Near-Infrared Fluorescence Imaging of Both Colorectal Cancer and Ureters Using a Low-Dose Integrin Targeted Probe

作者：Verbeek Floris P R; van der Vorst Joost R; Tummers Quirijn R J G; Boonstra Martin C; de Rooij Karien E; Loewik Clemens W G M; Valentijn A Rob P M; van de Velde Cornelis J H; Choi Hak Soo; Frangioni John V; Vahrmeijer Alexander L^*

来源：Annals of Surgical Oncology, 2014, 21(S4): S528-S537.

DOI：10.1245/s10434-014-3524-x

Background. Irradical tumor resections and iatrogenic ureteral injury remain a significant problem during lower abdominal surgery. The aim of the current study was to intraoperatively identify both colorectal tumors and ureters in subcutaneous and orthotopic animal models using cRGD-ZW800-1 and near-infrared (NIR) fluorescence. %26lt;br%26gt;Methods. The zwitterionic fluorophore ZW800-1 was conjugated to the tumor specific peptide cRGD (targeting integrins) and to the a-specific peptide cRAD. One nmol cRGD-ZW800-1, cRAD-ZW800-1, or ZW800-1 alone was injected in mice bearing subcutaneous HT-29 human colorectal tumors. Subsequently, cRGD-ZW800-1 was injected at dosages of 0.25 and 1 nmol in mice bearing orthotopic HT-29 tumors transfected with luciferase2. In vivo biodistribution and ureteral visualization were investigated in rats. Fluorescence was measured intraoperatively at several time points after probe administration using the FLARE imaging system. %26lt;br%26gt;Results. Both subcutaneous and orthotopic tumors could be clearly identified using cRGD-ZW800-1. A significantly higher signal-to-background ratio was observed in mice injected with cRGD-ZW800-1 (2.42 +/- 0.77) compared with mice injected with cRAD-ZW800-1 or ZW800-1 alone (1.21 +/- 0.19 and 1.34 +/- 0.19, respectively) when measured at 24 h after probe administration. The clearance of cRGD-ZW800-1 permitted visualization of the ureters and also generated minimal background fluorescence in the gastrointestinal tract. %26lt;br%26gt;Conclusions. This study appears to be the first to demonstrate both clear tumor demarcation and ureteral visualization after a single intravenous injection of a targeted NIR fluorophore. As a low dose of cRGD-ZW800-1 provided clear tumor identification, clinical translation of these results should be possible.

• 出版日期2014-12