Analytical and Bioanalytical Chemistry

, Volume 407, Issue 9, pp 2365–2371 | Cite as

Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy

  • Olga Reifschneider
  • Christian L. Schütz
  • Christoph Brochhausen
  • Gabriele Hampel
  • Tobias Ross
  • Michael Sperling
  • Uwe KarstEmail author
Research Paper
Part of the following topical collections:
  1. Spectrochemical Plasmas for Clinical and Biochemical Analysis


An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.


Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) Boron neutron capture therapy (BNCT) Tissue sections Quantification 



Parts of this study were supported by the Cells in Motion Cluster of Excellence (CiM-EXC 1003), Münster, Germany (project FF-2013-17). The contribution of Christian L. Schütz was generously supported by a grant provided by the Boehringer Ingelheim Foundation (Ingelheim, Germany).


  1. 1.
    Nielsen FH (1996) J Trace Elem Exp Med 9:215CrossRefGoogle Scholar
  2. 2.
    Nielsen FH (2000) Nutrition 16:512–514CrossRefGoogle Scholar
  3. 3.
    Başaran N, Duydu Y, Bolt HM (2012) J Trace Elem Med Biol 26:165–167CrossRefGoogle Scholar
  4. 4.
    Barth RF, Vicente MGH, Harling OK, Kiger WS, Riley KJ, Binns PJ, Wagner FM, Suzuki M, Aihara T, Kato I, Kawabata S (2012) Radiat Oncol 7:146CrossRefGoogle Scholar
  5. 5.
    Coderre JA, Morris GM (1999) Radiat Res 151:1–18CrossRefGoogle Scholar
  6. 6.
    Lu X-Q, Kiger WS (2009) Radiat Res 171:646–656CrossRefGoogle Scholar
  7. 7.
    Tonarini S, Pennisi M, Adorni-Braccesi A, Dini A, Ferrara G, Gonfiantini R, Wiedenbeck M, Goning M (2003) Geostand Newslett 27:21–39CrossRefGoogle Scholar
  8. 8.
    Nyomora AMS, Sah RN, Brown PH, Miller RO (1997) Fresenius J Anal Chem 357:1185–1191CrossRefGoogle Scholar
  9. 9.
    Linko S, Revitzer H, Zilliacus R, Kortesniemi M, Kouri M, Savolainen S (2008) Scand J Clin Lab Inv 68:696–702CrossRefGoogle Scholar
  10. 10.
    Probst TU, Berryman NG, Lemmen P, Weissfloch L, Auberger T, Gabel D, Carlsson J, Larsson B (1997) J Anal Atom Spectrom 12:1115–1122CrossRefGoogle Scholar
  11. 11.
    Schmitz T, Appelman K, Kudejova P, Schütz C, Kratz JV, Moss R, Otto G, Hampel G (2011) Appl Radiat Isotopes 69:936–941CrossRefGoogle Scholar
  12. 12.
    Schütz CL, Brochhausen C, Hampel G, Iffland D, Kuczewski B, Otto G, Schmitz T, Stieghorst C, Kratz JV (2012) Anal Bioanal Chem 404:1887–1895Google Scholar
  13. 13.
    Evangelista L, Jori G, Martini D, Sotti G (2013) Appl Radiat Isotopes 74:91–101CrossRefGoogle Scholar
  14. 14.
    Porcari P, Capuani S, D’Amore E, Lecce M, La Bella A, Fasano F, Migneco LM, Campanella R, Maraviglia B, Pastore FS (2008) Phys Med Biol 53:6979–6989CrossRefGoogle Scholar
  15. 15.
    Michel J, Sauerwein W, Wittig A, Balossier G, Zierold K (2003) J Microsc 210:25–34CrossRefGoogle Scholar
  16. 16.
    Arlinghaus HF, Spaar MT, Switzer RC, Kabalka GW (1997) Anal Chem 69:3169–3176CrossRefGoogle Scholar
  17. 17.
    Chandra S, Tjarks W, Lorey DR, Barth RF (2008) J Microsc 229:92–103CrossRefGoogle Scholar
  18. 18.
    Chandra S, Barth RF, Haider S, Yang W, Huo T, Shaikh AL, Kabalka GW (2013) Biodistribution and subcellular localization of an unnatural boron-containing amino acid (Cis-ABCPC) by imaging secondary ion mass spectrometry for neutron capture therapy of melanomas and gliomas. PLoS ONE 8:1–9Google Scholar
