The development of a new 10B delivery system, with higher selectivity for the tumor with respect to clinically used sodium borocaptate (BSH) and boronophenylalanine (BPA), underlies future improvements in clinical outcomes of Boron Neutron Capture Therapy. A 10B concentration measuring technique for biological samples is needed in order to evaluate the performance of the new boronated formulations. At the Triga Mark II nuclear facility in Pavia, two techniques have been set-up: Alpha Spectrometry (AS) [1] and Quantitative Neutron Capture Radiography (QNCR) [2]. The latter has been recently improved, to ensure a higher accuracy and an optimized efficiency when a high number of samples is analyzed. In the first QNCR set-up, described by M.A Gadan et al. [2] a suitable calibration curve and a sufficient resolution were achieved; however, there were still margin for improvements. Firstly it was necessary to reduce the timing of the overall procedure, caused by an etching time longer than 2 hours. Secondly, in order to reduce the background, only the tracks due to 7Li and α ions had to be visualized. The second condition would simplify the data acquisition, avoiding the implementation of the morphological track selection algorithm that was previously necessary to reject the tracks due to protons; this possibility would lead to an improvement of the resolution of the concentration measurement. These goals were reached employing PEW (KOH + C2H5OH + H2O) as a chemically etching solution at 70 ºC. This set-up decreased the etching time from 2 hours to 10 minutes. Moreover only tracks from 7Li and α ions are detected, decreasing by consequence the relative error of the calibration from 7% at 1σ of C.L to 5% at 1σ of C.L. . This improved neutron autoradiography method was then applied to 10B concentration measurements in tissues from small animals and cell cultures treated with new carriers, in the frame of the BNCT feasibility study for osteosarcoma [3]. The experiments were conduced testing three categories of carriers: gold nano-particles, liposomes and polymeric nano-particles and BPA as a reference. In particular, 10B loaded liposomes and BPA were administered to Sprague-Dawley rats bearing osteosarcoma. After treatment, healthy bone and muscle and the tumor mass were explanted and prepared for QNCR and AS. The results concerning boron biodistribution obtained in these tissues will be presented and discussed. Boron biodistribution obtained in vivo will be used in the following part of the experiment, consisting in in vivo irradiation of rats with osteosarcoma to test BNCT efficacy in tumor remission and BNCT toxicity for healthy tissues. [1] Silva Bortolussi. Boron Neutron Capture Therapy of Dissiminated Tumors. PhD thesis, Universitá degli studi di pavia Dottorato di ricerca in fisica, 2008. [2] M.A Gadan, S Bortolussi, I Postuma, F Ballarini, P Bruschi, N Protti, D Santoro, S Stella, L Cansolino, A Clerici, C Ferrari, A Zonta, C Zonta, and S Altieri. Set-up and calibration of a method to measure 10b concentration in biological samples by neutron autoradiography. Nuclear Instruments and Methods, pages 51–56, 2012. [3] Silva Bortolussi, Laura Ciani, Ian Postuma, Nicoletta Protti, Piero Bruschi, Cinzia Ferrari, Laura Cansolino, Luigi Panza, Sandra Ristori,Saverio Altieri. Boron concentration measurement by alpha spectrometry and quantitative neutron autoradiography in cell and tissue samples treated with different boronated formulations and administration protocols. Proceedings of 15th International Congress on Neutron Capture Therapy, 2012.

An improved neutron autoradiography set-up, applied to 10B concentration measurements for biological samples

POSTUMA, IAN;BORTOLUSSI, SILVA;PROTTI, NICOLETTA;BALLARINI, FRANCESCA;BRUSCHI, PIERO;PANZA, FABIO;FERRARI, CINZIA;CANSOLINO, LAURA;ALTIERI, SAVERIO
2013

Abstract

The development of a new 10B delivery system, with higher selectivity for the tumor with respect to clinically used sodium borocaptate (BSH) and boronophenylalanine (BPA), underlies future improvements in clinical outcomes of Boron Neutron Capture Therapy. A 10B concentration measuring technique for biological samples is needed in order to evaluate the performance of the new boronated formulations. At the Triga Mark II nuclear facility in Pavia, two techniques have been set-up: Alpha Spectrometry (AS) [1] and Quantitative Neutron Capture Radiography (QNCR) [2]. The latter has been recently improved, to ensure a higher accuracy and an optimized efficiency when a high number of samples is analyzed. In the first QNCR set-up, described by M.A Gadan et al. [2] a suitable calibration curve and a sufficient resolution were achieved; however, there were still margin for improvements. Firstly it was necessary to reduce the timing of the overall procedure, caused by an etching time longer than 2 hours. Secondly, in order to reduce the background, only the tracks due to 7Li and α ions had to be visualized. The second condition would simplify the data acquisition, avoiding the implementation of the morphological track selection algorithm that was previously necessary to reject the tracks due to protons; this possibility would lead to an improvement of the resolution of the concentration measurement. These goals were reached employing PEW (KOH + C2H5OH + H2O) as a chemically etching solution at 70 ºC. This set-up decreased the etching time from 2 hours to 10 minutes. Moreover only tracks from 7Li and α ions are detected, decreasing by consequence the relative error of the calibration from 7% at 1σ of C.L to 5% at 1σ of C.L. . This improved neutron autoradiography method was then applied to 10B concentration measurements in tissues from small animals and cell cultures treated with new carriers, in the frame of the BNCT feasibility study for osteosarcoma [3]. The experiments were conduced testing three categories of carriers: gold nano-particles, liposomes and polymeric nano-particles and BPA as a reference. In particular, 10B loaded liposomes and BPA were administered to Sprague-Dawley rats bearing osteosarcoma. After treatment, healthy bone and muscle and the tumor mass were explanted and prepared for QNCR and AS. The results concerning boron biodistribution obtained in these tissues will be presented and discussed. Boron biodistribution obtained in vivo will be used in the following part of the experiment, consisting in in vivo irradiation of rats with osteosarcoma to test BNCT efficacy in tumor remission and BNCT toxicity for healthy tissues. [1] Silva Bortolussi. Boron Neutron Capture Therapy of Dissiminated Tumors. PhD thesis, Universitá degli studi di pavia Dottorato di ricerca in fisica, 2008. [2] M.A Gadan, S Bortolussi, I Postuma, F Ballarini, P Bruschi, N Protti, D Santoro, S Stella, L Cansolino, A Clerici, C Ferrari, A Zonta, C Zonta, and S Altieri. Set-up and calibration of a method to measure 10b concentration in biological samples by neutron autoradiography. Nuclear Instruments and Methods, pages 51–56, 2012. [3] Silva Bortolussi, Laura Ciani, Ian Postuma, Nicoletta Protti, Piero Bruschi, Cinzia Ferrari, Laura Cansolino, Luigi Panza, Sandra Ristori,Saverio Altieri. Boron concentration measurement by alpha spectrometry and quantitative neutron autoradiography in cell and tissue samples treated with different boronated formulations and administration protocols. Proceedings of 15th International Congress on Neutron Capture Therapy, 2012.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11571/721426
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