Hyperpolarized C-13 MRI for Early Detection of Aggressive Prostate Cancer in Active Surveillance Patients

超极化 C-13 MRI 用于早期检测主动监测患者的侵袭性前列腺癌

• 批准号: 9913482
• 负责人: ROBERT A BOK
• 金额: $ 65.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-11 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913482
• 关键词: 3-Dimensional; Address; Biopsy; Biopsy Specimen; Bladder; Blood flow; Cancer Patient; Clinical; Critiques; Data; Detection; Diagnosis; Disease; Disease Progression; Early Diagnosis; Early treatment; Enrollment; FOLH1 gene; Gene Expression Profiling; Genomics; Gland; Gleason Grade for Prostate Cancer; Goals; Gold; Grant; Heterogeneity; Histologic; Image; Image Guided Biopsy; Imaging Techniques; Individual; Institution; Lesion; Life; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Metabolic; Methods; Modeling; Operative Surgical Procedures; Organ; Patients; Perfusion; Positron-Emission Tomography; Prostate; Prostatic Tissue; Protocols documentation; Pyruvate; Readiness; Research; Research Design; Resolution; Sampling Errors; Scanning; Schedule; Suggestion; Techniques; Testing; Tissues; United States National Institutes of Health; base; cancer imaging; cohort; cost; design; disorder risk; early detection biomarkers; follow-up; imaging biomarker; improved; magnetic resonance spectroscopic imaging; men; metabolic imaging; molecular imaging; multidisciplinary; novel; overtreatment; patient population; pre-clinical; prostate cancer progression; prostate lesions; response; serum PSA; standard of care; success; temporal measurement; tumor; uptake

PROJECT SUMMARY/ABSTRACT This revised project is designed to investigate a new safe, non-radioactive HP 13C mpMRI exam approach for creating a metabolic imaging solution for the unmet clinical need of detecting aggressive prostate cancer in patients prior to enrollment or on “Active Surveillance” with correlations to “gold standard” MR/US fusion- guided biopsy findings, and other clinical measures including current imaging parameters. This project was designed to fit the goals of PAR-16-089 Imaging and Biomarkers for Early detection of Aggressive Cancer that states: “The specific objective of this FOA is to stimulate and support cancer imaging and biomarker research to develop, optimize, and clinically validate novel methods” to address the ““unmet clinical need to more accurately identify early-stage aggressive cancers and distinguish lesions that are life threatening from those that are not”. In response to the prior critique, we have significantly modified this study application following the reviewers' suggestions and addressing their concerns. The clinicians on our multidisciplinary team designed this revised study based on their unmet need to identify which untreated prostate cancer patients (thousands per year) have only low risk disease and can be managed by Active Surveillance (AS) and which have aggressive cancer, missed on biopsy, but still organ-confined and should be treated. Molecular imaging with FDG- or PSMA-PET is used for detecting metastatic disease, but high uptake in the bladder and normal prostatic tissues hinders the critical detection of high-grade cancer within the prostate. Based on strong preliminary preclinical & patient data showing a significant correlation of elevated HP 13C-pyruvate to 13C-lactate conversion in high grade prostate cancer, our clinical team created this study design testing improved, safe, lower-cost HP 13C MR molecular imaging techniques as a 5min addition to a standard-of-care mpMRI exam with correlations to subsequent MR/US fusion-guided biopsy findings; “gold- standard” for this patient population. We aim to study patients (N=110) referred for mpMRI either to rule out missed aggressive disease at biopsy diagnosis prior to deciding on AS or as a consequence of a rising PSA while on AS. Also a subset (N=44) of these patients that enter AS, will be followed yearly with HP+mpMRI exams followed by MR/US fusion-guided biopsies in order to determine if a significant increase in kPL of any intra-prostatic lesion is an early predictor of disease progression (Gleason score upgrading). The success of this project could have exceptional clinical impact including: 1) Increased confidence that those entering AS do not have aggressive prostate cancer; 2) Early detection of aggressive cancer in AS patients; and 3) Improved guidance of biopsy and subsequent treatment of metabolically aggressive organ-confined cancer.

项目概要/摘要 该修订项目旨在研究一种新的安全、非放射性 HP 13C mpMRI 检查方法，用于 为检测侵袭性前列腺癌这一未满足的临床需求创建代谢成像解决方案 入组前或进行“主动监测”的患者与“金标准”MR/US 融合相关 - 引导活检结果和其他临床测量，包括当前成像参数。这个项目是 旨在符合 PAR-16-089 早期检测侵袭性癌症的成像和生物标志物的目标 指出：“该 FOA 的具体目标是刺激和支持癌症成像和生物标志物研究 开发、优化和临床验证新方法”，以解决“未满足的临床需求 准确识别早期侵袭性癌症，并区分危及生命的病变 那些不是”。为了回应之前的批评，我们根据以下内容对本研究应用程序进行了重大修改 审稿人的建议并解决他们的关切。 我们的多学科团队的临床医生根据他们未满足的需求设计了这项修订后的研究，以识别 未经治疗的前列腺癌患者（每年数千名）仅患有低风险疾病并且可以得到控制 通过主动监测（AS），患有侵袭性癌症，未进行活检，但仍局限于器官，并且 应该治疗。 FDG 或 PSMA-PET 分子成像可用于检测转移性疾病，但 膀胱和正常前列腺组织的高摄取阻碍了高级别癌症的关键检测 前列腺内。基于强有力的初步临床前和患者数据，显示出显着相关性 在高级别前列腺癌中，HP 13C-丙酮酸向 13C-乳酸的转化升高，我们的临床团队创造了这个 研究设计测试改进、安全、成本更低的 HP 13C MR 分子成像技术，作为 5 分钟的补充 标准护理 mpMRI 检查与后续 MR/US 融合引导活检结果的相关性； “金子- 该患者群体的“标准”。我们的目标是研究转诊进行 mpMRI 的患者 (N=110)，以排除 在决定是否患有 AS 之前或由于 PSA 升高而在活检诊断中错过了侵袭性疾病 在AS上时。此外，这些进入 AS 的患者的子集 (N=44) 将每年接受 HP+mpMRI 随访 检查后进行 MR/US 融合引导活检，以确定任何 kPL 是否显着增加 前列腺内病变是疾病进展的早期预测因子（格里森评分升级）。的成功 该项目可能会产生特殊的临床影响，包括：1) 增加进入 AS 的人的信心 没有侵袭性前列腺癌； 2）早期发现AS患者侵袭性癌症； 3) 改进 指导代谢侵袭性器官局限性癌症的活检和后续治疗。