Dual targeting heterodimer PET tracer [¹⁸F]AlF‑FAPI‑RGD in patients with rheumatoid arthritis: a pilot exploratory study

<b>Purpose:</b> Fibroblast-like synoviocytes and angiogenesis play crucial roles in the advancement of rheumatoid arthritis (RA). This prospective study aimed to assess the efficacy of [¹⁸F]AlF-FAPI-RGD, a dual-targeting heterodimer tracer that focuses on fibroblast activation protein (FAP) and integrin α_vβ₃, through PET/CT imaging for evaluating disease activity and response to treatment in RA. <b>Methods:</b> Twenty-eight participants with active RA (12 males and 16 females; mean age, 55 ± 9 years) underwent clinical evaluation of disease activity and [¹⁸F]AlF-FAPI-RGD PET/CT imaging at enrollment. Subsequently, after a 3-month period, a follow-up scan and clinical assessments were conducted on these participants. Imaging parameters such as PET-positive joint count (PJC), PET-positive articular index (PAI), average SUV_max (aSUV_max), and highest SUV_max (hSUV_max) in affected joints were compared with clinical and laboratory findings, as well as traditional imaging modalities. <b>Results:</b> [¹⁸F]AlF-FAPI-RGD PET/CT imaging produced high-quality images, revealing notable tracer uptake in the synovium of affected joints. [¹⁸F]AlF-FAPI-RGD demonstrated a higher positivity rate in detecting affected joints compared to the tender or swollen joint counts during clinical assessment (82.4% [342 of 415] vs 68.4% [284 of 415], respectively). Additionally, this imaging method successfully identified lung lesions with atypical respiratory symptoms in participants with RA. Following treatment, PJC, PAI, aSUV_max, and hSUV_max values significantly decreased in responders (<i>P</i> < 0.001), while no significant changes were observed in non-responders (<i>P</i> > 0.05). Furthermore, a notable association was found between the percentage change in certain PET parameters and modifications in specific clinical parameters. <b>Conclusion:</b> [¹⁸F]AlF-FAPI-RGD PET/CT represents a promising tool for the objective assessment of disease activity and treatment response in patients with RA. Furthermore, it may offer a novel imaging method for the early detection of subclinical RA and interstitial lung disease present with atypical respiratory symptoms.