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

Abstract

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]<i>N,N</i>-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide ([¹¹C]DPA-713) macrophage-targeting PET/CT tracer. <b>Methods:</b> 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. <b>Results:</b> Univariate regression analyses showed significant associations between mean SUV_peak of all joints at baseline (TJC44, <i>r</i> ² = 0.61; SJC44, <i>r</i> ² = 0.50; <i>P</i> < 0.001) and 4 wk (TJC44, <i>r</i> ² = 0.52; SJC44, <i>r</i> ² = 0.48; <i>P</i> < 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 (<i>r</i> ² = 0.67; <i>P</i> < 0.001). Multivariable analyses showed slightly increased correlations (<i>r</i> ² ≤ 0.75) by combining PET/CT and TJC44, SJC44, and C-reactive protein measurements. <b>Conclusion:</b> 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.