Efficacy of radiolabelled PD-L1-targeted nanobody in predicting and evaluating the combined immunotherapy and chemotherapy for resectable non-small cell lung cancer.

Background: This study aimed to assess the predictive and evaluative value of PD-L1 targeted Ga-THP-APN09 PET/CT in the neoadjuvant immunotherapy combined with chemotherapy for resectable non-small cell lung cancer (NSCLC), and to explore its potential in indicating immunotherapy-related adverse effects (irAEs).

Methods: Fifty patients with resectable NSCLC enrolled in this prospective study underwent baseline Ga-THP-APN09 PET/CT and F-FDG PET/CT, with follow-up F-FDG PET/CT conducted, additionally, 36 patients received follow-up Ga-THP-APN09 PET/CT. Surgery was performed following 2-4 cycles of toripalimab combined with chemotherapy if R0 resection was feasible. The major pathologic response (MPR) state of the post-operative specimen and the adverse effects following combined therapy were documented. The correlation between PD-L1 expression and baseline Ga-THP-APN09 PET/CT uptake was determined. The predictive and evaluative efficacies of baseline and follow-up Ga-THP-APN09 PET/CT, along with F-FDG PET/CT, in determining MPR, were compared.

Results: The SUV values of baseline Ga-THP-APN09 PET/CT were significantly higher in patients exhibiting high-positive PD-L1 expression compared to those with low-positive and negative expression (P = 0.001). And the SUV values of baseline Ga-THP-APN09 PET/CT in the response group, as determined by F-FDG PET/CT evaluation, were significantly higher than those in the non-response group (3.4 vs. 2.4, P < 0.001). Totally, 41 patients underwent surgery, of which 27 achieved MPR, while 14 did not. The SUV in baseline Ga-THP-APN09 PET/CT demonstrated statistical significance between the MPR and non-MPR groups, with area under the ROC curve (AUC) of 0.88 (95%CI: 0.77-0.99) in identifying MPR. However, the SUV in baseline F-FDG PET/CT failed to demonstrated significant predictive power, with AUC values of 0.68 (95%CI: 0.50-0.86, P = 0.076). While the SUV in follow-up Ga-THP-APN09 and F-FDG PET/CT, along with their change rate (ΔSUV%), demonstrated good predictive efficacy in identifying MPR, with AUC values of 0.81 (0.64-0.98), 0.91 (0.82-1.00), 0.93 (0.84-1.00), and 0.96 (0.89-1.00), respectively. Furthermore, the follow-up Ga-THP-APN09 PET/CT could remarkedly indicate the potential for thyroiditis.

Conclusion: Baseline Ga-THP-APN09 PET/CT alone could predict efficacy and assist in patient screening for immunotherapy combined chemotherapy in resectable NSCLC, and the follow-up Ga-THP-APN09 PET/CT and their change rates could aid in therapy evaluation. Additionally, follow-up Ga-THP-APN09 PET/CT could be utilized to monitor the immunotherapy-related thyroiditis during the therapy.

Trial Registration: NCT05156515, registered 8 December 2021, https://register.

Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S000BMSI%26;selectaction=Edit%26;uid=U000503E%26;ts=2%26;cx=zeghuw .