Objective <p>Axial spondyloarthritis (axSpA) is characterized by active inflammation and structural damage. To date, there is no imaging tool can alone visualize all those changes well. PET/CT imaging with gallium-68-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) provide extra ability for CT in detecting active inflammation in addition to its advantage in assessing structural damage. This study aims to explore the utility of ⁶⁸Ga-FAPI-46 PET/CT for assessing active inflammation in axSpA.</p> Methods <p>Between July 2023 to July 2024, 22 patients with axSpA and 12 healthy volunteers were prospectively enrolled. Disease activity and parameters associated with inflammation were evaluated at enrollment. Participants then underwent ⁶⁸Ga-FAPI-46 PET/CT for assessment of FAPI uptake across joints. ⁶⁸Ga-FAPI-46 uptake was semi-quantitatively evaluated by using a three-point scale. The sum of points was calculated to generate ⁶⁸Ga-FAPI-46 PET/CT-derived FAPI uptake scores. Patients receiving biologics therapy were grouped as responders or non-responders according to clinical follow-up.</p> Results <p>Compared to healthy volunteers, patients with axSpA exhibited significantly higher ⁶⁸Ga-FAPI-46 uptake in several joints, especially in spine (<i>p</i> &lt; 0.001). ⁶⁸Ga-FAPI-46 PET/CT scores in spine showed strong correlation with the Ankylosing Spondylitis Disease Activity Score (ASDAS), inflammatory indicators such as c-reactive protein (CRP), and inflammation visualized by magnetic resonance imaging (MRI). Biologic responders displayed markedly higher baseline ⁶⁸Ga-FAPI-46 PET/CT scores in the spine (median: 36.5 vs. 4.0, <i>p</i> = 0.017) and total joints (median: 53.5 vs. 11.0, <i>p</i> = 0.015) compared to non-responders.</p> Conclusion <p>⁶⁸Ga-FAPI-46 PET/CT has the potential to serve as a dual-function imaging tool, integrating the structural imaging capabilities of CT with the ability to detect inflammation.</p> Clinical trial registration <p>NCT05999643.</p>