Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California, San Diego, United States of America.
Department of Radiology, University of California, San Diego, United States of America.
PLoS One. 2018 Jul 2;13(7):e0197842. doi: 10.1371/journal.pone.0197842. eCollection 2018.
Molecular imaging with a fluorescent version of Tilmanocept may permit an accurate and facile detection of sentinel nodes of endometrial cancer. Tilmanocept accumulates in sentinel lymph nodes (SLN) by binding to a cell surface receptor unique to macrophages and dendritic cells. Four female Yorkshire pigs underwent cervical stromal injection of IRDye800-Tilmanocept, a molecular imaging agent tagged with near-infrared fluorescent dye and radiolabeled with gallium-68 and technetium-99m. PET/CT scans 1.5 hours post-injection provided pre-operative SLN mapping. Robotic-assisted lymphadenectomy was performed two days after injection, using the FireFly imaging system to identify nodes demonstrating fluorescent signal. After removal of fluorescent nodes, pelvic and periaortic node dissections were performed. Nodes were assayed for technetium-99m activity, and SLNs were established using the "10%-rule", requiring that the radioactivity of additional SLNs be greater than 10% of the "hottest" SLN. Thirty-four nodal samples were assayed ex vivo for radioactivity. All the SLNs satisfying the "10%-rule" were detected using the FireFly system. Five fluorescent nodes were detected, corresponding with preoperative PET/CT scan. Three pigs had one SLN and one pig had two SLNs, with 100% concordance between fluorescence and radioactivity. Fluorescent-labeled Tilmanocept permits real-time intraoperative detection of SLNs during robotic-assisted lymphadenectomy for endometrial cancer in a porcine model. When radiolabeled with gallium-68, Tilmanocept allows for preoperative localization of SLNs using PET/CT, and shows specificity to SLNs with persistent fluorescent signal, detectable using the FireFly system, for two days post-injection. In conclusion, these findings suggest that a phase I trial in human subjects is warranted, and that a long-term goal of an intra-operative administration of non-radioactive fluorescent-labeled Tilmanocept is possible.
荧光版替拉诺肽的分子成像可能允许准确且易于检测子宫内膜癌的前哨淋巴结。替拉诺肽通过与巨噬细胞和树突状细胞特有的细胞表面受体结合而积聚在前哨淋巴结 (SLN) 中。四只雌性约克夏猪接受了 IRDye800-Tilmanocept 的宫颈基质注射，IRDye800-Tilmanocept 是一种带有近红外荧光染料的分子成像剂，并用镓-68 和锝-99m 放射性标记。注射后 1.5 小时进行 PET/CT 扫描，提供术前 SLN 定位。注射后两天，使用 FireFly 成像系统进行机器人辅助淋巴结切除术，以识别显示荧光信号的节点。切除荧光节点后，进行盆腔和主动脉旁淋巴结解剖。对节点进行锝-99m 活性测定，并使用“10%-规则”建立 SLN，要求其他 SLN 的放射性大于“最热”SLN 的 10%。对 34 个淋巴结样本进行离体放射性测定。使用 FireFly 系统检测到所有满足“10%-规则”的 SLN。检测到五个荧光节点，与术前 PET/CT 扫描相对应。三只猪有一个 SLN，一只猪有两个 SLN，荧光和放射性之间有 100%的一致性。荧光标记的替拉诺肽允许在机器人辅助淋巴结切除术中实时术中检测子宫内膜癌的 SLN。当用镓-68 放射性标记时，替拉诺肽允许使用 PET/CT 进行术前 SLN 定位，并显示对 SLN 的特异性，具有持续的荧光信号，使用 FireFly 系统可在注射后两天检测到。总之，这些发现表明在人体中进行 I 期试验是合理的，并且在两天内进行术中给予非放射性荧光标记替拉诺肽的长期目标是可能的。
