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

项目摘要/摘要 该修订项目旨在研究一种新的安全、非放射性的Hp 13C mpMRI检查方法 为尚未满足的临床需求创建代谢成像解决方案以检测侵袭性前列腺癌 登记前或接受“积极监测”且与“黄金标准”MR/US融合相关的患者- 引导活检结果，以及其他临床测量，包括当前的成像参数。这个项目是 旨在符合PAR-16-089成像和生物标记物的目标，用于早期检测侵袭性癌症 声明：“FOA的具体目标是刺激和支持癌症成像和生物标记物研究 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和 不是的“。为了回应先前的批评，我们大幅修改了这项研究申请，遵循 审查人员的建议和解决他们所关注的问题。 我们多学科团队的临床医生根据他们尚未满足的需求设计了这项修订后的研究，以确定 哪些未经治疗的前列腺癌患者(每年数千人)只有低风险疾病，并且可以管理 通过主动监视(AS)，并且患有侵袭性癌症，未通过活检，但仍受器官限制和 应该得到治疗。FDG-或PSMA-PET分子成像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对高级别癌症的关键检测 在前列腺内。基于强大的初步临床前和患者数据显示显著的相关性 在高级别前列腺癌中，Hp 13C-丙酮酸到13C-乳酸的转化率升高，我们的临床团队创造了这个 研究设计测试改进、安全、低成本的HP 13C MR分子成像技术，作为5分钟的补充 标准护理mpMRI检查与随后的MR/US融合引导活检结果的相关性； 对这一患者群体来说是“标准”。我们的目标是研究转诊为mpMRI的患者(N=110)，以排除 在决定是否为AS或PSA升高的结果之前，活检诊断时漏诊了侵袭性疾病 在AS上的时候。此外，这些进入AS的患者中的一部分(N=44)将每年进行HP+mpMRI随访 检查后进行MR/US融合引导活检，以确定KPL是否显著增加 前列腺内病变是疾病进展的早期预测指标(Gleason评分升级)。的成功之处 这一项目可能会产生特殊的临床影响，包括：1)增强了那些以同样方式进入的人的信心 没有侵袭性前列腺癌；2)AS患者早期发现侵袭性癌症；以及3)情况有所改善 指导新陈代谢侵袭性器官受限癌的活检和后续治疗。

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.