Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101.
| Title: | Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101. |
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| Authors: | de Gooyer JM; Department of Radiology, Nuclear Medicine & Anatomy, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands. Jan-Marie.Gooyer@radboudumc.nl.; Department of Surgical Oncology, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands.; Elekonawo FMK; Department of Radiology, Nuclear Medicine & Anatomy, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands.; Department of Surgical Oncology, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands.; Bos DL; Department of Radiology, Nuclear Medicine & Anatomy, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands.; van der Post RS; Department of Pathology, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands.; Pèlegrin A; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier, France.; Framery B; SurgiMab, Montpellier, France.; Cailler F; SurgiMab, Montpellier, France.; Vahrmeijer AL; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.; de Wilt JHW; Department of Surgical Oncology, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands.; Rijpkema M; Department of Radiology, Nuclear Medicine & Anatomy, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands. |
| Source: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Nov 15; Vol. 26 (22), pp. 5934-5942. Date of Electronic Publication: 2020 Sep 08. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Denville, NJ : American Association for Cancer Research, c1995- |
| MeSH Terms: | Antibodies, Monoclonal/*pharmacology ; Carcinoembryonic Antigen/*isolation & purification ; Colorectal Neoplasms/*surgery ; Surgery, Computer-Assisted/*methods; Antibodies, Monoclonal/chemistry ; Carcinoembryonic Antigen/genetics ; Colorectal Neoplasms/diagnostic imaging ; Colorectal Neoplasms/pathology ; GPI-Linked Proteins/genetics ; GPI-Linked Proteins/isolation & purification ; Indium Radioisotopes/pharmacology ; Optical Imaging/methods ; Tissue Distribution/radiation effects ; Animals ; Cell Line, Tumor ; Heterografts ; Humans ; Mice ; Single Photon Emission Computed Tomography Computed Tomography |
| Abstract: | 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.; (©2020 American Association for Cancer Research.) |
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| Substance Nomenclature: | 0 (Antibodies, Monoclonal); 0 (CEACAM5 protein, human); 0 (Carcinoembryonic Antigen); 0 (GPI-Linked Proteins); 0 (Indium Radioisotopes); E9NGC49E0T (Indium-111) |
| Entry Date(s): | Date Created: 20200909 Date Completed: 20211122 Latest Revision: 20211122 |
| Update Code: | 20260130 |
| DOI: | 10.1158/1078-0432.CCR-20-2255 |
| PMID: | 32900795 |
| Database: | MEDLINE |
Journal Article