Heber Elisa M, Kueffer Peter J, Lee Mark W, Hawthorne M Frederick, Garabalino Marcela A, Molinari Ana J, Nigg David W, Bauer William, Hughes Andrea Monti, Pozzi Emiliano C C, Trivillin Verónica A, Schwint Amanda E
Department of Radiobiology, National Atomic Energy Commission, San Martin, Buenos Aires, Argentina.
Radiat Environ Biophys. 2012 May;51(2):195-204. doi: 10.1007/s00411-011-0399-0. Epub 2012 Jan 21.
Boron neutron capture therapy (BNCT) combines selective accumulation of (10)B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na(3) [ae-B(20)H(17)NH(3)], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.
硼中子俘获疗法（BNCT）将（10）B载体在肿瘤组织中的选择性积累与随后的中子照射相结合。我们之前在仓鼠颊囊口腔癌模型中证明了BNCT的治疗效果。BNCT的优化很大程度上取决于提高硼对肿瘤细胞的靶向性。为了最大限度地发挥BNCT治疗头颈癌的潜力，本研究的目的是在口腔癌模型中进行硼生物分布研究，采用两种不同的脂质体制剂，这两种制剂之前已针对不同的病理学进行了测试，即在BALB/c小鼠的实验性乳腺癌中进行测试：（1）MAC：脂质体在双层膜中掺入K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)]并包封高渗缓冲液，以每千克体重6毫克硼的剂量静脉注射，以及（2）MAC-TAC：脂质体在双层膜中掺入K[nido-7-CH(3)(CH(2))(15)-7,8-C(2)B(9)H(11)]并包封亲水性物质Na(3)[ae-B(20)H(17)NH(3)]的浓缩水溶液，以每千克体重18毫克硼的剂量静脉注射。在给药后的不同时间采集肿瘤、癌前和正常颊囊组织、脾脏、肝脏、肾脏和血液样本，并进行处理，通过电感耦合等离子体质谱法测量硼含量。所选制剂未观察到明显的临床毒性作用。MAC和MAC-TAC都将硼选择性地递送至肿瘤组织。MAC-TAC的绝对肿瘤值在48小时时达到峰值66.6±16.1 ppm，在54小时时达到43.9±17.6 ppm，肿瘤硼与癌前和正常组织的比率非常有利，使得这些方案特别值得进行放射生物学评估。获得的硼浓度值将在肿瘤中产生治疗性BNCT剂量，而不会超过RA-3热中子设施中癌前/正常组织的放射耐受性。
