Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
J Nucl Med. 2022 Jan;63(1):51-56. doi: 10.2967/jnumed.120.261864. Epub 2021 May 14.
In penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could potentially improve margin detection and reduce unnecessary excision of healthy tissue. Here, we present the first results of a prospective feasibility study for real-time intraoperative visualization of pSCC using a fluorescent mesenchymal-epithelial transition factor (c-MET) receptor targeting tracer (EMI-137). EMI-137 tracer performance was initially assessed ex vivo ( = 10) via incubation of freshly excised pSCC in a solution containing EMI-137 (500 nM). The in vivo potential of c-MET targeting and intraoperative tumor visualization was assessed after intravenous administration of EMI-137 to 5 pSCC patients scheduled for surgical resection using a cyanine-5 fluorescence camera. Fluorescence imaging results were related to standard pathologic tumor evaluation and c-MET immunohistochemistry. Three of the 5 in vivo patients also underwent a sentinel node resection after local administration of the hybrid tracer indocyanine green- Tc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. No tracer-related adverse events were encountered. Both ex vivo and in vivo, EMI-137 enabled c-MET-based tumor visualization in all patients. Histopathologic analyses showed that all pSCCs expressed c-MET, with expression levels of at least 70% in 14 of 15 patients. Moreover, the highest c-MET expression levels were seen on the outside rim of the tumors, and a visual correlation was found between c-MET expression and fluorescence signal intensity. No complications were encountered when combining primary tumor targeting with lymphatic mapping. As such, simultaneous use of cyanine-5 and indocyanine green in the same patient proved to be feasible. Fluorescence imaging of c-MET receptor- expressing pSCC tumors after intravenous injection of EMI-137 was shown to be feasible and can be combined with fluorescence-based lymphatic mapping. This combination is unique and paves the way toward further development of this surgical guidance approach.
在阴茎鳞状细胞癌（pSCC）中，主要的手术目的是在获得肿瘤安全性的前提下，尽可能减少对阴茎的损伤。受体特异性示踪剂可以为手术提供指导，从而有可能提高切缘检测的准确性，减少对健康组织的不必要切除。在这里，我们首次报道了一项前瞻性研究的初步结果，该研究旨在使用荧光间充质上皮转化因子（c-MET）受体靶向示踪剂（EMI-137）实时术中可视化 pSCC。通过将新鲜切除的 pSCC 置于含有 EMI-137（500 nM）的溶液中，体外评估了 EMI-137 示踪剂的性能（ = 10）。对 5 例计划行手术切除的 pSCC 患者，静脉注射 EMI-137 后，使用 Cy5 荧光相机评估 c-MET 靶向和术中肿瘤可视化的体内潜能。荧光成像结果与标准病理肿瘤评估和 c-MET 免疫组织化学相关联。在 5 例体内患者中，有 3 例还在局部给予混合示踪剂吲哚菁绿-Tc 纳米胶后进行了前哨淋巴结切除术，使用近红外荧光相机可对其进行成像。未发生与示踪剂相关的不良反应。无论是在体外还是体内，EMI-137 均使所有患者能够进行基于 c-MET 的肿瘤可视化。组织病理学分析显示，所有 pSCC 均表达 c-MET，其中 15 例患者中有 14 例的表达水平至少为 70%。此外，肿瘤外边缘的 c-MET 表达水平最高，并且 c-MET 表达与荧光信号强度之间存在视觉相关性。当将原发肿瘤靶向与淋巴定位相结合时，未发生任何并发症。因此，在同一患者中同时使用 Cy5 和吲哚菁绿是可行的。静脉注射 EMI-137 后，对表达 c-MET 的 pSCC 肿瘤进行荧光成像，结果表明该方法是可行的，并且可以与基于荧光的淋巴定位相结合。这种结合是独特的，为进一步开发这种手术指导方法铺平了道路。
