Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101

Abstract

Purpose:Intraoperative image guidance may aid in clinical decision making during surgical treatment of colorectal cancer. We developed the dual-labeled CEA-targeting tracer [¹¹¹In]In-DTPA-SGM-101 for pre- and intraoperative imaging of colorectal cancer. Subsequently we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient derived colorectal cancer samples, paving the way for rapid clinical translation. Experimental Design:SGM-101 was conjugated with p-isothiocyanatobenzyl (ITC)-diethylenetriaminepentaacetic acid (DTPA) and labeled with ¹¹¹In. The biodistribution of 3, 10, 30, and 100 μg [¹¹¹In]In-DTPA-SGM-101 was assessed in a dose escalation study in BALB/c nude mice with subcutaneous LS174T human colonic tumors followed by a study to determine the optimal time point for imaging. Mice with intraperitoneal LS174T tumors underwent microSPECT/CT imaging and fluorescence image-guided resection. In a final translational experiment, we incubated freshly resected human tumor specimens with the tracer and assessed the tumor-to-adjacent tissue ratio of both signals. Results:The optimal protein dose of [¹¹¹In]In-DTPA-SGM-101 was 30 μg (tumor-to-blood ratio 5.8 ± 1.1) and the optimal timepoint for imaging was 72 hours after injection (tumor-to-blood ratio 5.1 ± 1.0). In mice with intraperitoneal tumors, [¹¹¹In]In-DTPA-SGM-101 enabled preoperative SPECT/CT imaging and fluorescence image-guided resection. After incubation of human tumor samples overall fluorescence and radiosignal intensities were higher in tumor areas compared to adjacent non-tumor tissue(p < 0.001). Conclusions:[¹¹¹In]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence-guided tumor resection. Thus, [¹¹¹In]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radioguided localization and fluorescence-guided resection of colorectal cancer.