将新的抗病毒假说和放射性碘疗法应用于其他癌症,如乳腺癌、肺癌和多形性胶质母细胞瘤(GBM)?

Agata Czarnywojtek, Paweł Gut, Magdalena Borowska, Nadia Sawicka-Gutaj, Paweł Caputa, Beata Kos-Kudła, Marek Ruchała, Marzena Dworacka
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引用次数: 0

摘要

放射性碘治疗(RIT)是治疗良性和恶性甲状腺疾病的一种有效、安全和廉价的方法。放射性碘治疗是否也能在乳腺癌、肺癌或多形性胶质母细胞瘤(GBM)等疾病的治疗中发挥作用,这仍是一个悬而未决的问题。这些研究目前正在大鼠身上结合基因进行,但由于碘化钠合酶(NIS)的表达,评估 "纯 "RIT 对其他器官结节(包括良性和恶性结节)是否有效可能是一个有趣的挑战。1996 年 NIS 的克隆为将 NIS 用作强大的治疗转基因提供了机会。此外,NIS 还是一种敏感的报告基因,可通过使用放射性标记[¹²⁴I]碘化钠([¹²⁴I]NaI)或[18F]四氟硼酸盐([¹⁸F]TFB)进行高分辨率 PET 成像监测。根据已发表的正电子发射断层扫描(PET)结果,我们在表达 NIS 的胶质母细胞瘤正位动物模型中比较了[¹²⁴I]碘化钠和内部合成的[18F]TFB。结果显示,使用[¹⁸F]TFB可提高图像质量。基于这些结果,我们将能把使用非病毒基因递送载体的 NIS 基因治疗方法扩展到以 GBM 等低体积疾病为目标的正位肿瘤模型。在 GBM 中是否可以不使用 NIS 基因而只治疗 RIT?毕竟,不仅在甲状腺,而且在不同的肿瘤中都检测到了 NIS 交感蛋白。使用 RIT 完全无害,唯一的并发症就是甲状腺功能减退。事实上,最近的研究表明,以甲状腺癌为例,RIT 的最大值为 37000 MBq(1000 mCi)。当对脑肿瘤的治疗无法产生有益效果时(如神经外科手术、调节性电热疗、化疗、免疫疗法、癌症疫苗或溶瘤病毒),RIT 能否利用 NIS 带来一场 "革命"?
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A new antiviral hypothesis and radioactive iodine therapy to other cancers, such as breast cancer, lung cancer, and glioblastoma multiforme (GBM)?

Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT treatment also plays a role in the treatment of, for example, breast cancer, lung cancer, or glioblastoma multiforme (GBM). These studies are currently being carried out in rats in combination with genes, but it may be an interesting challenge to assess "pure" RIT alone, thanks to the expression of sodium iodide symporter (NIS), is effective in other organ nodules, both benign and malignant. Cloning of the NIS in 1996 provided an opportunity to use NIS as a powerful theranostic transgene. In addition, NIS is a sensitive reporter gene that can be monitored by high-resolution PET imaging using the radiolabels [¹²⁴I]sodium iodide ([¹²⁴I]NaI) or [18F] tetrafluoroborate ([¹⁸F]TFB). Based on published positron emission tomography (PET) results, [¹²⁴I]sodium iodide and internally synthesized [18F]TFB were compared in an orthotopic animal model of NIS-expressing glioblastoma. The results showed improved image quality using [¹⁸F]TFB. Based on these results, we will be able to extend the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumour models with low-volume disease such as GBM. Is it possible to treat RIT alone without using the NIS gene in GBM? After all, the NIS symporter was detected not only in the thyroid gland, but also in different tumours. The administration of RIT is completely harmless; the only complication is hypothyroidism. Indeed, recently it has been shown that, for example, in the case of thyroid cancer, the maximum RIT is 37000 MBq (1000 mCi). When beneficial effects of therapy in GBM are not possible (e.g. neurosurgery, modulated electro-hyperthermia, chemotherapy, immunotherapy, cancer vaccines, or oncolytic viruses), could RIT provide a "revolution" using NIS?

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