Sonoporation as an enhancing method for boron neutron capture therapy for squamous cell carcinomas

Abstract

BackgroundBoron neutron capture therapy (BNCT) is a selective radiotherapy that is dependent on the accumulation of 10B compound in tumors. Low-intensity ultrasound produces a transient pore on cell membranes, sonoporation, which enables extracellular materials to enter cells. The effect of sonoporation on BNCT was examined in oral squamous cell carcinoma (SCC) xenografts in nude mice.Materials and methodsTumor-bearing mice were administrated boronophenylalanine (BPA) or boronocaptate sodium (BSH) intraperitoneally. Two hours later, tumors were subjected to sonoporation using microbubbles followed by neutron irradiation.ResultsThe 10B concentration was higher in tumors treated with sonoporation than in untreated tumors, although the difference was not significant in BPA. When tumors in mice that received BPA intraperitoneally were treated with sonoporation followed by exposure to thermal neutrons, tumor volume was markedly reduced and the survival rate was prolonged. Such enhancements by sonoporation were not observed in mice treated with BSH-mediated BNCT.ConclusionsThese results indicate that sonoporation enhances the efficiency of BPA-mediated BNCT for oral SCC. Sonoporation may modulate the microlocalization of BPA and BSH in tumors and increase their intracellular levels.

Boron Carbide Particle as a Boron Compound for Boron Neutron Capture Therapy

“…If B 4 C particles are distributed between the epithelial cells of the covering skin, B 4 C-mediated BNCT may affect the viability of skin as well as tumours [20]. However, we did not observe any skin defects after BNCT in the present study.…”

“…Two hours later, the 10 B concentration in tumours was 10.21 ppm and the physical dose was 8.15 Gy. Neutron irradiation to these tumours decreased the tumor volume to 74% that of tumours treated neutron irradiation only after 42 days [20]. Since the systemic administration of B 4 C particles was considered to be inappropriate, we used B 4 C particles intratumorally at a concentration of 250 ppm; the calculated 10 B concentration was 38.94 ppm.…”

“…A LiF thermoplastic plate with a hole that defined the irradiation field was placed on the animal to expose the tumor-bearing leg only to the neutron beam. Neutron fluence was measured from the radioactivation of gold foil (3 mm in diameter, 0.05 mm thick) placed at the front and back of the tumors [19,20]. The average fluence of thermal neutrons was 7.98×10 12 n/cm 2 at 5 MW.…”

Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma

“…D N is the physical dose of nitrogen derived from the equation of 6.78 × 10 −14 (Gy cm 2 /wt.%) × nitrogen concentration (weight %) × thermal neutron fluence (1/cm 2 ). The numerical values above were taken from a previous study [12]. The physical dose of boron and nitrogen is caused by a capture reaction between the thermal neutrons and each nucleus.…”

‘Close-to-ideal’ Tumor Boron Targeting for Boron Neutron Capture Therapy is Possible With ‘less-than-ideal’ Boron Carriers Approved for Use in Humans

“…Some examples include the combined administration of BPA and BSH [12], blood-brain barrier disruption and convection-enhanced delivery for BPA administration in the case of brain tumors and slow infusion of BPA to improve boron targeting of infiltrating tumor cells [11], electroporation and sonoporation to improve BSH uptake [18], preloading with structural analogs such as l-DOPA or l-tyrosine to improve BPA uptake [19] and mild temperature hyperthermia to increase tumor blood flow [20].…”