68Ga-granzyme B (68Ga-NOTA-GSI) PET/CT for predicting immunotherapy response and progression free survival in NSCLC.

PURPOSE: This study aimed to evaluate 68Ga-NOTA-GSI PET/CT probe targeting granzyme B in assessing immune response and predicting progression‑free survival (PFS) in patients with non‑small cell lung cancer (NSCLC). METHODS: In this prospective single-center trial (ChiCTR2200062089), 41 stage IIIB/IV non-small lung cancer patients underwent 68Ga-NOTA-GSI PET/CT after 2 treatment cycles. Mann-Whitney U test and Fisher's exact test were used to analyze clinical and imaging characteristics of enrolled NSCLC patients. The performance of PET/CT parameters in evaluating immune response and 1-/2-year PFS was assessed using receiver operating characteristic (ROC) curves. Treatment response was evaluated by RECIST 1.1 after 4-6 cycles. ROC analysis, binary logistic regression, Kaplan-Meier survival analysis, and multivariable Cox regression were used to assess predictive performance, and a nomogram was constructed to predict 2-year PFS. RESULTS: Responders (n = 29) showed significantly higher SUVmax, SUVmean, and TBR than non-responders (n = 12) (all P < 0.05). SUVmax was an independent predictor of immune response (OR 15.6, 95% CI 1.419-172.2, P = 0.025). For PFS prediction, SUVmax achieved AUCs of 0.750 (1-year) and 0.837 (2-year), while SUVmean achieved AUCs of 0.727 and 0.815, respectively. Multivariable Cox regression identified SUVmax as an independent prognostic factor for 2-year PFS (HR 0.398, 95% CI 0.207-0.765, P = 0.006). The nomogram integrating SUVmax and tumor stage showed good discrimination (AUC 0.867, 95% CI 0.750-0.868) and calibration. CONCLUSION: ⁶⁸Ga-NOTA-GSI PET/CT parameters, particularly SUVmax, were valuable for both assessing immune response and PFS in NSCLC patients. The proposed nomogram may serve as a useful tool for personalized treatment decision‑making in immunotherapy.