Abstract
Measurement of boron concentration in biological tissues is a fundamental aspect of boron neutron capture therapy, because the outcome of the therapy depends on the distribution of boron at a cellular level, besides on its overall concentration. This work describes a measurement technique based on the spectroscopy of the charged particles emitted in the reaction 10B(n,α)7Li induced by thermal neutrons, allowing for a quantitative determination of the boron concentration in the different components that may be simultaneously present in a tissue sample, such as healthy cells, tumor cells and necrotic cells. Thin sections of tissue containing 10B are cut at low temperatures and irradiated under vacuum in a thermal neutron field. The charged particles arising from the sample during the irradiation are collected by a thin silicon detector, and their spectrum is used to determine boron concentration through relatively easy calculations. The advantages and disadvantages of this technique are here described, and validation of the method using tissue standards with known boron concentrations is presented.
Similar content being viewed by others
References
Agosteo S, Birattari C, D’Angelo G, Dal Corso F, Foglio Para A, Lippi I, Pola A, Zotto P (2003) Neutron spectrometry with a recoil radiator-silicon detector device. Nucl Instrum Methods A 515:589–604
Altieri S, Bortolussi S, Bruschi P, Fossati F, Vittor K, Nano R, Facoetti A, Chiari P, Bakeine J, Clerici A, Ferrari C, Salvucci O (2006) Boron absorption imaging in rat lung colon adenocarcinoma metastases. J Phys Conf Ser 41:484–495
Altieri S, Bortolussi S, Bruschi P, Chiari P, Fossati F, Stella S, Prati U, Roveda L, Zonta A, Zonta C, Ferrari C, Clerici A, Nano R, Pinelli T (2008) Neutron autoradiography imaging of selective boron uptake in human metastatic tumours. Appl Radiat Isot 66(12):1850–1855
Barth RF, Coderre JA, Graça H, Vicente M, Blue TE (2005) Boron Neutron Capture Therapy of cancer: current status and future prospects. Clin Cancer Res 11:3987–4002
Bortolussi S, Bakeine JG, Ballarini F, Bruschi P, Gadan MA, Protti N, Stella S, Clerici A, Ferrari C, Cansolino L, Zonta C, Zonta A, Nano R, Altieri S (2011) Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours. Appl Radiat Isot 69:394–398
Chandra S (2003) SIMS ion microscopy as a novel, practical tool for subcellular chemical imaging in cancer research. Appl Surf Sci 203–204:679–683
Chiaraviglio D, De Grazia F, Zonta A, Altieri S, Braghieri A, Fossati F, Pedroni P, Pinelli T, Perotti Specchairello A, Perlini G, Rief H (1989) Evaluation of selective boron absorption in liver tumours. Strahlenther Onkol 165(2/3):170–172
Coderre JA, Chanana AD, Joel DD, Elowitz EH, Micca PL, Nawrocky MM, Chadha M, Gebbers JO, Shady M, Peress NS, Slatkin DN (1998) Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity. Radiat Res 149:163–170
Ferrari C, Zonta C, Cansolino L, Clerici AM, Gaspari A, Altieri S, Bortolussi S, Stella S, Bruschi P, Dionigi P, Zonta A (2009) Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron capture therapy. Appl Radiat Isot 67:341–344
Fukuda H, Honda C, Wadabayashi N, Kobayashi T, Yoshino K, Hiratsuka J, Takahashi J, Akaizawa T, Abe Y, Ichihashi M, Mishima Y (1999) Pharmacokinetics of 10B-p-boronophenylalanine in tumors, skin and blood of melanoma patients: a study of boron neutron capture therapy for malignant melanoma. Melanoma Res 9:75–83
Gadan MA, Bortolussi S, Postuma I, Ballarini F, Bruschi P, Protti N, Santoro D, Stella S, Cansolino L, Clerici A, Ferrari C, Zonta A, Zonta C, Altieri S (2012) Set-up and calibration of a method to measure 10B concentration in biological samples by neutron autoradiography. Nucl Instrum Methods B 274:51–56
Imahori Y, Ueda S, Ohmori Y, Sakae K, Kusuki T, Kobayashi T, Takagaki M, Ono K, Ido T, Fujii R (1998) Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part I. Clin Cancer Res 4:1825–1832
Menéndez P, Roth BM, Pereira MD, Casal MR, González SJ, Feld DB, Santa Cruz GA, Kessler J, Longhino J, Blaumann H, Jiménez Rebagliati R, Calzetta Larrieu OA, Fernández C, Nievas SI, Liberman SJ (2009) BNCT for skin melanoma in extremities: updated Argentine clinical results. Appl Radiat Isot 67(7–8):50–53
Probst TU (1999) Methods for boron analysis in boron neutron capture therapy (BNCT). Rev Fresenius J Anal Chem 364:391–403
Protti N, Bortolussi S, Stella S, Gadan MA, De Bari A, Ballarini F, Bruschi P, Ferrari C, Clerici AM, Zonta C, Bakeine JG, Dionigi P, Zonta A, Altieri S (2009) Calculations of dose distributions in the lungs of a rat model irradiated in the thermal column of the TRIGA reactor in Pavia. Appl Radiat Isot 67:210–213
Protti N, Bortolussi S, Prata M, Bruschi P, Altieri S, Nigg D (2012) Neutron spectrometry for the University of Pavia TRIGA™ thermal neutron source facility. Trans Am Nucl Soc 107:1269–1272
Riley KJ, Harling O (1998) An improved prompt gamma neutron activation analysis facility using a focused diffracted neutron beam. Nucl Instrum Methods B 143(3):414–421
Stella S, Bortolussi S, Bruschi P, Portella C, Altieri S (2009) Measurement of a particle energy loss in biological tissue below 2 MeV. Nucl Instrum Methods B 267:2938–2943
Verbakel WFAR, Sauerwein W, Hideghety K, Stecher-Rasmussen F (2003) Boron concentrations in brain during boron neutron capture therapy: in vivo measurements from the phase I trial EORT 11961 using a gamma-ray telescope. Int J Radiat Oncol Biol Phys 55(3):743–756
Wittig A, Michel J, Moss RL, Stecher-Rasmussen F, Arlinghaus HF, Bendel P, Mauri PL, Altieri S, Hilger R, Salvadori PA, Menichetti L, Zamenhof R, Sauerwein WA (2008) Boron analysis and boron imaging in biological materials for Boron Neutron Capture Therapy (BNCT). Crit Rev Oncol Hematol 68:66–90
Ziegler JF, Biersack JP, Littmark U (1985) The stopping and range of ions in solids. Pergamon Press, Oxford. Code available on http://www.srim.org
Zonta A, Pinelli T, Prati U, Roveda L, Ferrari C, Clerici AM, Zonta C, Mazzini G, Dionigi P, Altieri S, Bortolussi S, Bruschi P, Fossati F (2009) Extra-corporeal liver BNCT for the treatment of diffuse metastases: what was learned and what is still to be learned. Appl Radiat Isot 67:67–75
Acknowledgments
The authors would like to thank Mr Piero Bruschi for his invaluable technical contribution.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bortolussi, S., Altieri, S. Boron concentration measurement in biological tissues by charged particle spectrometry. Radiat Environ Biophys 52, 493–503 (2013). https://doi.org/10.1007/s00411-013-0480-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00411-013-0480-y