1. Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
- Author
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Ramos-Gomes, Fernanda, Bode, Julia, Sukhanova, Alyona, Bozrova, Svetlana V., Saccomano, Mara, Mitkovski, Miso, Krueger, Julia Eva, Wege, Anja K., Stuehmer, Walter, Samokhvalov, Pavel S., Baty, Daniel, Chames, Patrick, Nabiev, Igor, Alves, Frauke, Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, Laboratoire de Recherche en Nanosciences - EA 4682 (LRN), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), National Research Nuclear University ( MEPhI), Department of Gynecology and Obstetrics [Regensburg, Germany], University Medical Center Regensburg [Germany]-University of Regensburg, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinic of Haematology and Medical Oncology [Göttingen, Germany], University Medical Center Groningen [Groningen] (UMCG)-Institute of Diagnostic and Interventional Radiology [Göttingen, Germany], Chames, Patrick, University of Regensburg-University Medical Center Regensburg [Germany], Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), and The National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) [Moscow, Russia]
- Subjects
Microscopy, Confocal ,Receptor, ErbB-2 ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,Science ,Transplantation, Heterologous ,Mice, Nude ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Single-Domain Antibodies ,Article ,Carcinoembryonic Antigen ,Mice ,Microscopy, Fluorescence, Multiphoton ,[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Neoplasm Micrometastasis ,Cell Line, Tumor ,Quantum Dots ,Animals ,Humans ,Medicine ,Female ,Fluorescent Dyes - Abstract
International audience; Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent quantum dots (QDs) for single-and two-photon detection and imaging of human micrometastases and disseminated tumour cells in ex vivo biological samples of breast and pancreatic metastatic tumour mouse models expressing human epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen (CEA). By staining thin (5–10 µm) paraffin and thick (50 µm) agarose tissue sections, we detected HER2-and CEA-positive human tumour cells infiltrating the surrounding tissues or metastasizing to different organs, including the brain, testis, lung, liver, and lymph nodes. Compared to conventional fluorescently labelled antibodies the sdAb-HER2-QD and sdAb-CEA-QD nanoprobes are superior in detecting micrometastases in tissue sections by lower photobleaching and higher brightness of fluorescence signals ensuring much better discrimination of positive signals versus background. Very high two-photon absorption cross-sections of QDs and small size of the nanoprobes ensure efficient imaging of thick tissue sections unattainable with conventional fluorescent probes. The nanobody–QD probes will help to improve early cancer diagnosis and prognosis of progression by assessing metastasis.
- Published
- 2018
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