Multimodal evaluation of 19F-BPA internalization in pancreatic cancer cells for boron capture and proton therapy potential applications

Andrea Ciardiello, Saverio Altieri, Francesca Ballarini, Valerio Bocci, Silva Bortolussi, Laura Cansolino, Daniele Carlotti, Mario Ciocca, Riccardo Faccini, Angelica Facoetti, Cinzia Ferrari, Luca Ficcadenti, Emiliano Furfaro, Stefano Giagu, Francesco Iacoangeli, Giampiero Macioce, Carlo Mancini-Terracciano, Andrea Messina, Luisa Milazzo, Severina PacificoSimona Piccolella, Ian Postuma, Dante Rotili, Valerio Vercesi, Cecilia Voena, Francesca Vulcano, Silvia Capuani

Research output: Contribution to journalArticlepeer-review


Purpose: One of the obstacles to the application of Boron Neutron Capture Therapy (BNCT) and Proton Boron Fusion Therapy (PBFT) concerns the measurement of borated carriers' biodistribution. The objective of the present study was to evaluate the in vitro internalization of the 19F-labelled p-boronophenylalanine (19F-BPA) in the human cancer pancreatic cell line (PANC-1) for the potential application of BNCT and PBFT in pancreatic cancer. The 19F-BPA carrier has the advantage that its bio-distribution may be monitored in vivo using 19F-Nuclear Magnetic Resonance (19F NMR). Materials and methods: The 19F-BPA internalization in PANC-1 cells was evaluated using three independent techniques on cellular samples left in contact with growing medium enriched with 13.6 mM 19F-BPA corresponding to a 11B concentration of 120 ppm: neutron autoradiography, which quantifies boron; liquid chromatography hyphenated to tandem mass spectrometry and UV-Diode Array Detection (UV-DAD), which quantifies 19F-BPA molecule; and 19F NMR spectroscopy, which detects fluorine nuclei. Results: Our studies suggested that 19F-BPA is internalized by PANC-1 cells. The three methods provided consistent results of about 50% internalization fraction at 120 ppm of 11B. Small variations (less than 15%) in internalization fraction are mainly dependent on the proliferation state of the cells. Conclusions: The ability of 19F NMR spectroscopy to study 19F-BPA internalization was validated by well-established independent techniques. The multimodal approach we used suggests 19F-BPA as a promising BNCT/PBFT carrier for the treatment of pancreatic cancer. Since the quantification is performed at doses useful for BNCT/PBFT, 19F NMR can be envisaged to monitor 19F-BPA bio-distribution during the therapy.

Original languageEnglish
Pages (from-to)75-84
Number of pages10
JournalPhysica Medica
Publication statusPublished - Feb 2022
Externally publishedYes


  • F-BPA
  • Boron neutron capture therapy
  • Magnetic resonance spectroscopy
  • Proton boron fusion therapy

ASJC Scopus subject areas

  • Biophysics
  • Radiology Nuclear Medicine and imaging
  • Physics and Astronomy(all)


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