Boron Neutron Capture Therapy (BNCT) is a bimodal
cancer treatment based on the selective accumulation of 10B in
tumors and concurrent irradiation with thermalized neutrons. The short-range, high-LET radiation produced by the capture of neutrons by 10B could potentially control
tumor while sparing normal tissue if the
boron compound targets
tumor selectively within the treatment volume. In previous studies, we proposed and validated the hamster cheek pouch model of
oral cancer for BNCT studies, proved that absolute and relative uptake of the clinically employed
boron compound boronophenylalanine (BPA) would be potentially therapeutic in this model and provided evidence of the efficacy of in vivo BPA-mediated BNCT to control hamster oral mucosa
tumors with virtually no damage to normal tissue. We herein present the biodistribution and pharmacokinetics of a lipophilic, carborane-containing
tetraphenylporphyrin (
CuTCPH) in the hamster
oral cancer model.
CuTCPH is a novel, non-toxic compound that may be advantageous in terms of selective and absolute delivery of
boron to
tumor tissues. For potentially effective BNCT,
tumor boron concentrations from a new agent should be greater than 30 ppm and
tumor/blood and
tumor/normal tissue
boron concentration ratios should be greater than 5/1 without causing significant toxicity. We administered
CuTCPH intraperitoneally (i.p.) as a single dose of 32 microg/g
body weight (b.w.) (10 microg B/g b.w.) or as four doses of 32 microg/g b.w. over 2 days. Blood (Bl) and tissues were sampled at 3, 6, 12, 24, 48, and 72 h in the single-dose protocol and at 1-4 days after the last injection in the multidose protocol. The tissues sampled were
tumor (T), precancerous tissue surrounding
tumor, normal pouch (N), skin, tongue, cheek and palate mucosa, liver, spleen, parotid gland and brain. The maximum mean B ratios for the single-dose protocol were T/N: 9.2/1 (12h) and T/Bl: 18.1/1 (72 h). The B value peaked to 20.7+/-18.5 ppm in
tumor at 24h. The multidose protocol maximum mean ratios were T/N: 11.9/1 (3 days) and T/Bl: 235/1 (4 days). Absolute
boron concentration in
tumor reached a maximum value of 116 ppm and a mean value of 71.5+/-48.3 ppm at 3 days. The fact that absolute and relative B values markedly exceeded the BNCT therapeutic threshold with no apparent toxicity may confer on this compound a therapeutic advantage.
CuTCPH-mediated BNCT would be potentially useful for the treatment of
oral cancer in an experimental model.