IGF::OT::IGF SBIR PHASE I TOPIC 350 QUANTIFICATION OF REDOX

目前的临床磁共振代谢成像技术受到灵敏度差的严重阻碍。动态核极化通过将极化从极化剂的高极化电子自旋转移到目标MRI探针的核自旋来解决这个问题。代谢物脱氢抗坏血酸（DHA）已被证明是一个很好的超极化探针的细胞氧化还原能力，提供了一个衡量细胞的能力，淬灭活性氧（ROS）。临床前研究已经证明，超极化DHA能够测量癌症和糖尿病诱导的肾脏氧化应激及其对治疗的反应中增加的还原能力，预计它对各种疾病具有广泛的适用性。随着超极化[1- 13 C]丙酮酸盐的13 C MRI的成功临床转化，HP [1- 13 C]DHA在患者中的使用正在积极进行。然而，HP [1- 13 C]DHA的时空分辨率受到使用当前基于三苯甲基的极化自由基获得的相对差的极化的严重阻碍。此外，HP DHA的广泛使用受到三苯甲基自由基的高成本的限制。第一阶段的工作重点是将DHA的极化增加2倍， Dynupol的极化剂，使各种疾病的细胞氧化还原成像具有更高的分辨率和灵敏度。

Current clinical magnetic resonance metabolic imaging techniques are severely hindered by poor sensitivity. Dynamic nuclear polarization solves this problem by transferring polarization from the highly-polarized electron spins of a polarization agent to the nuclear spins of the target MRI probe. The metabolite dehydroascorbic acid (DHA) has been shown to be an excellent hyperpolarized probe of cellular redox capacity providing a measure of the cells ability to quench reactive oxygen species (ROS). Pre-clinical studies have demonstrated hyperpolarized DHA's ability to measure increased reducing capacity in cancer and diabetes-induced renal oxidative stress and their response to therapy, and it’s anticipated to have broad applicability to a variety of diseases. With the successful clinical translation of 13C MRI of hyper polarized [1-13C] pyruvate, the use of HP [1-13C]DHA in patients is being actively pursued. However, the spatiotemporal resolution of HP [1-13C]DHA is severely hampered by the relatively poor polarization that is being obtained using the current trityl-based polarization radicals. Additionally, broad use of HP DHA is limited by the high cost of the trityl radicals. A Phase I effort will focus on increasing DHA’s polarization by 2-fold with Dynupol’s polarization agents, enabling higher resolution and sensitivity in cellular-redox imaging of a variety of diseases.