Hyperpolarized C-13 MRI Techniques to Monitor Radiation Therapy Response in Prostate Cancer Patients

项目摘要/摘要 本研究项目的目标是研究新的3D高级超极化(HP)13C-丙酮酸磁共振成像 前列腺癌立体定向全身放射治疗后代谢变化的定量监测技术 Hp 13C多参数1H MRI检测术后残留/进展期肿瘤的研究 RT，解决当前未得到满足的临床需求。这项研究试验很重要，因为RT经常导致过量 没有足够疗效的发病率和目前的成像方法不足以在临床上识别 放射治疗后的重大癌症。FDG-PET成像在前列腺癌中的应用受到很大限制，因为局限于 在这种情况下，膀胱中的大量排泄物阻碍了充分检测前列腺内信号的能力 即使在转移的环境中，摄取也存在显着的异质性，相当大比例的非 FDG渴望，但仍在代谢活跃和生长的肿瘤，原因与细胞内摄取和 诱捕FDG示踪剂。虽然我们使用PSMA-PET来识别转移性前列腺癌，但它不能提供 Hp 13C对前列腺癌侵袭性和治疗反应的代谢信息 在我们和其他地点进行的临床前和初步人体研究中证明了这一点。 最近在全球多个地点对这种新兴成像方法的患者研究表明，这种方法是可重复的。 使用这种安全、快速、高效的药物，可显著上调LDH催化的癌症中丙酮酸到乳酸的转化。 快速5min，非放射性分子Hp 13C MRI。它不仅证明了可行性，而且具有重要的价值。 生物医学信息的成本与PSMA-PET和其他PET检查相似或更低。本项目旨在研究 两组患者均行多参数(MP)1H MRI+HP 13C-丙酮酸MRI(HP 13C-mpMRI)：1)治疗前、治疗前、治疗后1个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个月、2个 在SBRT后3个月和1年后；以及2)表现出“生化衰竭”的患者，表明 放射治疗后的PSA在选择进一步挽救之前继续进行影像引导下的活检 治疗。我们通过处理先前的批评并包括新的初步报告来加强这一重新提交 数据应用新改进的惠普技术。我们的多学科研究团队在以下方面拥有丰富的经验 进行早期临床试验，并将前列腺癌成像科学家的专业知识与 医生/科学家和放射肿瘤学家推进我们的初步研究，以翻译和研究新的 HP 13C-丙酮酸mpMRI技术用于监测RT反应，以解决重要的未满足临床要求 前列腺癌患者治疗中的需要。

Project Summary/Abstract The goal of this research project is to investigate new 3D advanced hyperpolarized (HP) 13C-pyruvate MRI techniques to quantitatively monitor metabolic changes in prostate cancer following stereotactic body radiation therapy (SBRT) and to study HP 13C + multiparametric 1H MRI for detecting residual/progressive cancer following RT, addressing current unmet clinical needs. This research trial is important because RT too often causes excess morbidity without sufficient efficacy and current imaging approaches are inadequate in identifying clinically significant cancer following RT. FDG-PET imaging is significantly limited in prostate cancer since in the localized setting, significant excretion in the bladder precludes the ability to adequately detect signal within the prostate and even in the metastatic setting there is significant heterogeneity of uptake with substantial proportion of non- FDG avid, yet still metabolically active and growing tumors, for reasons related to intra-cellular uptake and trapping of the FDG tracer. While we use PSMA-PET, to identify metastatic prostate cancer, it does not provide the metabolic information on prostate cancer aggressiveness and response to therapy that HP 13C has demonstrated in preclinical and initial human studies at our and other sites. Recent patient studies of this emerging imaging approach at multiple sites world-wide have shown repeatable findings of greatly up-regulated LDH catalyzed pyruvate-to-lactate conversions in cancer using this safe, rapid, fast <5 min, non-radioactive molecular HP 13C MRI. It has demonstrated not only feasibility, but also valuable biomedical information at costs similar or less than PSMA-PET and other PET exams. This project aims to study two groups of patients with multiparametric (mp) 1H MRI with HP 13C-pyruvate MRI (HP 13C mpMRI); 1) Before, 3 months after, and 1 year following SBRT; and 2) patients exhibiting “biochemical failure” indicated by a rising PSA after radiation therapy who are going on to image-guided biopsies prior to selection of further salvage treatment. We strengthened this resubmission by addressing the prior critiques and including new preliminary data applying new improved HP technology. Our multidisciplinary research team has extensive experience in conducting early phase clinical trials and combines the expertise of prostate cancer imaging scientists with physician/scientists and radiation oncologists to advance our preliminary studies to translate and investigate new HP 13C-pyruvate mpMRI techniques for monitoring RT response in order to address important unmet clinical needs in the treatment of prostate cancer patients.