Suppr超能文献

基于 DOTA-姜黄素的潜在镓-68 标记放射性示踪剂用于结直肠癌细胞的研制:从合成到体内研究。

Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies.

机构信息

Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, via G. Campi 103, 41125 Modena, Italy.

Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Houston, TX 77054, USA.

出版信息

Molecules. 2019 Feb 12;24(3):644. doi: 10.3390/molecules24030644.

Abstract

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. Ga-DOTA-C21 exhibits decent stability (57 ± 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of Ga-DOTA-C21 is 3.57 ± 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3% ID/g), lungs (8.42 ± 0.8% ID/g), liver (5.81 ± 0.5% ID/g) and heart (4.70 ± 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.

摘要

结直肠癌是全世界男性中第三大常见癌症,女性中第二大常见癌症。我们最近报道,与正常人类淋巴细胞相比,用镓-68 标记的姜黄素复合物在 HT29 结直肠癌细胞和 K562 淋巴瘤细胞系中具有优先摄取作用。在本研究中,我们报告了一种新的镓-68 标记的姜黄素衍生物(Ga-DOTA-C21)及其作为结直肠癌早期检测标志物的初步验证。合成了前体和非放射性复合物,并通过分析方法对其进行了深入表征,然后用镓-68 对姜黄素进行了放射性标记。在 HT29 细胞中研究了探针的体外稳定性、细胞摄取、内化和外排特性,并在皮下荷 HT29 肿瘤模型的小鼠中研究了探针的体内靶向能力和生物分布。Ga-DOTA-C21 在生理介质中具有良好的稳定性(孵育 120 分钟后为 57 ± 3%),并在结直肠癌细胞系中表现出姜黄素介导的细胞积累(孵育 60 分钟内每毫克蛋白质摄取 121 ± 4 KBq 放射性示踪剂)。在荷 HT29 肿瘤的小鼠中,注射后 90 分钟,Ga-DOTA-C21 在肿瘤组织中的摄取量为每克组织 3.57 ± 0.3%注射剂量,肿瘤与肌肉的比值为 2.2 ± 0.2。在血液中记录到大量的放射性(12.73 ± 1.9% ID/g),放射性示踪剂在肠道(13.56 ± 3.3% ID/g)、肺(8.42 ± 0.8% ID/g)、肝(5.81 ± 0.5% ID/g)和心脏(4.70 ± 0.4% ID/g)中也有明显摄取。需要进一步研究以了解积累和清除的机制;然而,Ga-DOTA-C21 为开发用于结直肠癌成像的进一步放射性示踪剂提供了有成效的基础结构。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验