Glycan-Based Near-infrared Fluorescent (NIRF) Imaging of Gastrointestinal Tumors: a Preclinical Proof-of-Concept In Vivo Study.

Autor: Houvast RD; Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Baart VM; Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Bhairosingh SS; Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Cordfunke RA; Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands., Chua JX; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Vankemmelbeke M; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Parsons T; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Kuppen PJK; Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Durrant LG; Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK.; Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Vahrmeijer AL; Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Sier CFM; Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands. c.f.m.sier@lumc.nl.; Percuros BV, Leiden, the Netherlands. c.f.m.sier@lumc.nl.
Jazyk: angličtina
Zdroj: Molecular imaging and biology [Mol Imaging Biol] 2020 Dec; Vol. 22 (6), pp. 1511-1522. Date of Electronic Publication: 2020 Aug 11.
DOI: 10.1007/s11307-020-01522-8
Abstrakt: Purpose: Aberrantly expressed glycans in cancer are of particular interest for tumor targeting. This proof-of-concept in vivo study aims to validate the use of aberrant Lewis glycans as target for antibody-based, real-time imaging of gastrointestinal cancers.
Procedures: Immunohistochemical (IHC) staining with monoclonal antibody FG88.2, targeting Lewis a/c/x , was performed on gastrointestinal tumors and their healthy counterparts. Then, FG88.2 and its chimeric human/mouse variant CH88.2 were conjugated with near-infrared fluorescent (NIRF) IRDye 800CW for real-time imaging. Specific binding was evaluated in vitro on human gastrointestinal cancer cell lines with cell-based plate assays, flow cytometry, and immune-fluorescence microscopy. Subsequently, mice bearing human colon and pancreatic subcutaneous tumors were imaged in vivo after intravenous administration of 1 nmol (150 μg) CH88.2-800CW with the clinical Artemis NIRF imaging system using the Pearl Trilogy small animal imager as reference. One week post-injection of the tracer, tumors and organs were resected and tracer uptake was analyzed ex vivo.
Results: IHC analysis showed strong FG88.2 staining on colonic, gastric, and pancreatic tumors, while staining on their normal tissue counterparts was limited. Next, human cancer cell lines HT-29 (colon) and BxPC-3 and PANC-1 (both pancreatic) were identified as respectively high, moderate, and low Lewis a/c/x -expressing. Using the clinical NIRF camera system for tumor-bearing mice, a mean tumor-to-background ratio (TBR) of 2.2 ± 0.3 (Pearl: 3.1 ± 0.8) was observed in the HT-29 tumors and a TBR of 1.8 ± 0.3 (Pearl: 1.9 ± 0.5) was achieved in the moderate expression BxPC-3 model. In both models, tumors could be adequately localized and delineated by NIRF for up to 1 week. Ex vivo analysis confirmed full tumor penetration of the tracer and low fluorescence signals in other organs.
Conclusions: Using a novel chimeric Lewis a/c/x -targeting tracer in combination with a clinical NIRF imager, we demonstrate the potential of targeting Lewis glycans for fluorescence-guided surgery of gastrointestinal tumors.
Databáze: MEDLINE
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