title: 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.affiliation: Center for Infection and Inflammation Imaging Research.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Harper
authors.forename: Haofan
authors.initials: H
authors.lastname: Wang
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D005260:Female; D006099:Granuloma / Q000473:pathology; D008168:Lung / Q000473:pathology*; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D057054:Molecular Imaging / Q000379:methods*; D010586:Phagocytes / Q000737:chemistry; D011014:Pneumonia / Q000473:pathology; D011720:Pyrazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014376:Tuberculosis / Q000473:pathology*
chemical_list: D000081:Acetamides; C463819:Bzrp protein, mouse; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA
keywords: PET; macrophage; molecular imaging; pyrazolopyrimidine; translocator protein; tuberculosis
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