Preclinical studies are in progress to determine the potential of
boron neutron capture therapy (BNCT) for the treatment of
carcinomas of the head and neck. Recently, it has been demonstrated that various boronated
porphyrins can target a variety of
tumor types. Of the
porphyrins evaluated so far,
copper tetracarboranylphenyl
porphyrin (
CuTCPH) is potentially a strong candidate for clinical use. In the present investigation, the response of the oral mucosa to
CuTCPH-mediated
boron neutron capture (BNC) irradiation was assessed using the ventral surface of the tongue of adult male Fischer 344 rats, a standard rodent model.
CuTCPH was administered by
intravenous infusion, at a dose of 200 mg/kg
body weight, over a 48-h period. Three days after the end of the administration of
CuTCPH, biodistribution studies indicated very low levels of
boron (<2 microg/g) in the blood. Levels of
boron in tongue tissue were 39.0 +/- 3.8 microg/g at this time. This was the time selected for irradiation with single doses of thermal neutrons from the Brookhaven Medical Research Reactor. The estimated level of
boron-10 in the oral mucosa was used in the calculation of the physical radiation doses from the 10B(n,alpha)7Li reaction. This differs from the approach using the present generation of clinical
boron carriers, where
boron levels in blood at the time of irradiation are used for this calculation. Dose-response curves for the incidence of mucosal ulceration were fitted using probit analysis, and the doses required to produce a 50% incidence of the effect (ED50 +/- SE) were calculated. Analysis of the dose-effect data for
CuTCPH-mediated BNC irradiation, compared with those for X rays and thermal neutrons alone, gave a compound
biological effectiveness (CBE) factor of approximately 0.04. This very low CBE factor would suggest that there was relatively low accumulation of
boron in the key target epithelial stem cells of the oral mucosa. As a consequence, with low levels of
boron (<2 microg/g) in the blood, the response of the oral mucosa to
CuTCPH-mediated BNCT will be governed primarily by the radiation effects of the thermal neutron beam and not from the
boron neutron capture reaction [10B(n,alpha)7Li].