Assessment of murine collagen-induced arthritis by longitudinal non-invasive duplexed molecular optical imaging

Scales, Hannah E.; Ierna, Michelle; Smith, Karen; Ross, Kirsty; Meiklejohn, Gordon R.; Patterson-Kane, Janet C.; McInnes, Iain B.; Brewer, James M.; Garside, Paul; Maffia, Pasquale

doi:10.1093/rheumatology/kev361

Cited by 25 publications

(26 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of molecular imaging in autoimmune diseases is still in its infancy, but is gaining interest rapidly. There are few imaging techniques which have been used for in-vivo assessment of the preclinical model of autoimmune arthritis, which have focused on quantifying: (i) structural changes such as bone destruction [X-ray computed tomography (CT)] [18], magnetic resonance imaging (MRI) [19,20] and ultrasound [21]; and (ii) molecular or functional changes (PET) [5,6], single photon emission computed tomography (SPECT) [22] and optical imaging [23]. For a detailed review of these techniques, please refer to Mountz et al [24] and Put et al [25].…”

Section: Discussionmentioning

confidence: 99%

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

Mitra

Kundu-Raychaudhuri

Abria

et al. 2017

Clinical and Experimental Immunology

View full text Add to dashboard Cite

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 F-fluorodeoxyglucose positron emission tomography ( F-FDG) as an in-vivo screening tool for anti-inflammatory drugs using the mouse CIA model. The radiotracer F-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 F-FDG with the progression of the disease and a significant decrease in the post-treatment group. F-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 F-FDG PET as a tool for in-vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Mitra

Kundu-Raychaudhuri

Abria

et al. 2017

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Collapsing studies, we compared disease severity by cross-correlation analyses between the DAI and standard in vivo methods (joint size and arthritis scores), as well as between the DAI and ankle joint histopathology, the gold standard for disease assessment ( Seeuws et al, 2010 ; Scales et al, 2016 ) ( Table 2 ). Compared to standard in vivo methods, the DAI positively correlated with joint size and arthritis scores ( R = 0.84 and 0.87, respectively, P < 0.0001).…”

Section: Resultsmentioning

confidence: 99%

Development of the Digital Arthritis Index, a Novel Metric to Measure Disease Parameters in a Rat Model of Rheumatoid Arthritis

Lim¹,

Louie²,

Ford³

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

Despite a broad spectrum of anti-arthritic drugs currently on the market, there is a constant demand to develop improved therapeutic agents. Efficient compound screening and rapid evaluation of treatment efficacy in animal models of rheumatoid arthritis (RA) can accelerate the development of clinical candidates. Compound screening by evaluation of disease phenotypes in animal models facilitates preclinical research by enhancing understanding of human pathophysiology; however, there is still a continuous need to improve methods for evaluating disease. Current clinical assessment methods are challenged by the subjective nature of scoring-based methods, time-consuming longitudinal experiments, and the requirement for better functional readouts with relevance to human disease. To address these needs, we developed a low-touch, digital platform for phenotyping preclinical rodent models of disease. As a proof-of-concept, we utilized the rat collagen-induced arthritis (CIA) model of RA and developed the Digital Arthritis Index (DAI), an objective and automated behavioral metric that does not require human-animal interaction during the measurement and calculation of disease parameters. The DAI detected the development of arthritis similar to standard in vivo methods, including ankle joint measurements and arthritis scores, as well as demonstrated a positive correlation to ankle joint histopathology. The DAI also determined responses to multiple standard-of-care (SOC) treatments and nine repurposed compounds predicted by the SMarTRTM Engine to have varying degrees of impact on RA. The disease profiles generated by the DAI complemented those generated by standard methods. The DAI is a highly reproducible and automated approach that can be used in-conjunction with standard methods for detecting RA disease progression and conducting phenotypic drug screens.

show abstract

“…Filarial worms secrete a myriad of molecules under in vitro culture conditions, including enzyme activities such as triose phosphate isomerase, leucyl aminopeptidase and glutathione peroxidase [36,37]. More specific reagents are continually being developed to detect various disease states; for example, several reagents are already available that detect enzymatic activities of specific proteases, which are useful markers of pathologies such as arthritis, airway inflammation and tumor progression [38,39,40]. It may be possible in the future to utilise more specific reagents to detect secretory products of adult worms in vivo .…”

Section: Discussionmentioning

confidence: 99%

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

et al. 2016

View full text Add to dashboard Cite

Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals.

show abstract

Assessment of murine collagen-induced arthritis by longitudinal non-invasive duplexed molecular optical imaging

Cited by 25 publications

References 44 publications

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

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

Development of the Digital Arthritis Index, a Novel Metric to Measure Disease Parameters in a Rat Model of Rheumatoid Arthritis

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

Contact Info

Product

Resources

About