In-vivo quantitative assessment of the therapeutic response in a mouse model of collagen-induced arthritis using 18F-fluorodeoxyglucose positron emission tomography

A. Mitra, S. Kundu-Raychaudhuri, C. Abria, A. Rona, Abhijit Chaudhari, Siba P Raychaudhuri

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mouse collagen-induced arthritis (CIA) is the most commonly used animal model to investigate underlying pathogenesis of autoimmune arthritis and to demonstrate the therapeutic efficacy of novel drugs in autoimmune arthritis. The conventional read-outs of CIA are clinical score and histopathology, which have several limitations, including (i) subjected to observer bias; and (ii) longitudinal therapeutic efficacy of a new drug cannot be determined. Thus, a robust, non-invasive, in-vivo drug screening tool is currently an unmet need. Here we have assessed the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG) as an in-vivo screening tool for anti-inflammatory drugs using the mouse CIA model. The radiotracer 18F-FDG and a PET scanner were employed to monitor CIA disease activity before and after murine anti-tumour necrosis factor (TNF)-α antibody (CNTO5048) therapy in the mouse CIA model. Radiotracer concentration was derived from PET images for individual limb joints and on a per-limb basis, and Spearman's correlation coefficient (ρ) was determined with clinical score and histology of the affected limbs. CNTO5048 improved arthritis efficiently, as evidenced by clinical score and histopathology. PET showed an increased uptake of 18F-FDG with the progression of the disease and a significant decrease in the post-treatment group. 18F-FDG uptake patterns showed a strong correlation with clinical score (ρ = 0·71, P < 0·05) and histopathology (ρ = 0·76, P < 0·05). This study demonstrates the potential of 18F-FDG PET as a tool for in-vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalClinical and Experimental Immunology
Volume188
Issue number2
DOIs
StatePublished - May 1 2017

Fingerprint

Experimental Arthritis
Fluorodeoxyglucose F18
Positron-Emission Tomography
Arthritis
Preclinical Drug Evaluations
Extremities
Pharmaceutical Preparations
Therapeutics
Observer Variation
Therapeutic Uses
Disease Progression
Histology
Anti-Inflammatory Agents
Animal Models
Tumor Necrosis Factor-alpha
Joints
Antibodies

Keywords

  • anti-TNF
  • CIA
  • inflammation
  • PET

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "In-vivo quantitative assessment of the therapeutic response in a mouse model of collagen-induced arthritis using 18F-fluorodeoxyglucose positron emission tomography",
abstract = "Mouse collagen-induced arthritis (CIA) is the most commonly used animal model to investigate underlying pathogenesis of autoimmune arthritis and to demonstrate the therapeutic efficacy of novel drugs in autoimmune arthritis. The conventional read-outs of CIA are clinical score and histopathology, which have several limitations, including (i) subjected to observer bias; and (ii) longitudinal therapeutic efficacy of a new drug cannot be determined. Thus, a robust, non-invasive, in-vivo drug screening tool is currently an unmet need. Here we have assessed the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG) as an in-vivo screening tool for anti-inflammatory drugs using the mouse CIA model. The radiotracer 18F-FDG and a PET scanner were employed to monitor CIA disease activity before and after murine anti-tumour necrosis factor (TNF)-α antibody (CNTO5048) therapy in the mouse CIA model. Radiotracer concentration was derived from PET images for individual limb joints and on a per-limb basis, and Spearman's correlation coefficient (ρ) was determined with clinical score and histology of the affected limbs. CNTO5048 improved arthritis efficiently, as evidenced by clinical score and histopathology. PET showed an increased uptake of 18F-FDG with the progression of the disease and a significant decrease in the post-treatment group. 18F-FDG uptake patterns showed a strong correlation with clinical score (ρ = 0·71, P < 0·05) and histopathology (ρ = 0·76, P < 0·05). This study demonstrates the potential of 18F-FDG PET as a tool for in-vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.",
keywords = "anti-TNF, CIA, inflammation, PET",
author = "A. Mitra and S. Kundu-Raychaudhuri and C. Abria and A. Rona and Abhijit Chaudhari and Raychaudhuri, {Siba P}",
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T1 - In-vivo quantitative assessment of the therapeutic response in a mouse model of collagen-induced arthritis using 18F-fluorodeoxyglucose positron emission tomography

AU - Mitra, A.

AU - Kundu-Raychaudhuri, S.

AU - Abria, C.

AU - Rona, A.

AU - Chaudhari, Abhijit

AU - Raychaudhuri, Siba P

PY - 2017/5/1

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N2 - Mouse collagen-induced arthritis (CIA) is the most commonly used animal model to investigate underlying pathogenesis of autoimmune arthritis and to demonstrate the therapeutic efficacy of novel drugs in autoimmune arthritis. The conventional read-outs of CIA are clinical score and histopathology, which have several limitations, including (i) subjected to observer bias; and (ii) longitudinal therapeutic efficacy of a new drug cannot be determined. Thus, a robust, non-invasive, in-vivo drug screening tool is currently an unmet need. Here we have assessed the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG) as an in-vivo screening tool for anti-inflammatory drugs using the mouse CIA model. The radiotracer 18F-FDG and a PET scanner were employed to monitor CIA disease activity before and after murine anti-tumour necrosis factor (TNF)-α antibody (CNTO5048) therapy in the mouse CIA model. Radiotracer concentration was derived from PET images for individual limb joints and on a per-limb basis, and Spearman's correlation coefficient (ρ) was determined with clinical score and histology of the affected limbs. CNTO5048 improved arthritis efficiently, as evidenced by clinical score and histopathology. PET showed an increased uptake of 18F-FDG with the progression of the disease and a significant decrease in the post-treatment group. 18F-FDG uptake patterns showed a strong correlation with clinical score (ρ = 0·71, P < 0·05) and histopathology (ρ = 0·76, P < 0·05). This study demonstrates the potential of 18F-FDG PET as a tool for in-vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.

AB - Mouse collagen-induced arthritis (CIA) is the most commonly used animal model to investigate underlying pathogenesis of autoimmune arthritis and to demonstrate the therapeutic efficacy of novel drugs in autoimmune arthritis. The conventional read-outs of CIA are clinical score and histopathology, which have several limitations, including (i) subjected to observer bias; and (ii) longitudinal therapeutic efficacy of a new drug cannot be determined. Thus, a robust, non-invasive, in-vivo drug screening tool is currently an unmet need. Here we have assessed the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG) as an in-vivo screening tool for anti-inflammatory drugs using the mouse CIA model. The radiotracer 18F-FDG and a PET scanner were employed to monitor CIA disease activity before and after murine anti-tumour necrosis factor (TNF)-α antibody (CNTO5048) therapy in the mouse CIA model. Radiotracer concentration was derived from PET images for individual limb joints and on a per-limb basis, and Spearman's correlation coefficient (ρ) was determined with clinical score and histology of the affected limbs. CNTO5048 improved arthritis efficiently, as evidenced by clinical score and histopathology. PET showed an increased uptake of 18F-FDG with the progression of the disease and a significant decrease in the post-treatment group. 18F-FDG uptake patterns showed a strong correlation with clinical score (ρ = 0·71, P < 0·05) and histopathology (ρ = 0·76, P < 0·05). This study demonstrates the potential of 18F-FDG PET as a tool for in-vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.

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