Molecular Signals and Early Detection in Psoriatic Arthritis

For psoriatic arthritis (PsA), diagnostic delay of even a few months can translate into irreversible joint damage and long-term functional loss. However, early inflammatory changes often evade conventional imaging. Ultrasound and MRI have improved sensitivity compared with radiography, but they largely describe anatomy, rather than the underlying biology driving disease.

Against this backdrop, molecular imaging is gaining attention as a way to visualize active pathophysiologic processes in vivo, with potential implications for earlier diagnosis, risk stratification, and treatment monitoring. A 2025 review in Current Opinion in Rheumatology synthesizes the expanding literature on molecular imaging techniques in PsA, with particular emphasis on positron emission tomography (PET)-based approaches and emerging radiation-free modalities. The focus is not on replacing established imaging, but on defining where molecular signals may add clinically actionable information.

PET as a Window into Inflammatory Activity

Most molecular imaging data in PsA center on PET, typically combined with CT or MRI to provide whole-body anatomical context. Fluorodeoxyglucose (FDG) remains the most widely studied tracer. FDG uptake reflects increased glucose metabolism and, in PsA, localizes to inflamed joints, entheses, tendons, and characteristic sites such as distal interphalangeal joints and nail beds. Importantly, FDG PET can detect subclinical inflammation in patients with psoriasis who have not yet developed clinical arthritis, including asymptomatic enthesitis and vascular inflammation.

The review appropriately cautions that most individuals with subclinical FDG uptake do not go on to develop overt arthritis during follow-up. And FDG’s lack of specificity also remains a limitation, as uptake occurs in non-inflammatory tissues and comorbid conditions. Still, small longitudinal studies suggest FDG PET may have value in monitoring response to biologic therapy, with reductions in uptake paralleling clinical improvement.

Imaging New Bone Formation and Stromal Activation

Beyond FDG, newer tracers target processes more specific to PsA pathobiology. Sodium fluoride (NaF) PET highlights active osteoblastic bone formation, a hallmark of PsA that distinguishes it from purely erosive arthritides. Whole-body NaF PET/CT studies demonstrate uptake in both peripheral and axial sites, often in clinically silent lesions, underscoring the dissociation between symptoms and structural remodeling. Early data suggest NaF uptake can change within weeks of TNF inhibitor therapy, suggesting its potential as a biomarker of treatment response.

Fibroblast activation protein inhibitor (FAPI) tracers represent another step toward specificity. FAPI PET targets activated fibroblasts involved in tissue remodeling and chronic inflammation. In patients with psoriasis and arthralgia, FAPI uptake correlates with tender joints and entheses and appears to predict future PsA development independently of ultrasound findings. Comparative studies suggest FAPI uptake aligns more closely with clinical inflammatory activity than NaF, highlighting how different tracers may capture distinct disease dimensions.

Radiation-Free Alternatives for Superficial Disease

The review also discusses fluorescence optical imaging (FOI) and multispectral optoacoustic tomography (MSOT), two noninvasive, radiation-free techniques limited to superficial tissues. FOI, using indocyanine green, has shown sensitivity for detecting early and subclinical joint inflammation in the hands. PsA characteristic patterns using FOI include the “green nail” phenomenon, reflecting abnormal microvascular permeability within the nail–enthesis–joint unit. MSOT, an ultrasound-based technique assessing tissue oxygenation and composition, offers insights into immunometabolic changes in joints and entheses. While neither modality is suitable for whole-body assessment, both may complement existing tools in early disease or treatment monitoring.

Limitations and Next Steps

Across modalities, the authors emphasize recurring limitations: small cohorts, heterogeneous protocols, uncertain uptake thresholds, cost, and limited availability, particularly for PET. Radiation exposure remains a practical concern, though emerging total-body PET systems may mitigate dose and improve feasibility. Most importantly, comparative studies are lacking, leaving unanswered questions about when molecular imaging meaningfully alters management beyond ultrasound or MRI.

Clinical Perspective

Taken together, molecular imaging in PsA is shifting the conversation from where disease is located to what biology is active. FDG, NaF, and FAPI tracers each illuminate different aspects of inflammation and remodeling, suggesting future imaging strategies may be tailored to specific clinical questions rather than applied uniformly. For now, molecular imaging remains largely investigational, but its ability to visualize subclinical disease, systemic involvement, and early treatment effects positions it as a potentially valuable adjunct as PsA care moves toward earlier, more personalized intervention.

Reference:

Groothuizen S, van der Laken CJ. Molecular imaging of psoriatic arthritis. Curr Opin Rheumatol. 2025;37(4):282-288. doi:10.1097/BOR.0000000000001098