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Τhe morphology, physiology and immunology, of solid tumors exhibit spatial heterogeneity which complicates our understanding of cancer progression and therapy response. Understanding spatial heterogeneity necessitates high resolution in vivo imaging of anatomical and pathophysiological tumor information. We introduce  Rhodobacter  as bacterial reporter for multispectral optoacoustic (photoacoustic) tomography (MSOT). We show that endogenous bacteriochlorophyll  a  in  Rhodobacter  gives rise to strong optoacoustic signals >800 nm away from interfering endogenous absorbers. Importantly, our results suggest that changes in the spectral signature of  Rhodobacter  which depend on macrophage activity inside the tumor can be used to reveal heterogeneity of the tumor microenvironment. Employing non-invasive high resolution MSOT in longitudinal studies we show spatiotemporal changes of  Rhodobacter  spectral profiles in mice bearing 4T1 and CT26.WT tumor models. Accessibility of  Rhodobacter  to genetic modification and thus to sensory and therapeutic functions suggests potential for a theranostic platform organism.

Phototrophic purple bacteria as optoacoustic in vivo reporters of macrophage activity