Ultra-fast 15N Imaging in Choline in Cancer

癌症胆碱超快 15N 成像

• 批准号: 7321148
• 负责人: BRIAN David ROSS
• 金额: $ 25.8万
• 依托单位: HUNTINGTON MEDICAL RESEARCH INSTITUTES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7321148
• 关键词: Animals; Biochemical Pathway; Biological Markers; Brain; Brain Neoplasms; Caliber; Cancer Model; Cerebrum; Choline; Citric Acid Cycle; Detection; Diagnosis; Diagnostic; Early Diagnosis; End Point; 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; Rate; 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

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）：脑肿瘤的诊断通常被延迟，危及治疗结果。通过常规磁共振波谱（MRS）改善早期诊断，其中监测独特的肿瘤生物标志物胆碱，目前由于灵敏度差而仅限于较大的不可治疗的肿瘤。我们建议开发超快速13 C胆碱磁共振分子显微成像，能够实时体内监测肿瘤胆碱代谢，PASADENA是我们实验室优化的用于肿瘤学的新一代超灵敏、超快速体内MR成像技术，提供了超过10，000倍的信噪比。我们的目标是使用超快速多核成像技术在大鼠恶性脑肿瘤模型中确定超极化PASADENA试剂的功效。这将通过以下目标实现：目标1：PASADENA试剂体外超极化的表征。15 N-胆碱、13 C-胆碱和13 C-葡萄糖将被极化并成像，以确定极化程度并根据计算的T1弛豫时间确认去极化速率。这将使用已建立的极化转移和多核成像技术在体外和正常大鼠体内完成。目的2：确定体内肿瘤中每种PASADENA试剂的摄取和动力学。使用传统的9 L脑肿瘤大鼠模型，在输注PASADENA试剂后采集13 C和15 N 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，以确定与传统MRI和组织学相比，PASADENA的灵敏度有所提高。目的3：确定PASADENA试剂的专属性。将在更具侵袭性的9 L-VEGF+大鼠中采集PASADENA试剂的13 C和15 N MRI和MRS，并将肿瘤定位、摄取和动力学与目标2中测量的结果进行比较，以确定参数的特异性和诊断更具侵袭性的脑肿瘤。通过实现这些目标，我们期望开辟一个实时分子成像的新时代，当用于人类使用时，将提供早期诊断，分期和治疗监测，并改善恶性脑肿瘤患者的长期生存。