Imaging Chronic Tuberculous Lesions Using Sodium [(18)F]Fluoride Positron Emission Tomography in Mice - PubMed (original) (raw)

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

Alvaro A Ordonez et al. Mol Imaging Biol. 2015 Oct.

Abstract

Purpose: 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 [(18)F]fluoride (Na[(18)F]F) PET could be used to detect microcalcifications in a chronically Mycobacterium tuberculosis-infected murine model.

Procedures: C3HeB/FeJ mice, which develop necrotic and hypoxic TB lesions, were aerosol-infected with M. tuberculosis and imaged with Na[(18)F]F PET.

Results: Pulmonary TB lesions from chronically infected mice demonstrated significantly higher Na[(18)F]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.

Conclusion: Na[(18)F]F PET can be used for the detection of chronic TB lesions and could prove to be a useful noninvasive biomarker for TB studies.

Keywords: Chronic; Microcalcification; Na[18F]F; PET; Tuberculosis.

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Conflict of interest statement

Conflict of Interest. None of the authors report any financial or potential conflicts of interest.

Figures

Fig. 1

Fig. 1

Transverse, coronal, and sagittal sections from Na[18F]F PET/CT imaging performed on a chronically _M. tuberculosis_-infected, b acutely _M. tuberculosis_-infected, and c uninfected mice, 40 min post tracer injection. Radio-densities demonstrating TB lesions are clearly visible in the lungs of infected mice (a and b), but Na[18F]F PET signal is only noted in the chronically infected mice (arrows). Na[18F]F PET signal is also noted in bones and the urinary bladder (Bl). H heart.

Fig. 2

Fig. 2

Dynamic Na[18F]F PET imaging demonstrates significantly higher signal in a pulmonary lesions from chronically infected mice (blue) compared with acutely infected (red) or uninfected (dotted black) animals. No difference is evident in b the blood or c bone compartments amongst the three different groups. Three animals were imaged for each group. Data is represented as median and interquartile range.

Fig. 3

Fig. 3

Ex vivo biodistribution studies performed after completion of imaging. Na[18F]F uptake is significantly higher in the chronically infected lung tissues, while uptake is similar amongst the three different groups in other tissue compartments. Three animals were used for each group. Data is represented as median and interquartile range.

Fig. 4

Fig. 4

Histology sections from chronic (left panels) and acutely infected (middle panels) mice and uninfected (right panels) controls are shown. H&E staining (a), von Kossa staining for calcium phosphate deposits in black (b and c), Alizarin Red with calcium deposits visualized in red (d), and acid-fast staining for M. tuberculosis bacilli (e). Well-defined necrotic granulomas are noted on H&E staining in the _M. tuberculosis_-infected (acute and chronic) tissues. Von Kossa and Alizarin Red staining demonstrate deposits only in TB lesions from chronically infected tissues (b–d). AFB staining demonstrates large numbers of bacilli in infected (acute and chronic) tissues (e).

Fig. 5

Fig. 5

a Histology demonstrating pulmonary lesions in a _M. tuberculosis_-infected mouse with chronic infection. Higher magnification of a TB lesion (inset) demonstrates a classic granulomatous lesion with central necrosis (b) and a large number of M. tuberculosis bacilli seen with AFB staining (c). Microcalcifications represented as black and red deposits are evident on von Kossa (d) and Alizarin Red staining (e), respectively.

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