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Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

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Abstract

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 ± 6.6 for Sham, 7.8 ± 4.1 for Beam only, 4.4 ± 5.6 for BPA-BNCT I and 0.45 ± 0.20 for BPA-BNCT II; tumor nodule weight was 750 ± 480 mg for Sham, 960 ± 620 mg for Beam only, 380 ± 720 mg for BPA-BNCT I and 7.3 ± 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

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Acknowledgments

This study was supported in part by in-kind contributions from the US Department of Energy through Idaho National Laboratory, a grant from the National Agency for the Promotion of Science and Technology of Argentina (ANPCyT) and a grant from the National Research Council of Argentina (CONICET). The study sponsors were not involved in the study. The authors are indebted to the expert maintenance, radioprotection, and operation teams of RA-3.

Ethical standards

The experiments comply with the current laws of Argentina.

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Authors and Affiliations

  1. Department of Radiobiology, National Atomic Energy Commission, Avenida General Paz 1499, B1650KNA, San Martin, Province Buenos Aires, Argentina

    Verónica A. Trivillin, Andrea Monti Hughes, Marcela A. Garabalino, Ana J. Molinari, Elisa M. Heber, Maria E. Itoiz, Romina F. Aromando & Amanda E. Schwint

  2. Department of Research and Production Reactors, National Atomic Energy Commission, Presbítero Juan González y Aragon 15, B1802AYA, Ezeiza, Province Buenos Aires, Argentina

    Emiliano C. C. Pozzi & Paula Curotto

  3. National Research Council (CONICET), Buenos Aires, Argentina

    Verónica A. Trivillin, Lucas L. Colombo, Andrea Monti Hughes, Ana J. Molinari & Amanda E. Schwint

  4. Oncology Institute Angel H. Roffo, Ciudad Autónoma de Buenos Aires, Avenida San Martín 5481, Buenos Aires, Argentina

    Lucas L. Colombo & Jorge E. Cardoso

  5. CAECIHS, Universidad Abierta Interamericana (UAI), Buenos Aires, Argentina

    Lucas L. Colombo

  6. Department of Instrumentation and Control, National Atomic Energy Commission, Presbítero Juan González y Aragon 15, B1802AYA, Ezeiza, Province Buenos Aires, Argentina

    Silvia I. Thorp & Marcelo Miller

  7. Department Oral Pathology, Faculty of Dentistry, University of Buenos Aires, 1122 Ciudad Autónoma de Buenos Aires, Marcelo T. de Alvear 2142, Buenos Aires, Argentina

    Maria E. Itoiz & Romina F. Aromando

  8. Idaho National Laboratory, 2525 North Fremont Street, P.O. Box 1625, Idaho Falls, ID, 83415, USA

    David W. Nigg

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  1. Emiliano C. C. Pozzi
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  2. Verónica A. Trivillin
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  3. Lucas L. Colombo
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  4. Andrea Monti Hughes
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  7. Marcela A. Garabalino
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  9. Elisa M. Heber
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  10. Paula Curotto
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  11. Marcelo Miller
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  12. Maria E. Itoiz
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  14. David W. Nigg
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  15. Amanda E. Schwint
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Correspondence to Amanda E. Schwint.

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Pozzi, E.C.C., Trivillin, V.A., Colombo, L.L. et al. Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats. Radiat Environ Biophys 52, 481–491 (2013). https://doi.org/10.1007/s00411-013-0490-9

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