Noninvasive diagnosis and classification of kidney transplantation rejection by ¹⁸F-FAPI-04 PET/CT

Rejection, especially chronic rejection is a key factor influencing the prognosis of kidney transplantation patients. While ¹⁸F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT has been widely utilized for diagnosing various diseases, its diagnostic efficacy in kidney transplant rejection remains unexplored.

In this study, 24 kidney transplant recipients were prospectively enrolled and divided into a control cohort and a rejection cohort (KTR), which were further classified into acute rejection (AR), mixed rejection (MR), and chronic rejection (CR) subgroups. All patients underwent ¹⁸F-FAPI-04 PET/CT and ¹⁸F-FDG PET/CT scans, along with immunohistochemical FAP staining and Banff pathological scoring. The maximum and average standardized uptake values (SUVs) of the two imaging methods were calculated.

Compared with the control cohort, the KTR cohort showed significantly higher serum creatinine levels, lower estimated glomerular filtration rates, and lower hemoglobin levels. The SUVmax of ¹⁸F-FAPI-04 PET/CT in the allograft kidney cortex (AKC) and allograft kidney biopsy site (AKB) in the KTR cohort was significantly greater than that in the control cohort. The SUVmax of ¹⁸F-FDG PET/CT between the two cohorts was significantly different only in the AKC. For the KTR cohort, the SUVmax of ¹⁸F-FAPI-04 PET/CT in AKC and AKB was considerably greater than that of ¹⁸F-FDG PET/CT (5.5 vs. 2.8 and 3.6 vs. 2.5, respectively; both p < 0.01). In the CR cohort, the SUVmax of ¹⁸F-FAPI-04 PET/CT in the AKC, AKB, and allograft kidney medulla (AKM) was significantly greater (7.1, 5.3, and 3.2) than that of ¹⁸F-FDG PET/CT (2.5, 2.1 and 1.8) (p = 0.009, 0.009 and 0.016, respectively). The SUVmax of ¹⁸F-FAPI-04 PET/CT in AKB increased gradually in the AR, MR, and CR cohorts (2.8 vs. 3.6 vs. 5.3, p = 0.02). The above results were consistent with the SUVavg statistics. The number of FAP-positive stromal cells was different between the control and KTR groups and among the AR, MR, and CR subgroups.

¹⁸F-FAPI-04 PET/CT outperforms ¹⁸F-FDG PET/CT in distinguishing kidney transplant rejection, especially chronic rejection.