Hyperpolarized 13c NMR Studies of Prostate Cancer (RMI)

描述（由申请人提供）： 一个非凡的新技术，利用超极化13 C标记的探针有可能革命性的观察关键细胞代谢过程的非侵入性体内的MR。证明的原则动物研究已经证明了高达40,000倍的极化增强13 C标记的丙酮酸，提供足够的信号，肿瘤代谢物丙氨酸和乳酸盐的快速成像。在这个与GE Healthcare科学家的合作项目中，我们的目标是首次将联合收割机超极化13 C标记探针（如丙酮酸盐和乙酸盐）与高场人体MR扫描仪、优化的射频接收器和快速光谱成像脉冲序列相结合，以获得前列腺癌13 C代谢成像灵敏度的约4个数量级增加。前列腺癌的准确检测和表征仍然是个体前列腺癌患者的临床管理和监测治疗中的主要问题。虽然MRI和1H MR光谱成像的组合已经显示出改善前列腺癌检测和治疗前后表征的巨大前景，但该技术的价值目前受到其粗糙的空间和光谱分辨率的限制。使用13 C标记的丙酮酸盐和乙酸盐提供了同时评估通过多种生化途径（糖酵解、柠檬酸循环和脂肪酸合成）的代谢通量变化的可能性。所有这三种途径已被证明具有与人类前列腺癌的演变和进展相关的代谢扰动。在一系列涉及完整人前列腺活检、用13 C标记底物培养的人前列腺细胞系和注射13 C标记底物的转基因小鼠的离体HR-MAS光谱分析的研究中，我们将：（1）确定最能识别前列腺癌的存在并表征其侵袭性的关键13 C标记的代谢物，和（2）测定I3 C标记掺入关键代谢物的动力学以及I3 C标记代谢物的T1和T2弛豫时间。这些数据将与专门的射频探测器、快速13 C光谱成像脉冲序列以及数据重建和分析协议相结合，以在前列腺癌患者的初步研究中检测超极化13 C标记的代谢成像探针。

DESCRIPTION (provided by applicant): An extraordinary new technique utilizing hyperpolarized 13C labeled probes has the potential to revolutionize the observation of key cellular metabolic processes non-invasively in vivo by MR. Proof-of-principle animal studies have demonstrated up to 40,000 fold polarization enhancements of 13C labeled pyruvate, providing sufficient signal for rapid imaging of the tumor metabolites alanine and lactate. In this collaborative project with GE Healthcare scientists, we aim to, for the first time, combine hyperpolarized 13C labeled probes such as pyruvate and acetate with high field human MR scanners, optimized rf receivers and fast spectroscopic imaging pulse sequences, to obtain an approximately 4 order of magnitude increase in sensitivity for 13C metabolic imaging of prostate cancer. The accurate detection and characterization of prostate cancer remains a major problem in the clinical management of individual prostate cancer patients and in monitoring therapy. While a combination of MRI and 1H MR spectroscopic imaging has shown great promise for improving prostate cancer detection and characterization prior to and following therapy, the value of this technique is currently limited by its coarse spatial and spectral resolution. The use of 13C labeled pyruvate, and acetate provide the potential to simultaneously assess changes in metabolic fluxes through multiple biochemical pathways (glycolysis, citric acid cycle and fatty acid synthesis) simultaneously. All three of these pathways have been shown to have metabolic perturbations associated with the evolution and progression of human prostate cancer. In a series of studies involving ex vivo HR-MAS spectroscopic analysis of intact human prostate biopsies, human prostate cell lines cultured with 13C labeled substrates, and transgenic mice injected with 13C labeled substrate we will; (1) determine the key 13C labeled metabolites that best identify the presence of prostate cancer and characterize its aggressiveness, and (2) determine the kinetics of incorporation of I3C labels into the key metabolites as well as, the T1 and T2 relaxation times of the I3C labeled metabolites. This data will be combined with specialized rf detectors, fast 13C spectroscopic imaging pulse sequences, and data reconstruction and analysis protocols to detect hyperpolarized 13C labeled metabolic imaging probes in preliminary studies of prostate cancer patients.