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

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 SUV_max 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 (B_interaction = 0.495, P < 0.001) and T/NT (B_interaction = 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).

Keywords: 68Ga-citrate; Dihydroartemisinin; Rheumatoid arthritis.