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

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.