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

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.