Developing Radiocaine NaV imaging as a response monitoring biomarker for chronic pain

开发放射性卡因 NaV 成像作为慢性疼痛的反应监测生物标志物

• 批准号: 10794862
• 负责人: Mohab M Ibrahim
• 金额: $ 110.6万
• 依托单位: LUTROO IMAGING LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10794862
• 关键词: Absence of pain sensation; Acute; Address; Adult; Affect; Analgesics; Anatomy; Animal Model; Biodistribution; Biological Assay; Biological Markers; Caring; Chronic low back pain; Clinical; Clinical Trials; Dangerousness; Data; Decision Making; Development; Dexamethasone; Dose; Drug Kinetics; Economic Burden; Evaluation; Fluorine; Goals; Healthcare; Hour; Human; Image; Imaging Techniques; Individual; Injections; Intravenous; Lidocaine; Ligands; Local Anesthetics; Location; Low Back Pain; Magnetic Resonance Imaging; Measurement; Measures; Methodology; Monitor; Nature; Nerve; Nerve Block; Neurologic; Opioid; Pain; Pain Measurement; Pain intensity; Pain management; Patient Self-Report; Patients; Persistent pain; Phase I Clinical Trials; Phase II Clinical Trials; Population; Positioning Attribute; Positron-Emission Tomography; Publishing; Reporting; Research; Resort; Resources; Rodent Model; Roentgen Rays; Safety; Sample Size; Scanning; Severities; Signal Transduction; Sodium Channel; Source; Technology; Testing; Therapeutic; Time; Toxic effect; Validation; X-Ray Computed Tomography; chronic pain; chronic pain management; clinical practice; cohort; cost; dosimetry; experience; first-in-human; human subject; imaging agent; imaging biomarker; ineffective therapies; innovation; molecular imaging; non-invasive monitor; non-opioid analgesic; novel; opioid epidemic; pain behavior; pain reduction; pain relief; pain score; pain signal; painful neuropathy; pre-clinical; preclinical safety; preclinical toxicity; radiotracer; response; source localization; standard care; standard of care; success; therapeutic candidate; therapy development; tool; transmission process; treatment effect; treatment response; uptake; voltage

Summary/Abstract There are currently no biomarkers or tools capable of objectively measuring pain signals. Historically, pain in humans has been measured using subjective rating scales to determine its presence and severity. In animal models, pain is measured by semi-quantitative assays that rely on the observation of pain behaviors. Though useful, the inherently subjective nature of these measures has hampered both research and treatment efforts. The annual economic burden of chronic pain is estimated to exceed $800 billion in the USA alone, largely because inadequately managed pain requires disproportionately more healthcare resources. Similarly, clinical trials for pain therapies are the most expensive, and have the lowest success rate, of all neurological indications. Difficulty managing chronic pain has led to the opioid epidemic as many individuals turn to prescription painkillers as a means of relief, but often end up becoming addicted and resorting to more potent and dangerous opioids as their tolerance increases. Radiocaine is a novel positron emission tomography (PET) imaging agent that we are developing as a biomarker to address the issues in pain care and therapy development. Our recently published findings in a rodent model of neuropathic pain demonstrate the ability to localize the pain generator rapidly and accurately and objectively measure its signal intensity. Our ultimate goals are: 1) to change the evaluation of (experimental) pain therapies, and 2) the standard of care in pain assessment through molecular imaging. The use of pain imaging biomarker technology would allow for objective efficacy data (both pre-clinically and in clinical trials), and reduce costs by enabling smaller sample sizes due to more homogeneous populations, i.e. with a particular “pain signal,” and more accurate measurement of analgesic effects. The proposed study will evaluate Radiocaine in early-stage clinical trials. Successful results will set the stage for applied clinical trials that further develop this promising approach into a useful biomarker for transforming pain care.

摘要/摘要 目前还没有能够客观测量疼痛信号的生物标志物或工具。从历史上看， 已经使用主观评定量表测量人类以确定其存在和严重性。在动物 模型中，疼痛是通过依赖于疼痛行为观察的半定量测定来测量的。虽然 这些措施虽然有用，但其固有的主观性质妨碍了研究和治疗工作。 据估计，仅在美国，慢性疼痛的年度经济负担就超过8000亿美元， 因为不充分的疼痛管理需要不成比例的更多医疗资源。同样，临床 在所有神经适应症中，疼痛疗法的试验是最昂贵的，并且成功率最低。 难以管理慢性疼痛导致阿片类药物流行，因为许多人转向处方止痛药 作为一种缓解手段，但最终往往会上瘾，并诉诸更有效和危险的阿片类药物 因为他们的容忍度增加了。放射性卡因是一种新型正电子发射断层显像剂， 正在发展成为一种生物标志物，以解决疼痛护理和治疗开发中的问题。我们最近 已发表的神经性疼痛啮齿动物模型的研究结果证明了定位疼痛发生器的能力 快速、准确、客观地测量其信号强度。我们的最终目标是：1）改变 （实验性）疼痛治疗的评价，和2）通过分子生物学评估疼痛的护理标准 显像疼痛成像生物标志物技术的使用将允许客观的疗效数据（包括临床前和临床后）。 以及在临床试验中），并且由于更同质的群体而通过实现更小的样本量来降低成本， 即一个特殊的“疼痛信号”，以及更精确的止痛效果测量。拟定的研究将 在早期临床试验中评估放射性卡因。成功的结果将为应用临床试验奠定基础 进一步将这种有前途的方法发展成为一种有用的生物标志物，用于改变疼痛护理。