Background/Purpose: Musculoskeletal ultrasound, and specifically power Doppler ultrasound (PDUS), is more sensitive than clinical examination for the assessment of active synovitis in patients with rheumatoid arthritis (RA). In addition, PDUS is predictive of radiographic progression, response to therapy in patients with active disease and of flare in patients in remission. In clinical practice its routine use for assessing large numbers of joints is limited by time constraints. ^99mTc-NC100692 (Maraciclatide) is a tracer consisting of a peptide containing the RGD motif which binds with high affinity to the integrins α_vβ₃ and α_vβ₅ which are expressed on neoangiogenic blood vessels including those seen in the rheumatoid synovium. This proof-of-concept study aimed to investigate whether uptake of ^99mTc-NC100692 is seen in the joints of patients with active RA and whether this correlates with PDUS.

Methods: 5 patients with active RA (DAS28 >3.2) were recruited. Patients underwent clinical examination including 66/68 swollen/ tender joint counts followed by ultrasound examination of 38 joints with grey scale (GS) and power Doppler (PD) quantification. Each joint was scored on a semi-quantitative scale of 0-3 for GS and PD and a total score for each calculated for each patient. Within 24 hours of the ultrasound patients were injected with 75µg of ^99mTc-NC100692 (740MBq). Whole body planar views and dedicated views of the hands and feet were taken at multiple time points over 3 hours.  Images were scored by an observer blinded to the ultrasound findings as positive or negative uptake for each joint (binary score), and in addition a fully quantitative score was obtained for each joint by drawing a region of interest around the joint and correcting for background. The scores were summed to derive a total score for each patient. Ultrasound and ^99mTc-NC100692 scores were tested for correlation with Pearson’s correlation coefficient.

Results: Specific uptake of ^99mTc-NC100692 was seen in the joints in all patients with optimal uptake seen at around 2 hours. Specific uptake was also seen in inflamed tendon sheaths at the wrist and ankle. Significant correlation was not seen between DAS28 scores and US scores. Strong correlation was seen between PDUS and whole-body fully quantitative (r²=0.93, p=0.008) and binary (r²=0.88, p=0.019) ^99mTc-NC100692 scores . GSUS also correlated strongly with quantitative whole-body ^99mTc-NC100692 scores (r²=0.79, p=0.042). The imaging procedure was well-tolerated.

Conclusion: We have shown for the first time that a ^99mTc-labelled RGD peptide can specifically image inflamed joints in RA patients. Despite the small numbers, in this pilot study uptake was strongly correlated with PDUS. ^99mTc-NC100692-based planar imaging has the unique advantage of the capacity to image the whole body and hence the total synovial inflammatory load in a single quick acquisition. Furthermore the imaging equipment to perform these scans is widely available in nuclear imaging departments. Hence ^99mTc-NC100692 has potential as an alternative modality for quantifying synovial inflammation in RA patients. Larger studies are planned to investigate ^99mTc-NC100692 imaging in RA patients with a range of disease activities.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/whole-body-synovial-uptake-of-a-99mtc-labelled-rgd-peptide-is-highly-correlated-with-power-doppler-ultrasound/