Ultra-fast 15N Imaging in Choline in Cancer

癌症胆碱超快 15N 成像

• 批准号: 7638502
• 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/7638502
• 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

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）：诊断脑肿瘤通常会延迟，危害治疗结果。通过常规磁共振光谱（MRS）改善了早期诊断，其中监测独特的肿瘤生物标记物（胆碱）目前以较差的敏感性限于较大，无法治疗的肿瘤。我们建议开发超快速的13C胆碱磁共振分子微成像，能够实时监测肿瘤胆碱代谢的体内监测，Pasadena是一种新一代的超敏感的超敏感，超近似的超近似Intivo Intivo Inter Inter Inter Inter Inter Inten Vivo MR Imaging技术，可在我们的实验室中在我们的实验室中进行优化，以供O型on Cromicologogology使用，可增强信号，可增长的信号噪声超过10,000倍。我们的目标是使用超快速的多核成像技术在恶性脑肿瘤的大鼠模型中使用超极化帕萨迪纳试剂的疗效。这将通过以下目的完成：目标1：体外帕萨迪纳试剂超极化的表征。 15N-胆碱，13C-胆碱和13C-葡萄糖将被极化和成像，以确定极化程度，并确认从计算出的T1松弛时间中确定去极化速率。这将使用正常大鼠的体外和体内多核成像的既定技术来完成。目标2：确定体内肿瘤中每种帕萨迪纳试剂的摄取和动力学。使用常规的9L脑肿瘤大鼠模型，将在输注帕萨迪纳试剂后获得13C和15N MRI和MRS。通过在横截面和纵向研究中比较每种代谢产物的定义终点，与常规MRI和组织学相比，将在横截面和纵向研究中进行比较。目标3：确定帕萨迪纳试剂的特异性。将在更具侵略性的9L-VEGF+大鼠以及肿瘤的定位，摄取和动力学中，将获得13C和15N MRI和MRS和MRS，将其与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和诊断更具侵略性脑肿瘤的特异性。通过实现这些目标，我们期望开设一个新的实时分子成像时代，该时代将用于人类使用时，将为恶性脑肿瘤患者提供较早的诊断，分期和治疗监测，并改善长期生存。