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[锝]锝标记的脂质体:放射性标记、质量控制与评估。

[Tc]Technetium-Labeled Niosomes: Radiolabeling, Quality Control, and Evaluation.

作者信息

Ekinci Meliha, Çalışkan Emine Esin, Çakar Burak, İlem-Özdemir Derya, Uyanıkgil Yiğit, Çetin Uyanıkgil Emel Öykü

机构信息

Faculty of Pharmacy, Department of Radiopharmacy, Ege University, Bornova, 35040 Izmir, Türkiye.

Faculty of Pharmacy, Department of Pharmaceutical Technology, Department of Biopharmaceutics and Pharmacokinetics, Ege University, 35100 Izmir, Türkiye.

出版信息

ACS Omega. 2023 Feb 8;8(7):6279-6288. doi: 10.1021/acsomega.2c06179. eCollection 2023 Feb 21.

Abstract

The aim of this research was to develop technetium-99m ([Tc]Tc)-radiolabeled niosomes and evaluate the cancer cell incorporation capacity of radiolabeled niosomes. For this purpose, niosome formulations were developed by film hydration method, and prepared niosomes were characterized to particle size, polydispersity index (PdI), ζ-potential value, and image profile. Then, niosomes were radiolabeled with [Tc]Tc using stannous salts (chloride) as a reducing agent. The radiochemical purity (RP) and stability in different mediums of the niosomes were assessed by ascending radioactive thin-layer chromatography (RTLC) and radioactive ultrahigh-performance liquid chromatography (R-UPLC) methods. Also, the partition coefficient value of radiolabeled niosomes was determined. The cell incorporation of [Tc]Tc-labeled niosome formulations, as well as reduced/hydrolyzed (R/H)-[Tc]NaTcO in the HT-29 (human colorectal adenocarcinoma) cells, was then assessed. According to the obtained results, the spherical niosomes had a particle size of 130.5 ± 1.364 nm, a PdI value of 0.250 ± 0.023, and a negative charge of -35.4 ± 1.06 mV. The niosome formulations were effectively radiolabeled with [Tc]Tc using 500 μg mL stannous chloride for 15 min, and RP was found to be over 95%. [Tc]Tc-niosomes showed good stability in every system for up to 6 h. The log  value of radiolabeled niosomes was found as -0.66 ± 0.02. Compared to R/H-[Tc]NaTcO (34.18 ± 1.56%), the incorporation percentages of [Tc]Tc-niosomes (88.45 ± 2.54%) were shown to be higher in cancer cells. In conclusion, the newly developed [Tc]Tc-niosomes showed good prototype for potential use in nuclear medicine imaging in the near future. However, further investigations, such as drug encapsulation and biodistribution studies, should be performed, and our studies are continuing.

摘要

本研究的目的是开发锝-99m([Tc]Tc)放射性标记的脂质体,并评估放射性标记脂质体对癌细胞的摄取能力。为此,采用薄膜水化法制备脂质体制剂,并对制备的脂质体进行粒径、多分散指数(PdI)、ζ电位值和图像轮廓表征。然后,以氯化亚锡作为还原剂,用[Tc]Tc对脂质体进行放射性标记。通过上行放射性薄层色谱(RTLC)和放射性超高效液相色谱(R-UPLC)方法评估脂质体在不同介质中的放射化学纯度(RP)和稳定性。此外,还测定了放射性标记脂质体的分配系数值。随后评估了[Tc]Tc标记的脂质体制剂以及还原/水解(R/H)-[Tc]NaTcO在HT-29(人结肠腺癌)细胞中的摄取情况。根据所得结果,球形脂质体的粒径为130.5±1.364nm,PdI值为0.250±0.023,负电荷为-35.4±1.06mV。使用500μg/mL氯化亚锡对脂质体制剂进行15分钟的有效放射性标记,发现RP超过95%。[Tc]Tc-脂质体在每个系统中长达6小时都显示出良好的稳定性。放射性标记脂质体的log值为-0.66±0.02。与R/H-[Tc]NaTcO(34.18±1.56%)相比,[Tc]Tc-脂质体在癌细胞中的摄取百分比(88.45±2.54%)更高。总之,新开发的[Tc]Tc-脂质体在不久的将来显示出在核医学成像中潜在应用的良好原型。然而,应进行进一步的研究,如药物包封和生物分布研究,我们的研究仍在继续。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d66/9948160/81b519e927f7/ao2c06179_0002.jpg

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