Viaggi M, Dagrosa M A, Longhino J, Blaumann H, Calzetta O, Kahl S B, Juvenal G J, Pisarev M A
Department of Radiobiology, Constituyentes Atomic Center, Av del Libertador 8250, 1429 Buenos Aires, Argentina.
Appl Radiat Isot. 2004 Nov;61(5):905-9. doi: 10.1016/j.apradiso.2004.05.005.
We have shown the selective uptake of borophenylalanine (BPA) by undifferentiated human thyroid cancer (UTC) ARO cells both in vitro and in vivo. Moreover, a 50% histologic cure of mice bearing the tumor was observed when the complete boron neutron capture therapy was applied. More recently we have analyzed the biodistribution of BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha,beta-dihydroxyethyl)-deutero-porphyrin IX) and showed that when BOPP was injected 5 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 (38-45 ppm with both compounds vs. 20 ppm with BPA alone). Five days post the i.p BOPP injection and 1h after BPA the ratios were: tumor/blood 3.75; tumor/distal skin 2. Other important ratios were tumor/thyroid 6.65 and tumor/lung 3.8. The present studies were performed in mice transplanted with ARO cells and injected with BOPP and BPA. Only in mice treated with the neutron beam and injected with the boronated compounds we observed a 100% control of tumor growth. Two groups of mice received different total absorbed doses: 3.00 and 6.01 Gy, but no further improvement in the outcome was found compared to the previous results using BPA alone (4.3 Gy).
我们已证明,未分化人甲状腺癌(UTC)ARO细胞在体外和体内均能选择性摄取硼苯丙氨酸(BPA)。此外,当应用完整的硼中子俘获疗法时,观察到荷瘤小鼠有50%的组织学治愈。最近,我们分析了BOPP(2,4-双-(α,β-二羟乙基)-氘代卟啉IX的四碳硼烷羧酸酯)的生物分布,结果显示,在注射BPA前5天注射BOPP,腹腔注射BPA 60分钟后处死动物,发现肿瘤对硼的摄取显著增加(两种化合物的硼摄取量均为38 - 45 ppm,而单独使用BPA时为20 ppm)。腹腔注射BOPP 5天后及注射BPA 1小时后的比率为:肿瘤/血液3.75;肿瘤/远端皮肤2。其他重要比率为肿瘤/甲状腺6.65和肿瘤/肺3.8。本研究是在移植了ARO细胞并注射了BOPP和BPA的小鼠中进行的。只有在用中子束治疗并注射了含硼化合物的小鼠中,我们观察到肿瘤生长得到了100%的控制。两组小鼠接受了不同的总吸收剂量:3.00和6.01 Gy,但与之前单独使用BPA(4.3 Gy)的结果相比,未发现结果有进一步改善。