CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis

Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Theeuwes, Wessel F. [verfasserIn] Di Ceglie, Irene Dorst, Daphne N. Blom, Arjen B. Bos, Desiree L. Vogl, Thomas Tas, Sander W. Jimenez-Royo, Pilar Bergstrom, Mats Cleveland, Matthew van der Kraan, Peter M. Laverman, Peter Koenders, Marije I. van Lent, Peter L. van den Bosch, Martijn H. J.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	CD64 Rheumatoid arthritis Macrophage Molecular imaging Preclinical models

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Arthritis Research & Therapy - London : BioMed Central, 1999, 25(2023), 1 vom: 31. Aug.
Übergeordnetes Werk:	volume:25 ; year:2023 ; number:1 ; day:31 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s13075-023-03147-y

Katalog-ID:	SPR052946401

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520			\|a Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo.
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allfields	10.1186/s13075-023-03147-y doi (DE-627)SPR052946401 (SPR)s13075-023-03147-y-e DE-627 ger DE-627 rakwb eng Theeuwes, Wessel F. verfasserin aut CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. CD64 (dpeaa)DE-He213 Rheumatoid arthritis (dpeaa)DE-He213 Macrophage (dpeaa)DE-He213 Molecular imaging (dpeaa)DE-He213 Preclinical models (dpeaa)DE-He213 Di Ceglie, Irene aut Dorst, Daphne N. aut Blom, Arjen B. aut Bos, Desiree L. aut Vogl, Thomas aut Tas, Sander W. aut Jimenez-Royo, Pilar aut Bergstrom, Mats aut Cleveland, Matthew aut van der Kraan, Peter M. aut Laverman, Peter aut Koenders, Marije I. aut van Lent, Peter L. aut van den Bosch, Martijn H. J. aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 25(2023), 1 vom: 31. Aug. (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:25 year:2023 number:1 day:31 month:08 https://dx.doi.org/10.1186/s13075-023-03147-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2023 1 31 08
spelling	10.1186/s13075-023-03147-y doi (DE-627)SPR052946401 (SPR)s13075-023-03147-y-e DE-627 ger DE-627 rakwb eng Theeuwes, Wessel F. verfasserin aut CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. CD64 (dpeaa)DE-He213 Rheumatoid arthritis (dpeaa)DE-He213 Macrophage (dpeaa)DE-He213 Molecular imaging (dpeaa)DE-He213 Preclinical models (dpeaa)DE-He213 Di Ceglie, Irene aut Dorst, Daphne N. aut Blom, Arjen B. aut Bos, Desiree L. aut Vogl, Thomas aut Tas, Sander W. aut Jimenez-Royo, Pilar aut Bergstrom, Mats aut Cleveland, Matthew aut van der Kraan, Peter M. aut Laverman, Peter aut Koenders, Marije I. aut van Lent, Peter L. aut van den Bosch, Martijn H. J. aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 25(2023), 1 vom: 31. Aug. (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:25 year:2023 number:1 day:31 month:08 https://dx.doi.org/10.1186/s13075-023-03147-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2023 1 31 08
allfields_unstemmed	10.1186/s13075-023-03147-y doi (DE-627)SPR052946401 (SPR)s13075-023-03147-y-e DE-627 ger DE-627 rakwb eng Theeuwes, Wessel F. verfasserin aut CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. CD64 (dpeaa)DE-He213 Rheumatoid arthritis (dpeaa)DE-He213 Macrophage (dpeaa)DE-He213 Molecular imaging (dpeaa)DE-He213 Preclinical models (dpeaa)DE-He213 Di Ceglie, Irene aut Dorst, Daphne N. aut Blom, Arjen B. aut Bos, Desiree L. aut Vogl, Thomas aut Tas, Sander W. aut Jimenez-Royo, Pilar aut Bergstrom, Mats aut Cleveland, Matthew aut van der Kraan, Peter M. aut Laverman, Peter aut Koenders, Marije I. aut van Lent, Peter L. aut van den Bosch, Martijn H. J. aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 25(2023), 1 vom: 31. Aug. (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:25 year:2023 number:1 day:31 month:08 https://dx.doi.org/10.1186/s13075-023-03147-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2023 1 31 08
allfieldsGer	10.1186/s13075-023-03147-y doi (DE-627)SPR052946401 (SPR)s13075-023-03147-y-e DE-627 ger DE-627 rakwb eng Theeuwes, Wessel F. verfasserin aut CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. CD64 (dpeaa)DE-He213 Rheumatoid arthritis (dpeaa)DE-He213 Macrophage (dpeaa)DE-He213 Molecular imaging (dpeaa)DE-He213 Preclinical models (dpeaa)DE-He213 Di Ceglie, Irene aut Dorst, Daphne N. aut Blom, Arjen B. aut Bos, Desiree L. aut Vogl, Thomas aut Tas, Sander W. aut Jimenez-Royo, Pilar aut Bergstrom, Mats aut Cleveland, Matthew aut van der Kraan, Peter M. aut Laverman, Peter aut Koenders, Marije I. aut van Lent, Peter L. aut van den Bosch, Martijn H. J. aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 25(2023), 1 vom: 31. Aug. (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:25 year:2023 number:1 day:31 month:08 https://dx.doi.org/10.1186/s13075-023-03147-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2023 1 31 08
