Imaging Chronic Tuberculous Lesions Using Sodium [18F]Fluoride Positron Emission Tomography in Mice

Calcification is a hallmark of chronic tuberculosis (TB) in humans, often noted years to decades (after the initial infection) on chest radiography, but not visualized well with traditional positron emission tomography (PET). We hypothesized that sodium [F-18]fluoride (Na[F-18]F) PET could be used to detect microcalcifications in a chronically Mycobacterium tuberculosis-infected murine model. C3HeB/FeJ mice, which develop necrotic and hypoxic TB lesions, were aerosol-infected with M. tuberculosis and imaged with Na[F-18]F PET. Pulmonary TB lesions from chronically infected mice demonstrated significantly higher Na[F-18]F uptake compared with acutely infected or uninfected animals (P < 0.01), while no differences were noted in the blood or bone compartments (P > 0.08). Ex vivo biodistribution studies confirmed the imaging findings, and tissue histology demonstrated microcalcifications in TB lesions from chronically infected mice, which has not been demonstrated previously in a murine model. Na[F-18]F PET can be used for the detection of chronic TB lesions and could prove to be a useful noninvasive biomarker for TB studies.