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

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 SUV_peak 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 SUV_peak of metacarpophalangeal joints at 4 wk and SUV_peak 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.