Ex vivo fluorescence imaging of selected tissues from animals injected with 25 μg of either DFO-CNC-Cy5 or NOTA-CNC-Cy5 at 24 h p.i. corroborated the biodistribution pattern seen with the radiolabeled cellulose nanocrystals. For DFO-CNC-Cy5, intense fluorescence was seen in the RES, the liver and the spleen, with residual signal in the lung and the blood pool. For NOTA-CNC-Cy5, the bulk of the signal was seen in the spleen, with slight fluorescence present in the liver and lung.