A Radioluminescent Metal-Organic Framework for Monitoring 225 Ac in Vivo .

225 Ac is considered as one of the most promising radioisotopes for alpha-therapy because its emitted high-energy α-particles can efficiently damage tumor cells. However, it also represents a significant threat to healthy tissues owing to extremely high radiotoxicity if targeted therapy fails. This calls for a pressing requirement of monitoring the biodistribution of 225 Ac in vivo during the treatment of tumors. However, the lack of imageable photons or positrons from therapeutic doses of 225 Ac makes this task currently quite challenging. We report here a nanoscale luminescent europium-organic framework (EuMOF) that allows for fast, simple, and efficient labeling of 225 Ac in its crystal structure with sufficient 225 Ac-retention stability based on similar coordination behaviors between Ac 3+ and Eu 3+ . After labeling, the short distance between 225 Ac and Eu 3+ in the structure leads to exceedingly efficient energy transduction from 225 Ac-emitted α-particles to surrounding Eu 3+ ions, which emits red luminescence through a scintillation process and produces sufficient photons for clearcut imaging. The in vivo intensity distribution of radioluminescence signal originating from the 225 Ac-labeled EuMOF is consistent with the dose of 225 Ac dispersed among the various organs determined by the radioanalytical measurement ex vivo , certifying the feasibility of in vivo directly monitoring 225 Ac using optical imaging for the first time. In addition, 225 Ac-labeled EuMOF displays notable efficiency in treating the tumor. These results provide a general design principle for fabricating 225 Ac-labeled radiopharmaceuticals with imaging photons and propose a simple way to in vivo track radionuclides with no imaging photons, including but not limited to 225 Ac.