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Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes
by
Kucharski, Amir
, Achilefu, Samuel
, Liang, Kexian
, Springer, Luke E.
, Tsen, Shaw-Wei D.
, Sudlow, Gail
, Sharmah Gautam, Krishna
, Tang, Rui
, Pham, Christine T. N.
in
Amino acids
/ Animals
/ Ankle
/ Annexin A2
/ Annexins
/ Antibodies
/ Antirheumatic agents
/ Arthritis
/ Arthritis, Experimental - diagnostic imaging
/ Arthritis, Experimental - drug therapy
/ Arthritis, Rheumatoid - diagnostic imaging
/ Arthritis, Rheumatoid - drug therapy
/ Chondrocytes
/ Drug therapy
/ Drug utilization
/ Erythema
/ Fluorescence microscopy
/ Health aspects
/ Inflammatory arthritis
/ Iodine
/ Laboratories
/ Medicine
/ Medicine & Public Health
/ Methods
/ Mice
/ Near-infrared fluorescent imaging
/ Optical Imaging
/ Orthopedics
/ Patient outcomes
/ Patients
/ Peptides
/ Phenols
/ Phosphorylation
/ Prognosis
/ Radiation
/ Remission (Medicine)
/ Research Article
/ Rheumatoid arthritis
/ Rheumatology
/ Treatment response monitoring
/ Tyrosine
2021
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Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes
by
Kucharski, Amir
, Achilefu, Samuel
, Liang, Kexian
, Springer, Luke E.
, Tsen, Shaw-Wei D.
, Sudlow, Gail
, Sharmah Gautam, Krishna
, Tang, Rui
, Pham, Christine T. N.
in
Amino acids
/ Animals
/ Ankle
/ Annexin A2
/ Annexins
/ Antibodies
/ Antirheumatic agents
/ Arthritis
/ Arthritis, Experimental - diagnostic imaging
/ Arthritis, Experimental - drug therapy
/ Arthritis, Rheumatoid - diagnostic imaging
/ Arthritis, Rheumatoid - drug therapy
/ Chondrocytes
/ Drug therapy
/ Drug utilization
/ Erythema
/ Fluorescence microscopy
/ Health aspects
/ Inflammatory arthritis
/ Iodine
/ Laboratories
/ Medicine
/ Medicine & Public Health
/ Methods
/ Mice
/ Near-infrared fluorescent imaging
/ Optical Imaging
/ Orthopedics
/ Patient outcomes
/ Patients
/ Peptides
/ Phenols
/ Phosphorylation
/ Prognosis
/ Radiation
/ Remission (Medicine)
/ Research Article
/ Rheumatoid arthritis
/ Rheumatology
/ Treatment response monitoring
/ Tyrosine
2021
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Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes
by
Kucharski, Amir
, Achilefu, Samuel
, Liang, Kexian
, Springer, Luke E.
, Tsen, Shaw-Wei D.
, Sudlow, Gail
, Sharmah Gautam, Krishna
, Tang, Rui
, Pham, Christine T. N.
in
Amino acids
/ Animals
/ Ankle
/ Annexin A2
/ Annexins
/ Antibodies
/ Antirheumatic agents
/ Arthritis
/ Arthritis, Experimental - diagnostic imaging
/ Arthritis, Experimental - drug therapy
/ Arthritis, Rheumatoid - diagnostic imaging
/ Arthritis, Rheumatoid - drug therapy
/ Chondrocytes
/ Drug therapy
/ Drug utilization
/ Erythema
/ Fluorescence microscopy
/ Health aspects
/ Inflammatory arthritis
/ Iodine
/ Laboratories
/ Medicine
/ Medicine & Public Health
/ Methods
/ Mice
/ Near-infrared fluorescent imaging
/ Optical Imaging
/ Orthopedics
/ Patient outcomes
/ Patients
/ Peptides
/ Phenols
/ Phosphorylation
/ Prognosis
/ Radiation
/ Remission (Medicine)
/ Research Article
/ Rheumatoid arthritis
/ Rheumatology
/ Treatment response monitoring
/ Tyrosine
2021
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Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes
Journal Article
Non-invasive monitoring of arthritis treatment response via targeting of tyrosine-phosphorylated annexin A2 in chondrocytes
2021
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Overview
Background
The development and optimization of therapies for rheumatoid arthritis (RA) is currently hindered by a lack of methods for early non-invasive monitoring of treatment response. Annexin A2, an inflammation-associated protein whose presence and phosphorylation levels are upregulated in RA, represents a potential molecular target for tracking RA treatment response.
Methods
LS301, a near-infrared dye-peptide conjugate that selectively targets tyrosine 23-phosphorylated annexin A2 (pANXA2), was evaluated for its utility in monitoring disease progression, remission, and early response to drug treatment in mouse models of RA by fluorescence imaging. The intraarticular distribution and localization of LS301 relative to pANXA2 was determined by histological and immunohistochemical methods.
Results
In mouse models of spontaneous and serum transfer-induced inflammatory arthritis, intravenously administered LS301 showed selective accumulation in regions of joint pathology including paws, ankles, and knees with positive correlation between fluorescent signal and disease severity by clinical scoring. Whole-body near-infrared imaging with LS301 allowed tracking of spontaneous disease remission and the therapeutic response after dexamethasone treatment. Histological analysis showed preferential accumulation of LS301 within the chondrocytes and articular cartilage in arthritic mice, and colocalization was observed between LS301 and pANXA2 in the joint tissue.
Conclusions
We demonstrate that fluorescence imaging with LS301 can be used to monitor the progression, remission, and early response to drug treatment in mouse models of RA. Given the ease of detecting LS301 with portable optical imaging devices, the agent may become a useful early treatment response reporter for arthritis diagnosis and drug evaluation.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Animals
/ Ankle
/ Annexins
/ Arthritis, Experimental - diagnostic imaging
/ Arthritis, Experimental - drug therapy
/ Arthritis, Rheumatoid - diagnostic imaging
/ Arthritis, Rheumatoid - drug therapy
/ Erythema
/ Iodine
/ Medicine
/ Methods
/ Mice
/ Near-infrared fluorescent imaging
/ Patients
/ Peptides
/ Phenols
/ Treatment response monitoring
/ Tyrosine
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