Yttrium-90-doped metal-organic frameworks (MOFs) for low-dose rate intratumoral radiotherapy

Qi, X.; Fedotova, A.; Yu, Z.; Polyanskaya, A.; Shen, N.; Egorova, B.; Bagrov, D.; Slastnikova, T.; Rosenkranz, A.; Patriarche, G.; Nevolin, Y.; Permyakova, A.; Fedotov, S.; Lepoitevin, M.; Kalmykov, S.; Serre, C.; Durymanov, M.

doi:10.1101/2024.09.14.613012

bioRxiv · 10.1101/2024.09.14.613012

Yttrium-90-doped metal-organic frameworks (MOFs) for low-dose rate intratumoral radiotherapy

Qi, X.·Fedotova, A.·Yu, Z.·Polyanskaya, A.·Shen, N.·Egorova, B.·Bagrov, D.·Slastnikova, T.·Rosenkranz, A.·Patriarche, G.·Nevolin, Y.·Permyakova, A.·Fedotov, S.·Lepoitevin, M.·Kalmykov, S.·Serre, C.·Durymanov, M.

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Abstract

Brachytherapy, or intratumoral radiation therapy, is a highly effective treatment option for localized tumors. Herein, we engineered injectable and biodegradable metal-organic frameworks (MOFs) to deliver the therapeutic radioisotope yttrium-90 (90Y). Particles of bimetallic MIL-100(Fe,Y) and Y-BTC, doped with 90Y and 88Y, were synthesized in a single step and retained radioyttrium in various buffer solutions. Tumor injectability and radioisotope retention were evaluated using tumor-bearing mice. In vivo analysis and calculations showed that radiolabeled MIL-100(Fe,Y) emitted more than 38% of its radioactivity, while Y-BTC emitted greater than 75% of its radioactivity, through 7 days at the tumor site upon intratumoral injection, without significant yttrium accumulation in off-target tissues. The anticancer effects of MIL-100(Fe,Y,90Y) and 90Y,Y-BTC particles were assessed using 3D multicellular tumor spheroids and a tumor-bearing mouse model, respectively. 90Y-doped MIL-100(Fe,Y) particles penetrated A549 tumor spheroids and caused superior cytotoxic effects compared to non-radioactive particles or 90YCl3, added at the same dose. Brachytherapy with 90Y-doped Y-BTC MOFs induced inhibition of B16F1 melanoma tumor growth and resulted in an increased median survival of 8.5 days compared to 4.5 days in untreated mice. This study exhibits the feasibility to prepare radioactive 90Y-containing biodegradable, non-toxic MOF particles that are advantageous for low-dose rate internal radiotherapy.

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Qi, X., Fedotova, A., Yu, Z., Polyanskaya, A., Shen, N., Egorova, B., Bagrov, D., Slastnikova, T., Rosenkranz, A., Patriarche, G., Nevolin, Y., Permyakova, A., Fedotov, S., Lepoitevin, M., Kalmykov, S., Serre, C., Durymanov, M.. 2024-09-20. Yttrium-90-doped metal-organic frameworks (MOFs) for low-dose rate intratumoral radiotherapy. https://doi.org/10.1101/2024.09.14.613012

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