Herein we propose and validate the hamster cheek pouch model of
oral cancer for
boron neutron capture therapy (BNCT) studies. This model serves to explore new applications of the technique, study the biology and radiobiology of BNCT, and assess the uptake of
boron compounds and response of
tumor, precancerous tissue, and clinically relevant normal tissues. These issues are central to evaluating and improving the therapeutic gain of BNCT. The success of BNCT is dependent on the absolute amount of
boron in the
tumor, and the
tumor:blood and
tumor:normal tissue
boron concentration ratios. Within this context, biodistribution studies are pivotal.
Tumors were induced in the hamsters with a
carcinogenesis protocol that uses dimethyl-1,2-benzanthracene and mimics spontaneous
tumor development in human oral mucosa. The animals were then used for biodistribution and pharmacokinetic studies of boronophenylalanine (BPA). Blood,
tumor, precancerous pouch tissue surrounding
tumor, normal pouch tissue, tongue, skin, cheek mucosa, palate mucosa, liver, and spleen, were sampled at 0-12 h after administration of 300 mg BPA/kg. The data reveal selective uptake of BPA by
tumor tissue and, to a lesser degree, by precancerous tissue. Mean
tumor boron concentration was 36.9 +/- 17.5 ppm at 3.5 h and the mean
boron ratios were 2.4:1 for
tumor:normal pouch tissue and 3.2:1 for
tumor:blood. Higher doses of BPA (600 and 1200 mg BPA/kg) increased
tumor uptake. Potentially therapeutic absolute
boron concentrations, and
tumor:normal tissue and
tumor:blood ratios can be achieved in the hamster
oral cancer model using BPA as the delivery agent.