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


METHODS
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.


CONCLUSIONS
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.
Center for Infection and Inflammation Imaging Research, Johns Hopkins University, 1550 Orleans Street, CRB-II, Rm 1.09, Baltimore, MD, USA.|Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA.|Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Alvaro A
AA
Ordonez
Center for Infection and Inflammation Imaging Research, Johns Hopkins University, 1550 Orleans Street, CRB-II, Rm 1.09, Baltimore, MD, USA.|Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA.|Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Vincent P
VP
DeMarco
Center for Infection and Inflammation Imaging Research, Johns Hopkins University, 1550 Orleans Street, CRB-II, Rm 1.09, Baltimore, MD, USA.|Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA.|Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Mariah H
MH
Klunk
Center for Infection and Inflammation Imaging Research, Johns Hopkins University, 1550 Orleans Street, CRB-II, Rm 1.09, Baltimore, MD, USA.|Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA.|Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Supriya
S
Pokkali
Center for Infection and Inflammation Imaging Research, Johns Hopkins University, 1550 Orleans Street, CRB-II, Rm 1.09, Baltimore, MD, USA. sjain5@jhmi.edu.|Center for Tuberculosis Research, Johns Hopkins University, Baltimore, MD, USA. sjain5@jhmi.edu.|Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA. sjain5@jhmi.edu.
Sanjay K
SK
Jain
D000818:Animals; D002908:Chronic Disease; D005260:Female; D005462:Fluorine Radioisotopes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008168:Lung / Q000473:pathology; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D012969:Sodium Fluoride / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014376:Tuberculosis / Q000000981:diagnostic imaging*
D005462:Fluorine Radioisotopes; D012969:Sodium Fluoride
Chronic; Microcalcification; Na[18F]F; PET; Tuberculosis