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

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 17; no. 10; p. 1367
• Main Authors: Palmieri, Mónica A, Monti Hughes, Andrea, Trivillin, Verónica A, Garabalino, Marcela A, Ramos, Paula S, Thorp, Silvia I, Curotto, Paula, Pozzi, Emiliano C C, Nuez Martínez, Miquel, Teixidor, Francesc, Viñas, Clara, Schwint, Amanda E
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-10-2024; MDPI
• Subjects: Animals; Biodistribution; biodistribution studies; BNCT; Boron; boron carrier; Boron-neutron capture therapy; Cancer therapies; Chemotherapy; Diagnosis; Dosage and administration; Drug therapy; Head & neck cancer; Head and neck cancer; Medical research; metallacarborane; Mucositis; Na[o-COSAN]; Neutrons; Oral cancer; Quality of life; Remission (Medicine); Testing; Toxicity; Tumors; Argentina; BNCT; boron neutron capture therapy; biodistribution studies; head and neck cancer; hamster; metallacarborane; Na[o-COSAN]; boron carrier
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17101367

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(C
B
H
)
], 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-C
B
H
]
-carborane, along with the cesium and sodium salts of [
-
COSAN] cobaltabis(dicarbollide) are reported here for the first time.
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.
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.
Na[
-
COSAN] would be potentially useful to treat head and neck cancer with BNCT.