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

• 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
• 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

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.

项目摘要 由于缺乏工具和新的替代品，前列腺癌的分子标志的鉴定是困难的。 局限于活检检测，通常是由前列腺特异性抗原的高表达所激发的。然而，钠 通道似乎提供了一种可用于跟踪前列腺癌的替代介质。在 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 深入了解前列腺肿瘤生物学。这项提案的最终目的是获得 在分子领域开展有竞争力、独立的研究职业所需的技能 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 领导一个研究团队（包括代表性不足的学生），主要对使用合成药物感兴趣。 方法和开发传感器驱动的技术来识别前列腺癌-方法， 将适用于其他疾病。基于我在合成化学方面的背景和我广泛的 开发荧光/PET探针平台的经验，研究计划集中在开发一个 由生物活性毒液肽组成的多模式治疗诊断剂， 靶向钠通道NaV1.7以追踪前列腺癌细胞的潜力。合在一起，接下来的 步骤是使用新开发的治疗诊断剂在荧光成像和光动力治疗， 体内前列腺癌肿瘤。一旦我用一个新的探测平台开发出这些技术， 其独特地适合于对前列腺癌进行体内荧光/PDT实验。这份提案将考验我的 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，以帮助通过跟踪钠通道在体内鉴定前列腺癌。 K99阶段的成功需要世界级领导者的指导和指导：托马斯博士 Reiner，核成像探针和研究肺和脑的策略开发的领导者 癌症和最近的周围神经系统，和格伦金博士，一个国际知名的专家， 毒液说明，重点是慢性疼痛，癫痫和脑中风。拟议项目将 毫无疑问地扩展到适用于其它临床相关病症的其它理化活性肽， 如运动损伤、家庭暴力、癌症幸存者和战士的爆炸伤。