Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 145, Issue 27, Pages 14679-14685Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.3c02325
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By using a nanoscale luminescent europium-organic framework (EuMOF), Ac-225 can be efficiently labeled in its crystal structure with sufficient retention stability. The close proximity between Ac-225 and Eu3+ allows for efficient energy transduction, generating enough photons for clear imaging. This study demonstrates the feasibility of directly monitoring Ac-225 in vivo using optical imaging, and EuMOF also shows notable effectiveness in tumor treatment.
Ac-225 is considered as one of the most promisingradioisotopesfor alpha-therapy because its emitted high-energy & alpha;-particlescan efficiently damage tumor cells. However, it also represents asignificant threat to healthy tissues owing to extremely high radiotoxicityif targeted therapy fails. This calls for a pressing requirement ofmonitoring the biodistribution of Ac-225 in vivo during the treatment of tumors. However, the lack of imageable photonsor positrons from therapeutic doses of Ac-225 makes thistask currently quite challenging. We report here a nanoscale luminescenteuropium-organic framework (EuMOF) that allows for fast, simple, andefficient labeling of Ac-225 in its crystal structure withsufficient Ac-225-retention stability based on similar coordinationbehaviors between Ac3+ and Eu3+. After labeling,the short distance between Ac-225 and Eu3+ inthe structure leads to exceedingly efficient energy transduction from(225)Ac-emitted & alpha;-particles to surrounding Eu3+ ions, which emits red luminescence through a scintillation processand produces sufficient photons for clearcut imaging. The in vivo intensity distribution of radioluminescence signaloriginating from the Ac-225-labeled EuMOF is consistentwith the dose of Ac-225 dispersed among the various organsdetermined by the radioanalytical measurement ex vivo, certifying the feasibility of in vivo directlymonitoring Ac-225 using optical imaging for the first time.In addition, Ac-225-labeled EuMOF displays notable efficiencyin treating the tumor. These results provide a general design principlefor fabricating Ac-225-labeled radiopharmaceuticals withimaging photons and propose a simple way to in vivo track radionuclides with no imaging photons, including but not limitedto Ac-225.
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