Effective PET Imaging in Liver Cancer

肝癌的有效 PET 成像

• 批准号: 8260310
• 负责人: Zhenghong Lee
• 金额: $ 40.84万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8260310
• 关键词: 2' -fluoro-5-methylarabinosyluracil; Acetates; Aftercare; Animal Model; Antiviral Agents; Arabinofuranosyluracil; Biological Assay; Cancer Etiology; Cell Proliferation; Cessation of life; Characteristics; Choline; Country; Data; Deoxyglucose; Detection; Development; Early Diagnosis; Effectiveness; Enzymes; Evaluation; Frequencies; Funding; Health; Hepatic Tissue; Hepatitis; Hepatitis B; Human; Image; Incidence; Infection; Investigation; Label; Lesion; Liver; Malignant Neoplasms; Malignant neoplasm of liver; Measurement; Measures; Medical Imaging; Metabolism; Modeling; Molecular; Names; Outcome; Performance; Positron-Emission Tomography; Premalignant; Primary carcinoma of the liver cells; Process; Pyrimidine Nucleosides; Quantitative Evaluations; Radiolabeled; Resistance; Series; Staging; Stereoisomer; Thymidine; Thymine; Time; Tissues; Tracer; Uncertainty; United States; United States National Institutes of Health; Validation; Viral; Virus Diseases; Woodchuck; analog; base; cancer imaging; enantiomer; glucose uptake; interest; meetings; mortality; nucleoside analog; oncology; radiotracer; research study; response; treatment response; tripolyphosphate; tumor progression; uptake

DESCRIPTION (provided by applicant): Hepatocellular Carcinoma (HCC) is increasing in frequency and mortality in United States, and the rapid increase of HCC incidence correlates with increase in hepatitis viral infection. Early diagnosis and accurate assessment of treatment response require a reliable, localized, repeatable, and quantitative measure. Medical imaging offers such a means for non-invasive, repeated, and quantitative evaluation of the progression or status of HCC. However, the main PET tracer currently used for oncology imaging, [18F]-FDG, has been shown to be ineffective for imaging HCC since many HCCs do not show FDG uptake in contrast to the surrounding hepatic tissues, which has led to a high false negative rate. Other tracers such as [11C]- Acetate and [11C]-Choline have shown some uptake in HCC although the utilities of these existing tracers are still unclear. There is an urgent need for an effective imaging tracer that can be used in HCC for early detection and assessment of early response to treatment. In this application, we propose to study a new radiolabeled PET tracer L-FMAU for its performance in HCC imaging. The molecule was developed initially as an anti-viral agent. Its mirrored stereoisomer, D-FMAU, a nucleoside analog, has been labeled for PET imaging although its usefulness for imaging primary liver cancer such as HCC is in doubt due to the high background uptake in the liver. L-FMAU, on the other hand, is a non-natural nucleoside analog and has been the focal interest of recent radiolabeling development for PET imaging. There is a real potential for L-FMAU to be a PET tracer for imaging HCC based on our preliminary results. We will conduct thorough investigations for the mechanisms responsible for L-FMAU's transport, metabolism, degradation (or resistance to it) in the liver tissue and liver cancer, and will correlate PET imaging data with characteristics of the cancer to evaluate L-FMAU's utility i imaging HCC. PUBLIC HEALTH RELEVANCE: Our study evaluates a new PET tracer for effective imaging of hepatocellular carcinoma (HCC). FDG, the available PET tracer commonly used for oncological applications, is ineffective for HCC imaging due to a high false negative rate. The new imaging tracer, L- FMAU has shown great promise. We will investigate the molecular mechanisms for its use in liver cancer imaging. Specifically, we will examine its performance for early detection and assessment of early response to the treatment of HCC. Upon successful development and evaluation as proposed, the use of this new tracer will meet the urgent need for effective PET imaging for HCC, which is increasing rapidly in frequency and mortality in United States.

描述（由申请人提供）：肝细胞癌（HCC）在美国的频率和死亡率正在增加，HCC发病率的迅速增加与肝炎病毒感染的增加相关。早期诊断和对治疗反应的准确评估需要可靠，本地化，可重复和定量措施。医学成像为HCC的进展或状态的非侵入性，重复和定量评估提供了这种手段。但是，目前用于肿瘤学成像的主要宠物示踪剂[18F] -FDG已被证明是对HCC成像的无效成像，因为与周围的肝组织相比，许多HCC并未显示出FDG的摄取，这导致了很高的假阴性。尽管这些现有示踪剂的实用程序仍然不清楚，但其他示踪剂，例如[11C] - 乙酸和[11C] - 胆碱也表现出了一些吸收。迫切需要有效的成像示踪剂，可以在HCC中用于早期检测和评估对治疗的早期反应。在此应用中，我们建议研究新的放射标记的宠物示踪剂L-FMAU在HCC成像中的性能。该分子最初是作为抗病毒剂开发的。它的镜像立体异构体D-fmau（一种核苷类似物）被标记为PET成像，尽管由于肝脏中的背景摄入量很高，因此对成像原发性肝癌（如HCC）（例如HCC）的有用性令人怀疑。另一方面，L-fmau是一种非天然核苷类似物，一直是最近放射性标记开发PET成像的焦点。根据我们的初步结果，L-fmau成为对HCC进行成像的宠物示踪剂具有真正的潜力。我们将对负责L-FMAU的运输，代谢，降解（或对其抗性）的机制进行彻底的研究，并将PET成像数据与癌症的特征相关联，以评估L-FMAU的实用性I对HCC的成像。公共卫生相关性：我们的研究评估了一种新的宠物示踪剂，用于有效的肝细胞癌（HCC）成像。 FDG是通常用于肿瘤应用的可用PET示踪剂，由于高伪负率，HCC成像无效。新的成像示踪剂l-fmau表现出了巨大的希望。我们将研究其在肝癌成像中使用的分子机制。具体而言，我们将研究其对早期对HCC治疗的早期反应的早期检测和评估的性能。一旦成功地开发和评估，该新示踪剂的使用将满足迫切需要对HCC进行有效的PET成像，HCC的频率和死亡率迅速增加。