Quantitative PET Imaging of Hepatocellular Carcinoma (HCC)

肝细胞癌 (HCC) 的定量 PET 成像

• 批准号: 10267667
• 负责人: Henry Charles Manning
• 金额: $ 58.74万
• 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/10267667
• 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：肝细胞癌的定量宠物成像 有关肝细胞癌（HCC）患者治疗的临床决策 通过常规的解剖成像方式。这些方法，即磁共振成像（MRI） 和X射线计算机断层扫描（CT），几乎没有有关细胞和分子基础的信息 单个肿瘤。 HCC是肝脏最常见的原发性肿瘤，代表了主要的医疗保健 美国（美国）和其他地方的挑战。美国癌症协会估计诊断更大 今年，美国比42,000例新的肝癌病例。与更频繁诊断的癌症相反 美国和经常使用精确癌症药物（例如结肠或乳房）的肝脏发病率 癌症和肝癌相关​​的死亡都在增加。改进了早期检测HCC的工具，可能 迫切需要治愈阶段和预测未来肿瘤行为的工具。分子成像与正电子 排放断层扫描（PET）是独特的准备提供这些工具的，但需要新颖的示踪剂。这 常规18F-FDG PET的敏感性是临床肿瘤学中最常用的方法，在HCC中受到限制 以及其他具有更大潜力的示踪剂，例如11c-乙酸盐，遭受了技术限制，以防止其 广泛的临床用途。该应用程序的总体目标是临床评估创新的宠物成像 示踪剂有可能在HCC患者的护理中个性化决策。我们建议 进行（S）-4-（3- [18F]氟丙基）-L-谷氨酸（18F-FSPG）PET的第一个定量成像临床试验 在HCC的情况下。作为反映肿瘤谷氨酸转运的新兴宠物示踪剂，已显示18F-FSPG PET 多种肿瘤环境（包括乳腺癌，肺癌和脑癌）的临床安全性和功效。我们的初步 范德比尔特患者的试验队列中的数据以及在亚洲进行的试验临床研究（n = 5），这表明 使用18F-FSPG PET即使在肝硬化中也可以提高HCC的检测的可行性，这是一种合并症 降低了常规成像方法的有效性。我们的研究具有三个具体目标。在患者中 接受HCC治疗的手术，我们将（1）评估18F-FSPG PET的关系，病理学 和癌症代谢； （2）将18F-FSPG PET与患者的标准标准诊断成像进行比较 与HCC和良性肝病变； （3）将18F-FSPG与11C-乙酸盐和HCC中的18F-FDG进行比较 和背景肝。这项研究有可能在非侵入性分子成像中建立新作用 为HCC患者提供个性化癌症护理。