[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(申请人提供)：前列腺癌是美国最常见的癌症，也是影响男性癌症死亡的第二大原因。在根治性前列腺癌根治术后血清前列腺特异性抗原(PSA)水平可检测到的男性中，大约30%的人局部复发，而大约40%的人预计会有远处的疾病。其余30%的PSA复发男性将不会有基于标准成像方法的可检测到的疾病。在这一重大公共卫生问题的临床背景下，需要一种准确的基于成像的方法作为早期发现疾病的工具变得显而易见。如果疾病局限于前列腺窝，可以考虑挽救放射治疗。对于患有转移性前列腺癌的男性，在PSA复发时去除雄激素(手术或内科)仍然是治疗的基石。我们实验室初步研究的令人鼓舞的结果和其他研究人员的辅助结果促使我们研究[F-18]-2‘-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil(F-18FMAU)正电子发射断层扫描在前列腺癌成像评估中的潜在诊断价值]。FMAU是我们实验室首次开发的一种胸苷类似物，它被胸苷激酶磷酸化并结合到DNA中，因此有助于肿瘤增殖的成像。F-18FMAU在骨骼和膀胱中没有或几乎没有蓄积，这使其成为前列腺癌成像的潜在理想的PET放射性示踪剂。在这项临床前翻译分子成像项目中，我们建议使用microPET成像系统地研究转移的、局部的异种移植瘤以及人前列腺癌的原位动物模型中F-18FMAU的摄取水平和程度。我们还将检查肿瘤摄取水平与潜在关键分子标志物(增殖指数、Ki-67和雄激素受体，AR)之间的相关性。我们的项目将为未来F-18 FMAU在前列腺癌男性患者中的诊断成像临床试验奠定坚实的基础，特别是在一大群患有生化故障且根据标准成像研究定义没有可定位疾病的男性中。公共卫生相关性：前列腺癌是美国最常见的癌症，也是影响男性死亡的第二大癌症，是一个日益严重的公共卫生问题。早期发现复发和转移性疾病可以及早进行适当的治疗，从而有助于提高生活质量和总体存活率。我们的动物项目以正电子发射断层扫描(PET)为基础，使用一种专用于肿瘤增殖的试剂(F-18FMAU)，形成了未来在大量男性患者中进行成像临床试验所需的坚实基础，这些患者出现PSA复发，根据目前的标准成像研究，没有可定位的疾病。