TY - JOUR T1 - c-MET Receptor–Targeted Fluorescence on the Road to Image-Guided Surgery in Penile Squamous Cell Carcinoma Patients JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 51 LP - 56 DO - 10.2967/jnumed.120.261864 VL - 63 IS - 1 AU - Hielke M. de Vries AU - Elise Bekers AU - Matthias N. van Oosterom AU - M. Baris Karakullukcu AU - Henk G. van AU - der Poel AU - Fijs W.B. van Leeuwen AU - Tessa Buckle AU - Oscar R. Brouwer Y1 - 2022/01/01 UR - http://jnm.snmjournals.org/content/63/1/51.abstract N2 - 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). Methods: EMI-137 tracer performance was initially assessed ex vivo (n = 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– 99mTc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. Results: 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. Conclusion: 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. ER -