[18F] AlF-NOTA-FAPI-04 PET/CT for non-invasive assessment of tubular injury in kidney diseases

Abstract

ABSTRACT Background [18F] AlF-NOTA-FAPI-04 is a novel positron emission tomography (PET) ligand, which specifically targets fibroblast activation protein (FAP) expression as a FAP inhibitor (FAPI). We analysed the diagnostic value of [18F] AlF-NOTA-FAPI-04 PET/CT for the non-invasive assessment of kidney interstitial inflammation and fibrosis in different renal pathologies. Methods Twenty-six patients (14 males and 12 females; mean age, 50.5 ± 16.5 years) with a wide range of kidney diseases and 10 patients (six males and four females; mean age, 55.4 ± 8.6 years) without known evidence of renal disease as disease controls underwent [18F] AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues obtained from kidney biopsies were stained with haematoxylin and eosin, periodic acid-Schiff, Masson's trichome, and periodic acid–silver methenamine. Immunohistochemical staining was also performed to assess the expression of α-smooth muscle actin (αSMA) and FAP. Renal parenchymal FAPI uptake reflected by maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) measurements on PET/CT was analysed against pathohistological findings. Results We found that renal parenchymal FAPI uptake was significantly higher in patients with various kidney diseases than in control patients in this study (SUVmax = 4.3 ± 1.8 vs 1.9 ± 0.4, SUVmean=3.9 ± 1.7 vs 1.5 ± 0.4, respectively; all P < 0.001). All kidney diseases, both in acute and chronic kidney disease, had increased renal parenchymal uptake to varying degrees. The correlation analysis indicated a positive association between the SUVmax and the tubulointerstitial inflammation (TII), interstitial fibrosis and tubular atrophy (IF/TA), and TII + IF/TA scores (r = 0.612, 0.681, and 0.754, all P < 0.05), and between the SUVmean and the TII, IF/TA, and TII + IF/TA scores (r = 0.603, 0.700, and 0.748, all P < 0.05). Furthermore, we found significant positive correlations between both SUVmax and the SUVmean with SMA and FAP staining scores (r = 0.686 and 0.732, r = 0.667 and 0.739, respectively; both P < 0.001). Conclusions [18F] AlF-NOTA-FAPI-04 PET/CT is clinically available for the comprehensive and non-invasive assessment of tubular injury in various kidney diseases.