Quantitative PET Imaging of Hepatocellular Carcinoma (HCC)

肝细胞癌 (HCC) 的定量 PET 成像

• 批准号: 9890526
• 负责人: Henry Charles Manning
• 金额: $ 58.58万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9890526
• 关键词: Acetates; American Cancer Society; Asia; Benign; Biology; Brain; Breast; Cessation of life; Cirrhosis; Clinical; Clinical Management; Clinical Oncology; Clinical Research; Clinical Trials; Colon; Colon Carcinoma; Data; Data Analyses; Decision Making; Detection; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic tests; Discrimination; Effectiveness; Eligibility Determination; Emission-Computed Tomography; Evaluation; Excision; Exhibits; Feasibility Studies; Future; Glutamates; Glutamic Acid; Goals; Healthcare; Human; Image; Imaging Device; Incidence; Individual; Intervention; Lesion; Liver; Liver neoplasms; Lung; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of brain; Malignant neoplasm of liver; Malignant neoplasm of lung; Measures; Methodology; Methods; Modality; Molecular; Oncology; Operative Surgical Procedures; Pathology; Patient Care; Patient Schedules; Patient Selection; Patients; Pattern; Pilot Projects; Positron-Emission Tomography; Primary Malignant Neoplasm of Liver; Primary Neoplasm; Primary carcinoma of the liver cells; Protocols documentation; Randomized; Role; Safety; Schedule; Sensitivity and Specificity; Specimen; Staging; Standardization; Testing; Tracer; Transplant Recipients; Tumor Tissue; United States; X-Ray Computed Tomography; anatomic imaging; clinical imaging; cohort; comorbidity; fluorodeoxyglucose; imaging approach; imaging modality; imaging study; immunohistochemical markers; improved; innovation; insight; liver transplantation; malignant breast neoplasm; metabolic profile; molecular imaging; non-invasive imaging; novel; novel diagnostics; personalized care; personalized decision; pharmacokinetic model; precision oncology; prevent; prospective; quantitative imaging; research clinical testing; standard of care; statistics; tool; tumor; tumor behavior; tumor metabolism; uptake

PROJECT SUMMARY/ABSTRACT: Quantitative PET Imaging of Hepatocellular Carcinoma Clinical decisions regarding the treatment of patients with hepatocellular carcinoma (HCC) remain largely guided by conventional, anatomical imaging modalities. These methods, namely magnetic resonance imaging (MRI) and x-ray computed tomography (CT), provide little information about the cellular and molecular underpinnings of individual tumors. HCC is the most common primary tumor of the liver and represents a major healthcare challenge in the United States (US) and elsewhere. The American Cancer Society estimates diagnosis of greater than 42,000 new cases of liver cancer in the US this year. In contrast to cancers more frequently diagnosed in the US and for which precision cancer medicine is routinely employed, such as colon or breast, incidence of liver cancer and liver cancer-associated deaths are both increasing. Improved tools to detect HCC at early, potentially curable stages, and tools to predict future tumor behavior are urgently needed. Molecular imaging with positron emission tomography (PET) is uniquely poised to provide those tools, yet novel tracers are required. The sensitivity of routine 18F-FDG PET, the most commonly utilized approach in clinical oncology, is limited in HCC, and other tracers that exhibit greater potential, such as 11C-acetate, suffer technical limitations that prevent their broad clinical use. The overarching goal of this application is to clinically evaluate an innovative PET imaging tracer that has the potential to personalize decision making in the care of patients with HCC. We propose to conduct the first quantitative imaging clinical trial of (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid (18F-FSPG) PET in the setting of HCC. As an emerging PET tracer reflecting tumor glutamate transport, 18F-FSPG PET has shown clinical safety and efficacy in multiple tumor settings, including breast, lung, and brain cancer. Our preliminary data in a pilot cohort of Vanderbilt patients, as well as a pilot clinical study conducted in Asia (n = 5), suggest the feasibility of using 18F-FSPG PET to improve the detection of HCCs even among cirrhosis, a comorbidity that diminishes the effectiveness of conventional imaging approaches. Our study has three Specific Aims. In patients undergoing surgery for treatment of HCC, we will (1) evaluate the relationship between 18F-FSPG PET, pathology and cancer metabolism; (2) compare 18F-FSPG PET with standard-of-care (SOC) diagnostic imaging in patients with HCC and benign liver lesions; and (3) compare uptake of 18F-FSPG with 11C-acetate and 18F-FDG in HCC and background liver. This study has the potential to establish a new role for non-invasive molecular imaging in the delivery of individualized cancer care for patients with HCC.

项目摘要/摘要：肝细胞癌的定量 PET 成像 关于肝细胞癌 (HCC) 患者治疗的临床决策在很大程度上仍受指导 通过传统的解剖成像方式。这些方法，即磁共振成像（MRI） 和 X 射线计算机断层扫描 (CT)，提供的有关细胞和分子基础的信息很少 单个肿瘤。 HCC 是肝脏最常见的原发性肿瘤，代表着一项主要的医疗保健 美国和其他地方的挑战。美国癌症协会估计诊断范围更大 美国今年新增肝癌病例超过 42,000 例。与更频繁地诊断出的癌症相比 在美国，常规采用精准癌症治疗的国家，例如结肠癌或乳腺癌，肝癌的发病率 癌症和肝癌相关​​的死亡人数都在增加。改进的工具可尽早检测 HCC 迫切需要可治愈的阶段和预测未来肿瘤行为的工具。正电子分子成像 发射断层扫描 (PET) 具有独特的能力来提供这些工具，但需要新颖的示踪剂。这 常规 18F-FDG PET（临床肿瘤学中最常用的方法）在 HCC 中的敏感性有限， 以及其他表现出更大潜力的示踪剂，例如 11C-乙酸盐，都受到技术限制，阻碍了其应用 临床用途广泛。该应用的总体目标是临床评估创新的 PET 成像 示踪剂有可能使 HCC 患者的护理决策个性化。我们建议 进行第一个(S)-4-(3-[18F]氟丙基)-L-谷氨酸(18F-FSPG) PET定量成像临床试验 在 HCC 的情况下。作为一种反映肿瘤谷氨酸转运的新兴PET示踪剂，18F-FSPG PET已显示 在多种肿瘤环境中的临床安全性和有效性，包括乳腺癌、肺癌和脑癌。我们的初步 范德比尔特患者试点队列的数据以及在亚洲进行的试点临床研究（n = 5）表明 使用 18F-FSPG PET 提高 HCC 检测的可行性，甚至在肝硬化中也是如此，肝硬化是一种合并症， 降低了传统成像方法的有效性。我们的研究有三个具体目标。在患者中 接受手术治疗 HCC 时，我们将 (1) 评估 18F-FSPG PET、病理学之间的关系 和癌症代谢； (2) 将 18F-FSPG PET 与患者标准护理 (SOC) 诊断成像进行比较 患有 HCC 和良性肝脏病变； (3) 比较 HCC 中 18F-FSPG 与 11C-乙酸盐和 18F-FDG 的摄取 和背景肝脏。这项研究有可能在非侵入性分子成像领域发挥新作用 为 HCC 患者提供个体化癌症护理。