  19. 19.
    Marchetti I, Menichetti L, Kusmic C, de las Heras LA, Salvadori P, Fuoco R, Belloni F, ĹAbbate A, Betti M (2009) Spectrochim Acta B 64:911–920CrossRefGoogle Scholar
  20. 20.
    Yokoyama K, Miyatake S-I, Kajimoto Y, Kawabata S, Doi A, Yoshida T, Okabe M, Kirihata M, Ono K, Kuroiwa T (2007) Radiat Res 167:102–109CrossRefGoogle Scholar
  21. 21.
    Kiger WS, Micca PL, Morris GM, Coderre JA (2002) Radiat Prot Dosim 99:409–412CrossRefGoogle Scholar
  22. 22.
    Bortolussi S, Pinto JM, Thorp SI, Farias RO, Soto MS, Sztejnberg M, Pozzi ECC, Gonzalez SJ, Gadan MA, Bellino AN, Quintana J, Altieri S, Miller M (2001) Appl Radiat Isotopes 69:1924–1927CrossRefGoogle Scholar
  23. 23.
    Portu A, Carpano M, Dagrosa A, Nievas S, Pozzi E, Thorp S, Cabrini R, Liberman S, Saint Martin G (2011) Appl Radiat Isotopes 69:1698–1701CrossRefGoogle Scholar
  24. 24.
    Portu A, Carpano M, Dagrosa A, Cabrini RL, Saint Martin G (2013) Biotech Histochem 88:217–221CrossRefGoogle Scholar
  25. 25.
    Schütz C, Brochhausen C, Altieri S, Bartholomew K, Bortolussi S, Enzmann F, Gabel D, Hampel G, Kirkpatrick CJ, Kratz JV, Minouchehr S, Schmidberger H, Otto G (2011) Radiat Res 176:388–396CrossRefGoogle Scholar
  26. 26.
    Becker JS, Dietze H-J (2000) Fresen J Anal Chem 368:23–30CrossRefGoogle Scholar
  27. 27.
    Pisonero J, Fernández B, Günther D (2009) J Anal Atom Spectrom 24:1145–1160CrossRefGoogle Scholar
  28. 28.
    Ghazi AM, Wataha J, O’Dell N, Singh B, Simmons R, Shuttleworth S (2002) J Anal Atom Spectrom 17:1295–1299CrossRefGoogle Scholar
  29. 29.
    Becker JS, Zoriy M, Matusch A, Wu B, Salber D, Palm C, Becker JS (2010) Mass Spectrom Rev 29:156–175Google Scholar
  30. 30.
    Pugh JAT, Cox AG, McLeod CW, Bunch J, Whitby B, Gordon B, Kalber T, White E (2011) J Anal Atom Spectrom 26:1667–1673CrossRefGoogle Scholar
  31. 31.
    Reifschneider O, Wehe CA, Diebold K, Becker C, Sperling M, Karst U (2013) J Anal Atom Spectrom 28:989–993CrossRefGoogle Scholar
  32. 32.
    Becker JS, Zoriy MV, Pickhardt C, Palomero-Gallagher N, Zilles K (2005) Anal Chem 77:3208–3216CrossRefGoogle Scholar
  33. 33.
    Zoriy MV, Dehnhardt M, Matusch A, Becker JS (2008) Spectrochim Acta B 63:375–382CrossRefGoogle Scholar
  34. 34.
    Reifschneider O, Wehe CA, Raj I, Ehmcke J, Ciarimboli G, Sperling M, Karst U (2013) Metallomics 5:1440–1447Google Scholar
  35. 35.
    Gabel D, Holstein H, Larsson B, Gille L, Ericson G, Sacker D, Som P, Fairchild RG (1987) Cancer Res 47:5451–5454Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Olga Reifschneider
    • 1
  • Christian L. Schütz
    • 2
  • Christoph Brochhausen
    • 3
  • Gabriele Hampel
    • 2
  • Tobias Ross
    • 2
  • Michael Sperling
    • 1
    • 4
  • Uwe Karst
    • 1
    Email author
  1. 1.Institute of Inorganic and Analytical ChemistryUniversity of MünsterMünsterGermany
  2. 2.Institute of Nuclear ChemistryUniversity of MainzMainzGermany
  3. 3.Institute of PathologyUniversity of MainzMainzGermany
  4. 4.European Virtual Institute for Speciation Analysis (EVISA)MünsterGermany

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