Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential Elisa M. HeberPeter J. KuefferMark W. Lee Jr. • M. Frederick Hawthorne • Marcela A. GarabalinoAna J. MolinariDavid W. NiggWilliam Bauer • Andrea Monti HughesEmiliano C. C. PozziVeronica A. TrivillinAmanda E. Schwint

Boron neutron capture therapy (BNCT) com- bines selective accumulation of 10 B carriers in tumor tissue with subsequent neutron irradiation. We previously dem- onstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9 H11) in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9H11) in the bilayer mem- brane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 (ae-B20H17NH3), administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post- administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No osten- sible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceed- ing radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.