Department of Radiology and Biomedical Imaging, University of California San Francisco (UCSF), 1700 fourth St., Byers Hall 203, San Francisco, California 94158, USA.
J Am Chem Soc. 2009 Dec 9;131(48):17591-6. doi: 10.1021/ja9049355.
Hyperpolarized (13)C labeled molecular probes have been used to investigate metabolic pathways of interest as well as facilitate in vivo spectroscopic imaging by taking advantage of the dramatic signal enhancement provided by DNP. Due to the limited lifetime of the hyperpolarized nucleus, with signal decay dependent on T(1) relaxation, carboxylate carbons have been the primary targets for development of hyperpolarized metabolic probes. The use of these carbon nuclei makes it difficult to investigate upstream glycolytic processes, which have been related to both cancer metabolism as well as other metabolic abnormalities, such as fatty liver disease and diabetes. Glucose carbons have very short T(1)s (<1 s) and therefore cannot be used as an in vivo hyperpolarized metabolic probe of glycolysis. However, the pentose analogue fructose can also enter glycolysis through its phosphorylation by hexokinase and yield complementary information. The C(2) of fructose is a hemiketal that has a relatively longer relaxation time (approximately 16 s at 37 degrees C) and high solution state polarization (approximately 12%). Hyperpolarized [2-(13)C]-fructose was also injected into a transgenic model of prostate cancer (TRAMP) and demonstrated difference in uptake and metabolism in regions of tumor relative to surrounding tissue. Thus, this study demonstrates the first hyperpolarization of a carbohydrate carbon with a sufficient T(1) and solution state polarization for ex vivo spectroscopy and in vivo spectroscopic imaging studies.
已使用（13）C 标记的高极化分子探针来研究代谢途径，同时利用 DNP 提供的显著信号增强作用来促进体内光谱成像。由于极化核的有限寿命，信号衰减取决于 T1 弛豫，羧酸盐碳已成为开发高极化代谢探针的主要目标。这些碳原子的使用使得难以研究上游糖酵解过程，糖酵解过程与癌症代谢以及其他代谢异常（如脂肪肝疾病和糖尿病）有关。葡萄糖碳的 T1 非常短（<1 s），因此不能用作体内糖酵解的高极化代谢探针。然而，戊糖类似物果糖也可以通过己糖激酶的磷酸化进入糖酵解，并产生互补信息。果糖的 C（2）是一个半缩醛，其弛豫时间相对较长（在 37°C 时约为 16 s），溶液状态极化率高（约为 12%）。高极化[2-（13）C]果糖也被注射到前列腺癌（TRAMP）的转基因模型中，并在肿瘤区域与周围组织相比显示出不同的摄取和代谢。因此，这项研究首次展示了具有足够 T1 和溶液状态极化率的碳水化合物碳的极化，可用于离体光谱和体内光谱成像研究。
