Pilot Human Studies of FMAU PET in Prostate Cancer

FMAU PET 在前列腺癌中的人体试点研究

• 批准号: 9036232
• 负责人: HOSSEIN JADVAR
• 金额: $ 23.71万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-04 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9036232
• 关键词: Affect; Animal Model; Arabinofuranosyluracil; Area; Behavior; Biochemical; Biological Markers; Biopsy; Cancer Detection; Cancer Etiology; Case Study; Cell Proliferation; Cellular Stress; Cessation of life; Characteristics; Clinical; Clinical Management; Clinical Trials; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Evaluation; Funding; Gleason Grade for Prostate Cancer; Goals; Grant; Health Care Costs; Histopathology; Human; Image; Image Analysis; Image Guided Biopsy; Indolent; Institutional Review Boards; Investigation; Investigational New Drug Application; Kinetics; Lesion; Magnetic Resonance Imaging; Malignant neoplasm of prostate; Morbidity - disease rate; Natural History; Organ; Outcome; Patients; Phase; Physiology; Positioning Attribute; Positron-Emission Tomography; Primary Neoplasm; Probability; Procedures; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Recurrence; Reporting; Research; Resistance; Risk; S-Phase Fraction; Schedule; Serum; Specificity; Staging; Time; Tracer; Transrectal Ultrasound; Tumor Biology; United States Food and Drug Administration; X-Ray Computed Tomography; base; cancer site; clinically relevant; digital; experience; human TK2 protein; image guided; imaging modality; improved; interest; men; non-invasive imaging; pre-clinical; preclinical evaluation; prospective; prostate biopsy; public health relevance; rectal; screening; targeted imaging; thymidine kinase 1; tumor; uptake

 DESCRIPTION (provided by applicant): Prostate cancer affects 1 in 6 men and is the second leading cause of cancer death. Definitive diagnosis is based on systematic transrectal ultrasound (TRUS)-guided prostate biopsy typically prompted by the widespread use of prostate specific antigen (PSA) screening. However, this procedure misses about 40% of prostate cancers leading to repeat biopsies at significant patient morbidity and healthcare cost. Therefore, there is an unmet critical need for image-guided biopsy that maximizes the probability of detection of clinically relevant tumors in order to circumvent the current underdiagnsois (and undertreatment) of lethal tumors and conversely overdiagnosis (and overtreatment) of indolent tumors. Image-guided prostate tumor detection and characterization will pave the way for rational treatment management strategy including the emerging focal therapy for organ-confined high grade tumors. Multiparametric magnetic resonance imaging (mpMRI) has been reported to offer relatively high specificity but variable sensitivity for prostat cancer detection. The potential use of positron emission tomography (PET) with a variety of tracers has primarily focused on the biochemical recurrence and the castrate-resistant metastatic phases of the disease. There is currently paucity of data for any PET tracer relevant to the accurate detection, localization, and characterization of primary tumor in patients with suspected prostate cancer, particularly after an initial negative standard TRUS guided biopsy. We have had a long record of interest and experience with the synthesis and evaluation of the cellular proliferation and cellular stress biomarker, 18F-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (18F-FMAU) in conjunction with PET. Our efforts have included completion of an R21-funded preclinical evaluation of 18F-FMAU in animal models of prostate cancer, and since the prior review, attainment of sufficient funds for an IRB-RDRC approved proof-of-concept clinical case study in one patient, and recent submission of an Investigational New Drug application to the US Food and Drug Administration. We are now in a strategic position to continue along this line of research with additional pilot human-based feasibility tria. Therefore, the objective of this revised R21 proposal is to perform a systematic study of 18F-FMAU in men with suspected primary prostate cancer for detection, localization and characterization of primary tumor at the time of initial diagnosis. The two specific aims of this proposal are: 1) to perform a prospective clinical imaging evaluation of 18F-FMAU PET/CT for detection and localization of primary tumor in 40 men with suspected prostate cancer based on elevated/rising prostate specific antigen level including those with prior negative biopsy who are scheduled to undergo clinical mpMRI and TRUS-guided biopsy procedure, and 2) to examine the associations between the PET and mpMRI derived imaging parameters and the biopsy histopathology parameters as well as serum prostate specific antigen level and kinetics. The underlying hypothesis is that 18F-FMAU accumulates in primary prostate cancer allowing for image-directed biopsy with an uptake level that is reflective of tumor proliferation index. We believe that addition of 18F-FMAU PET/CT in conjunction with mpMRI directed prostate biopsy will markedly improve the current status quo and impact the diagnostic evaluation of men with suspected prostate cancer.

 描述（由适用提供）：前列腺癌影响6人中有1人，是癌症死亡的第二大原因。确定性诊断基于系统的转直直肠超声（TRUS）指导的前列腺活检，通常是由于前列腺特异性抗原（PSA）筛查的宽度使用而引起的。但是，该程序错过了约40％的前列腺癌，导致重复活检，其患者发病率和医疗保健费用很高。因此，对图像引导的活检的不满意需求最大化临床相关肿瘤的检测可能性，以避免当前致命肿瘤的诊断不足（和不足）的诊断不足（和不足），相反，过度诊断（和过度处理）。图像引导的前列腺肿瘤检测和表征将为理性治疗管理策略铺平道路，包括用于器官限制的高级肿瘤的新兴局灶性治疗。据报道，多参数磁共振成像（MPMRI）具有相对较高的特异性，但对前列腺癌检测的灵敏度可变。阳性发射断层扫描（PET）与各种示踪剂的潜在使用主要集中在生化复发和疾病的castrate抗性转移阶段。目前，与可疑前列腺癌患者的原发性肿瘤的准确检测，定位和表征相关的任何PET示踪剂的数据很少，尤其是在初始标准TRUS引导活检后。我们在综合和评估细胞增殖和细胞应激生物标志物（18F-2'-氟-5-甲基-1-甲基-1-贝塔 - 甲基-1-甲基-1-甲基尿酸胸膜尿素（18f-fmaU））的合成和评估方面具有很长的记录和经验。我们的努力包括在前列腺癌的动物模型中完成了R21资助的18F-FMAU的临床前评估，并且自先前的审查以来，在一名患者中为IRB-RDRC批准的概念证明临床案例研究提供了足够的资金，以及一名患者的临床案例研究，以及最近提交了对美国食品和药物管理的研究性新药应用。现在，我们处于战略地位，可以继续沿着这一研究以及其他基于人类的可行性三亚州进行研究。因此，该修订后的R21提案的目的是对怀疑原发性前列腺癌的男性进行18F-FMAU的系统研究，以在初次诊断时对原发性肿瘤进行检测，定位和表征。 The two specific aims of this proposal are: 1) to perform a prospective clinical imaging evaluation of 18F-FMAU PET/CT for detection and localization of primary tumor in 40 men with suspected prostate cancer based on elevated/rising prostate specific antigen level including those with prior negative biopsy who are scheduled to undergo clinical mpMRI and TRUS-guided biopsy procedure, and 2) to examine the associations between the PET and MPMRI得出的成像参数以及活检组织病理学参数以及血清前列腺特异性抗原水平和动力学。基本的假设是，18F-FMAU积累在原发性前列腺癌中，允许进行图像指导的活检，其摄取水平反映了肿瘤增殖指数。我们认为，与MPMRI指挥前列腺活检一起添加18F-FMAU PET/CT将显着改善当前现状并影响可疑前列腺癌男性的诊断评估。