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The Evaluation of 68Ga-Citrate PET/CT Imaging for Dihydroartemisinin in the Treatment of Rheumatoid Arthritis

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Abstract

Purpose

We aimed to use 68Ga-citrate, a labeled product of gallium (iron analog), combined with positron emission tomography/computed tomography (PET/CT) to non-invasively evaluate the potential of the iron-responsive product dihydroartemisinin (DHA) in the treatment of rheumatoid arthritis.

Procedures

From the establishment of chicken II collagen-induced arthritis (CIA) rat model over 40 days, 20 rats with one-to-one corresponding arthritis index (AI) scores were randomly divided into two groups. One group received oral DHA (at a dose of 1.5 ml/(kg day), containing 20 mg DHA per 1 ml) for 15 days; the other group received stroke-physiological saline solution (SSS, 1.5 ml/(kg day) for 15 days. 68Ga-citrate micro-PET/CT imaging was performed on day 0 (D0), day 5 (D5), day 10 (D10), and day 15 (D15) of oral administration. After data reconstruction, the cross-sectional length “d” of the ankle joint of each rat was measured on the transverse CT, and the SUVmax of the ankle joint and muscle background was measured for statistical analysis. After micro-PET/CT collection, the ankle joint tissue was observed by HE staining.

Results

The ankle joint swelling in the DHA group was significantly suppressed, but the SSS group showed no significant suppression. 68Ga-citrate micro-PET/CT imaging results and microscope observation confirmed this finding. Statistical analysis indicated that the time tendency of AI score (Binteraction = 0.495, P < 0.001) and T/NT (Binteraction = 1.345, P < 0.001) were discrepant between DHA and SSS groups. The AI score and T/NT of the DHA group gradually increased with time, while the SSS group score gradually decreased. Furthermore, the Spearman correlation coefficient was used to describe the relationship between “d” and T/NT, which was positively correlated (r = 0.855, P < 0.001).

Conclusions

This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (68Ga-citrate).

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Funding

This work was funded by the Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University/Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, China

    Zi Wang, Liang Cai & Yue Chen

  2. Faculty of Chinese Medicine, Macau University of Science and Technology and State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, Macau, People’s Republic of China

    Zi Wang & Liang Cai

  3. Department of Neurosurgery, Dazhou Central Hospital, Dazhou, Sichuan, China

    Yu Hou

Authors
  1. Zi Wang
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  2. Yu Hou
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Correspondence to Yue Chen.

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The authors declare that they have no conflict of interest.

Ethical Approval

All studies were approved by the Ethics Committee of Southwestern Medical University, and all applicable institutional and/or national guidelines for the care and use of animals were followed.

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Zi Wang and Yu Hou contribute equally to this work.

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Wang, Z., Hou, Y., Cai, L. et al. The Evaluation of 68Ga-Citrate PET/CT Imaging for Dihydroartemisinin in the Treatment of Rheumatoid Arthritis. Mol Imaging Biol 23, 30–37 (2021). https://doi.org/10.1007/s11307-020-01534-4

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  • DOI: https://doi.org/10.1007/s11307-020-01534-4

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