To synthesize N-¹⁸F-fluoroethyl-tofacitinib, and explore its feasibility in the diagnosis of rheumatoid arthritis (RA).

The " two-step method" was used to modify tofacitinib with ¹⁸F-fluoroethyl, and the labeling rate and radiochemical purity of the probe were measured by high performance liquid chromatography (HPLC), and the stabilities of the probe in vivo and in vitro were investigated. BALB/c mice (normal group; n=3) and collagen-induced arthritis (CIA) model mice (CIA group; n=3) were injected with N-¹⁸F-fluoroethyl-tofacitinib and CIA model mice injected with tofacitirrib and N-¹⁸F-fluoroethyl-tofacitinib were as blocking group (n=3). All mice underwent microPET imaging and the percentage injection dose per gram of tissue (%ID/g) and the uptake ratio of inflamed joints to muscle (T/M) were calculated. One-way analysis of variance and the least significant difference (LSD) t test were used to analyze the data.

The synthesis time of N-¹⁸F-fluoroethyl-tofacitinib was about 120 min, with the yield approximately 1%, the specific activity >13.6 GBq/μmol, and the radiochemical purity >99%. After the probe incubated with PBS, plasma or in vivo for 2 h, the radiochemical purity was still more than 95%. MicroPET imaging showed that 30 min after injection, the uptake of N-¹⁸F-fluoroethyl-tofacitinib in the inflamed joints of CIA group was higher than that of normal group and blocking group ((10.22±1.64), (2.71±0.26) and (2.81±0.33) %ID/g; F=58.26, t values: 7.83, 7.67, P values: 0.001, 0.002). The T/M of CIA group was also higher than that of normal group and blocking group (24.73±5.77, 2.75±1.36 and 2.89±0.54; F=40.64, t values: 6.42, 6.53, P values: 0.003, 0.003).

N-¹⁸F-fluoroethyl-tofacitinib is successfully prepared and it is stable in vitro with good imaging performance in vivo. It may be used in clinic for the diagnosis of RA.

Arthritis, rheumatoid; Piperidines; Protein kinase inhibitors; Janus kinase 1; Chemistry techniques, synthetic; Positron-emission tomography; Mice