Yoony Y J Gent1, Nazanin Ahmadi1, Alexandre E Voskuyl1, Nikie Hoetjes1, Cornelis van Kuijk1, Karin Britsemmer1, Franktien Turkstra1, Maarten Boers1, Otto S Hoekstra1, Conny J van der Laken2. 1. From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade. 2. From the Department of Rheumatology, Department of Radiology and Nuclear Medicine, Department of Clinical Epidemiology and Biostatistics, Vrije Universiteit University Medical Center; Department of Rheumatology, Jan van Breemen Research Institute/Reade, Amsterdam, the Netherlands.Y.Y.J. Gent, MD; A.E. Voskuyl, MD, PhD; C.J. van der Laken, MD, PhD, Department of Rheumatology; N. Ahmadi, MD; N. Hoetjes; C. van Kuijk, MD, PhD, Professor; O.S. Hoekstra, MD, PhD, Professor, Department of Radiology and Nuclear Medicine; M. Boers, MD, PhD, Professor, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Britsemmer, MD; F. Turkstra, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute/Reade. j.vanderlaken@vumc.nl.
Abstract
OBJECTIVE: To determine whether macrophage targeting by (R)-11C-PK11195 positron emission tomography (PET) can visualize subclinical joint inflammation in patients with rheumatoid arthritis (RA) without clinical arthritis during or after treatment, with flare as clinical outcome measure. METHODS: (R)-11C-PK11195 PET and contrast-enhanced magnetic resonance imaging (MRI) of hands/wrists were performed in 29 patients with RA without clinical arthritis. (R)-11C-PK11195 PET uptake (semiquantitative score 0-3) in metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient) was scored and summed to obtain a cumulative PET score (range 0-66). Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) was performed on similar joints. Synovitis and bone marrow edema scores (>1) were summed to obtain a cumulative MRI score (range 0-288). Occurrence of flare was determined during 3-year followup. RESULTS: Flare was observed in 17/29 patients (59%). (R)-11C-PK11195 PET showed enhanced tracer uptake in 16/29 patients (55%), of which 11 (69%) developed a flare. Highest cumulative PET scores (>6, n=3) corresponded with highest cumulative MRI scores (>39) and were related to development of flare in hands/wrists within 6 months. Cumulative PET scores of patients developing a flare were higher than those of patients without a flare [median (interquartile range) 2 (0-4.5) vs 0 (0-1), p<0.05]. In contrast, no significant differences were found between cumulative MRI scores of patients with and without a flare. CONCLUSION: (R)-11C-PK11195 PET showed enhanced uptake, pointing to presence of subclinical synovitis in over half of patients without clinical arthritis. (R)-11C-PK11195 PET may be of value for prediction of exacerbation of RA, since cumulative PET scores > 1 were associated with development of flare within 3 years.
OBJECTIVE: To determine whether macrophage targeting by (R)-11C-PK11195 positron emission tomography (PET) can visualize subclinical joint inflammation in patients with rheumatoid arthritis (RA) without clinical arthritis during or after treatment, with flare as clinical outcome measure. METHODS:(R)-11C-PK11195 PET and contrast-enhanced magnetic resonance imaging (MRI) of hands/wrists were performed in 29 patients with RA without clinical arthritis. (R)-11C-PK11195 PET uptake (semiquantitative score 0-3) in metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient) was scored and summed to obtain a cumulative PET score (range 0-66). Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) was performed on similar joints. Synovitis and bone marrow edema scores (>1) were summed to obtain a cumulative MRI score (range 0-288). Occurrence of flare was determined during 3-year followup. RESULTS: Flare was observed in 17/29 patients (59%). (R)-11C-PK11195 PET showed enhanced tracer uptake in 16/29 patients (55%), of which 11 (69%) developed a flare. Highest cumulative PET scores (>6, n=3) corresponded with highest cumulative MRI scores (>39) and were related to development of flare in hands/wrists within 6 months. Cumulative PET scores of patients developing a flare were higher than those of patients without a flare [median (interquartile range) 2 (0-4.5) vs 0 (0-1), p<0.05]. In contrast, no significant differences were found between cumulative MRI scores of patients with and without a flare. CONCLUSION:(R)-11C-PK11195 PET showed enhanced uptake, pointing to presence of subclinical synovitis in over half of patients without clinical arthritis. (R)-11C-PK11195 PET may be of value for prediction of exacerbation of RA, since cumulative PET scores > 1 were associated with development of flare within 3 years.
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