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Comparative Study
. 2016 May;19(5):452-8.
doi: 10.1111/1756-185X.12410. Epub 2014 Jun 26.

In vivo quantification of mouse autoimmune arthritis by PET/CT

Smriti Kundu-Raychaudhuri  1   2 , Anupam Mitra  2   3 , Ananya Datta-Mitra  1   2 , Abhijit J Chaudhari  4 , Siba P Raychaudhuri  1   2
Affiliations
Comparative Study

In vivo quantification of mouse autoimmune arthritis by PET/CT

Smriti Kundu-Raychaudhuri et al. Int J Rheum Dis. 2016 May.

Abstract

Aim: To quantify the progression and severity of mouse collagen-induced arthritis (CIA) using an in vivo imaging tool, (18) F-fluorodeoxyglucose ((18) F-FDG) PET/CT and validate it against gold standard 'histopathological' evaluation.

Method: The PET radiotracer (18) F-FDG, a marker for glucose metabolism, was injected in mice at different stages of CIA and the radiotracer distribution was imaged using a PET scanner. A sequential CT scan provided correlated anatomy. Radiotracer concentration was derived from PET/CT images for individual limb joints and on a per-limb basis at different stages of the disease. The imaging outcomes were subjected to correlation analysis with concurrently measured clinical and histological score.

Results: Clinical and histological score, and hence disease severity, showed a strong linear correlation (r(2) = 0.71, P = 0.001 and r(2) = 0.87, P < 0.001, respectively) with radiotracer concentration measured from PET/CT during the progression of CIA.

Conclusions: The strong positive correlation of the (18) F-FDG PET/CT findings with the histopathological evaluation at different stages of the disease suggest the potential of this imaging tool for the non-invasive assessment of progression and severity in mouse autoimmune arthritis. Thus, in preclinical studies, (18) F-FDG PET/CT can be considered as a non-invasive tool to develop novel therapies of inflammatory arthritis.

Keywords: PET/CT; in vivo imaging; inflammation; mouse CIA; quantification.

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Figures

Figure 1
Figure 1
Study flowchart. CS: clinical score; HS: histological score; CII: type II bovine collagen; CFA: complete Freund's adjuvant; IFA: incomplete Freund's adjuvant
Figure 2
Figure 2
18F-FDG PET/CT quantifies in vivo disease severity in mouse CIA model; a montage of representative photographs of the hind limb of the same mouse as disease progressed; (A) Clinical score (CS); (B) histopathology (5x); and (C) representative maximum-intensity projection of 18F-FDG PET. The pseudo-color in PET indicates higher glucose metabolism, hence increased cellular metabolic activity. The yellow arrows in (B) represent sites of pannus and yellow stars represent cellular infiltrates. (D) Representative fused 18F-FDG PET/CT image showing the increased uptake of 18F-FDG in the affected joints of CIA mouse at day 56. Data were presented as Mean±SD. T-tests were used to determine the statistical differences between groups/time points.
Figure 3
Figure 3
18F-FDG PET/CT uptake positively correlated with clinical and histopathological score at different stages of CIA. (A) Bar diagram showing the progression of clinical score (CS), histological score (HS) and 18F-FDG PET/CT uptake (PET/CT) at different stages of the disease. (B) Line diagram showing the correlation of PET/CT uptake (kBq/cc) with clinical (CS) and histopathological score (HS) at different stages of CIA (n=14). The coefficient of determination (R-squared) between measures over time was computed is shown. *p<0.05; **p<0.01
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