Validation of an Intraoperative Neuro-Monitoring Contrast Agent for Cranial Nerves

脑神经术中神经监测造影剂的验证

基本信息

批准号：
10745031
负责人：
Junior Arturo Gonzales-Arevalo
金额：
$ 24.9万
依托单位：
CLEVELAND STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10745031
关键词：
Accidents Address Athletic Injuries Binding Proteins Biochemical Biodistribution Biological Biological Markers Biopsy Blast Injuries Brain Cancer Biology Cancer Etiology Cancer Patient Cancer Survivor Cells Cessation of life Chemicals Chemotherapy-induced peripheral neuropathy Contrast Media Cranial Nerves Detection Development Diabetic Neuropathies Diagnosis Disease Disulfides Drug Kinetics Electrophysiology (science)Epilepsy Family Fluorescence Generations Goals Hand Hepatocyte Human Hypersensitivity Image Imaging Device Immunohistochemistry Implant Individual International LAPC4 LNCaP Libraries Light Malignant neoplasm of brain Malignant neoplasm of lung Malignant neoplasm of prostate Measures Medical Mentors Methodology Methods Molecular Mus Natural Products Natural Source PC3 cell line PUVA Photochemotherapy Patients Peptides Performance Peripheral Nervous System Phase Physiological Plasma Proteins Positron-Emission Tomography Postoperative Pain Property Prostate Cancer therapy Prostate-Specific Antigen Prostatic Neoplasms Proteins Radioisotopes Research Research Personnel Serum Services Site Sodium Channel Specificity Spiders Stratification Stroke Structure Synthesis Chemistry System Technology Testing Tissues Tracer Tumor Biology Underrepresented Students United States Up-Regulation Validation Venoms Whole Blood Xenograft procedure anticancer research assault bacteriochlorin bioimaging cancer cell cancer diagnosis cancer type career castration resistant prostate cancer chelation chronic pain chronic painful condition clinically relevant cohort design enantiomer experience experimental study fluorescence imaging human disease imaging probe in vivo interest lipid solubility male member mouse model multimodality near infrared dye novel nuclear imaging patch clamp peptide structure prostate cancer cell prostate cancer model prostate cancer risk receptor scaffold sensor skills subcutaneous success theranostics tool tumor voltage gated channel warfighter

项目摘要

Project Summary Due to a lack of tools and new alternatives, the identification of molecular hallmarks of prostate cancer is limited to biopsy detection, usually motivated by high expression of prostate-specific antigen. However, sodium channels appear to present an alternative medium through which prostate cancer can be tracked. In the current research, I plan to interrogate models of prostate cancer, use a venom peptide to investigate NaV1.7 and develop a deep understanding of prostate tumor biology. The ultimate goal of this proposal is to acquire the necessary skills to launch a competitive, independent research career in the field of molecular fluorescence/PDT imaging and treatment, specializing in prostate cancer research. My long-term career goal is to lead a team of researchers (that includes underrepresented students) primarily interested in using synthetic methodologies and developing sensor- driven technologies to identify prostate cancer — approaches that once developed will apply to other diseases. Building on my background in synthetic chemistry and my extensive experience developing fluorescent/PET probe platforms, the research plan centers on the development of a multi-modal theranostic agent comprised of a bio-active venom peptide, a light-driven system that has the potential to target sodium channel NaV1.7 to track prostate cancer cells. Taken together, the next subsequent steps are to use the newly developed theranostic agent in fluorescent imaging and photodynamic therapy of prostate cancer tumors in vivo. Once I develop these technologies with a novel probe platform, I will be uniquely suited to perform in vivo fluorescent/PDT experiments with prostate cancer. The proposal will test my hypothesis that natural venom peptides combined to a sensor can inform a fantastic approach and a reliable theranostic agent to aid in the identification of prostate cancer in vivo via the tracking of sodium channels. Necessary to the success of the K99 phase is the guidance and mentoring of world-class leaders: Dr. Thomas Reiner, leader in the development of nuclear imaging probes and strategies to investigate lung and brain cancers and recently the peripheral nervous system, and Dr. Glenn King, an internationally renowned expert in venom elucidation with a focus on chronic pain, epilepsy and brain stroke. The proposed project will undoubtedly expand to other physiochemically active peptides applicable to other clinically relevant conditions, such as sports injuries, domestic assaults, cancer survivors and blast injuries in warfighters.

项目概要由于缺乏工具和新的替代方案，前列腺癌分子标志的识别还很困难。仅限于活检检测，通常由前列腺特异性抗原的高表达引起。通道似乎提供了一种可以追踪前列腺癌的替代媒介。目前的研究，我计划询问前列腺癌模型，使用毒液肽来研究 NaV1.7 并加深对前列腺肿瘤生物学的了解该提案的最终目标是获得。在分子领域开展有竞争力的独立研究生涯的必要技能荧光/PDT成像和治疗，专门从事前列腺癌研究。我的长期职业目标是。领导一个主要对使用合成材料感兴趣的研究人员团队（包括代表性不足的学生）开发方法和传感器驱动技术来识别前列腺癌——曾经的方法基于我在合成化学方面的背景和广泛的研究，我开发出的方法将适用于其他疾病。拥有开发荧光/PET探针平台的经验，该研究计划的重点是开发多模式治疗诊断剂由生物活性毒液肽组成，这是一种光驱动系统，具有靶向钠通道 NaV1.7 来追踪前列腺癌细胞的潜力。步骤是在荧光成像和光动力治疗中使用新开发的治疗诊断剂一旦我用新颖的探针平台开发这些技术，我将成为体内前列腺癌肿瘤。非常适合对前列腺癌进行体内荧光/PDT 实验。该提案将测试我的方案。假设天然毒液肽与传感器结合可以提供一种奇妙的方法和可靠的方法治疗诊断剂通过跟踪钠通道帮助体内识别前列腺癌。 K99阶段的成功需要世界级领导者的指导和指导：Thomas博士 Reiner，核成像探针和研究肺和大脑策略开发的领导者癌症和最近的周围神经系统，以及国际知名专家 Glenn King 博士拟议项目将重点关注慢性疼痛、癫痫和脑中风的毒液阐明。毫无疑问扩展到适用于其他临床相关病症的其他理化活性肽，例如运动损伤、家庭暴力、癌症幸存者和战士爆炸伤。