Molecular Imaging of Retrograde Nerve Transport

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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. PUBLIC HEALTH RELEVANCE: Nerve diseases cause a great deal of harm, ranging from blindness, to paralysis to amputations on diabetics because of neuropathy. Despite this burden of disease, we have no imaging contrast agents to effectively image nerves. We propose to develop an agent for Neurography, analogous to Angiography.