[⁶⁸Ga]Ga-NODAGA-SNA006 PET/CT Reveals CD8⁺ T-Cell Dynamics in Lung Cancer Progression and Anti-PD-1 Response

Heterogeneous response to anti-programmed cell death protein 1 (PD-1) immunotherapy in lung cancer necessitates reliable biomarkers for monitoring systemic CD8⁺ T-cell dynamics. This study used [⁶⁸Ga]Ga-NODAGA-SNA006, a CD8-targeted PET tracer, to evaluate CD8⁺ T-cell distribution in relation to disease progression and treatment response. Methods: Fourteen patients with stage II-IV lung cancer underwent baseline [⁶⁸Ga]Ga-NODAGA-SNA006 PET/CT and blood CD8⁺ T-cell quantification. Eight patients receiving anti-PD-1-based chemoimmunotherapy underwent PET/CT and blood analyses before treatment and after 2 treatment cycles. SUV_max was measured in tumors (along with the tumor-to-background ratio), the spleen, the liver, and axial (sternum, T12, pelvis) and appendicular (femur) bone marrow. Correlations with disease stage, peripheral blood CD8⁺ T-cell quantification, programmed death ligand 1 (PD-L1) expression, and tumor reduction were assessed. Results: Patients with stage IV disease patients exhibited a lower peripheral blood CD8⁺ T-cell count and percentage (P < 0.05), whereas the SUV_max in the spleen (P < 0.05) and axial bone marrow (sternum, T12, pelvis; P < 0.01) was higher than that in patients with earlier-stage disease. Peripheral blood CD8⁺ T-cell percentage was correlated with SUV_max in the spleen (r ² = 0.38, P < 0.05) and axial bone marrow sites (most significant in sternum: r ² = 0.68, P < 0.001). After anti-PD-1 therapy, analysis of combined "axial skeleton SUV" (sternum, T12, pelvis) revealed a significant interaction between time and PD-L1 group (P < 0.001): SUV increased in the low PD-L1 (<10%) group but decreased in the high PD-L1 (≥10%) group. Changes in peripheral blood CD8⁺ T-cell count and percentage were not significant. Tumor shrinkage was not significantly correlated with peripheral blood CD8⁺ T-cell percentage or T-cell dynamics. For all target lesions, tumor shrinkage showed moderate positive correlations with baseline lesion SUV_max (r ² = 0.30, P < 0.01) and baseline tumor-to-background ratio (r ² = 0.34, P < 0.001) and a strong positive correlation with the reduction in lesion SUV_max after treatment (r ² = 0.44, P < 0.01). Conclusion: [⁶⁸Ga]Ga-NODAGA-SNA006 PET/CT revealed systemic CD8 ⁺ T-cell depletion and splenic/axial marrow sequestration in advanced lung cancer. During anti-PD-1 therapy, CD8 ⁺ T cells redistribute on the basis of PD-L1 status. Baseline intratumoral CD8 ⁺ T-cell density and early on-treatment SUV_max reduction are robust imaging biomarkers of response, outperforming peripheral blood monitoring.