BORON NEUTRON CAPTURE THERAPY AND THE EXPRESSION OF LAT1, GLUT1, GALECTINS AND DNA REPAIR MACHINERY IN HAMSTER ORAL TUMORS

<b>Background and Aims</b>: Boron Neutron Capture Therapy (BNCT) is a tumor selective particle radiotherapy that combines preferential accumulation of ¹⁰B compounds and neutron irradiation. BPA (boronophenylalanine) has been used in clinical trials. LAT1 is responsible for its uptake in tumor cells and is upregulated in Head and Neck Cancer (HNC). Our group studied BPA biodistribution and BPA/BNCT in the hamster cheek pouch oral cancer model. In this model, exophytic tumors are surrounded by a precancerous tissue which develops additional tumors and where mucositis is induced after BNCT. We previously reported LAT1 expression in these tumors, in the precancerous and normal pouch tissue. The aim of the present study was to evaluate LAT1 and other molecules of interest in HNC like GLUT1 (a potential transporter for boron compounds and biomarker of aggressiveness), Galectins (GAL1 and GAL3, immunomodulators) and its DNA repair machinery. We also assess if BPA/BNCT affects the expression of these molecules in this oral cancer model.<br/><br/><b>Methods</b>: Tumor-bearing hamsters were divided in [no BPA, 3 animals], [BPA 300 mg/kg euthanized at 3h post injection, 3 animals], [SHAM irradiation: BPA 300 mg/kg euthanized at 1h/4h/24h/10 days post sham irradiation, 3 animals per time point], [BNCT: BPA 300 mg/kg euthanized at 1h/4h/24h/10 days post irradiation, 3 animals per time point]. Tumor bearing and contralateral normal pouches were excised for immunohistochemistry (IHC) and q-PCR for gene expression evaluation.<br/><br/><b>Results</b>: LAT1 IHC and q-PCR results showed that tumor cells are strongly LAT1 positive, with increased LAT1 expression with BPA treatment (p&lt;0.05). LAT1 was also IHC positive in the precancerous and normal pouch tissue. GLUT1 and GAL1 were also upregulated with BPA treatment. Sham and BNCT groups are under study.<br/><br/><b>Conclusions</b>: BPA could be modulating LAT1, GLUT1 and GAL1 in the hamster cheek pouch oral cancer model. LAT1 IHC in the basal epithelium of precancerous and normal tissue was also positive, explaining the accumulation of BPA and consequent mucositis after BNCT. This study provides additional evidence that the hamster oral cancer model is suitable for evaluating BNCT, tumor progression and immunobiomarkers, being useful for the design and development of new BNCT strategies.