Carbon-11 Labeled Sarcosine: Mechanism of Action and Initial Performance in Prostate Cancer

碳 11 标记的肌氨酸：前列腺癌的作用机制和初始表现

• 批准号: 8808815
• 负责人: Morand Ruediger Piert
• 金额: $ 15.14万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-08 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8808815
• 关键词: Amino Acids; Attenuated; Benign; Biodistribution; Biopsy; Cancer Detection; Carbon; Choline; Clinical; Clinical Management; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic Neoplasm Staging; Disease; Dose; Effectiveness; Enzymes; Epithelial Cells; Evaluation; Glycine; Goals; Healthcare Systems; Human; Image; Imagery; Individual; Indolent; Label; Lead; Lesion; Life; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Fragmentography; Measurement; Measures; Medical Imaging; Metabolic; Metabolic Pathway; Metabolism; Metastatic Prostate Cancer; Metastatic to; Modeling; Monitor; Mus; Neoplasm Metastasis; Newly Diagnosed; Nodal; Organ; PSA screening; Pathology; Pathway interactions; Patients; Performance; Phase; Phenotype; Pilot Projects; Play; Positron-Emission Tomography; Production; Prostate; Prostatectomy; Radiation; Radiometry; Recurrence; Recurrent disease; Regulation; Research Design; Resistance; Role; Safety; Sampling; Sarcosine; Sarcosine dehydrogenase; Selection for Treatments; Solid; Staging; Subgroup; Techniques; Time; Tissue Sample; Tissues; Tracer; Transferase; Translations; Tumor Tissue; United States; X-Ray Computed Tomography; Xenograft Model; base; cancer imaging; cancer site; cancer therapy; clinically significant; cost; improved; intravenous injection; men; metabolomics; molecular imaging; novel; pilot trial; pre-clinical; prostate biopsy; prostate cancer model; public health relevance; radiotracer; response; success; tumor; tumor progression; uptake; volunteer

 DESCRIPTION (provided by applicant): The performance of current prostate cancer (PCa) imaging is unsatisfactory. Clinicians need a diagnostic imaging approach that reveals primary PCa location, its clinical significance and predicts its malignant potential. Furthermore, the detection of recurrent disease is often difficult after definitive treatment, hampering effective local salvage treatments. Also given new systemic treatment option in metastatic PCa, the selection of treatment options and monitoring of treatment success early (via imaging) may benefit patients and reduce costs by avoiding ineffective systemic treatments. Using metabolomic profiling, tissue levels of sarcosine have been identified to be elevated in primary PCa with further increase during PCa progression. Our preclinical data show that micro-PET with 11C- sarcosine outperforms 11C-choline in prostate cancer tumor models. Based on these encouraging data, we hypothesize that PET imaging with 11C-sarcosine is able to identify primary and metastatic PCa for staging and response evaluation in humans. The study goals are to conduct a pilot trial using 11C- sarcosine as PET tracer for PCa and to evaluate the uptake mechanisms and metabolic pathways of 11C-sarcosine in human PCa tissue. Objectives: (1) Development of 11C-sarcosine as PET tracer for human use, (2) conduction of a pilot study with 11C-sarcosine in human prostate cancer subjects to collect preliminary efficacy and to assess feasibility, (3) measurement of the human radiation dosimetry of 11C-sarcosine, and (4) assessment of sarcosine uptake regulation in human prostate cancer tissue samples. Study design: The current 11C-sarcosine production will be modified according to GMP standards (aim 1). To assess aim 2, human prostate cancer subjects will undergo PET/CT imaging with 11C-sarcosine and 11C-choline to directly compare biodistribution and tumor uptake. The study will include PCa subjects undergoing prostatectomy (group A) and recurrent and/or metastatic disease (group B). The human radiation dosimetry of 11C-sarcosine is determined in normal volunteers (aim 3). For aim 4, tumor tissue samples will undergo standard pathology and target metabolite analysis based on liquid-and-gas- chromatography mass spectrometry techniques to specifically assess the metabolic pathways for sarcosine in prostate cancer and to compare these with 11C-sarcosine uptake measurements. Impact: If successful, this study would lead to a novel molecular imaging strategy for PCa, differentiating PCa from normal benign tissues, and overcome current limitation in staging and monitoring prostate cancer treatments.

 描述（由申请人提供）：当前前列腺癌（PCa）成像的性能不令人满意。临床医生需要一种诊断性成像方法，以揭示原发性PCa的位置，其临床意义，并预测其恶性潜力。此外，在确定性治疗后，复发性疾病的检测通常是困难的，这阻碍了有效的局部挽救治疗。此外，考虑到转移性PCa的新的全身治疗选择，治疗选择的选择和治疗成功的早期监测（通过成像）可以使患者受益，并通过避免无效的全身治疗来降低成本。使用代谢组学分析，已经确定肌氨酸的组织水平在原发性PCa中升高，并且在PCa进展期间进一步增加。我们的临床前数据显示，在前列腺癌肿瘤模型中，具有11 C-肌氨酸的微PET优于11 C-胆碱。基于这些令人鼓舞的数据，我们假设11 C-肌氨酸PET成像能够识别原发性和转移性PCa，用于人类分期和反应评估。本研究的目的是使用11 C-肌氨酸作为PCa的PET示踪剂进行初步试验，并评估11 C-肌氨酸在人PCa组织中的摄取机制和代谢途径。目的：（1）开发11 C-肌氨酸作为人体PET示踪剂，（2）在人类前列腺癌受试者中进行11 C-肌氨酸的初步研究，以收集初步疗效并评估可行性，（3）测量11 C-肌氨酸的人体辐射剂量，以及（4）评估人类前列腺癌组织样本中肌氨酸的摄取调节。研究设计：将根据GMP标准（目的1）修改当前的11 C-肌氨酸生产。为了评估目标2，人类前列腺癌受试者将接受11 C-肌氨酸和11 C-胆碱的PET/CT成像，以直接比较生物分布和肿瘤摄取。本研究将包括接受前列腺切除术（A组）和复发性和/或转移性疾病（B组）的PCa受试者。对正常志愿者进行了~（11）C-肌氨酸人体辐射剂量测定（目的3）。对于目标4，将对肿瘤组织样本进行基于液相和气相色谱质谱技术的标准病理学和靶代谢物分析，以专门评估前列腺癌中肌氨酸的代谢途径，并将其与11 C-肌氨酸摄取测量值进行比较。影响：如果成功，这项研究将导致一种新的PCa分子成像策略，将PCa与正常良性组织区分开来，并克服目前在分期和监测前列腺癌治疗方面的局限性。