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成像的显像剂，使神经能够被成像所见。我们的显像剂将类似于血管造影剂，用于使血管在成像时可见，但适用于神经。这将使我们能够展示神经的解剖和功能，这是目前很难做到的，并将改善我们可以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善的成像中受益，太多的疾病无法列出，但包括：防止前列腺癌手术后导致勃起功能障碍的神经束受损。防止颈部手术后因喉返神经损伤而失声。正确诊断脊柱突出所致神经受压。早期诊断糖尿病导致脚部感觉丧失的神经疾病，并监测这种神经疾病的治疗，看看它是否有效。提高神经损伤或脊髓损伤所致瘫痪的诊断和治疗水平。如果我们改善了神经成像，失明、耳聋和许多其他神经疾病可以得到更好的诊断、更好的治疗，甚至可能从一开始就预防。我们认为神经成像(神经成像)是一种平台技术，可以改善神经疾病患者的日常临床护理；也对该领域的临床、基础和转化性研究产生很大影响。我们已经证明，我们可以在小鼠的坐骨神经(腿)神经内使用荧光标记的试剂进行神经成像，并且我们可以使用这一技术来显示常用有毒化疗药物(奥沙利铂)对神经运输的影响。在这一应用中，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性神经疾病的脑神经，2-开发我们的试剂的新变种，以提高我们使用核医学扫描仪进行成像的能力，并增加生物发光和正电子发射断层成像的成像能力，以及3-确定我们的试剂在常见神经疾病的动物模型中的有效性和实用性，如神经创伤、中毒或辐射损伤。我们从这个项目中了解到的信息将向我们展示如何推动这种显像剂在患者中的使用。

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.