[(125)I]FIAU imaging in a preclinical model of lung infection: quantification of bacterial load.

Abstract

2'-Fluoro-2'-deoxy-1β-D-arabinofuranosyl-5-[(125)I]iodouracil ([(125)I]FIAU), a substrate for the thymidine kinase (TK) present in most bacteria, has been used as an imaging agent for single photon emission computed tomography (SPECT) in an experimental model of lung infection. Using SPECT-CT we show that [(125)I]FIAU is specific for bacterial infection rather than sterile inflammation. We report [(125)I]FIAU lung uptake values of 1.26 ± 0.20 percent injected dose per gram (%ID/g) in normal controls, 1.69 ± 0.32 %ID/g in lung inflammation and up to 7.14 ± 1.09 %ID/g in lung infection in ex vivo biodistribution studies at 24 h after intranasal administration of bacteria. Images of [(125)I]FIAU signal within lung can be used to estimate the number of bacteria present, with a limit of detection of 10(9) colony forming units per mL on the X-SPECT scanner. [(125)I]FIAU-Based bacterial imaging may be useful in preclinical models to facilitate the development of new antibiotics, particularly in cases where a corresponding human trial is planned.