Relationship Between Tumor Immune Markers and Fluorine-18-α-Methyltyrosine ([18F]FAMT) Uptake in Patients with Lung Cancer.

Abstract

3-[18F]Fluoro-α-methyl-L-tyrosine ([18F]FAMT) is an amino acid positron emission tomography (PET) tracer specific for cancer detection by assessment of tumor amino acid metabolism. Little is known on whether or not the uptake of [18F]FAMT within cancer cells is associated with the expression of programmed death ligand-1 (PD-L1), a predictor of anti-PD-1 antibody efficacy. We conducted a clinicopathological study to assess the expression of PD-L1 and the presence of tumor-infiltrating lymphocytes (TILs) in patients with non-small cell lung cancer (NSCLC) diagnosed by PET. A total of 75 patients with NSCLC who underwent [18F]FAMT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET were enrolled in the study. Tumor specimens were stained by immunohistochemistry for glucose transporter 1 (Glut1), PD-L1 (using different antibody clones including E1L3N and 28-8), CD3, CD4, and CD8. The uptake of [18F]FAMT was correlated with clinicopathological variables. High uptake of [18F]FAMT was significantly associated with disease staging, initial treatment (surgical resection or chemotherapy), and the expression of PD-L1 (E1L3N). The value of the maximum standardized uptake value (SUVmax) for [18F]FAMT was significantly correlated with PD-L1 (E1L3N) expression, Glut1, and the SUVmax for [18F]FDG in patients with histological results of adenocarcinoma (AC) and advanced disease. A validation cohort for anti-PD-L1 using clone 28-8 showed a statistically significant correlation between SUVmax for [18F]FAMT and the expression of PD-L1 (28-8) and between the expression of PD-L1 (E1L3N) and PD-L1 (28-8). The uptake of [18F]FAMT on PET imaging was significantly correlated with PD-L1 expression in NSCLC, especially in patients with AC and advanced disease.