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

项目总结/摘要 本修订项目旨在研究一种新的安全、非放射性HP 13 C mpMRI检查方法， 为检测侵袭性前列腺癌的未满足的临床需求创造代谢成像解决方案， 入组前或接受“主动监测”的患者，与“金标准”MR/US融合相关- 引导活检发现和其他临床测量，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， 他说：“该FOA的具体目标是促进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和 这不是“。为了回应先前的批评，我们在以下情况下对本研究申请进行了重大修改： 审查员的建议，并解决他们的关切。 我们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，以确定 未经治疗的前列腺癌患者（每年数千人）只有低风险疾病，可以管理 通过主动监测（AS），患有侵袭性癌症，活检时错过，但仍然局限于器官， 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中的高摄取阻碍了高级别癌症的关键检测 在前列腺内。基于强有力的初步临床前和患者数据，显示了以下因素的显著相关性： 在高级别前列腺癌中HP 13 C-丙酮酸转化为13 C-乳酸的升高，我们的临床团队创建了这个 研究设计测试了改进的、安全的、低成本的HP 13 C MR分子成像技术，作为5分钟的补充， 与后续MR/US融合引导活检结果相关的标准护理mpMRI检查;“gold- “标准”是针对这一人群的。我们的目标是研究转诊接受mpMRI的患者（N=110），以排除 在决定AS之前或由于PSA升高而在活检诊断时漏诊侵袭性疾病 在AS。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，以确定是否有任何kPL显著增加 前列腺内病变是疾病进展的早期预测因子（Gleason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）增加对进入AS的人的信心 没有侵袭性前列腺癌; 2）早期检测AS患者的侵袭性癌症; 3）改善 指导活检和代谢侵袭性器官局限性癌症的后续治疗。

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.