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

Autor: Elekonawo FMK; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. fortune.elekonawo@radboudumc.nl., Lütje S; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., Franssen GM; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., Bos DL; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., Goldenberg DM; Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ, USA., Boerman OC; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands., Rijpkema M; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: EJNMMI research [EJNMMI Res] 2019 Sep 04; Vol. 9 (1), pp. 86. Date of Electronic Publication: 2019 Sep 04.
DOI: 10.1186/s13550-019-0551-4
Abstrakt: 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.
Databáze: MEDLINE
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