Washington University School of Medicine, St. Louis, MO, USA.
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA.
J Cereb Blood Flow Metab. 2023 Aug;43(8):1382-1389. doi: 10.1177/0271678X231160891. Epub 2023 Mar 30.
Many groups have reported lymphatic and glymphatic structures in animal and human brains, but tracer injection into the human brain to demonstrate real-time lymphatic drainage and mapping has not been described. We enrolled patients undergoing standard-of-care resection or stereotactic biopsy for suspected intracranial tumors. Patients received peritumoral injections of Tc-tilmanocept followed by planar or tomographic imaging. Fourteen patients with suspected brain tumors were enrolled. One was excluded from analysis because of tracer leakage during injection. There was no drainage of Tc-tilmanocept to regional lymph nodes in any of the patients. On average, after correcting for radioactive decay, 70.7% (95% CI: 59.9%, 81.6%) of the tracer in the injection site and 78.1% (95% CI: 71.1%, 85.1%) in the whole-head on the day of surgery remained the morning after, with variable radioactivity in the subarachnoid space. The retained fraction was much greater than expected based on the clearance rate from non-brain injection sites. In this pilot study, the lymphatic tracer Tc-tilmanocept was injected into the brain parenchyma, and there was no drainage outside the brain to the cervical lymph nodes. Our work demonstrates an inefficiency of drainage from peritumoral brain parenchyma and highlights a therapeutic opportunity to improve immunosurveillance of the brain.
许多团队已经在动物和人类大脑中报告了淋巴和神经胶质淋巴系统的存在,但尚未描述将示踪剂注入人脑以证明实时淋巴引流和绘图的情况。我们招募了接受标准护理切除术或立体定向活检以怀疑患有颅内肿瘤的患者。患者接受 Tc-替拉曼诺普注射,然后进行平面或断层成像。共纳入 14 名疑似脑肿瘤患者。由于注射过程中示踪剂泄漏,1 名患者被排除在分析之外。在任何患者中,均未观察到 Tc-替拉曼诺普引流至区域淋巴结。平均而言,在纠正放射性衰变后,注射部位的 70.7%(95%置信区间:59.9%,81.6%)和手术当天整个头部的 78.1%(95%置信区间:71.1%,85.1%)的示踪剂在手术次日早晨仍有残留,蛛网膜下腔的放射性物质存在差异。与非脑部注射部位的清除率相比,保留的分数要高得多。在这项初步研究中,将淋巴示踪剂 Tc-替拉曼诺普注入脑实质中,并且没有向颈部淋巴结引流到脑外。我们的工作表明,从肿瘤周围脑实质引流的效率低下,并突显了改善大脑免疫监视的治疗机会。