3'-deoxy-3'-F-fluorothymidine PET imaging of lymphoid tissues in patients with advanced non-small cell lung cancer undergoing anti-programmed cell death-1 therapy.

Background: Anti-programmed cell death-1 (anti-PD-1) therapy has become the standard immunotherapy for patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the organs influenced by PD-1 inhibitors on a patient's tumor immunity. We examined the changes in lymphoid tissue proliferation before and after PD-1 inhibitor treatment using 3'-deoxy-3'-[F]-fluorothymidine (F-FLT) positron emission tomography (PET). This study included 25 patients with advanced NSCLC who underwent F-FLT PET before and 2 and 6 weeks after the initiation of PD-1 inhibitor treatment. We determined the average standardized uptake value (SUV) in the spleen, maximum SUV (SUV) in the lymph nodes, and the SUV, SUV, proliferative vertebral volume (PVV), and total vertebral proliferation (TVP) in the thoracolumbar vertebral bodies using F-FLT PET and blood test data. The relationship between the rate of change in these parameters before and after treatment and the tumor response was evaluated.

Results: The baseline F-FLT accumulation in the lymphoid tissues or blood test data between the progressive disease (PD) and non-PD groups were not significantly different. In the spleen and lymph nodes, changes in F-FLT accumulation from baseline to 2 or 6 weeks did not differ between the non-PD and PD groups. However, mediastinal lymph node accumulation tended to increase transiently at week 2 compared to that before treatment initiation (median SUV 2.19 vs. 2.64, P = 0.073). Regarding changes in vertebral accumulation in the non-PD group, the SUV, and PVV were significantly lower at weeks 2 and 6. In the percent changes in F-FLT accumulation of the vertebrae after the treatment initiation, the PD group was significantly higher than the non-PD group at the 6-week evaluation (median ΔTVP0-6, 17.0% vs. -13.0%, P = 0.0080).

Conclusions: In patients with advanced NSCLC who achieved a tumor response, proliferation decreased in the bone marrow, but not in the spleen or lymph nodes, 6 weeks after treatment initiation. F-FLT PET can help monitor changes in tumor immunity in each lymphoid tissue and may serve as a biomarker for the response to immune checkpoint inhibitor therapy.