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

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2024 Oct 26

PMID 39459007

Authors

Monica A Palmieri

Andrea Monti Hughes

Veronica A Trivillin

Marcela A Garabalino

Paula S Ramos

Silvia I Thorp

Paula Curotto

Emiliano C C Pozzi

Miquel Nuez Martinez

Francesc Teixidor

Clara Vinas

Amanda E Schwint

Affiliations

Soon will be listed here.

Abstract

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(CBH)], abbreviated as Na[-COSAN]) in the hamster cheek pouch oral cancer model and the Na[-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of B-enriched trimethylammonium salt of -[7,8-CBH]-carborane, along with the cesium and sodium salts of [-COSAN] cobaltabis(dicarbollide) are reported here for the first time.

Methods: Hamsters bearing tumors were injected with Na[-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[B--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[-COSAN] exhibited no toxicity. Although biodistribution studies employing Na[-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[-COSAN]/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[-COSAN] would be potentially useful to treat head and neck cancer with BNCT.

Citing Articles

Current Insights into the Radiobiology of Boron Neutron Capture Therapy and the Potential for Further Improving Biological Effectiveness.

Punshon L, Fabbrizi M, Phoenix B, Green S, Parsons J Cells. 2025; 13(24.

PMID: 39768156 PMC: 11674336. DOI: 10.3390/cells13242065.

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