Transplutonium actinides are among the heaviest elements whose macroscale chemical properties can be experimentally tested. Being scarce and hazardous, their chemistry is rather unexplored, and they have traditionally been considered a rather homogeneous group, with most of their characteristics extrapolated from lanthanide surrogates. Newly emerged applications for these elements, combined with their persistent presence in nuclear waste, however, call for a better understanding of their behavior in complex living systems. In this work, we explored the biodistribution and excretion profiles of four transplutonium actinides (248Cm, 249Bk, 249Cf and 253Es) in a small animal model, and evaluated their in vivo sequestration and decorporation by two therapeutic chelators, diethylenetriamine pentaacetic acid and 3,4,3-LI(1,2-HOPO). Notably, the organ deposition patterns of those transplutonium actinides were element-dependent, particularly in the liver and skeleton, where lower atomic number radionuclides showed up to 7-fold larger liver/skeleton accumulation ratios. Nevertheless, the metal content in multiple organs was significantly decreased for all tested actinides, particularly in the liver, after administering the therapeutic agent 3,4,3-LI(1,2-HOPO) post-contamination. Lastly, the systematic comparison of the radionuclide biodistributions showed discernibly element-dependent organ depositions, which may provide insights into design rules for new bio-inspired chelating systems with high sequestration and separation performance.