Non-invasive assessment of IgA nephropathy severity with [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging

Renal biopsy plays a crucial role in diagnosing and assessing the severity of immunoglobulin A nephropathy (IgAN), despite being an invasive procedure with potential risk of failure. Our study focused on evaluating the capability of [¹⁸F]AlF-NOTA-FAPI-04 PET/CT in identifying the extent of pathological alterations in IgAN.

Twenty patients (13 males and 7 females; mean age, 44 ± 16 years) with newly diagnosed primary IgAN and 10 patients (7 males and 3 females; mean age, 51 ± 4 years) without known renal disease underwent [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues from biopsies were stained with various techniques and examined using immunofluorescence. The Oxford classification was used to evaluate pathological indicators. Immunohistochemical staining was conducted to assess α-smooth muscle actin (αSMA) and fibroblast activation protein (FAP) expression. Renal FAPI uptake measured by positron emission tomography/computed tomography (PET/CT) (maximum and mean standardized uptake value, SUV_max and SUV_mean) was correlated with histological findings.

The renal parenchymal FAPI uptake was significantly higher in IgAN patients compared with control patients (SUV_max = 3.9 ± 1.3 vs 1.9 ± 0.4, SUV_mean = 3.6 ± 1.2 vs 1.5 ± 0.4; all P < .001). We identified a significant difference in renal parenchymal FAPI uptake among the various categories of the Oxford classification. Correlation analysis revealed a positive association between SUV_max and interstitial fibrosis and tubular atrophy, as well as tubulointerstitial inflammation scores in scarred cortex and non-scarred cortex (r = 0.637, 0.593 and 0.491, all P < .05), Similar associations were observed between SUV_mean and these scores (r = 0.641, 0.592 and 0.479, all P < .05). Furthermore, significant positive correlations were observed between SUV_max or SUV_mean and the staining scores for glomerular αSMA and FAP, as well as for tubulointerstitial αSMA and FAP (all P < .01).

[¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging offers IgAN patients a non-invasive and reproducible auxiliary modality to monitor disease progression.