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
Boron neutron capture therapy (BNCT) is based on the preferential uptake of <sup>10</sup>B 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 im...
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MDPI AG
2023-07-01
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| author | Debora N. Frydryk Benitez Mónica A. Palmieri Yanina V. Langle Andrea Monti Hughes Emiliano C. C. Pozzi Silvia I. Thorp Marcela A. Garabalino Paula Curotto Paula S. Ramos María L. Paparella Lucas Polti Ana Eiján Amanda E. Schwint Verónica A. Trivillin |
| author_facet | Debora N. Frydryk Benitez Mónica A. Palmieri Yanina V. Langle Andrea Monti Hughes Emiliano C. C. Pozzi Silvia I. Thorp Marcela A. Garabalino Paula Curotto Paula S. Ramos María L. Paparella Lucas Polti Ana Eiján Amanda E. Schwint Verónica A. Trivillin |
| author_sort | Debora N. Frydryk Benitez |
| collection | DOAJ |
| description | Boron neutron capture therapy (BNCT) is based on the preferential uptake of <sup>10</sup>B 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 <sup>10</sup>B in tumors. At 7 weeks post-treatment, the ratio of tumor volume post-/pre-BNCT was significantly smaller for all BNCT groups vs. SHAM (<i>p</i> < 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% (<i>p</i> ≤ 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 mm<sup>3</sup> vs. 30% for SHAM (<i>p</i> ≤ 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<sup>+</sup> was elevated for Comb-BNCT+GLN vs. SHAM (<i>p</i> ≤ 0.01), and NK was elevated for Comb-BNCT vs. SHAM (<i>p</i> ≤ 0.05). Comb-BNCT improved therapeutic efficacy and reduced radiotoxicity compared to BPA-BNCT and induced an immune response and an abscopal effect. |
| first_indexed | 2024-03-11T00:54:00Z |
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| spelling | doaj.art-8fbb51dc3f5748a1846e00e32e7030d82023-11-18T20:09:54ZengMDPI AGLife2075-17292023-07-01137153810.3390/life13071538Therapeutic 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 RatsDebora N. Frydryk Benitez0Mónica A. Palmieri1Yanina V. Langle2Andrea Monti Hughes3Emiliano C. C. Pozzi4Silvia I. Thorp5Marcela A. Garabalino6Paula Curotto7Paula S. Ramos8María L. Paparella9Lucas Polti10Ana Eiján11Amanda E. Schwint12Verónica A. Trivillin13Comisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaDepartamento 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, ArgentinaFacultad 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, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaFacultad Odontología, Universidad de Buenos Aires (UBA), M.T. de Alvear 2142, Ciudad Autónoma de Buenos Aires C1122AAH, ArgentinaFacultad Odontología, Universidad de Buenos Aires (UBA), M.T. de Alvear 2142, Ciudad Autónoma de Buenos Aires C1122AAH, ArgentinaFacultad 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, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaComisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, ArgentinaBoron neutron capture therapy (BNCT) is based on the preferential uptake of <sup>10</sup>B 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 <sup>10</sup>B in tumors. At 7 weeks post-treatment, the ratio of tumor volume post-/pre-BNCT was significantly smaller for all BNCT groups vs. SHAM (<i>p</i> < 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% (<i>p</i> ≤ 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 mm<sup>3</sup> vs. 30% for SHAM (<i>p</i> ≤ 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<sup>+</sup> was elevated for Comb-BNCT+GLN vs. SHAM (<i>p</i> ≤ 0.01), and NK was elevated for Comb-BNCT vs. SHAM (<i>p</i> ≤ 0.05). Comb-BNCT improved therapeutic efficacy and reduced radiotoxicity compared to BPA-BNCT and induced an immune response and an abscopal effect.https://www.mdpi.com/2075-1729/13/7/1538BNCTRA-3 nuclear reactorGlutamineOligo-Fucoidanradiotoxicityabscopal effect |
| spellingShingle | Debora N. Frydryk Benitez Mónica A. Palmieri Yanina V. Langle Andrea Monti Hughes Emiliano C. C. Pozzi Silvia I. Thorp Marcela A. Garabalino Paula Curotto Paula S. Ramos María L. Paparella Lucas Polti Ana Eiján Amanda E. Schwint Verónica A. Trivillin 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 Life BNCT RA-3 nuclear reactor Glutamine Oligo-Fucoidan radiotoxicity abscopal effect |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | BNCT RA-3 nuclear reactor Glutamine Oligo-Fucoidan radiotoxicity abscopal effect |
| url | https://www.mdpi.com/2075-1729/13/7/1538 |
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