Portu Agustina, Molinari Ana Julia, Thorp Silvia Inés, Pozzi Emiliano César Cayetano, Curotto Paula, Schwint Amanda Elena, Saint Martin Gisela
National Atomic Energy Commission (CNEA) , San Martin, Buenos Aires , Argentina.
Int J Radiat Biol. 2015 Apr;91(4):329-35. doi: 10.3109/09553002.2014.995381. Epub 2015 Jan 24.
We previously reported the therapeutic efficacy of Sequential Boron Neutron Capture Therapy (Seq-BNCT), i.e., BPA (boronophenylalanine) - BNCT followed by GB-10 (decahydrodecaborate) - BNCT 1 or 2 days later, in the hamster cheek pouch oral cancer model. We have utilized the neutron autoradiography methodology to study boron microdistribution in tissue. The aim was to use this method to evaluate if the distribution of GB-10 is altered by prior application of BPA-BNCT in Sequential BNCT protocols.
Extensive qualitative and quantitative autoradiography analyses were performed in the following groups: G1 (animals without boron); G2 (animals injected with BPA); G3 (animals injected with GB-10); G4 (same as G3, 24 h after BPA-BNCT); and G5 (same protocol as G4, 48 h interval).
A detailed study of boron localization in the different tissue structures of tumor, premalignant and normal tissue in the hamster cheek pouch was performed. GB-10 accumulated preferentially in non-neoplastic connective tissue, whereas for BPA neoplastic cells showed the highest boron concentration. Boron distribution was less heterogeneous for GB-10 than for BPA. In premalignant and normal tissue, GB-10 and BPA accumulated mostly in connective tissue and epithelium, respectively.
BPA-BNCT could alter boron microlocalization of GB-10 administered subsequently. Boron targeting homogeneity is essential for therapeutic success.
我们之前报道了序贯硼中子俘获疗法（Seq-BNCT），即在仓鼠颊囊口腔癌模型中，先进行BPA（硼苯丙氨酸）-BNCT，1或2天后再进行GB-10（十氢十硼酸酯）-BNCT的治疗效果。我们利用中子放射自显影方法研究硼在组织中的微观分布。目的是使用该方法评估在序贯BNCT方案中，预先应用BPA-BNCT是否会改变GB-10的分布。
对以下几组进行了广泛的定性和定量放射自显影分析：G1组（未注射硼的动物）；G2组（注射BPA的动物）；G3组（注射GB-10的动物）；G4组（与G3组相同，但在BPA-BNCT后24小时）；G5组（与G4组方案相同，间隔48小时）。
对仓鼠颊囊肿瘤、癌前组织和正常组织的不同组织结构中的硼定位进行了详细研究。GB-10优先积聚在非肿瘤性结缔组织中，而对于BPA，肿瘤细胞显示出最高的硼浓度。GB-10的硼分布比BPA的异质性小。在癌前组织和正常组织中，GB-10和BPA分别主要积聚在结缔组织和上皮中。
BPA-BNCT可能会改变随后给予的GB-10的硼微观定位。硼靶向的均匀性对于治疗成功至关重要。
