The hamster cheek pouch as a model of oral cancer for boron neutron capture therapy studies: selective delivery of boron by boronophenylalanine.
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.
Kreimann
E L
EL
Department of Radiobiology, National Atomic Energy Commission, 1429 Buenos Aires, Argentina.
Itoiz
M E
ME
Dagrosa
A
A
Garavaglia
R
R
Farías
S
S
Batistoni
D
D
Schwint
A E
AE
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001895:Boron / Q000097:blood / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002273:Carcinogens; D002610:Cheek; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000532:radiotherapy*; D010649:Phenylalanine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D001896:Boron Compounds; D002273:Carcinogens; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; D015127:9,10-Dimethyl-1,2-benzanthracene; D001895:Boron; C033685:4-boronophenylalanine