3'-deoxy-3'-18F-fluorothymidine PET imaging of lymphoid tissues in patients with advanced non-small cell lung cancer undergoing anti-programmed cell death-1 therapy.

Abstract

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'-[¹⁸F]-fluorothymidine (¹⁸F-FLT) positron emission tomography (PET). This study included 25 patients with advanced NSCLC who underwent ¹⁸F-FLT PET before and 2 and 6 weeks after the initiation of PD-1 inhibitor treatment. We determined the average standardized uptake value (SUV_mean) in the spleen, maximum SUV (SUV_max) in the lymph nodes, and the SUV_max, SUV_mean, proliferative vertebral volume (PVV), and total vertebral proliferation (TVP) in the thoracolumbar vertebral bodies using ¹⁸F-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 ¹⁸F-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 ¹⁸F-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_max 2.19 vs. 2.64, P = 0.073). Regarding changes in vertebral accumulation in the non-PD group, the SUV_max, and PVV were significantly lower at weeks 2 and 6. In the percent changes in ¹⁸F-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. ¹⁸F-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.