Abstract
AB010. Therapeutic efficacy and radiotoxicity of boron neutron capture therapy employing oligo-fucoidan and glutamine as adjuvants in an experimental model
Debora N. Frydryk Benitez1, Mónica A. Palmieri2, Yanina Langle3, Emiliano C. C. Pozzi1, Silvia I. Thorp1, Marcela A. Garabalino1, Andrea Monti Hughes1,4, Paula Curotto1, Paula S. Ramos1, María L. Paparella5, Lucas Polti5, Ana Eiján3,4, Amanda E. Schwint1,4, Verónica A. Trivillin1,4
1Comisión Nacional de Energía Atómica (CNEA), Buenos Aires, Argentina;
2Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina;
3Instituto de Oncología Ángel H. Roffo, Área Investigación, Universidad de Buenos Aires, Buenos Aires, Argentina;
4Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina;
5Facultad Odontología, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
Correspondence to: Verónica A. Trivillin, B.Sc. Comisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, B1650 Villa Maipú, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Email: verotrivillin@gmail.com; trivillin@cnea.gov.ar.
Background: Boron neutron capture therapy (BNCT) combines selective tumor uptake of 10B compounds and neutron irradiation. The aim of this study was to evaluate the therapeutic efficacy and radiotoxicity of [boronophenylalanine (BPA) + decahydrodecaborate (GB-10)]-BNCT (Comb-BNCT) alone or combined with oligo-fucoidan or glutamine, compared to the standard BPA-BNCT protocol. Also, the systemic immune response expressed in the spleen was evaluated for the Comb-BNCT group alone or combined with oligo-fucoidan or glutamine.
Methods: BDIX rats were injected subcutaneously in the right hind flank with DHD/K12/TRb syngeneic colon cancer cells. Three weeks later, the tumor-bearing legs were treated locally with BNCT at the RA-3 nuclear reactor. The thermal neutron fluence at the irradiation position was 4.2×1012 n/cm2 for all protocols. (I) Comb-BNCT: BPA 31 mg 10B/kg body weight (bw) + GB-10 34 mg 10B/kg bw, intravenous (i.v.). (II) Comb-BNCT + oligo-fucoidan: same as (I) + oligo-fucoidan (200 mg/mL) once a week for 7 weeks, joint oral and topical administration. (III) Comb-BNCT + glutamine: same as (I) + glutamine (40 mg/mL) once a week for 7 weeks, with wet compresses. (IV) BPA-BNCT: 46.5 mg 10B /kg bw. (V) Sham: same manipulation, no treatment.
Results: Boron biodistribution studies showed therapeutic values above 20 ppm 10B. Although they were similar for tumor, surrounding skin, and blood, the effect on tumor was selective. The post-/pre-BNCT ratio of tumor volume at 7 weeks post-treatment was significantly lower for all the BNCT groups vs. Sham (P<0.05). Using the end-point “incidence of tumors that underwent a reduction to ≤50% of initial tumor volume” to further assess therapeutic response, results were 62% for Comb-BNCT alone, 80% for Comb-BNCT + glutamine, 73% for Comb-BNCT + oligo-fucoidan, and 30% for BPA-BNCT. The incidence of severe dermatitis at 2 weeks (when the peak occurs) was 100% for BPA-BNCT, while for Comb-BNCT, Comb-BNCT + oligo-fucoidan, and Comb-BNCT + glutamine, it was below 70% (P≤0.05). At the systemic level, an increase in CD8+ cells for Comb-BNCT + glutamine vs. Sham (P≤0.01), and an increase in natural killer (NK) cells for Comb-BNCT vs. Sham (P≤0.05) were observed.
Conclusions: Comb-BNCT improves therapeutic efficacy and reduces radiotoxicity compared to standard BNCT (BPA-BNCT). Comb-BNCT activated a systemic immune response. Oligo-Fucoidan and Glutamine contributed to therapeutic benefit.
Keywords: Boron neutron capture therapy (BNCT); oligo-fucoidan; glutamine; radiotoxicity; systemic immune response
Acknowledgments
The drugs and supplies were provided by Hi-Q Marine Biotech, Taiwan to D.N.F.B., M.A.P., E.C.C.P., M.A.G., A.M.H., P.S.R., A.E.S., and V.A.T.
Funding: Funding: This research was supported by grants from Fundación Balseiro to V.A.T., and from Agencia de Promoción Científica y Tecnológica, Argentina to D.N.F.B., M.A.P., E.C.C.P., M.A.G., A.M.H., P.S.R., A.M.E., A.E.S., and V.A.T., with salary and partial funding provided by the National Atomic Energy Commission (CNEA), Argentina to D.N.F.B., M.A.P., E.C.C.P., S.I.T., M.A.G., A.M.H., P.C., P.S.R., A.E.S., and V.A.T. A complementary salary was funded by the National Scientific and Technical Research Council (CONICET) to A.E.S. and V.A.T. Additional support was provided by grants from Universidad de Buenos Aires to Y.L. with salary and partial funding from Universidad de Buenos Aires – Instituto Roffo for Y.L. and salary support for M.L.P. and L.P. from University of Buenos Aires, School of Dentistry, Oral Pathology Department, Surgical Pathology Laboratory and for M.A.P. University of Buenos Aires, Faculty of Exact and Natural Sciences, Argentina. Partial funding for A.M.H. was funded from Instituto de Oncología Ángel H. Roffo-Facultad de Medicina-Universidad de Buenos Aires.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-ab010/coif). Equipment, drugs, or supplies and travel were provided by Hi-Q Marine Biotech and Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación. The salary and partial funding provided by the National Atomic Energy Commission (CNEA), Argentina and grants from Agencia de Promoción Científica y Tecnológica, Argentina. Y.L. reports that she received salary and partial funding from Universidad de Buenos Aires – Instituto Roffo and grants and support from Universidad de Buenos Aires. M.L.P. and L.P. received a salary from University of Buenos Aires, School of Dentistry, Oral Pathology Department, Surgical Pathology Laboratory and M.A.P. received a salary from University of Buenos Aires, Faculty ofExact and Natural Sciences, Argentina. Partial funding for A.M.H. was funded from Instituto de Oncología Ángel H. Roffo-Facultad de Medicina-Universidad de Buenos Aires. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The animal study protocol was approved by the Institutional Review Board National Atomic Energy Commission Animal Care and Use Committee (CICUAL-CNEA, No. 04/year 2021).
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/tro-25-ab010
Cite this abstract as: Frydryk Benitez DN, Palmieri MA, Langle Y, Pozzi ECC, Thorp SI, Garabalino MA, Monti Hughes A, Curotto P, Ramos PS, Paparella ML, Polti L, Eiján A, Schwint AE, Trivillin VA. AB010. Therapeutic efficacy and radiotoxicity of boron neutron capture therapy employing oligo-fucoidan and glutamine as adjuvants in an experimental model. Ther Radiol Oncol 2025;9:AB010.
