Multimodal CEA-targeted image-guided colorectal cancer surgery using 111In-labeled SGM-101

Colorectal Cancer
09/09/2020

Clin Cancer Res. 2020 Sep 8:clincanres.2255.2020. doi: 10.1158/1078-0432.CCR-20-2255. Online ahead of print.

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.