Molecular Imaging of Retrograde Nerve Transport

描述（由申请人提供）：我们寻求开发一种用于神经造影的显像剂，使神经在成像中可见。我们的显像剂将类似于血管造影剂，用于使血管在成像中可见，但适用于神经。这将使我们能够展示神经的解剖结构和功能，这是目前很难做到的，这将改善我们为神经疾病患者提供的预防、诊断和治疗选择。有许多神经疾病可以从改进的成像技术中受益，不胜枚举，但包括：预防前列腺手术后神经束损伤导致勃起功能障碍。防止颈部手术后因喉返神经损伤而失声。正确诊断脊柱椎间盘突出引起的神经挤压。早期诊断因糖尿病导致的足部感觉丧失的神经疾病，并监测这种神经病变的治疗，看看它是否有效。改善神经损伤或脊髓损伤所致瘫痪的诊断和治疗。如果我们改进了神经成像技术，就可以更好地诊断、治疗失明、耳聋和许多其他神经疾病，甚至可能从一开始就预防这些疾病的发生。我们认为神经成像（Neurography）是一种平台技术，可以改善神经疾病患者的日常临床护理；并且对该领域的临床、基础和转化研究也有很大的影响。我们已经证明，我们可以在小鼠的坐骨（腿）神经内用荧光标记剂进行神经造影，我们可以用它来显示常用的有毒化疗药物（奥沙利铂）对神经运输的影响。在这个应用程序中，我们希望：1 .将我们的经验扩展到其他解剖部位，特别是经常发生致残神经疾病的脑神经；2 .开发我们试剂的新变体，以提高我们的核医学扫描仪成像能力，并增加生物发光和正电子发射断层成像能力；3 .确定我们试剂在常见神经疾病动物模型中的有效性和实用性，如创伤性、毒性或辐射性神经损伤。我们从这个项目中学到的信息将告诉我们如何将这种显像剂用于患者。

DESCRIPTION (provided by applicant): We seek to develop an imaging agent for Neurography, to allow nerves to be rendered visible to imaging. Our imaging agent will be analogous to Angiographic contrast agents used to make blood vessels visible to imaging, but applied to nerves. This will allow us to show both the anatomy and function of nerves, something that is currently very difficult to do, and will improve the preventative, diagnostic and therapeutic options we can offer to patients with nerve diseases. There are many nerve diseases that could benefit from improved imaging, too many to list but including: Preventing damage to the nerve bundles leading to erectile dysfunction after prostate surgery. Preventing loss of voice after neck surgery due to recurrent laryngeal nerve damage. Correctly diagnosing pinched nerves due to herniated disks in the spine. Diagnosing nerve disease leading to loss of sensation in the feet due to diabetes earlier, and monitoring treatments for this neuropathy to see if it is working effectively. Improving diagnosis and treatment in paralysis due to nerve trauma or spinal cord injury. Blindness, deafness and many other nerve diseases could be diagnosed better, treated better or perhaps even prevented from happening in the first place if we had improved nerve imaging. We see nerve imaging (Neurography) as a platform technology that could improve the day-to-day clinical care of patients with nerve disease; and also have a high impact on clinical, basic and translational research in the field. We have already shown that we can do Neurography with a fluorescently labeled agent within the sciatic (leg) nerves of mice and that we can use this to show the effects of a toxic chemotherapeutic in common use (oxaliplatin) on nerve transport. In this application we hope to: 1-extend our experience to other anatomic sites, specifically the cranial nerves where crippling nerve disease frequently occurs, 2-develop new variants of our agent to improve our imaging abilities with nuclear medicine scanners, and add imaging capabilities with bio- luminescent and positron emission tomography imaging, and 3-determine the effectiveness and utility of our agents in animal models of common nerve diseases like traumatic, toxic or radiation injury to the nerves. The information we learn from this project will show us how to move this imaging agent forward for use in patients.