Mamede A C, Abrantes A M, Pires A S, Tavares S D, Serra M E, Maia J M, Botelho M F
Biophysics/Biomathematics Institute, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Curr Radiopharm. 2012 Apr;5(2):106-12. doi: 10.2174/1874471011205020106.
Vitamin C exists in two forms: the reduced (ascorbic acid--AA) and oxidized form (dehydroascorbic acid--DHA). This is a nutrient whose benefits are long known and widely publicized, being most of them related to its antioxidant action. As an antioxidant, the main role of vitamin C is to neutralize free radicals, reducing oxidative stress. However, some controversial studies suggest that this nutrient may have a preventive and therapeutic role in cancer disease due to their possible pro-oxidant activity, promoting the formation of reactive oxygen species that can induce cell death in cancer cells. This factor, coupled with the decrease of antioxidant enzymes and increase of decompartmentalized transition metals in tumor cells may result in the selective cytotoxicity of vitamin C and the subsequent revelation of its therapeutic potential. In this way the first purpose of this work was radioactively label the reduced form of vitamin C with Tc-99m, its quality control by HPLC and the time stability. The second purpose was to use the radioactive complex 99mTc-AA in in vitro and in vivo studies in order to evaluate its uptake by colorectal cancer cells and biodistribution in mices, respectively. The results suggest that the pharmaceutical formulation developed, which was reproducible and stable over time, was residually taken up by colorectal cancer cells. Future studies are needed to deepen our understanding about the radioactive complex 99mTc-AA and clarify the mechanisms of action of vitamin C in oncologic disease.
维生素C以两种形式存在：还原形式（抗坏血酸——AA）和氧化形式（脱氢抗坏血酸——DHA）。这是一种其益处早已为人所知且广泛宣传的营养素，其中大多数益处与其抗氧化作用有关。作为一种抗氧化剂，维生素C的主要作用是中和自由基，减轻氧化应激。然而，一些有争议的研究表明，这种营养素可能因其潜在的促氧化活性而在癌症疾病中具有预防和治疗作用，促进活性氧的形成，活性氧可诱导癌细胞死亡。这一因素，再加上肿瘤细胞中抗氧化酶的减少和分隔化过渡金属的增加，可能导致维生素C的选择性细胞毒性及其治疗潜力的后续显现。通过这种方式，这项工作的首要目的是用99mTc对维生素C的还原形式进行放射性标记，通过高效液相色谱法对其进行质量控制并检测其时间稳定性。第二个目的是在体外和体内研究中使用放射性复合物99mTc-AA，分别评估其被结肠癌细胞摄取的情况以及在小鼠体内的生物分布。结果表明，所开发的药物制剂具有可重复性且随时间稳定，能被结肠癌细胞残留摄取。未来需要开展更多研究以加深我们对放射性复合物99mTc-AA的理解，并阐明维生素C在肿瘤疾病中的作用机制。
