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制备和评估一种新的放射性示踪剂锝-99m-6-肼基烟酰胺-酪氨酸作为单光子发射断层扫描肿瘤检测的靶向剂。

Preparation and assessment of a new radiotracer technetium-99m-6-hydrazinonicotinic acid-tyrosine as a targeting agent in tumor detecting through single photon emission tomography.

机构信息

Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran.

Radiation Applications Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.

出版信息

Bioorg Chem. 2020 Nov;104:104181. doi: 10.1016/j.bioorg.2020.104181. Epub 2020 Aug 26.

Abstract

The goal of investigation was to bring up an impressive way to synthesize technetium-99 m-6-hydrazinonicotinic acid-tyrosine (Tc-HYNIC-Tyr), a newfound radiotracer, and to assess the capacity of being as a tumor scintigraphy agent. The conjugate was prepared by solid phase method using tritely chloride resin. The precursor HYNIC-Tyr was labeled with Tc which was accomplished at 100 °C through the coligands tricine and EDDA. Furthermore, the serum albumin binding, cellular attachment, organs uptake and tumor accumulation were measured. C6 glioma cells were used for cellular and tumor uptake studies. Tc-HYNIC-Tyr was prepared with labeling yield of >99% (n = 3). Radiotracer showed stability in serum proteins in incubates temperature. Specific cellular attachment of radiotracer was noticeable in C6 glioma cells with dissociation constant in nano molar range (21.03 ± 1.54 nM). The amount of uptake in C6 rat glioma xenograft was 2.61 ± 0.12 percent of injection dose per gram after 30 min. In whole-body scintigraphy, C6 glioma tumor was easy to be traced and interpreted at 1 h after administration of radiotracer. Our data suggest that Tc-HYNIC-Tyr, a new radiotracer based on amino acid, efficiently differentiates the tumor cells and goes into them. Our results indicate that this radiotracer has excellent capacity to detect tumor cells in rat and to be included as a radiopharmaceutical for detecting cancer tumors.

摘要

研究的目的是提出一种令人印象深刻的方法来合成锝-99m-6-肼基烟酸-酪氨酸(Tc-HYNIC-Tyr),这是一种新发现的放射性示踪剂,并评估其作为肿瘤闪烁显像剂的能力。该缀合物是通过固相法使用三氯甲烷树脂制备的。前体 HYNIC-Tyr 与 Tc 标记,在 100°C 下通过共配体三肽和 EDDA 完成。此外,还测量了血清白蛋白结合、细胞附着、器官摄取和肿瘤积聚。C6 神经胶质瘤细胞用于细胞和肿瘤摄取研究。Tc-HYNIC-Tyr 的标记产率>99%(n=3)。放射性示踪剂在孵育温度下的血清蛋白中表现出稳定性。放射性示踪剂在 C6 神经胶质瘤细胞中的特异性细胞附着明显,解离常数在纳摩尔范围内(21.03±1.54nM)。在 C6 大鼠神经胶质瘤异种移植中,30 分钟后每克注射剂量的摄取量为 2.61±0.12%。在全身闪烁显像中,在给予放射性示踪剂后 1 小时,C6 神经胶质瘤肿瘤易于追踪和解释。我们的数据表明,Tc-HYNIC-Tyr,一种基于氨基酸的新型放射性示踪剂,能够有效地区分肿瘤细胞并进入肿瘤细胞。我们的结果表明,这种放射性示踪剂具有在大鼠中检测肿瘤细胞的优异能力,并可作为用于检测癌症肿瘤的放射性药物。

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