2003 Article Biodistribution In-vivo Studies Year 2003

Biodistribution of a carborane-containing porphyrin as a targeting agent for Boron Neutron Capture Therapy of oral cancer in the hamster cheek pouch

Archives of Oral Biology, 2003

Authors:   Erica Kreimann,Michiko Miura,María Itoiz,Elisa Heber,Ricardo Garavaglia,Daniel Batistoni,Raúl Rebagliati,María Roberti,Peggy Micca,Jeffrey Coderre,Amanda Schwint,
Journal: Archives of Oral Biology
Abstract: 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 boronophenytalanine (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 tetraphenyiporphyrin (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 μg/g body weight (b.w.) (10 μg B/g b.w.) or as four doses of 32 μg/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 (12 h) and T/Bl: 18.1/1 (72 h). The B value peaked to 20.7 ± 18.5 ppm in tumor at 24 h. 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. © 2003 Elsevier Science Ltd. All rights reserved.