[F18]FMAU in Prostate Cancer

[F18]前列腺癌中的 FMAU

• 批准号: 7758689
• 负责人: HOSSEIN JADVAR
• 金额: $ 21.51万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7758689
• 关键词: 2' -fluoro-5-methylarabinosyluracil; Ablation; Acetates; Affect; Androgen Receptor; Androgens; Animal Model; Animals; Arabinofuranosyluracil; Biochemical; Bladder; Bone Marrow; Cancer Etiology; Cell Proliferation; Cessation of life; Choline; Clinical; Clinical Trials; DNA; Data; Deposition; Detection; Diagnostic; Diagnostic Imaging; Disease; Distant; Early Diagnosis; Environment; Failure; Fossa; Foundations; Future; Human; Image; Image Analysis; Implant; Injection of therapeutic agent; Label; Laboratories; Left; Lesion; Localized Disease; Malignant neoplasm of prostate; Medical; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Metastatic/Recurrent; Methods; Modeling; Molecular; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Patients; Physiological; Positron-Emission Tomography; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Public Health; Publishing; Quality of life; Radiation therapy; Radical Prostatectomy; Recurrence; Relapse; Research Personnel; S-Phase Fraction; Second Primary Cancers; Serum; Site; Soft Tissue Neoplasms; Solid; Subcutaneous Tissue; The Sun; Thymidine; Thymidine Kinase; Time; Tissues; Tracer; United States; Ventricular; Xenograft Model; Xenograft procedure; analog; base; bone; clinically relevant; deprivation; imaging modality; improved; men; men' s group; molecular imaging; molecular marker; mouse model; neoplastic cell; pre-clinical; public health relevance; radiotracer; soft tissue; tool; tumor; tumor xenograft; uptake; urinary

DESCRIPTION (provided by applicant): Prostate cancer is the most common cancer and the second leading cause of cancer death affecting men in the United States. Approximately 30% of men with detectable serum prostate-specific antigen (PSA) levels after curative radical prostatectomy have local recurrences while about 40% are expected to have distant disease. The remaining 30% of men with PSA relapse will not have detectable disease based on standard imaging methods. The need for an accurate imaging-based method as a tool for detecting the disease early becomes obvious in this clinical setting of major public health concern. If the disease is localized in the prostate fossa, salvage radiation therapy may be considered. In men with metastatic prostate cancer, androgen deprivation (surgical or medical) at the time of PSA relapse remains to be the cornerstone of treatment. Encouraging results from preliminary studies at our laboratory and ancillary results from other researchers have prompted us to investigate the potential diagnostic utility of positron emission tomography (PET) with [F- 18]-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (F-18 FMAU) in the imaging evaluation of prostate cancer. FMAU, first developed in our laboratory, is a thymidine analog that is phosphorylated by thymidine kinase and incorporated in the DNA and therefore is useful for imaging tumor proliferation. F-18 FMAU has no or very little accumulation in bone and in urinary bladder that renders it as a potentially ideal PET radiotracer for imaging in prostate cancer. We propose in this preclinical translational molecular imaging project to systematically study the level and extent of F-18 FMAU uptake in metastatic, localized xenograft as well as orthotopic animal models of human prostate cancer using microPET imaging. We will also examine the correlations among the tumor uptake level and the underlying key molecular markers (proliferation index, Ki-67 and androgen receptor, AR). Our project will form the solid foundation that is needed for future diagnostic imaging clinical trials of F-18 FMAU in men with prostate cancer, specifically in the large group of men who present with biochemical failure and by definition have no localizable disease based on standard imaging studies. PUBLIC HEALTH RELEVANCE: Prostate cancer is a growing public health problem as the most common cancer and the second leading cause of cancer death affecting men in the United States. Early detection of recurrent and metastatic disease allows early appropriate treatment that can then help in enhancing quality of life and overall survival. Our animal project is based on positron emission tomography (PET) with an agent specific for tumor proliferation (F-18 FMAU) forming the solid foundation that is needed for future imaging clinical trials in the large group of men who present with PSA relapse and no localizable disease based on current standard imaging studies.

描述（由申请人提供）：前列腺癌是最常见的癌症，也是影响美国男性的癌症死亡的第二大原因。治愈性前列腺切除术后可检测到的血清前列腺特异性抗原（PSA）水平的男性中，约有30％的男性患有局部复发，而预计约40％的人会患有远距离疾病。其余30％的PSA复发男性将基于标准成像方法没有可检测的疾病。在这种主要公共卫生问题的临床环境中，需要一种基于成像的方法作为早期检测疾病的工具的需求显而易见。如果该疾病位于前列腺窝中，则可以考虑打捞辐射疗法。在患有前列腺癌的男性中，PSA复发时的雄激素剥夺（手术或医疗）仍然是治疗的基石。在我们的实验室和其他研究人员的辅助结果的初步研究结果的令人鼓舞的结果促使我们使用[F-18] -2'-2'-氟-5-甲基-1-甲基-1-甲基-1-甲基-D-二 - 亚挑战 - 二 - 二 - 二 - 二 - 二 - 二 - 二甲酰胺基尿素（FMAU）的潜在诊断效用（PET）在想象中的特点癌。 FMAU是在我们实验室首次开发的，是一种胸苷类似物，由胸苷激酶磷酸化并掺入DNA中，因此对于成像肿瘤增殖很有用。 F-18 FMAU在骨骼和膀胱中没有或很少的积聚，它使其成为前列腺癌成像的潜在理想宠物放射性示踪剂。我们在这个临床前翻译分子成像项目中提出，使用Micropet Imaging系统地研究转移性，局部异种移植物以及人类前列腺癌的原位动物模型中F-18 FMAU摄取的水平和程度。我们还将检查肿瘤摄取水平和基本关键分子标记物之间的相关性（增殖指数，KI-67和雄激素受体，AR）。我们的项目将构成F-18 FMAU的未来诊断成像临床试验所需的坚实基础，特别是在大量患有生物化学衰竭的男性中，并且根据标准成像研究，没有局部疾病。公共卫生相关性：前列腺癌是最常见的公共卫生问题，是最常见的癌症，也是影响美国男性的癌症死亡的第二大原因。早期发现复发性和转移性疾病的早期允许早期适当的治疗方法，从而有助于提高生活质量和整体生存。我们的动物项目基于正电子发射断层扫描（PET），其特异性的肿瘤增殖（F-18 FMAU）构成了稳固的基础，这是在大批男性中进行未来成像临床试验所需的固体基础，这些男性基于当前的标准成像研究，这些男性都有PSA复发且无局部疾病的临床疾病。