Pisarev Mario A, Dagrosa Maria A, Thomasz Lisa, Juvenal Guillermo
Departamento de Radiobiología, Centro Atómico Constituyentes, Av. General Paz 1499,1650 San Martin, Buenos Aires, Argentina.
Medicina (B Aires). 2006;66(6):569-73.
Undifferentiated thyroid carcinoma (UTC) is an aggressive tumor with a poor prognosis due to the lack of an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of boron by the tumor and its activation by a neutron beam, releasing lithium-7 and an alpha particle that will kill the tumor cells by their high linear energy transfer (LET). In previous studies we have shown a selective uptake of borophenylalanine (10BPA) in a human UTC cell line (ARO) and in NIH nude mice implanted with this cell line. When these animals were injected with BPA and irradiated with an appropriated neutron beam, we observed a 100% of tumor growth control and a 50% of histological cure when the initial tumor volume was 50 mm3 or less. Further studies with BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha, beta-dihydroxyethyl)-deutero-porphyrin IX) showed that when this porphyrin was injected 5-7 days before BPA, and the animals were sacrificed 60 min after the i.p. injection of BPA, a significant increase in boron uptake by the tumor was found (45-38 ppm with both compounds vs. 20 ppm with BPA alone). The application of BNCT using the combination of boron compounds showed a 100% of complete remission in tumors with initial volumes under 50 mm3. Dogs suffer spontaneous UTC, with a similar biological behavior to the human tumor, and a selective uptake of BPA. These results open the possibility of applying BNCT to UTC.
未分化甲状腺癌(UTC)是一种侵袭性肿瘤,由于缺乏有效治疗,预后较差。硼中子俘获疗法(BNCT)基于肿瘤对硼的选择性摄取以及硼被中子束激活,释放出锂-7和一个α粒子,该α粒子通过其高线性能量传递(LET)杀死肿瘤细胞。在先前的研究中,我们已证明硼苯丙氨酸(10BPA)在人UTC细胞系(ARO)以及植入该细胞系的NIH裸鼠中具有选择性摄取。当给这些动物注射BPA并用合适的中子束进行照射时,我们观察到当初始肿瘤体积为50立方毫米或更小时,肿瘤生长控制率达100%,组织学治愈率达50%。对BOPP(2,4-双-(α,β-二羟乙基)-氘代卟啉IX的四碳硼烷羧酸酯)的进一步研究表明,当在注射BPA前5 - 7天注射这种卟啉,且在腹腔注射BPA后60分钟处死动物时,发现肿瘤对硼的摄取显著增加(两种化合物联合使用时硼摄取量为45 - 38 ppm,而单独使用BPA时为20 ppm)。使用硼化合物组合进行BNCT治疗,初始体积小于50立方毫米的肿瘤完全缓解率达100%。犬类会自发患UTC,其生物学行为与人类肿瘤相似,且对BPA有选择性摄取。这些结果为将BNCT应用于UTC开辟了可能性。