PT  - JOURNAL ARTICLE
AU  - de Gooyer, Jan Marie
AU  - Elekonawo, Fortuné M.K.
AU  - Bos, Desirée L.
AU  - van der Post, Rachel S.
AU  - Pèlegrin, André
AU  - Framery, Bérénice
AU  - Cailler, Françoise
AU  - Vahrmeijer, Alexander L.
AU  - de Wilt, Johannes H.W.
AU  - Rijpkema, Mark
TI  - Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using <sup>111</sup>In-Labeled SGM-101
AID  - 10.1158/1078-0432.CCR-20-2255
DP  - 2020 Nov 15
TA  - Clinical Cancer Research
PG  - 5934--5942
VI  - 26
IP  - 22
4099  - http://clincancerres.aacrjournals.org/content/26/22/5934.short
4100  - http://clincancerres.aacrjournals.org/content/26/22/5934.full
SO  - Clin Cancer Res2020 Nov 15; 26
AB  - Purpose: Intraoperative image guidance may aid in clinical decision-making during surgical treatment of colorectal cancer. We developed the dual-labeled carcinoembryonic antigen–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–diethylenetriaminepentaacetic acid (DTPA) and labeled with Indium-111 (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 timepoint for imaging. Mice with intraperitoneal LS174T tumors underwent micro-SPECT/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 with adjacent nontumor tissue (P < 0.001).Conclusions: [111In]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence image–guided tumor resection. Thus, [111In]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radio-guided localization and fluorescence image–guided resection of colorectal cancer.