Monti Hughes A, Heber E M, Pozzi E, Nigg D W, Calzetta O, Blaumann H, Longhino J, Nievas S I, Aromando R F, Itoiz M E, Trivillin V A, Schwint A E
Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires, Argentina.
Appl Radiat Isot. 2009 Jul;67(7-8 Suppl):S313-7. doi: 10.1016/j.apradiso.2009.03.070. Epub 2009 Mar 27.
We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.
我们之前已证明,在仓鼠颊囊口腔癌模型中,由硼苯丙氨酸(BPA)、GB - 10(Na₂¹⁰B₁₀H₁₀)以及(GB - 10 + BPA)介导的硼中子俘获疗法(BNCT)在控制肿瘤方面具有疗效,且对正常组织无放射性毒性。在此,我们在仓鼠颊囊中建立了一种新的场癌化和癌前病变(在此统称为癌前组织)实验模型,以探究相同的BNCT方案对癌前组织中第二原发性肿瘤发生发展的长期潜在抑制作用。临床上,第二原发性肿瘤复发发生在场癌化组织中,导致治疗失败。我们进行了硼生物分布研究,随后进行了体内BNCT研究,并进行了8个月的随访。所有3种BNCT方案均使癌前组织中的肿瘤发生发展出现统计学上的显著减少,最大抑制率达到77% - 100%。随访结束时(8个月),BPA - BNCT和(GB - 10 + BPA) - BNCT的抑制作用持续保持在51%,而GB - 10 - BNCT的抑制作用在2个月后消退。同样,仅照射束也引起肿瘤发生发展的显著但短暂的减少。未观察到正常组织的放射性毒性。在用BPA - BNCT或(GB - 10 + BPA) - BNCT治疗8个月后,未发生肿瘤的癌前颊囊已恢复到正常(未癌化)颊囊的宏观和组织学外观。BNCT潜在的新临床应用可能在于其抑制局部区域复发的能力。