allfieldsSound	10.1186/s13075-023-03147-y doi (DE-627)SPR052946401 (SPR)s13075-023-03147-y-e DE-627 ger DE-627 rakwb eng Theeuwes, Wessel F. verfasserin aut CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. CD64 (dpeaa)DE-He213 Rheumatoid arthritis (dpeaa)DE-He213 Macrophage (dpeaa)DE-He213 Molecular imaging (dpeaa)DE-He213 Preclinical models (dpeaa)DE-He213 Di Ceglie, Irene aut Dorst, Daphne N. aut Blom, Arjen B. aut Bos, Desiree L. aut Vogl, Thomas aut Tas, Sander W. aut Jimenez-Royo, Pilar aut Bergstrom, Mats aut Cleveland, Matthew aut van der Kraan, Peter M. aut Laverman, Peter aut Koenders, Marije I. aut van Lent, Peter L. aut van den Bosch, Martijn H. J. aut Enthalten in Arthritis Research & Therapy London : BioMed Central, 1999 25(2023), 1 vom: 31. Aug. (DE-627)326646418 (DE-600)2041668-4 1478-6354 nnns volume:25 year:2023 number:1 day:31 month:08 https://dx.doi.org/10.1186/s13075-023-03147-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 25 2023 1 31 08
language	English
source	Enthalten in Arthritis Research & Therapy 25(2023), 1 vom: 31. Aug. volume:25 year:2023 number:1 day:31 month:08
sourceStr	Enthalten in Arthritis Research & Therapy 25(2023), 1 vom: 31. Aug. volume:25 year:2023 number:1 day:31 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CD64 Rheumatoid arthritis Macrophage Molecular imaging Preclinical models
isfreeaccess_bool	true
container_title	Arthritis Research & Therapy
authorswithroles_txt_mv	Theeuwes, Wessel F. @@aut@@ Di Ceglie, Irene @@aut@@ Dorst, Daphne N. @@aut@@ Blom, Arjen B. @@aut@@ Bos, Desiree L. @@aut@@ Vogl, Thomas @@aut@@ Tas, Sander W. @@aut@@ Jimenez-Royo, Pilar @@aut@@ Bergstrom, Mats @@aut@@ Cleveland, Matthew @@aut@@ van der Kraan, Peter M. @@aut@@ Laverman, Peter @@aut@@ Koenders, Marije I. @@aut@@ van Lent, Peter L. @@aut@@ van den Bosch, Martijn H. J. @@aut@@
publishDateDaySort_date	2023-08-31T00:00:00Z
hierarchy_top_id	326646418
id	SPR052946401
language_de	englisch
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RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. 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author	Theeuwes, Wessel F.
spellingShingle	Theeuwes, Wessel F. misc CD64 misc Rheumatoid arthritis misc Macrophage misc Molecular imaging misc Preclinical models CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis
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topic_title	CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis CD64 (dpeaa)DE-He213 Rheumatoid arthritis (dpeaa)DE-He213 Macrophage (dpeaa)DE-He213 Molecular imaging (dpeaa)DE-He213 Preclinical models (dpeaa)DE-He213
topic	misc CD64 misc Rheumatoid arthritis misc Macrophage misc Molecular imaging misc Preclinical models
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title	CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis
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title_full	CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis
author_sort	Theeuwes, Wessel F.
journal	Arthritis Research & Therapy
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author_browse	Theeuwes, Wessel F. Di Ceglie, Irene Dorst, Daphne N. Blom, Arjen B. Bos, Desiree L. Vogl, Thomas Tas, Sander W. Jimenez-Royo, Pilar Bergstrom, Mats Cleveland, Matthew van der Kraan, Peter M. Laverman, Peter Koenders, Marije I. van Lent, Peter L. van den Bosch, Martijn H. J.
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author-letter	Theeuwes, Wessel F.
doi_str_mv	10.1186/s13075-023-03147-y
title_sort	cd64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis
title_auth	CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis
abstract	Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. © The Author(s) 2023
abstractGer	Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. © The Author(s) 2023
abstract_unstemmed	Background Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker. Objectives We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging. Methods First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement. Results We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [111In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. Conclusion Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo. © The Author(s) 2023
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title_short	CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis
url	https://dx.doi.org/10.1186/s13075-023-03147-y
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author2	Di Ceglie, Irene Dorst, Daphne N. Blom, Arjen B. Bos, Desiree L. Vogl, Thomas Tas, Sander W. Jimenez-Royo, Pilar Bergstrom, Mats Cleveland, Matthew van der Kraan, Peter M. Laverman, Peter Koenders, Marije I. van Lent, Peter L. van den Bosch, Martijn H. J.
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CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis

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