First estimation of the clinical utility of boronotyrosine as a boron delivery compound for boron neutron capture therapy in head and neck cancer.

Boronotyrosine (BTS) is a candidate boron delivery compound for Boron Neutron Capture Therapy (BNCT). In comparison to the current standard, boronophenylalanine (BPA), BTS provides higher solubility and improved specificity, retention, and tumor control in small animal models. The purpose of this work is to estimate the advantages of BTS for BNCT of human head and neck cancer. Biodistributions of BTS and BPA were measured after bolus injection using a human hypopharyngeal cancer xenograft model in CB17 SCID mice. Pharmaco-kinetic (P-K) models were used to allow bolus response to be generalized to arbitrary infusion schedules. Allometric scaling was used to predict human biodistributions from these models. A treatment planning study of 11 head and neck cancer patients was performed to compare the BNCT dose distributions achievable using BTS and BPA. The scaled P-K model boron concentration predictions for BPA were consistent with published measurements in human blood, tumor, and skin. Simulated infusions in a human patient gave mean tumor boron concentration during treatment of 57.2 ppm and 89.3 ppm for BPA and BTS, respectively. Tumor-to-blood and tumor-to-skin boron concentration ratios were 3.7:1 and 2.1:1 for BPA and 12.0:1 and 1.8:1 for BTS. GTV D95% increased from mean 29.5 Gy-Eq [26.4 Gy-Eq - 34.3 Gy-Eq] with BPA to 40.7 Gy-Eq [32.7 Gy-Eq - 58.3 Gy-Eq] with BTS for identical skin and mucosa dose constraints. BTS also demonstrated 10 %-40 % reduction in dose to parotid glands, spinal cord and non-specified normal tissue. These results motivate further development and testing of BTS as a delivery compound for BNCT.