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

基本信息

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
项目类别：
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

项目摘要

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（通过应用程序提供）：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成像方法，该方法揭示了主要的PCA位置，其临床意义并预测其恶性潜力。此外，在确定治疗后通常很难发现复发性疾病，从而阻碍了有效的局部打捞治疗。还为转移性PCA提供了新的全身治疗选择，治疗选择和早期治疗成功（通过成像）的选择可能会使患者受益并通过避免无效的全身治疗来降低成本。使用代谢组分析，已经确定肌苷的组织水平在原代PCA中升高，并且在PCA进展过程中进一步增加。我们的临床前数据表明，在前列腺癌肿瘤模型中，带有11C-肌氨酸的微型PET优于11C-胆碱。基于这些令人鼓舞的数据，我们假设使用11C-甲壳虫的PET成像能够识别主要和转移性PCA，以进行人类分期和响应评估。研究目标是使用11C-六骨作为PCA的PET示踪剂进行试验试验，并评估人PCA组织中11C-甲状腺素的摄取机理和代谢途径。 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 efficiency and to assessment feasibility, (3) measurement of the human radiation dosimetry of 11C-sarcosine, and (4) assessment of sarcosine uptake regulation in human prostate cancer tissue samples.研究设计：当前的11C - 萨尔科斯生产将根据GMP标准进行修改（AIM 1）。为了评估AIM 2，人类前列腺癌受试者将使用11C-甲壳虫和11C-胆碱进行PET/CT成像，以直接比较生物分布和肿瘤摄取。该研究将包括接受前列腺切除术（A组）和复发和/或转移性疾病（B组）的PCA受试者。在正常志愿者中确定11C-六骨的人体辐射剂量法（AIM 3）。对于AIM 4，肿瘤组织样品将基于液态色谱质谱技术进行标准病理和靶向代谢物分析，以专门评估前列腺癌中肌氨酸的代谢途径，并将其与11C-甲状腺素的摄取测量结果进行比较。影响：如果成功的话，这项研究将导致PCA的新型分子成像策略，将PCA与正常良性组织区分开，并克服分期和监测前列腺癌处理中的当前局限性。