A Radioluminescent Metal–Organic Framework for Monitoring 225Ac in Vivo

²²⁵Ac 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 ²²⁵Ac in vivo during the treatment of tumors. However, the lack of imageable photons or positrons from therapeutic doses of ²²⁵Ac 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 ²²⁵Ac in its crystal structure with sufficient ²²⁵Ac-retention stability based on similar coordination behaviors between Ac³⁺ and Eu³⁺. After labeling, the short distance between ²²⁵Ac and Eu³⁺ in the structure leads to exceedingly efficient energy transduction from²²⁵Ac-emitted α-particles to surrounding Eu³⁺ 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 ²²⁵Ac-labeled EuMOF is consistent with the dose of ²²⁵Ac dispersed among the various organs determined by the radioanalytical measurement ex vivo, certifying the feasibility of in vivo directly monitoring ²²⁵Ac using optical imaging for the first time. In addition, ²²⁵Ac-labeled EuMOF displays notable efficiency in treating the tumor. These results provide a general design principle for fabricating ²²⁵Ac-labeled radiopharmaceuticals with imaging photons and propose a simple way to in vivo track radionuclides with no imaging photons, including but not limited to ²²⁵Ac.