Ultra-fast 15N Imaging in Choline in Cancer

癌症胆碱超快 15N 成像

• 批准号: 7860692
• 负责人: BRIAN David ROSS
• 金额: $ 8.63万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7860692
• 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）：脑肿瘤的诊断常常被延迟，从而危及治疗结果。传统磁共振波谱（MRS）可以监测独特的肿瘤生物标志物胆碱，从而改善早期诊断，但由于敏感性较差，目前仅限于较大的、无法治疗的肿瘤。我们建议开发超快速 13C 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 是我们实验室优化用于肿瘤学的新一代超灵敏、超快速体内 MR 成像技术，可提供超过 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恶性脑肿瘤大鼠模型中确定超极化 PASADENA 试剂的功效。这将通过以下目标来实现： 目标 1：PASADENA 试剂体外超极化的表征。 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 弛豫时间确认去极化率。这将使用正常大鼠体外和体内的极化转移和多核成像的既定技术来完成。目标 2：确定每种 PASADENA 试剂在体内肿瘤中的摄取和动力学。使用传统的9L脑肿瘤大鼠模型，输注PASADENA试剂后将获得13C和15N MRI和MRS。通过确定的终点，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 的敏感性有所提高。目标 3：确定 PASADENA 试剂的特异性。将在更具侵袭性的 9L-VEGF+ 大鼠中获得 PASADENA 试剂的 13C 和 15N 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并诊断更具侵袭性的脑肿瘤。通过实现这些目标，我们期望开启实时分子成像的新时代，当其转化为人类使用时，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。