Macrophage-Targeted [11C]DPA-713 PET/CT Imaging for Early Therapeutic Evaluation of Anti-Tumor Necrosis Factor Treatment in Rheumatoid Arthritis.

Anti-tumor necrosis factor (aTNF) treatment of rheumatoid arthritis (RA) requires 3-6 mo to establish efficacy, with 50%-70% response. Quantitative macrophage-targeting PET/CT previously proved to accurately represent RA activity and treatment response. This study investigated early aTNF treatment efficacy assessment using the [11C]N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide ([11C]DPA-713) macrophage-targeting PET/CT tracer.

Methods

Two whole-body [11C]DPA-713 PET/CT scans, at baseline and 4 wk, were performed in 20 patients without exposure to biologic agents before starting aTNF treatment. Tracer uptake in joints was quantified by determination of SUVs in 44 joints at baseline and 4 wk of aTNF treatment. Mean SUVs of all joints and specific joint clusters were related to clinical evaluation of the 44 included joints for tenderness (tender joint count of 44 joints [TJC44]) and swelling (swollen joint count of 44 joints [SJC44]) at 26 wk using linear regression analyses. In addition, multivariable analysis, including both PET/CT and concurrent clinical outcome of independent measures versus dependent TJC44 or SJC44 at 26 wk, was performed.

Results

Univariate regression analyses showed significant associations between mean SUVpeak of all joints at baseline (TJC44, r 2 = 0.61; SJC44, r 2 = 0.50; P < 0.001) and 4 wk (TJC44, r 2 = 0.52; SJC44, r 2 = 0.48; P < 0.001) and TJC44 or SJC44 at 26 wk. For specific joint clusters, high correlations were found between SUVpeak of metacarpophalangeal joints at 4 wk and SUVpeak of SJC44 at 26 wk (r 2 = 0.67; P < 0.001). Multivariable analyses showed slightly increased correlations (r 2 ≤ 0.75) by combining PET/CT and TJC44, SJC44, and C-reactive protein measurements.

Conclusion

Early quantitative [11C]DPA-713 PET/CT measurements at baseline and 4 wk of aTNF treatment are associated with clinical disease activity at 26 wk. Therefore, quantitative macrophage [11C]DPA-713 PET/CT may have potential clinical value for early prediction of aTNF treatment response in patients with RA.