Comparison of metabolic parameters of Ga-68 FAPI PET/CT and F-18 FDG PET/CT with PD L-1 expression in non-small cell lung cancer (2024)

Abstract

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Introduction: Lung cancer is one of the most common cancers, causing significant morbidity and mortality. F-18 FDG PET/CT has a proven value in diagnosing and staging lung cancers, including small cell lung cancer (NSCLC). Programmed cell death ligand1 (PD-L1) is expressed on the tumor cell and has a potential role as a biomarker to predict patients in which immunotherapy may be beneficial. The correlation between the FDG avidity and PD-L1 is well documented. Ga-68 FAPI PET/CT has recently emerged as a promising modality for evaluating NSCLC. In the present study, we aimed to compare the metabolic parameters of F-18 FDG PET/CT and Ga-68 FAPI PET/CT in NSCLC patients and their correlation with PD-L1 expression.

Methods: In this study, participants with newly diagnosed NSCLC were recruited prospectively. All the participants underwent F-18 FDG PET/CT and Ga-68 FAPI PET/CT within seven to ten days. Immunohistochemistry was performed in all the available tissue specimens of the participants (adenocarcinoma and squamous cell carcinoma). Formalin-fixed tissue sections of these patients were stained using an anti-PD-L1 antibody (Roche Ventana SP263 clone) per the institutional protocol. During the staining of each batch, appropriate positive (human placenta and tonsil) and negative controls (obtained by omitting the primary antibody) were used. Slides were evaluated for membranous staining. The average percentage of positivity from all areas of the tumor was taken for the overall percentage tumor proportion score (TPS) for PD-L1 positivity in tumor cells. Alveolar macrophages and necrotic cells were excluded from scoring. Membranous (complete circumferential or partial linear plasma membrane) and cytoplasmic granular staining at any intensity in tumor cells were considered positive. PD-L1 expression was considered negative if TPS <1% and positive if TPS is 1-49 and ≥50%. PET parameters like SUVmax, SUVmean, Tumor lesion glycolysis (TLG) metabolic tumor volume (MTV) were calculated for FDG PET while SUVmax, SUV mean, MTV, and total lesion fibroblastic activity (TLFA) for FAPI PET and compared with the PD-L1 positive expression. Additionally lesion to mediastinal blood pool ratio was also calculated for FDG and FAPI PET. Spearman’s correlation coefficient test was performed to determine the correlation between the PD-L1 expression and various metabolic parameters. P values of < 0.05 were considered statistically significant.

Results: Forty-five participants were recruited for the study. Five refused to undergo FAPI PET/CT and were excluded from the study. The remaining 40 participants (27 men, aged 58 ± 9 years) underwent both the PET/CT and were included. PD-L1 expression was positive in 40% (16/40). Spearman’s correlation coefficient test showed a positive correlation of PD-L1 expression with SUV max (spearman’s rho = 0.352, p=0.026), SUV peak (spearman’s rho = 0.334, p=0.035), SUV mean (spearman’s rho = 0.360, p=0.023) and lesion to mediastinal blood pool SUVmax ratio (spearman’s rho = 0.404, p=0.01) on FDG thus demonstrating SUV max, SUV peak, and SUV mean predicted PD-L1 protein expression in NSCLC patients. There was no significant correlation of PD-L1 expression with total lesion glycolysis (TLG) and metabolic tumor volume (MTV) on FDG. Spearman’s correlation coefficient showed no significant correlation between PD-L1 expression with SUVmax, SUVmean, SUVpeak, TLFA and MTV (p>0.2). However, lesion to background mediastinal blood pool SUVmax demonstrated a statistically significant correlation with PD-L1 expression (spearman’s rho = 0.318, p=0.046) on FAPI PET.

Conclusions: The results demonstrated that SUVmax, SUVmean, and SUVpeak of FDG PET were related to the PD-L1 expression, while MTV and TLG did not correlate. Lesion to mediastinal blood pool SUVmax ratio on FAPI PET has been shown to predict the PD-L1 expression in NSCLC. The significance of these values can be determined in large prospective studies.