Reproducibility of Hyperpolarized Pyruvate Metabolic Imaging in Prostate Cancer

 描述（由申请人提供）：前列腺癌表现出巨大的生物多样性范围，目前对非手术治疗的临床评估通常不充分，因为研究表明，当依赖于血清前列腺特异性抗原（PSA）水平达到最低点或依赖于使用经直肠超声引导活检的癌症组织学确认时，不准确。对于前列腺癌的存在、侵袭性、激素状态和对治疗的早期反应的更敏感和特异性的分子成像生物标志物，仍然存在关键的临床需求。一种非凡的新技术，超极化磁共振（HP MR），有可能改变我们询问体内代谢的方式。通过利用13 C标记的内源性底物，我们能够使用常规MRI对代谢中间体及其后续下游产物进行非侵入性成像。在前列腺癌的情况下，这为研究前列腺癌代谢及其作为肿瘤侵袭性和对治疗干预的反应的函数的调节提供了潜在的无价工具。这项早期成像临床试验的目的是表征这项新技术（使用[1- 13 C]丙酮酸盐的HP MR）在2个前列腺癌患者队列中的重现性。在第一个队列（n = 20）中，患者将在不到3周的时间内使用动态磁共振波谱序列（动态）进行两次成像。这些数据将用于确定生物标志物动态及其向腺体输送的变异性。在第二个队列（n = 20）中，与第一个队列类似，使用高分辨率三维MR光谱成像序列（3D MRSI）对患者进行两次成像，以确定整个前列腺中HP生物标志物的再现性，并评估HP乳酸盐与前列腺癌生物学之间的关系。该提案的首要目标是确定患者中HP丙酮酸代谢成像的再现性，这可用作使用该技术进行未来研究的基准，并确定其告知前列腺生物学的能力。

 DESCRIPTION (provided by applicant): Prostate cancers demonstrate a tremendous range in biologic diversity and the current clinical assessment of response to non-surgical therapy is often inadequate because studies have shown inaccuracies when relying upon serum prostate specific antigen (PSA) levels reaching a nadir or upon the histological confirmation of cancer using transrectal ultrasound guided biopsies. There remains a critical clinical need for more sensitive and specific molecular imaging biomarkers of prostate cancer presence, aggressiveness, hormonal status and early response to therapy. An extraordinary new technique, hyperpolarized magnetic resonance (HP MR), has the potential to change the way we interrogate metabolism in vivo. Through the utilization of 13C labeled endogenous substrates we are able to non-invasively image a metabolic intermediate and its subsequent downstream products using conventional MRI. In the setting of prostate cancer, this provides a potentially invaluable tool for the study of prostate cancer metabolism and its modulation as a function of tumor aggressiveness and response to therapeutic intervention. The objective of this early stage clinical trial in imaging is to characterize the reproducibility of this new technique,HP MR with [1-13C] pyruvate in 2 cohorts of prostate cancer patients. In the first cohort (n = 20), patients will be imaged twice in less than 3 weeks using a dynamic magnetic resonance spectroscopy sequence (Dynamic). This data will be used to determine the variability in biomarker dynamics and their delivery to the gland. In a second cohort (n = 20), patients will be imaged twice, analogous to the first cohort, using a high-resolution three- dimensional MR spectroscopic imaging sequence (3D MRSI) in order to determine the reproducibility of HP biomarkers across the entire prostate and assess the relationship between HP Lactate and prostate cancer biology. It is the overarching goal of this proposal to determine the reproducibility of HP pyruvate metabolic imaging in patients, which can be used as a benchmark for future studies using this technique, and determine its ability to inform on prostate biology.