A multimodal molecular imaging approach targeting urokinase plasminogen activator receptor for the diagnosis, resection and surveillance of urothelial cell carcinoma

Autor: Massimo Resnati, Victor M Baart, Rob C.M. Pelger, Timo Schomann, Peter J. K. Kuppen, Maaike H. van der Mark, Vincent Q. Sier, Hugo de Jonge, Gabriel van der Pluijm, Marion M. Deken, Luisa Iamele, Shadhvi S. Bhairosingh, Alexander L. Vahrmeijer, Andrew P. Mazar, Cornelis F. M. Sier, Geertje van der Horst
Rok vydání: 2021
Předmět:
0301 basic medicine
Cancer Research
Fluorescence-lifetime imaging microscopy
medicine.drug_class
Mice
Nude
Apoptosis
Monoclonal antibody
Receptors
Urokinase Plasminogen Activator
Flow cytometry
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Tumor Cells
Cultured
Image guided surgery
medicine
Animals
Humans
Cell Proliferation
Mice
Inbred BALB C
TUR surgery
Bladder cancer
medicine.diagnostic_test
business.industry
Transurethral resection
Optical Imaging
Antibodies
Monoclonal
Epithelial cell adhesion molecule
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
Molecular Imaging
3. Good health
Urokinase receptor
Radical cystectomy
030104 developmental biology
Surgery
Computer-Assisted
Urinary Bladder Neoplasms
Oncology
chemistry
EpCAM
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Female
Photoacoustic imaging
Molecular imaging
business
Zdroj: European Journal of Cancer
European Journal of Cancer, 146, 11-20. ELSEVIER SCI LTD
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2021.01.001
Popis: With a 5-year recurrence rate of 30-78%, urothelial cell carcinoma (UCC) rates amongst the highest of all solid malignancies. Consequently, after transurethral resection, patients are subjugated to life-long endoscopic surveillance. A multimodal near-infrared (NIR) fluorescence-based imaging strategy can improve diagnosis, resection and surveillance, hence increasing quality of life.Methods: Expression of urokinase plasminogen activator receptor (uPAR) and epithelial cell adhesion molecule (EpCAM) are determined on paraffin-embedded human UCC using immunohistochemistry and on UCC cell lines by flow cytometry. MNPR-101, a humanised monoclonal antibody targeting uPAR is conjugated to IRDye800CW and binding is validated in vitro using surface plasmon resonance and cell-based binding assays. In vivo NIR fluorescence and photoacoustic three-dimensional (3D) imaging are performed with subcutaneously growing human UM-UC-31uc2 cells in BALB/c-nude mice. The translational potential is confirmed in a metastasising UM-UC-31uc2 orthotopic mouse model. InfliximabIRDye800CW and rituximab-IRDye800CW are used as controls.Results: UCCs show prominent uPAR expression at the tumour-stroma interface and EpCAM on epithelial cells. uPAR and EpCAM are expressed by 6/7 and 4/7 UCC cell lines, respectively. In vitro, MNPR-101-IRDye800CW has a picomolar affinity for domain 2-3 of uPAR. In vivo fluorescence imaging with MNPR-101-IRDye800CW, specifically delineates both subcutaneous and orthotopic tumours with tumour-to-background ratios reaching as high as 6.8, differing significantly from controls (p < 0.0001). Photoacoustic 3D in depth imaging confirms the homogenous distribution of MNPR-101-IRDye800CW through the tumour.Conclusions: MNPR-101-IRDye800CW is suitable for multimodal imaging of UCC, awaiting clinical translation. (C) 2021 The Author(s). Published by Elsevier Ltd.
Databáze: OpenAIRE
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