Real Time Metabolic Imaging to Interrogate Early Detection and Prevention of Pancreatic Cancer

实时代谢成像探讨胰腺癌的早期检测和预防

• 批准号: 10744576
• 负责人: Jose S Enriquez
• 金额: $ 3.72万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744576
• 关键词: Alanine; Anatomy; Animal Model; Animals; Area; Biochemical; Biological Markers; Biology; Cancer Center; Cancer Detection; Cancer Etiology; Cessation of life; Clinical; Contrast Media; Cyst; Data Analyses; Detection; Development; Diagnosis; Disease; Disease Progression; Doctor of Medicine; Doctor of Philosophy; Early Diagnosis; Educational process of instructing; Fellowship; Future; Genetic Models; Genetically Engineered Mouse; Genomics; Goals; Histological Techniques; Image; Imaging Techniques; Immunoprevention; Immunotherapy; Indolent; Inflammation; Institution; Laboratories; Learning; Lesion; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Mentors; Metabolic; Metabolism; Methodology; Methods; Modality; Modeling; Monitor; Morphology; Non-Invasive Detection; Pancreas; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraepithelial Neoplasia; Pattern; Phase; Positron-Emission Tomography; Postdoctoral Fellow; Prevalence; Prevention; Prevention Measures; Prevention strategy; Production; Public Speaking; Pyruvate; Recommendation; Research; Research Project Grants; Research Proposals; Scientist; Sensitivity and Specificity; Signal Transduction; Specificity; Survival Rate; Symptoms; Techniques; Time; Tissues; Training; Translating; United States; Warburg Effect; Work; Writing; cancer imaging; cancer prevention; cancer type; chronic pancreatitis; detection method; efficacy evaluation; efficacy testing; extracellular; high risk; human subject; imaging approach; imaging modality; imaging system; in vivo; in vivo imaging; innovation; metabolic imaging; metabolomics; molecular imaging; mouse model; neoplastic; non-invasive imaging; non-invasive monitor; novel; overtreatment; pancreatic cancer model; pancreatic ductal adenocarcinoma model; pre-clinical; premalignant; prevent; skills; specific biomarkers; success; tool; transcriptomics; tumor; tumor microenvironment

Project Summary Pancreatic ductal adenocarcinoma (PDAC) has a median 5-year survival of only 11%, and early diagnosis of PDAC is recognized as one of the highest priority areas by the NCI, with a focus on identification of more sensitive and specific biomarkers and imaging strategies in discernible preneoplastic lesions. The overarching goal of this proposal is to develop the capability of non-invasively detecting advanced pancreatic intraepithelial neoplasia (PanIN) precursor lesions in pancreas prior to invasive disease in human subjects using two magnetic resonance imaging-based tools: a) hyperpolarized metabolic imaging (HP MR) and b) acidoCEST MRI. Hyperpolarization increases the signal of conventional MRI by over 10,000-fold. AcidoCEST MRI uses a clinically approved contrast agent to quantitatively measure the extracellular pH (pHe) in the tumor microenvironment. The application of dual acidoCEST and HP MR is innovative as they interrogate two different but related biochemical features of PanINs: extracellular pH (pHe) and dynamic metabolic flux (HP lactate-to- pyruvate and HP alanine-to-pyruvate ratios), respectively. Together, this approach provides an exciting opportunity to identify and understand early metabolic aberrations and biomarkers associated with these early lesions, to enable detection of advanced pancreatic preneoplastic lesions as well as pancreatic cancer at the smallest size, for which no methods of detection currently exist. This is a transitional research proposal with multiple sponsors for the F99 phase. Including the laboratories of Pratip Bhattacharya, Ph.D. in the Department of Cancer Systems Imaging and Florencia McAllister, M.D. in the Department of Clinical Cancer Prevention, both at MD Anderson Cancer Center with the following two aims. Aim 1, the F99 phase, is to demonstrate and validate the sensitivity and specificity of dynamic hyperpolarized metabolic biomarkers in the detection and monitoring the progression of pancreatic premalignant lesions to PDAC and compare these to a chronic pancreatitis model. Aim 2, the K00 phase research direction, is to demonstrate detection of PanIN with a combination of HP MR and acidoCEST and to determine the efficacy of immunoprevention on PanIN models. The success of this proposal has the potential for leading to practice changing recommendations for non-invasively detecting and monitoring advanced PanIN lesions and incipient pancreatic cancer, as well as to non-invasively assess the immunopreventive measures for cancer prevention. Also included in this proposal is a fellowship training plan to be conducted in both the F99 and K00 phases. They include additional training in metabolomic data analysis, research skills in small animal handling, histological and imaging techniques, public speaking, and scientific writing during the F99 phase. For the K00 phase the training plan include establishing dual-imaging modalities, develop immunopreventative strategies, mentoring and teaching future scientists, and inter-departmental or institutional networking.

项目摘要 胰腺导管腺癌（PDAC）的中位5年生存率仅为11％，并且早期 NCI认为PDAC的诊断是最高优先级领域之一，重点是鉴定 在可识别的肿瘤病变中，更灵敏，更特定的生物标志物和成像策略。这 该提案的总体目标是发展非侵入性检测高级胰腺的能力 上皮内肿瘤（PANIN）在人类受试者的侵入性疾病之前使用胰腺的前体病变 两个基于磁共振成像的工具：a）超极化的代谢成像（HP MR）和b）酸索 MRI。超极化使常规MRI的信号增加了10,000倍以上。酸环MRI使用 临床认可的对比剂，以定量测量肿瘤中细胞外pH（PHE） 微环境。双重酸索和HP MR的应用是创新的，因为它们询问了两种不同的 但是PANIN的相关生化特征：细胞外pH（PHE）和动态代谢通量（HP乳酸到乳酸盐） 丙酮酸和HP丙氨酸与丙酮酸比）。这种方法共同提供了一种令人兴奋的 识别和理解与这些早期相关的早期代谢畸变和生物标志物的机会 病变，以便检测晚期胰腺前塑性病变以及胰腺癌 最小的大小，目前不存在检测方法。 这是F99阶段的多个赞助商的过渡研究建议。包括 Pratip Bhattacharya博士实验室在癌症系统成像部和佛罗伦萨 麦卡利斯特（McAllister），医学博士预防临床癌症部的医学博士，均位于MD安德森癌症中心 以下两个目标。 AIM 1（F99阶段）是为了证明和验证动态的灵敏度和特异性 在检测和监测胰腺预示出的进展中，超极化的代谢生物标志物 病变以PDAC并将其与慢性胰腺炎模型进行比较。 AIM 2，K00相研究方向， 是通过HP MR和酸索的组合证明Panin的检测并确定功效 Panin模型的免疫预防。该提议的成功有可能导致实践 更改针对非侵入性检测和监测高级Panin病变和初期的建议 胰腺癌以及非侵入性评估预防癌症的免疫预防措施。 该提案还包括一个奖学金培训计划，将在F99和K00中进行 阶段。它们包括代谢组数据分析，小动物处理技巧的其他培训， 在F99阶段，组织学和成像技术，公开演讲和科学写作。对于K00 阶段培训计划包括建立双重成像模式，制定免疫预防策略， 指导和教导未来的科学家，以及部门间或机构网络。