Imaging T-cell dynamics in tumors using [18F]F-AraG PET: a Phase 1 study with STING agonist and PD-1 blockade therapy

Abstract Immunotherapies have revolutionized cancer treatment, yet tools for monitoring immune activation in vivo remain limited. This pilot study investigates the potential of [ 18 F]F-AraG PET to visualize activated T-cell dynamics and to assess the immunomodulatory effects of the STING agonist GSK3745417 ± PD-1 inhibitor dostarlimab. Four patients with advanced solid tumors underwent Baseline [ 18 F]FDG PET/CT, tumor biopsy and [ 18 F]F-AraG PET. GSK3745417 was administered intravenously weekly, with triweekly dostarlimab initiated in Week 2. On-treatment [ 18 F]F-AraG PET scans were acquired at Week 1 and Week 6, accompanied by a biopsy in Week 6. [ 18 F]F-AraG uptake in tumors and organs was quantified using peak tissue-to-plasma ratios. Biopsies were analyzed with imaging mass cytometry, histopathology and multiplex immunohistochemistry (mIHC). Best overall responses were partial response (patient A), stable disease (C/D) and progressive disease (B). Patient A demonstrated the highest Baseline [ 18 F]F-AraG uptake in tumors and stronger increase than other patients at Week 1. Changes in [¹⁸F]F‑AraG uptake from Baseline to Week 6 showed concordance with changes in CD8⁺Ki67⁺TIM3⁻ T‑cell density in the three evaluable patients. mIHC supported the contribution of T-cells to the [ 18 F]F-AraG PET signal. These findings support further clinical application of [ 18 F]F-AraG PET to visualize T-cell dynamics and to assess immunomodulatory effects of (immune)therapies.