2013 Article In-vivo Studies Radiobiology Year 2013

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

Radiation and Environmental Biophysics, 2013

Authors:   Emiliano Pozzi,Verónica Trivillin,Lucas Colombo,Andrea Hughes,Silvia Thorp,Jorge Cardoso,Marcela Garabalino,Ana Molinari,Elisa Heber,Paula Curotto,Marcelo Miller,Maria Itoiz,Romina Aromando,David Nigg,Amanda Schwint,
Journal: Radiation and Environmental Biophysics
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. © 2013 Springer-Verlag Berlin Heidelberg.