Preclinical Positron Emission Tomography (PET) of\nProsthetic Joint Infection Using a Nitro-Prodrug of 2‑[<sup>18</sup>F]F‑<i>p</i>‑Aminobenzoic Acid ([<sup>18</sup>F]F-PABA)

Deep-seated\nbacterial infections are difficult to detect and diagnose\ndue to the lack of specific clinical imaging modalities. Therefore,\nthe bacteria-specific positron emission tomography radiotracer 2-[<sup>18</sup>F]fluoro-4-nitrobenzoic acid ([<sup>18</sup>F]FNB) was developed,\nwhich is reduced to 2-[<sup>18</sup>F]fluoro-4-aminobenzoic acid ([<sup>18</sup>F]F-PABA) by bacterial nitroreductases and has improved pharmacokinetics\ncompared to the parent compound. PET imaging demonstrated that the\nuptake of 2-[<sup>18</sup>F]fluoro-4-nitrobenzoic acid in a clinically\nrelevant <i>Staphylococcus aureus</i> prosthetic joint infection\nmodel was up to ∼4-fold higher in the infected joint compared\nto the contralateral joint. 2-[<sup>18</sup>F]Fluoro-4-nitrobenzoic\nacid was also able to distinguish infection from inflammation in a\nsurgical inflammation model. Based on the mouse radiation dosimetry\nresults, the calculated effective dose of 2-[<sup>18</sup>F]fluoro-4-nitrobenzoic\nacid was well below the whole-body radiation dose limit established\nby the Food and Drug Administration for humans. In addition, no treatment-related\nmicroscopic changes in organ histopathology were observed in a mouse\nacute toxicity study. Overall, these data suggest that 2-[<sup>18</sup>F]fluoro-4-nitrobenzoic acid is a specific and effective imaging\nagent for noninvasively diagnosing prosthetic joint infections.