Relationship between PD-L1 expression and [¹⁸F]FAPI versus [¹⁸F]FDG uptake on PET/CT in lung cancer

To investigate the correlation between [¹⁸F] labeled fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET)/computed tomography (CT) uptake and programmed death ligand 1 (PD-L1) expression in lung cancer and evaluate the predictive value of [¹⁸F]FAPI PET/CT for PD-L1 expression compared with [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) PET/CT.

This single-center retrospective study consecutively enrolled patients with pathologically confirmed lung cancer who underwent [¹⁸F]FAPI and [¹⁸F]FDG PET/CT scans within 2 weeks, with a minimum interval of 20 h. PD-L1 expression was assessed using immunohistochemistry and stratified into three groups. PET/CT uptake parameters included the maximum standard uptake value (SUV_max) in the biopsy tumor or mediastinal metastasis lymph nodes area and the mean SUV_s (SUV_mean) of normal tissue (lung and blood). The ratios of SUV_max to the SUV_mean for each normal tissue were denoted as the tumor-to-background ratios (TBR_lung and TBR_blood). All statistical analyses were conducted using IBM SPSS Statistics. Normality was assessed, and for non-normally distributed data, the Kruskal-Wallis and Mann-Whitney U tests were applied. Associations between variables were evaluated using Spearman's rank correlation. All tests were two-sided, with a P-value < 0.05 considered statistically significant.

Among the 75 cases included on the final analysis, the TBR_blood and TBR_lung derived from [¹⁸F]FAPI PET/CT were significantly positively correlated with PD-L1 expression (r = 0.32, P < 0.01; r = 0.26, P < 0.05). Additionally, cases with high PD-L1 expression showed significantly higher [¹⁸F]FAPI uptake values (mean TBR_lung=36.16; mean TBR_blood=10.75) compared with those with low PD-L1 expression (mean TBR_lung=25.10; mean TBR_blood=8.04). No statistically significant correlation was observed between [¹⁸F]FDG uptake values and PD-L1 expression level. Receiver operating characteristic analysis identified TBR_blood on [¹⁸F]FAPI PET/CT with a cutoff value of 7.76 (area under the curve = 0.68, P < 0.01, sensitivity = 75%, and specificity = 53.49%) as a significant predictor of the level of PD-L1 expression.

[¹⁸F]FAPI uptake was positively correlated with PD-L1 expression in lung cancer. The combination of [¹⁸F]FAPI PET/CT and PD-L1 expression may offer a more comprehensive approach to assessing the response of lung cancer to immunotherapy.

This study was approved by the Clinical Research Ethics Committee of our institution (institutional review board approval no. SDZLEC2021-112-02).