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Ultra-fast 15N Imaging in Choline in Cancer

癌症胆碱超快 15N 成像

基本信息

批准号：
8127910
负责人：
BRIAN David ROSS
金额：
$ 16.66万
依托单位：
HUNTINGTON MEDICAL RESEARCH INSTITUTES
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8127910
关键词：
Animals Biochemical Pathway Biological Markers Brain Brain Neoplasms Caliber Cancer Model Cerebrum Choline Citric Acid Cycle Detection Diagnosis Diagnostic Early Diagnosis Event Functional Imaging Generations Glucose Glucose Transporter Glutamates Goals Histology Human Image Imaging Techniques In Vitro Infusion procedures Kinetics Label Laboratories Longitudinal Studies Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Malignant Neoplasms Malignant neoplasm of brain Measures Metabolic Metabolic Marker Metabolism Modeling Molecular Monitor Neurons Noise Nuclear One-Step dentin bonding system Outcome Patients Positron-Emission Tomography Rattus Reagent Relaxation Research Personnel Resolution Signal Transduction Solutions Specificity Spectrum Analysis Staging Stream Techniques Therapeutic Time Translating Treatment outcome Vascular Endothelial Growth Factors glucose uptake improved in vivo molecular imaging oncology programs stable isotope tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Diagnosis of brain tumors is often delayed, jeopardizing therapeutic outcomes. Improved early diagnosis by conventional magnetic resonance spectroscopy (MRS), in which a unique tumor bio-marker, choline is monitored, is currently limited to larger, untreatable tumors by poor sensitivity. We propose to develop ultra- fast 13C choline magnetic resonance molecular micro-imaging, capable of real-time in vivo monitoring of tumor choline metabolism, PASADENA, a new generation of ultra-sensitive, ultra-fast in vivo MR imaging techniques optimized in our Laboratory for use in oncology, provides an increased signal to noise over 10,000 fold. It is our goal to determine the efficacy of hyperpolarized PASADENA reagents, using ultra-fast multinuclear imaging techniques in rat models of malignant brain tumor. This will be accomplished through the following aims: Aim 1: Characterization of hyperpolarization of PASADENA reagents in vitro. 15N-choline, 13C-choline, and 13C-glucose will be polarized and imaged to determine the degree of polarization and confirm depolarization rates from the calculated T1 relaxation times. This will be accomplished using established techniques of polarization transfer and multinuclear imaging in vitro and in vivo in normal rat. Aim 2: Determine the uptake and kinetics of each PASADENA reagent in tumors in vivo. Using a conventional 9L brain tumor rat model, 13C and 15N MRI and MRS will be acquired after infusion of the PASADENA reagent. Through defined End-Points, uptake and kinetics for each metabolite will be compared in cross-sectional and longitudinal studies, to establish improved sensitivity of PASADENA compared to conventional MRI and histology. Aim 3: Determine the specificity of the PASADENA reagents. 13C and 15N MRI and MRS of PASADENA reagents will be acquired in the more aggressive 9L-VEGF+ rats and tumor localization, uptake, and kinetics will be compared with those measured in Aim 2 to determine the specificity of the parameters and for diagnosis of more aggressive brain tumors. By achieving these aims we expect to open a new era of real-time molecular imaging which when translated for human use will provide earlier diagnosis, staging and therapeutic monitoring and improved long-term survival for patients with malignant brain tumors.

描述（由申请人提供）：脑肿瘤的诊断常常被延误，危及治疗结果。通过传统磁共振波谱（MRS）改进早期诊断，其中监测独特的肿瘤生物标志物胆碱，目前仅限于较大的，无法治疗的肿瘤，敏感性较差。我们建议开发超快速13C胆碱磁共振分子微成像，能够实时监测肿瘤胆碱代谢，PASADENA，新一代超灵敏，超快速的体内磁共振成像技术，在我们的实验室优化用于肿瘤学，提供增加的信号比噪声超过10,000倍。我们的目标是利用超快多核成像技术确定超极化PASADENA试剂在大鼠恶性脑肿瘤模型中的疗效。目的1:PASADENA试剂在体外超极化的表征。15n -胆碱、13c -胆碱和13c -葡萄糖将被极化并成像，以确定极化程度，并根据计算的T1弛豫时间确定去极化率。这将在正常大鼠体内和体外利用已建立的极化转移和多核成像技术来完成。目的2：确定每种PASADENA试剂在体内肿瘤中的摄取和动力学。采用常规9L脑肿瘤大鼠模型，输注PASADENA试剂后进行13C、15N MRI和MRS。通过定义的终点，将在横断面和纵向研究中比较每种代谢物的摄取和动力学，以建立与传统MRI和组织学相比，PASADENA的灵敏度提高。目的3：确定PASADENA试剂的特异性。将在侵袭性更强的9L-VEGF+大鼠中获得PASADENA试剂的13C和15N MRI和MRS，并将与Aim 2中测量的肿瘤定位、摄取和动力学进行比较，以确定参数的特异性并用于更强侵袭性脑肿瘤的诊断。通过实现这些目标，我们期望开启实时分子成像的新时代，当转化为人类使用时，将为恶性脑肿瘤患者提供早期诊断、分期和治疗监测，并提高长期生存率。