A Comparative Study of Two Boron Compounds for BNCT

KREIMANN EL; MIURA M; ITOIZ ME; GARAVAGLIA R; CODERRE JA; SCHWINT AE

Córdoba, ARGENTINA

Congreso; Annual Meeting of Argentine Society for Dental Research. SAIO XXXIII; 2000

Argentine Society for Dental Research

Boron Neutron Capture Therapy (BNCT) is based on the capture reaction between Boron atoms and thermal neutrons that gives rise to high LET, short-range, lethal particles. The technique causes a therapeutic effect on tumor without causing significant damage to normal tissue if the Boron compound selectively targets tumor. The efforts of the worldwide BNCT community are largely devoted to the development of new Boron compounds that may afford a therapeutic advantage in terms of absolute uptake in tumor and larger Tumor/Normal Tissue (T/N) and Tumor/Blood (T/B) ratios. In a previous study we validated the use of the hamster cheek pouch carcinogenesis model for BNCT studies. We herein present a comparative study of the biodistribution, in this model, of a compound that has already been used in clinical trials (boronophenylalanine-BPA), and a new compound (a lipophilic boronated porphyrin-CuTCPH). The Boron content was evaluated in blood and tissues at different times after the adminstration of the compound by ICP-AES. The maximum ratios of B content were T/N: 53.33/1 and T/B: 3633/1 for CuTCPH and T/N: 6.33/1 and T/B: 8.95/1 for BPA. The maximum absolute tumor values were 106.40 ppm B for CuTCPH and 64.40 ppm B for BPA. With both compounds precancerous tissue (P)  around tumor exhibited a tendency to incorporate more B than normal tissue but less than tumor: T: 68.02 ± 25.00, P: 10.29 ± 3.16, N: 3.42 ± 3.14 ppm B for CuTCPH; T: 27.8 ± 11.00, P: 17.35 ± 2.69, N: 11.54 ± 5.32 ppm B for BPA.. The uptake of both compounds by normal intraoral tissues was similar to that of normal pouch. Both BPA and CuTCPH are non toxic at the doses employed. BPA deposits absolute and relative amounts of B in tumor that are compatible with a therapeutic effect. CuTCPH would afford a therapeutic advantage over BPA in that it deposits larger absolute amounts of B in tumor and uptake is more selective as regards normal tissue and blood. Future studies will determine its therapeutic efficacy in BNCT that is conditioned by variables currently under study such as compound subcellular localization. The selective incorporation of B to precancerous tissue regarding normal tissue with both compounds would suggest the possibility of achieving a therapeutic effect in premalignant tissue.