A pretargeted multimodal approach for image-guided resection in a xenograft model of colorectal cancer

• Published in: EJNMMI research Vol. 9; no. 1; pp. 86 - 8
• Main Authors: Elekonawo, Fortuné M. K., Lütje, Susanne, Franssen, Gerben M., Bos, Desirée L., Goldenberg, David M., Boerman, Otto C., Rijpkema, Mark
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 04.09.2019; Springer Nature B.V; SpringerOpen
• Subjects: Antigens; Antihistamines; Cancer; Carcinoembryonic antigen; Cardiac Imaging; Colorectal cancer; Computed tomography; Feasibility studies; Fluorescence; Glycine; IgG antibody; Image-guided; Imaging; Infrared imagery; Infrared imaging; Medical imaging; Medicine; Medicine & Public Health; Near-infrared fluorescence; Nuclear Medicine; Oncology; Original Research; Orthopedics; Pretargeting; Radiolabelling; Radiology; Tumors; Xenotransplantation; Carcinoembryonic antigen; Image-guided; Pretargeting; Colorectal cancer; Near-infrared fluorescence
• ISSN: 2191-219X; 2191-219X
• DOI: 10.1186/s13550-019-0551-4

Background Image-guided surgery may improve surgical outcome for colorectal cancer patients. Here, we evaluated the feasibility of a pretargeting strategy for multimodal imaging in colorectal cancer using an anti-carcinoembryonic antigen (CEA) x anti-histamine-succinyl-glycine (HSG) bispecific antibody (TF2) in conjunction with the dual-labeled diHSG peptide (RDC018), using both a fluorophore for near-infrared fluorescence imaging and a chelator for radiolabeling. Methods Nude mice with subcutaneous (s.c) CEA-expressing LS174T human colonic tumors and CEA-negative control tumors were injected with TF2. After 16 h, different doses of 111 In-labeled IMP-288 (non-fluorescent) or its fluorescent derivative RDC018 were administered to compare biodistributions. MicroSPECT/CT and near-infrared fluorescence imaging were performed 2 and 24 h after injection. Next, the biodistribution of the dual-labeled humanized anti-CEA IgG antibody [ 111 In]In-DTPA-hMN-14-IRDye800CW (direct targeting) was compared with the biodistribution of 111 In-RDC018 in mice with TF2-pretargeted tumors, using fluorescence imaging and gamma counting. Lastly, mice with intraperitoneal LS174T tumors underwent near-infrared fluorescence image-guided resection combined with pre- and post-resection microSPECT/CT imaging. Results 111 In-RDC018 showed specific tumor targeting in pretargeted CEA-positive tumors (21.9 ± 4.5 and 10.0 ± 4.7% injected activity per gram (mean ± SD %IA/g), at 2 and 24 hours post-injection (p.i.), respectively) and a biodistribution similar to 111 In-IMP288. Both fluorescence and microSPECT/CT images confirmed preferential tumor accumulation. At post mortem dissection, intraperitoneal tumors were successfully identified and removed using pretargeting with TF2 and 111 In-RDC018. Conclusion A pretargeted approach for multimodal image-guided resection of colorectal cancer in a preclinical xenograft model is feasible, enables preoperative SPECT/CT, and might facilitate intraoperative fluorescence imaging.