 18F-FDS rapidly and selectively accumulates in Enterobacteriaceae. In a murine myositis model, 18F-FDS PET rapidly differentiated infection from sterile inflammation [87]. 18F-FDS was determined to be safe and well tolerated after a single intravenous dose was injected into healthy human volunteers to assess biodistribution and radiation dosimetry [88].

In a prospective investigation of 26 patients, 18F-FDS PET/CT was safe, rapidly localized Enterobacterales infections and differentiated them from sterile inflammation and tumor. Follow-up imaging in the same patients performed for monitoring antibiotic treatment demonstrated decreased uptake correlating with clinical improvement [89].

#### **5.3 Antimicrobial peptides**

Antimicrobial peptides (AMPs) bind to the bacterial cell membrane. Their expression may be constant or induced by contact with microbes. They also may be transported to sites of infection by leukocytes [90]. Radiolabeled synthetic fragments of ubiquicidin, a naturally occurring human AMP that targets bacteria, possess the

#### *PET Imaging of Infection DOI: http://dx.doi.org/10.5772/intechopen.110633*

ability to differentiate infection from sterile inflammation and have shown potential for monitoring treatment in staphylococcus aureus infections [91–93].

Although 99mTc labeled AMPS have been used in most investigations, preclinical data indicate that 68Ga labeled AMPS can be used to detect and localize infection [94]. 68Ga-DOTA-TBIA101 successfully detected *E. coli*-infected muscle tissue in mice. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy [95]. Although these results are encouraging, at the present time human data are too few to draw any conclusions about the clinical utility of these agents.
