Hyperpolarized [1-13C]-ascorbic and dehydroascorbic acid: vitamin C as a probe for imaging redox status in vivo.
Hyperpolarized [1-13C]-ascorbic and dehydroascorbic acid: vitamin C as a probe for imaging redox status in vivo.
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DOI：
10.1021/ja2045925
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发表时间：
2011-08-03
影响因子：
15
通讯作者：
Brindle, Kevin M.
中科院分区：
文献类型：
--
作者：
Bohndiek, Sarah E.;Kettunen, Mikko I.;Hu, De-en;Kennedy, Brett W. C.;Boren, Joan;Gallagher, Ferdia A.;Brindle, Kevin M.
13C标记的代谢底物在体外的动态核极化(DNP)及其随后的静脉给药允许在体内检测超极化底物的位置及其随后转化为其他代谢产物的动力学。我们报道了维生素C的还原和氧化形式[1-13C]-抗坏血酸(AA)和[1-13C]-脱氢抗坏血酸(DHA)的超极化，并评价了它们作为肿瘤氧化还原状态探针的性能。在pH 3.2时，两种形式的溶液极化分别为10.5±1.3%和5.1±0.6%，而在pH 7.0时，[1-13C]-AA和[1-13C]-DHA的保留极化分别为5.1±0.6%和8.2±1.1%。这些标记核的自旋-晶格弛豫时间(T1‘S)在9.4T处较长：AA核为15.9±0.7 S，DHA核为20.5±0.9 S。在小鼠淋巴瘤细胞悬液中观察到[1-13C]-AA的胞外氧化和[1-13C]-DHA的胞内还原。体外监测到DHA与细胞抗氧化剂谷胱甘肽的自发反应，其反应速度比细胞悬浮液中观察到的速度低约100倍，表明酶参与了细胞内的还原。在体内的淋巴瘤肿瘤中也检测到[1-13C]-DHA的减少。相反，在相同的肿瘤中没有检测到[1-13C]-AA的氧化，这与肿瘤维持减少的微环境的概念是一致的。这项研究表明，超极化的13C标记的维生素C可以作为体内氧化还原状态的非侵入性生物标志物，具有转化为临床的潜力。
Dynamic nuclear polarization (DNP) of 13C-labeled metabolic substrates in vitro and their subsequent intravenous administration allow both the location of the hyperpolarized substrate and the dynamics of its subsequent conversion into other metabolic products to be detected in vivo. We report here the hyperpolarization of [1-13C]-ascorbic acid (AA) and [1-13C]-dehydroascorbic acid (DHA), the reduced and oxidized forms of vitamin C, respectively, and evaluate their performance as probes of tumor redox state. Solution-state polarization of 10.5 ± 1.3% was achieved for both forms at pH 3.2, whereas at pH 7.0, [1-13C]-AA retained polarization of 5.1 ± 0.6% and [1-13C]-DHA retained 8.2 ± 1.1%. The spin–lattice relaxation times (T1's) for these labeled nuclei are long at 9.4 T: 15.9 ± 0.7 s for AA and 20.5 ± 0.9 s for DHA. Extracellular oxidation of [1-13C]-AA and intracellular reduction of [1-13C]-DHA were observed in suspensions of murine lymphoma cells. The spontaneous reaction of DHA with the cellular antioxidant glutathione was monitored in vitro and was approximately 100-fold lower than the rate observed in cell suspensions, indicating enzymatic involvement in the intracellular reduction. [1-13C]-DHA reduction was also detected in lymphoma tumors in vivo. In contrast, no detectable oxidation of [1-13C]-AA was measured in the same tumors, consistent with the notion that tumors maintain a reduced microenvironment. This study demonstrates that hyperpolarized 13C-labeled vitamin C could be used as a noninvasive biomarker of redox status in vivo, which has the potential to translate to the clinic.
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影响因子：
3.5
作者：
Halliwell, B
通讯作者：
Halliwell, B
影响因子：
5.7
作者：
Bohndiek SE;Kettunen MI;Hu DE;Witney TH;Kennedy BW;Gallagher FA;Brindle KM
通讯作者：
Brindle KM
影响因子：
2.8
作者：
Battisti, Vanessa;Maders, Liesi D. K.;Morsch, Vera M.
通讯作者：
Morsch, Vera M.
影响因子：
82.9
作者：
Day, Sam E.;Kettunen, Mikko I.;Brindle, Kevin M.
通讯作者：
Brindle, Kevin M.
影响因子：
2.9
作者：
Himmelreich, U;Drew, KN;Kuchel, PW
通讯作者：
Kuchel, PW