评估[64Cu]CuCl2 在胶质母细胞瘤球体内的治疗潜力。

IF 3.1 3区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Catarina I G Pinto, André D M Branco, Sara Bucar, Alexandra Fonseca, Antero J Abrunhosa, Cláudia L da Silva, Joana F Guerreiro, Filipa Mendes
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引用次数: 0

摘要

背景:胶质母细胞瘤是一种侵袭性极强的恶性肿瘤,预后极差:胶质母细胞瘤是一种侵袭性极强的恶性肿瘤,预后极差。由于胶质母细胞瘤的增殖速度加快,会形成缺氧区,其特点是铜(Cu)浓度增加。有鉴于此,64Cu 作为一种可能治疗胶质母细胞瘤的放射性核素引起了人们的关注。特别是,[64Cu]CuCl2 会在胶质母细胞瘤中蓄积,被认为是正电子发射断层扫描的合适制剂。在此,我们通过研究[64Cu]CuCl2在先进的三维胶质母细胞瘤细胞模型中的治疗效果,进一步探索其治疗潜力。首先,我们从三种胶质母细胞瘤(T98G、U373 和 U87)和一种非肿瘤星形胶质细胞系中建立了球形细胞。然后,我们通过分析球形细胞的生长、存活率和细胞增殖能力,评估了球形细胞对[64Cu]CuCl2 暴露的治疗反应。随后,我们研究了导致治疗结果的可能机制,包括 64Cu 的吸收、铜转运体(CTR1)的表达水平、癌症干细胞群的存在以及活性氧(ROS)的产生:结果表明,[64Cu]CuCl2 能显著降低球形细胞的生长和存活率,同时也影响细胞的增殖能力。64Cu 的吸收、癌症干样细胞的存在和 ROS 的产生与治疗反应一致。然而,CTR1的表达水平与摄取水平并不一致,这表明64Cu的摄取可能涉及其他机制:总之,我们的研究结果进一步支持了[64Cu]CuCl2作为胶质母细胞瘤治疗剂的潜力,揭示了可能参与治疗反应的潜在机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of the theranostic potential of [64Cu]CuCl2 in glioblastoma spheroids.

Background: Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS).

Results: Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu.

Conclusions: Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.

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来源期刊
EJNMMI Research
EJNMMI Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-
CiteScore
5.90
自引率
3.10%
发文量
72
审稿时长
13 weeks
期刊介绍: EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies. The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.
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