Therapeutic Efficacy, Radiotoxicity and Abscopal Effect of BNCT at the RA-3 Nuclear Reactor Employing Oligo-Fucoidan and Glutamine as Adjuvants in an Ectopic Colon Cancer Model in Rats

DEBORA N. FRYDRYK BENITEZ; MÓNICA A. PALMIERI; YANINA V. LANGLE; ANDREA MONTI HUGHES; EMILIANO C. C. POZZI; SILVIA I. THORP,; MARCELA A. GARABALINO, ANDREA MONTI HUGHES,1,2 PAULA CUROTTO,1, IARA S. SANTA CRUZ,1 PAULA RAMOS,1 M.E. ITOIZ; PAULA S. RAMOS,; MARÍA L. PAPARELLA; LUCAS POLTI; ANA EIJÁN; AMANDA E. SCHWINT; VERÓNICA A. TRIVILLIN,

LIFE

MDPI

Lugar: Basel; Año: 2023 vol. 13

2075-1729

Abstract: Boron neutron capture therapy (BNCT) is based on the preferential uptake of 10B compounds by tumors, followed by neutron irradiation. The aim of this study was to assess, in an ectopiccolon cancer model, the therapeutic efficacy, radiotoxicity, abscopal effect and systemic immuneresponse associated with (BPA/Borophenylalanine+GB-10/Decahydrodecaborate)-BNCT (CombBNCT) alone or in combination with Oligo-Fucoidan (O-Fuco) or Glutamine (GLN), compared tothe “standard” BPA-BNCT protocol usually employed in clinical trials. All treatments were carriedout at the RA-3 nuclear reactor. Boron biodistribution studies showed therapeutic values above20 ppm 10B in tumors. At 7 weeks post-treatment, the ratio of tumor volume post-/pre-BNCTwas significantly smaller for all BNCT groups vs. SHAM (p < 0.05). The parameter “incidence oftumors that underwent a reduction to ≤50% of initial tumor volume” exhibited values of 62% forComb-BNCT alone, 82% for Comb-BNCT+GLN, 73% for Comb-BNCT+O-Fuco and only 30% forBPA-BNCT. For BPA-BNCT, the incidence of severe dermatitis was 100%, whereas it was significantlybelow 70% (p ≤ 0.05) for Comb-BNCT, Comb-BNCT+O-Fuco and Comb-BNCT+GLN. Consideringtumors outside the treatment area, 77% of Comb-BNCT animals had a tumor volume lower than50 mm3 vs. 30% for SHAM (p ≤ 0.005), suggesting an abscopal effect of Comb-BNCT. Inhibition ofmetastatic spread to lymph nodes was observed in all Comb-BNCT groups. Considering systemicaspects, CD8+ was elevated for Comb-BNCT+GLN vs. SHAM (p ≤ 0.01), and NK was elevatedfor Comb-BNCT vs. SHAM (p ≤ 0.05). Comb-BNCT improved therapeutic efficacy and reducedradiotoxicity compared to BPA-BNCT and induced an immune response and an abscopal effect.Keywords: BNCT; RA-3 nuclear reactor; Glutamine; Oligo-Fucoidan; radiotoxicity; abscopal effect;BPA and GB-10; biodistribution; lymph nodes; systemic immune response