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

Catherine A. Foss, Jamie S. Harper, Haofan Wang, Martin G. Pomper, Sanjay K. Jain

Research output: Contribution to journalArticlepeer-review

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 [125I]iodo-DPA-713 single-photon emission computed tomography (SPECT). Ex vivo biodistribution and correlative immunofluorescence studies were also performed. Results. [125I]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 [125I]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 [ 125I]iodo-DPA-713 SPECT (4.06 ±0.52) versus [ 18F]fluorodeoxyglu-cose (FDG) positron emission tomography (PET) (2.00 ± 0.28) performed in the same mice (P = .004). Conclusions. [ 125I]Iodo-DPA-713 accumulates specifically in tuberculosis-associated inflammatory lesions by selective retention within macrophages and phagocytic cells. [125I]Iodo-DPA-713 SPECT provides higher lesion-specific signal-to-noise ratios than [18F]FDG PET and may prove to be a more specific biomarker to monitor tuberculosis in situ.

Original languageEnglish (US)
Pages (from-to)2067-2074
Number of pages8
JournalJournal of Infectious Diseases
Volume208
Issue number12
DOIs
StatePublished - Dec 15 2013

Keywords

  • Macrophage
  • Molecular imaging
  • PET
  • Pyrazolopyrimidine
  • Translocator protein
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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