Large-scale visualization of nanoparticle kinetics is essential for optimizing drug delivery and characterizing in vivo toxicity associated with engineered nanomaterials. Real-time tracking of nanoparticulate agents across multiple murine organs is hindered with the currently available whole-body preclinical imaging systems due to limitations in contrast, sensitivity, spatial, or temporal resolution. Herein, we demonstrate rapid volumetric tracking of gold nanoagent kinetics and biodistribution in mice at a suborgan level with single-sweep volumetric optoacoustic tomography (sSVOT). The imaging system accomplishes whole-body three-dimensional scans in less than 1.8 s, further attaining a high spatial resolution of 130 μm and sub-picomolar sensitivity. We visualized the clearance dynamics of purposely synthesized gold nanorods and nanorod clusters, featuring different sizes and surface chemistries as well as their corresponding accumulation within the liver and spleen. The newly discovered capacity to image rapid whole-body kinetics down to suborgan scales opens up new avenues for the development and characterization of diagnostic and therapeutic nanoagents.

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