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
Author:
Frydryk Benitez Debora N.1, Palmieri Mónica A.2, Langle Yanina V.3, Monti Hughes Andrea14ORCID, Pozzi Emiliano C. C.1, Thorp Silvia I.1, Garabalino Marcela A.1ORCID, Curotto Paula1, Ramos Paula S.1, Paparella María L.5, Polti Lucas5, Eiján Ana34ORCID, Schwint Amanda E.14ORCID, Trivillin Verónica A.14
Affiliation:
1. Comisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, Argentina 2. Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Av. Int. Güiraldes 2160, 4 Piso, Pab. II, Ciudad Autónoma de Buenos Aires C1428EGA, Argentina 3. Facultad de Medicina, Instituto de Oncología Ángel H. Roffo (IOAHR), Universidad de Buenos Aires, Av. S. Martín 5481, Área de Investigación, Ciudad Autónoma de Buenos Aires C1417DTB, Argentina 4. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina 5. Facultad Odontología, Universidad de Buenos Aires (UBA), M.T. de Alvear 2142, Ciudad Autónoma de Buenos Aires C1122AAH, Argentina
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 ectopic colon cancer model, the therapeutic efficacy, radiotoxicity, abscopal effect and systemic immune response associated with (BPA/Borophenylalanine+GB-10/Decahydrodecaborate)-BNCT (Comb-BNCT) alone or in combination with Oligo-Fucoidan (O-Fuco) or Glutamine (GLN), compared to the “standard” BPA-BNCT protocol usually employed in clinical trials. All treatments were carried out at the RA-3 nuclear reactor. Boron biodistribution studies showed therapeutic values above 20 ppm 10B in tumors. At 7 weeks post-treatment, the ratio of tumor volume post-/pre-BNCT was significantly smaller for all BNCT groups vs. SHAM (p < 0.05). The parameter “incidence of tumors that underwent a reduction to ≤50% of initial tumor volume” exhibited values of 62% for Comb-BNCT alone, 82% for Comb-BNCT+GLN, 73% for Comb-BNCT+O-Fuco and only 30% for BPA-BNCT. For BPA-BNCT, the incidence of severe dermatitis was 100%, whereas it was significantly below 70% (p ≤ 0.05) for Comb-BNCT, Comb-BNCT+O-Fuco and Comb-BNCT+GLN. Considering tumors outside the treatment area, 77% of Comb-BNCT animals had a tumor volume lower than 50 mm3 vs. 30% for SHAM (p ≤ 0.005), suggesting an abscopal effect of Comb-BNCT. Inhibition of metastatic spread to lymph nodes was observed in all Comb-BNCT groups. Considering systemic aspects, CD8+ was elevated for Comb-BNCT+GLN vs. SHAM (p ≤ 0.01), and NK was elevated for Comb-BNCT vs. SHAM (p ≤ 0.05). Comb-BNCT improved therapeutic efficacy and reduced radiotoxicity compared to BPA-BNCT and induced an immune response and an abscopal effect.
Funder
National Atomic Energy Commission (CNEA), Argentina HI-Q MARINE BIOTECH INTERNATIONAL LTD, Taiwan Balseiro Foundation/CNEA, Argentina
Subject
Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics
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