Noninvasive molecular imaging of tuberculosis-associated inflammation with radioiodinated DPA-713.

Abstract

BACKGROUND:

Increased expression of translocator protein (TSPO) is a feature of microglial and macrophage activation. Since activated macrophages are key components of tuberculosis-associated inflammation, we evaluated radioiodinated DPA-713, a synthetic ligand of TSPO, for in vivo imaging of host response.

METHODS:

Mice were infected with aerosolized Mycobacterium tuberculosis and evaluated using whole-body [(125)I]iodo-DPA-713 single-photon emission computed tomography (SPECT). Ex vivo biodistribution and correlative immunofluorescence studies were also performed.

RESULTS:

[(125)I]Iodo-DPA-713 SPECT imaging clearly delineated tuberculosis-associated pulmonary inflammation in live animals. Biodistribution studies confirmed radiotracer specificity for inflamed pulmonary tissues. Immunofluorescence studies demonstrated that TSPO is highly expressed in CD68(+) macrophages and phagocytic cells within tuberculosis lesions and that [(125)I]DPA-713 specifically accumulates within these cells. Coadministration of excess unlabelled DPA-713 abrogated both the SPECT and ex vivo fluorescence signals. Lesion-specific signal-to-noise ratios were significantly higher with [(125)I]iodo-DPA-713 SPECT (4.06 ± 0.52) versus [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) (2.00 ± 0.28) performed in the same mice (P = .004).

CONCLUSIONS:

[(125)I]Iodo-DPA-713 accumulates specifically in tuberculosis-associated inflammatory lesions by selective retention within macrophages and phagocytic cells. [(125)I]Iodo-DPA-713 SPECT provides higher lesion-specific signal-to-noise ratios than [(18)F]FDG PET and may prove to be a more specific biomarker to monitor tuberculosis in situ.

• Authors: Catherine A Foss, Jamie S Harper, Haofan Wang, Martin G Pomper, Sanjay K Jain
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 208 Issue 12 Pg. 2067-74 (Dec 15 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23901092 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Acetamides
• Bzrp protein, mouse
• N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide
• Pyrazoles
• Pyrimidines
• Receptors, GABA

Topics

• Acetamides (chemistry, pharmacokinetics)
• Animals
• Female
• Granuloma (pathology)
• Lung (pathology)
• Macrophages (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Molecular Imaging (methods)
• Phagocytes (chemistry)
• Pneumonia (pathology)
• Pyrazoles (chemistry, pharmacokinetics)
• Pyrimidines (chemistry, pharmacokinetics)
• Receptors, GABA (metabolism)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)
• Tuberculosis (pathology)