He Peng, Zhang Bing, Zou Yuan, Zhang Yan, Zha Zhihao, Long Yali, Qiu Jia, Shen Wanqing, Lin Xiaoping, Li Zhoulei, Zhang Xiangsong
Department of Nuclear Medicine & Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Department of Ultrasound Medicine & Ultrasonic Medical Engineering Key Laboratory of Nanchong City, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
Transl Oncol. 2021 May;14(5):101055. doi: 10.1016/j.tranon.2021.101055. Epub 2021 Mar 4.
L-ascorbic acid (AA) was reported to have an anti-cancer effect over 40 years. In recent years, several ongoing clinical trials are exploring the safety and efficacy of intravenous high-dose AA for cancer treatment. The lack of appropriate imaging modality limits the identification of potentially suitable patients for AA treatment. This study focuses on identifying AA-sensitive tumor cells using molecular imaging. 6-Deoxy-6-[F] fluoro-L-ascorbic Acid (F-DFA), a structural analog of AA, was synthesized and labeled to visualize the metabolism of AA in vivo. Colorectal cancer (CRC) cell lines with high and low expression of sodium-dependent vitamin C transporters 2 (SVCT2) were used for a series of cellular uptake tests. PET imaging was performed on xenograft tumor-bearing mice. More AA uptake was observed in CRC cells with high SVCT2 expression than in cells with low SVCT2 expression. The substrate (unlabeled AA) can competitively inhibit the F-DFA tracer uptake by CRC cells. The biodistribution of F-DFA in mice showed high radioactivity was seen in organs such as adrenal glands, kidneys, and liver that were known to have high concentrations of AA. Both PET imaging and tissue distribution showed that cancer cells with high SVCT2 expression enhanced the accumulation of F-DFA in mice after tumor formation. Immunohistochemistry was used to verify the corresponding results. As a radiotracer, F-DFA can provide powerful imaging information to identify tumor with high affinity of AA, and SVCT2 can be a potential biomarker in this process.
据报道，L-抗坏血酸（AA）在40多年前就被发现具有抗癌作用。近年来，多项正在进行的临床试验正在探索静脉注射高剂量AA治疗癌症的安全性和有效性。缺乏合适的成像方式限制了对可能适合接受AA治疗的患者的识别。本研究聚焦于利用分子成像识别对AA敏感的肿瘤细胞。合成并标记了AA的结构类似物6-脱氧-6-[F]氟-L-抗坏血酸（F-DFA），以可视化AA在体内的代谢情况。使用钠依赖性维生素C转运蛋白2（SVCT2）高表达和低表达的结直肠癌（CRC）细胞系进行了一系列细胞摄取试验。对荷瘤异种移植小鼠进行了PET成像。观察到SVCT2高表达的CRC细胞比SVCT2低表达的细胞摄取更多的AA。底物（未标记的AA）可竞争性抑制CRC细胞对F-DFA示踪剂的摄取。F-DFA在小鼠体内的生物分布显示，在已知AA浓度较高的肾上腺、肾脏和肝脏等器官中可见高放射性。PET成像和组织分布均显示，肿瘤形成后，SVCT2高表达的癌细胞增强了F-DFA在小鼠体内的蓄积。采用免疫组织化学法验证相应结果。作为一种放射性示踪剂，F-DFA可为识别对AA具有高亲和力的肿瘤提供有力的成像信息，而SVCT2可能是这一过程中的潜在生物标志物。
