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Targeting of fibroblast activation protein in rheumatoid arthritis patients: imaging and ex vivo photodynamic therapy.
Dorst, Daphne N; Rijpkema, Mark; Buitinga, Mijke; Walgreen, Birgitte; Helsen, Monique M A; Brennan, Evan; Klein, Christian; Laverman, Peter; Ramming, Andreas; Schmidkonz, Christian; Kuwert, Torsten; Schett, Georg; van der Kraan, Peter M; Gotthardt, Martin; Koenders, Marije I.
Afiliación
  • Dorst DN; Department of Medical Imaging: Nuclear Medicine.
  • Rijpkema M; Department of Experimental Rheumatology, Radboudumc, Nijmegen.
  • Buitinga M; Department of Medical Imaging: Nuclear Medicine.
  • Walgreen B; Department of Nutrition and Movement Sciences, Maastricht University.
  • Helsen MMA; Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
  • Brennan E; Department of Experimental Rheumatology, Radboudumc, Nijmegen.
  • Klein C; Department of Experimental Rheumatology, Radboudumc, Nijmegen.
  • Laverman P; Department of Experimental Rheumatology, Radboudumc, Nijmegen.
  • Ramming A; Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland.
  • Schmidkonz C; Department of Medical Imaging: Nuclear Medicine.
  • Kuwert T; Department of Medicine 3, Friedrich Alexander University Erlangen-Nürnberg and Universtitätsklinikum.
  • Schett G; Deutsches Zentrum für Immuntherapie.
  • van der Kraan PM; Clinic of Nuclear Medicine, University Hospital Erlangen, Erlangen, Germany.
  • Gotthardt M; Clinic of Nuclear Medicine, University Hospital Erlangen, Erlangen, Germany.
  • Koenders MI; Department of Medicine 3, Friedrich Alexander University Erlangen-Nürnberg and Universtitätsklinikum.
Rheumatology (Oxford) ; 61(7): 2999-3009, 2022 07 06.
Article en En | MEDLINE | ID: mdl-34450633
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fotoquimioterapia / Artritis Reumatoide Límite: Humans Idioma: En Revista: Rheumatology (Oxford) Asunto de la revista: REUMATOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fotoquimioterapia / Artritis Reumatoide Límite: Humans Idioma: En Revista: Rheumatology (Oxford) Asunto de la revista: REUMATOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido