RESUMO
OBJECTIVE: BNCT is a tumour cell targeted radiation therapy. Uniform targeting of heterogeneous tumours with therapeutically effective boron carriers would contribute to a therapeutic effect on all tumour cell populations and avoid radioresistant fractions. This remains an unresolved challenge. The aim of the present study was to evaluate the degree of variation in boron content delivered by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and the combined administration of (BPA+GB-10) in different portions of tumour, precancerous tissue around tumour and normal pouch tissue in the hamster cheek pouch oral cancer model. MATERIALS AND METHODS: Samples of different areas of tumour, precancerous tissue and normal pouch tissue were taken from tumour-bearing hamsters, 3h post-administration of i.p. BPA (15.5mg B/kg b.w.), or i.v. GB-10 (50mg B/kg b.w.), or 3h and 1.5h post-administration respectively of i.v. GB-10 (34.5mg B/b.w.) and sequential i.p. injections of BPA (total dose 31mg B/kg b.w.) given jointly. Boron content was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The degree of homogeneity in boron targeting was assessed in terms of the coefficient of variation (V: [S.D./mean]x100) of boron values. Statistical analysis of the results was performed by one-way ANOVA and the least significant difference test. RESULTS: GB-10 and GB-10 plus BPA achieved respectively a statistically significant 1.8- and 3.3-fold increase in targeting homogeneity over BPA. CONCLUSIONS: The combined boron compound administration protocol contributes to homogeneous targeting of heterogeneous tumours and would be expected to increase therapeutic efficacy of BNCT.
Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Bucais/metabolismo , 9,10-Dimetil-1,2-benzantraceno , Animais , Boroidretos/farmacocinética , Compostos de Boro/farmacocinética , Bochecha , Cricetinae , Modelos Animais de Doenças , Mesocricetus , Mucosa Bucal/metabolismo , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/radioterapia , Fenilalanina/análogos & derivados , Fenilalanina/farmacocinética , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/radioterapiaRESUMO
OBJECTIVE: We previously proposed the hamster cheek pouch model of oral cancer for BNCT studies. We herein present the biodistribution of a non-toxic boron compound, GB-10 (Na(2)(10)B10H10), in this model to assess its potential for BNCT or BNCT enhanced Fast Neutron Therapy. MATERIALS AND METHODS: We evaluated the uptake and retention of GB-10 in tumour and precancerous tissue and in potentially dose-limiting, clinically relevant normal tissues. RESULTS: Mean tumour boron concentration delivered by GB-10 (50mgB/kg) peaked to 77.7+/-28.0 ppm at 20min post-administration and remained at therapeutically useful values of 31.9+/-21.4 ppm at 3h. The clearance rate for normal tissues was faster than for tumour tissue. The consistently low brain and spinal cord values would preclude normal tissue toxicity. The uptake of GB-10 by precancerous tissue may be of potential use in the treatment of field cancerized areas. GB-10 was deposited homogeneously in different tumour areas, an asset when treating heterogenous tumours. The data suggests that the joint administration of BPA and GB-10 may improve the therapeutic efficacy of BNCT. CONCLUSIONS: GB-10 is a potential boron carrier for BNCT of head and neck tumours and for BNCT-FNT.