Non-invasive molecular imaging of fibrosis using a collagen-targeted peptidomimetic of the platelet collagen receptor glycoprotein VI
| Autor: | Julien Muzard, Dominique Le Guludec, Martine Jandrot-Perrus, Alain Meulemans, Jean-Baptiste Michel, Laure Sarda-Mantel, Liliane Louedec, Stéphane Loyau, Claudie Bantsimba-Malanda, Joëlle Marchal-Somme, Florence Hervatin, Philippe Billiald |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Diagnostic Imaging
Tail Pathology medicine.medical_specialty Science Blotting Western Scars Biochemistry/Biomimetic Chemistry Platelet Membrane Glycoproteins In Vitro Techniques Platelet membrane glycoprotein In vivo Fibrosis Medicine Animals Radionuclide Imaging Biochemistry/Biomacromolecule-Ligand Interactions Aorta Multidisciplinary business.industry medicine.disease In vitro Rats Radiology and Medical Imaging/PET and SPECT Imaging medicine.symptom GPVI business Peptides Preclinical imaging Ex vivo Cardiovascular Disorders/Myocardial Infarction Research Article |
| Zdroj: | PLoS ONE, Vol 4, Iss 5, p e5585 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | BackgroundFibrosis, which is characterized by the pathological accumulation of collagen, is recognized as an important feature of many chronic diseases, and as such, constitutes an enormous health burden. We need non-invasive specific methods for the early diagnosis and follow-up of fibrosis in various disorders. Collagen targeting molecules are therefore of interest for potential in vivo imaging of fibrosis. In this study, we developed a collagen-specific probe using a new approach that takes advantage of the inherent specificity of Glycoprotein VI (GPVI), the main platelet receptor for collagens I and III.Methodology/principal findingsAn anti-GPVI antibody that neutralizes collagen-binding was used to screen a bacterial random peptide library. A cyclic motif was identified, and the corresponding peptide (designated collagelin) was synthesized. Solid-phase binding assays and histochemical analysis showed that collagelin specifically bound to collagen (Kd 10(-7) M) in vitro, and labelled collagen fibers ex vivo on sections of rat aorta and rat tail. Collagelin is therefore a new specific probe for collagen. The suitability of collagelin as an in vivo probe was tested in a rat model of healed myocardial infarctions (MI). Injecting Tc-99m-labelled collagelin and scintigraphic imaging showed that uptake of the probe occurred in the cardiac area of rats with MI, but not in controls. Post mortem autoradiography and histological analysis of heart sections showed that the labeled areas coincided with fibrosis. Scintigraphic molecular imaging with collagelin provides high resolution, and good contrast between the fibrotic scars and healthy tissues. The capacity of collagelin to image fibrosis in vivo was confirmed in a mouse model of lung fibrosis.Conclusion/significanceCollagelin is a new collagen-targeting agent which may be useful for non-invasive detection of fibrosis in a broad spectrum of diseases. |
| Databáze: | OpenAIRE |
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