Comparative Study of [18F]DPA714 and [18F]FDG PET Tracers in an Experimental Model of Pulmonary Tuberculosis

Purpose: Tuberculosis (TB) continues to afflict global health. Therefore, a deeper understanding of the host response mechanisms that underly pathogenesis versus disease control upon infection with Mycobacterium tuberculosis (Mtb) is required to leverage the development of improved therapeutic or prophylactic TB treatment regimens. In the present work positron emission tomography (PET) using [18F]DPA714 is piloted as a tracer of the mitochondrial translocator protein TSPO that mainly targets macrophages. Procedures: We compared two tracers: [18F]DPA714 to the widely applied marker [18F]FDG to visualize the development of experimental pulmonary TB in three rhesus monkeys (Macaca mulatta), that were infected with Mtb by repeated low dose exposure. Next to baseline recordings prior to infectious challenge, two PETs at a two-weeks interval were acquired early after the manifestation of TB infection for each of the respective tracers. Results & Conclusions: Here, we demonstrate that both PET tracers detected Mtb infection. The inflammatory response tracked by [18F]FDG progressively increased in line with the developing TB pathology, while [18F]DPA714 showed a transient signal in lungs and lung-draining hilar lymph nodes. This study underpins the potential value of different tracers to investigate cellular and molecular host response cascades in experimental medicine settings, in this case, into a (transient) local involvement of myeloid immune cell activation versus inflammation-associated glucose consumption in pulmonary TB.