Ultra-fast 15N Imaging in Choline in Cancer

描述(由申请人提供)：脑肿瘤的诊断经常被推迟，危及治疗结果。通过监测一种独特的肿瘤生物标志物胆碱，通过传统的磁共振波谱(MRS)改善早期诊断，目前仅限于较大的、无法治疗的肿瘤，因为敏感性较差。我们建议开发超快13C胆碱磁共振分子显微成像，能够在体内实时监测肿瘤胆碱代谢，Pasadena是我们实验室为用于肿瘤学而优化的新一代超灵敏、超快在体磁共振成像技术，提供超过10,000倍的信号噪声比。我们的目标是利用超快多核成像技术在大鼠恶性脑瘤模型中确定超极化帕萨迪纳试剂的有效性。这将通过以下目标来实现：目标1：体外表征帕萨迪纳试剂的超极化。15N-胆碱、13C-胆碱和13C-葡萄糖将被极化和成像，以确定极化程度和根据计算的T1弛豫时间确定去极化速率。这将使用已建立的极化转移和多核成像技术在正常大鼠的体外和体内完成。目的2：测定各帕萨迪纳试剂在肿瘤体内的摄取和动力学。采用常规的9L大鼠脑肿瘤模型，注入帕萨迪纳试剂后，可获得13C和15N的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，以确定与常规核磁共振和组织学相比，帕萨迪纳的敏感性更高。目的3：测定帕萨迪纳试剂的特异性。帕萨迪纳试剂的13C和15N MRI和MRS将在更具侵袭性的9L-VEGF+大鼠身上获得，肿瘤的定位、摄取和动力学将与AIM 2中测量的结果进行比较，以确定这些参数的特异性，并用于更具侵袭性的脑肿瘤的诊断。通过实现这些目标，我们预计将开启实时分子成像的新纪元，当翻译为人类使用时，将为恶性脑瘤患者提供更早的诊断、分期和治疗监测，并提高长期存活率。

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.