Targeting of fibroblast activation protein in rheumatoid arthritis patients: imaging and ex vivo photodynamic therapy.

Autor:	Dorst DN; Department of Medical Imaging: Nuclear Medicine.; Department of Experimental Rheumatology, Radboudumc, Nijmegen., Rijpkema M; Department of Medical Imaging: Nuclear Medicine., Buitinga M; Department of Nutrition and Movement Sciences, Maastricht University.; Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands., Walgreen B; Department of Experimental Rheumatology, Radboudumc, Nijmegen., Helsen MMA; Department of Experimental Rheumatology, Radboudumc, Nijmegen., Brennan E; Department of Experimental Rheumatology, Radboudumc, Nijmegen., Klein C; Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland., Laverman P; Department of Medical Imaging: Nuclear Medicine., Ramming A; Department of Medicine 3, Friedrich Alexander University Erlangen-Nürnberg and Universtitätsklinikum.; Deutsches Zentrum für Immuntherapie., Schmidkonz C; Clinic of Nuclear Medicine, University Hospital Erlangen, Erlangen, Germany., Kuwert T; Clinic of Nuclear Medicine, University Hospital Erlangen, Erlangen, Germany., Schett G; Department of Medicine 3, Friedrich Alexander University Erlangen-Nürnberg and Universtitätsklinikum.; Deutsches Zentrum für Immuntherapie., van der Kraan PM; Department of Experimental Rheumatology, Radboudumc, Nijmegen., Gotthardt M; Department of Medical Imaging: Nuclear Medicine., Koenders MI; Department of Experimental Rheumatology, Radboudumc, Nijmegen.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2022 Jul 06; Vol. 61 (7), pp. 2999-3009.
DOI:	10.1093/rheumatology/keab664
Abstrakt:	Objective: Activated synovial fibroblasts are key effector cells in RA. Selectively depleting these based upon their expression of fibroblast activation protein (FAP) is an attractive therapeutic approach. Here we introduce FAP imaging of inflamed joints using 68Ga-FAPI-04 in a RA patient, and aim to assess feasibility of anti-FAP targeted photodynamic therapy (FAP-tPDT) ex vivo using 28H1-IRDye700DX on RA synovial explants. Methods: Remnant synovial tissue from RA patients was processed into 6 mm biopsies and, from several patients, into primary fibroblast cell cultures. Both were treated using FAP-tPDT. Cell viability was measured in fibroblast cultures and biopsies were evaluated for histological markers of cell damage. Selectivity of the effect of FAP-tPDT was assessed using flow cytometry on primary fibroblasts and co-cultured macrophages. Additionally, one RA patient intravenously received 68Ga-FAPI-04 and was scanned using PET/CT imaging. Results: In the RA patient, FAPI-04 PET imaging showed high accumulation of the tracer in arthritic joints with very low background signal. In vitro, FAP-tPDT induced cell death in primary RA synovial fibroblasts in a light dose-dependent manner. An upregulation of cell damage markers was observed in the synovial biopsies after FAP-tPDT. No significant effects of FAP-tPDT were noted on macrophages after FAP-tPDT of neighbouring fibroblasts. Conclusion: In this study the feasibility of selective FAP-tPDT in synovium of rheumatoid arthritis patients ex vivo is demonstrated. Furthermore, this study provides the first indication that FAP-targeted PET/CT can be used to image arthritic joints, an important step towards application of FAP-tPDT as a targeted locoregional therapy for RA. (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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