Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new “B2” configuration of the RA-6 nuclear reactor
Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new “B2” configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in “B1” experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94–96%) than in control (16%) and BO groups (9–38%), and did not differ significantly from the “B1” results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.
KeywordsBoron neutron capture therapy (BNCT) RA-6 configuration Hamster cheek pouch oral cancer model Histamine Mucositis Precancerous tissue
This work was partially supported by the U.S. Department of Energy through Idaho National Laboratory and grants from the National Agency for the Promotion of Science and Technology of Argentina and the National Institute of Cancer, Argentina. The authors acknowledge the expert advice of Dr. Sara J. González (CNEA, CONICET).
Compliance with ethical standards
Partially supported by the U.S. Department of Energy through Idaho National Laboratory (no. 00011369) and grants from the National Agency for the Promotion of Science and Technology of Argentina (no. 2010-0175) and the National Institute of Cancer (no. 1006/2016), Argentina.
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the National Atomic Energy Commission (CNEA).
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