ObjectiveTo evaluate the feasibility of the novel programmed death-ligand 1 (PD-L1)-targeted PET/CT molecular probe for evaluating PD-L1 expression and tumor heterogeneity in patients with non-small cell lung cancer (NSCLC).

MethodsFrom October 2023 to October 2024, 30 patients (21 males, 9 females; age 69(58, 75) years) with newly diagnosed NSCLC at the First Affiliated Hospital of Xiamen University were prospectively enrolled. All patients underwent PET/CT imaging 1 h after intravenous administration of ⁶⁸Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-DK224, and SUV _max was calculated. Immunohistochemical staining on biopsy samples of patients were performed and the PD-L1 tumor proportion score (TPS) was calculated. The differences of SUV _max between two groups were compared by using Mann-Whitney U test.

ResultsOf 30 patients, 31 biopsy specimens were obtained including 24 primary lesion biopsies, 1 lymph node lesion biopsy, and 6 metastatic lesion biopsies, with 16 TPS<1%, 9 1%≤TPS<50% and 6 TPS≥50%. PD-L1-positive tumors showed relatively high uptake of ⁶⁸Ga-NOTA-DK224. The SUV _max of TPS≥1% group was significantly higher than that of TPS<1% group (6.9(5.1, 7.7) vs 3.8(3.1, 4.2); Z=-4.47, P<0.001), and SUV _max of TPS≥50% group was significantly higher than that of TPS<50% group (8.6(7.3, 12.4) vs 4.2(3.7, 5.3); Z=-3.65, P<0.001). Of 30 patients, 24 had multiple metastatic lesions with 212 lesions in total. The median fold difference was 2.3 (range: 1.4-6.0), and the median CV was 28.3% (range: 11.7%-61.6%).

Conclusion ⁶⁸Ga-NOTA-DK224 PET/CT is able to accurately and comprehensively reflect PD-L1 expression and tumor heterogeneity in primary and metastatic NSCLC.