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

超极化 C-13 MRI 技术监测前列腺癌患者的放射治疗反应

• 批准号: 10653171
• 负责人: ROBERT A BOK
• 金额: $ 65.26万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653171
• 关键词: 3-Dimensional; Address; Biochemical; Bladder; Cancer Patient; Clinical; Critiques; Data; Detection; Development; Excretory function; Exhibits; FOLH1 gene; Failure; Gland; Goals; Heterogeneity; Human; Image; Image Guided Biopsy; Institution; Interdisciplinary Study; Investigation; Isotopes; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Measurable Disease; Measures; Medical Imaging; Metabolic; Metastatic Prostate Cancer; Methods; Modeling; Molecular; Monitor; Morbidity - disease rate; Neoplasm Metastasis; Pathologic; Patients; Pelvis; Phase; Physicians; Positron-Emission Tomography; Progressive Disease; Proliferating; Prostate; Prostate Cancer therapy; Pyruvate; Pyruvate Metabolism Pathway; Radiation Monitoring; Radiation Oncologist; Radiation therapy; Reaction Time; Regimen; Research; Research Design; Research Project Grants; Residual Cancers; Residual state; Resolution; Roentgen Rays; Safety; Schedule; Scientist; Screening for Prostate Cancer; Signal Transduction; Site; Stains; Techniques; Technology; Testing; Time; Tracer; Translating; Translations; cancer radiation therapy; clinically significant; cohort; cost; design; detector; disorder risk; early phase clinical trial; experience; fluorodeoxyglucose positron emission tomography; high risk; imaging approach; imaging biomarker; imaging scientist; improved; innovation; men; metabolic abnormality assessment; molecular imaging; novel; pre-clinical; radiation response; single photon emission computed tomography; temporal measurement; treatment response; tumor; uptake

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.

项目概要/摘要 该研究项目的目标是研究新型 3D 高级超极化 (HP) 13C-丙酮酸 MRI 立体定向身体辐射后定量监测前列腺癌代谢变化的技术 治疗 (SBRT) 并研究 HP 13C + 多参数 1H MRI 以检测术后残留/进展性癌症 RT，解决当前未满足的临床需求。这项研究试验很重要，因为放疗常常会导致过量 没有足够疗效的发病率，并且当前的成像方法不足以进行临床识别 放疗后出现严重癌症。 FDG-PET 成像在前列腺癌中显着受限，因为其局限性 在这种情况下，膀胱中的大量排泄妨碍了充分检测前列腺内信号的能力 即使在转移性环境中，摄取也存在显着的异质性，其中相当大比例的非 FDG 强烈，但仍然具有代谢活性并且肿瘤不断生长，原因与细胞内摄取和 FDG示踪剂的捕获。虽然我们使用 PSMA-PET 来识别转移性前列腺癌，但它不提供 HP 13C 所具有的有关前列腺癌侵袭性和治疗反应的代谢信息 在我们和其他站点的临床前和初步人体研究中得到了证明。 最近在全球多个地点对这种新兴成像方法进行的患者研究显示出可重复性 使用这种安全、快速、 快速 <5 分钟、非放射性分子 HP 13C MRI。不仅证明了其可行性，而且具有价值 生物医学信息的成本与 PSMA-PET 和其他 PET 检查相似或更低。该项目旨在研究 两组患者进行多参数（mp）1H MRI 和 HP 13C-丙酮酸 MRI（HP 13C mpMRI）； 1）之前， SBRT 后 3 个月和 1 年； 2) 患者出现“生化衰竭”，表现为“生化衰竭” 放射治疗后的 PSA，在选择进一步挽救之前要进行图像引导活检 治疗。我们通过解决之前的批评并包括新的初步意见来加强这次重新提交 数据采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，以转化和研究新的 HP 13C-丙酮酸 mpMRI 技术用于监测 RT 反应，以解决重要的未满足的临床问题 前列腺癌患者的治疗需求。