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

Fortuné M K Elekonawo; Susanne Lütje; Gerben M Franssen; Desirée L Bos; David M Goldenberg; Otto C Boerman; Mark Rijpkema

doi:10.1186/s13550-019-0551-4

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

EJNMMI Res. 2019 Sep 4;9(1):86. doi: 10.1186/s13550-019-0551-4.

Authors

Fortuné M K Elekonawo¹, Susanne Lütje², Gerben M Franssen², Desirée L Bos², David M Goldenberg³, Otto C Boerman², Mark Rijpkema²

Affiliations

¹ Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. fortune.elekonawo@radboudumc.nl.
² Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
³ Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ, USA.

Abstract

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 ¹¹¹In-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 [¹¹¹In]In-DTPA-hMN-14-IRDye800CW (direct targeting) was compared with the biodistribution of ¹¹¹In-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: ¹¹¹In-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 ¹¹¹In-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 ¹¹¹In-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.

Keywords: Carcinoembryonic antigen; Colorectal cancer; Image-guided; Near-infrared fluorescence; Pretargeting.