[¹⁸F]FAPI PET/CT-based scoring systems for patient assessment in IgG4-related disease

¹⁸F-Fibroblast activation protein inhibitor ([¹⁸F]FAPI) positron emission tomography (PET)/CT is an emerging tool for detecting IgG4-related disease (IgG4-RD). However, standardised quantitative analysis and image scoring present ongoing challenges in patients with IgG4-RD.

To establish organ-specific reference thresholds for IgG4-RD involvement on [¹⁸F]FAPI PET/CT images, and to develop a novel, clinically applicable scoring system to monitor disease activity in patients with IgG4-RD.

This retrospective study recruited 85 patients with IgG4-RD and 10 healthy individuals, all of whom underwent [¹⁸F]FAPI PET/CT. Organ-specific uptake thresholds were defined as [¹⁸F]FAPI uptake greater than the maximal standardised uptake value +3 SD in the corresponding anatomical regions of healthy individuals. Moreover, we developed a novel method, [¹⁸F]FAPI PET/CT Activity Score of IgG4-RD (FPAS-IgG4), for scoring disease activity using a logistic regression model with receiver operating characteristics curve analysis.

Among 85 patients with IgG4-RD, 64 lesions suspected of IgG4-RD involvement were biopsied and 58 (90.6%) of these lesions were positive for IgG4. [¹⁸F]FAPI PET/CT achieved a sensitivity, specificity and accuracy of 86.2%, 83.3% and 85.9%, respectively, for detecting IgG4-RD based on organ-specific uptake thresholds. The active disease group had a higher FPAS-IgG4 than the inactive disease group (5.2±3.0 vs 1.7±1.3, p<0.0001). FPAS-IgG4 >2 showed a sensitivity of 93.2% and a specificity of 73.1% in distinguishing between active and inactive disease. Multivariable logistic regression analysis demonstrated that FPAS-IgG4 was strongly associated with active IgG4-RD (p=0.001).

[¹⁸F]FAPI PET/CT could be a valuable tool for monitoring the activity of IgG4-RD, aiding in disease stratification.