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

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.