Cobaltabis(Dicarbollide) [<i>o</i>-COSAN]⁻ for Boron Neutron Capture Therapy of Head and Neck Cancer: Biodistribution and Irradiation Studies in an Experimental Oral Cancer Model

• Auteurs principaux: Mónica A. Palmieri (Auteur), Andrea Monti Hughes (Auteur), Verónica A. Trivillin (Auteur), Marcela A. Garabalino (Auteur), Paula S. Ramos (Auteur), Silvia I. Thorp (Auteur), Paula Curotto (Auteur), Emiliano C. C. Pozzi (Auteur), Miquel Nuez Martínez (Auteur), Francesc Teixidor (Auteur), Clara Viñas (Auteur), Amanda E. Schwint (Auteur)
• Format: Livre
• Publié: MDPI AG, 2024-10-01T00:00:00Z.
• Sujets: article
• Accès en ligne: Connect to this object online.

Résumé

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3'-Co(C₂B₉H₁₁)₂], abbreviated as Na[<i>o</i>-COSAN]) in the hamster cheek pouch oral cancer model and the Na[<i>o</i>-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of ¹⁰B-enriched trimethylammonium salt of <i>nido</i>-[7,8-C₂¹⁰B₉H₁₂]⁻<i>o</i>-carborane, along with the cesium and sodium salts of [<i>o</i>-¹⁰COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[<i>o</i>-COSAN] (7.5 mg B/kg) and euthanized at different time-points after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[¹⁰B-<i>o</i>-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[<i>o</i>-¹⁰COSAN] exhibited no toxicity. Although biodistribution studies employing Na[<i>o</i>-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[<i>o</i>-¹⁰COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[<i>o</i>-¹⁰COSAN] would be potentially useful to treat head and neck cancer with BNCT.

Description

10.3390/ph17101367
1424-8247