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...

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Main Authors: Masayuki Sato, Yukihiro Umeda, Tetsuya Tsujikawa, Tetsuya Mori, Akikazu Shimada, Tomoaki Sonoda, Makiko Yamaguchi, Chisato Honjo, Yuko Waseda, Yasushi Kiyono, Tamotsu Ishizuka, Hidehiko Okazawa
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Language:English
Published: SpringerOpen 2025-04-01
Series:EJNMMI Research
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Online Access:https://doi.org/10.1186/s13550-025-01225-7
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author Masayuki Sato
Yukihiro Umeda
Tetsuya Tsujikawa
Tetsuya Mori
Akikazu Shimada
Tomoaki Sonoda
Makiko Yamaguchi
Chisato Honjo
Yuko Waseda
Yasushi Kiyono
Tamotsu Ishizuka
Hidehiko Okazawa
author_facet Masayuki Sato
Yukihiro Umeda
Tetsuya Tsujikawa
Tetsuya Mori
Akikazu Shimada
Tomoaki Sonoda
Makiko Yamaguchi
Chisato Honjo
Yuko Waseda
Yasushi Kiyono
Tamotsu Ishizuka
Hidehiko Okazawa
author_sort Masayuki Sato
collection DOAJ
description 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 (SUVmean) in the spleen, maximum SUV (SUVmax) in the lymph nodes, and the SUVmax, SUVmean, 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 SUVmax 2.19 vs. 2.64, P = 0.073). Regarding changes in vertebral accumulation in the non-PD group, the SUVmax, 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.
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spelling doaj-art-cd10063278db47cbbf366bf27c0380ad2025-08-20T01:56:01ZengSpringerOpenEJNMMI Research2191-219X2025-04-0115111210.1186/s13550-025-01225-73′-deoxy-3′-18F-fluorothymidine PET imaging of lymphoid tissues in patients with advanced non-small cell lung cancer undergoing anti-programmed cell death-1 therapyMasayuki Sato0Yukihiro Umeda1Tetsuya Tsujikawa2Tetsuya Mori3Akikazu Shimada4Tomoaki Sonoda5Makiko Yamaguchi6Chisato Honjo7Yuko Waseda8Yasushi Kiyono9Tamotsu Ishizuka10Hidehiko Okazawa11Department of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Radiology, Faculty of Medical Sciences, University of FukuiBiomedical Imaging Research Center, University of FukuiDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiBiomedical Imaging Research Center, University of FukuiDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of FukuiBiomedical Imaging Research Center, University of FukuiAbstract 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 (SUVmean) in the spleen, maximum SUV (SUVmax) in the lymph nodes, and the SUVmax, SUVmean, 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 SUVmax 2.19 vs. 2.64, P = 0.073). Regarding changes in vertebral accumulation in the non-PD group, the SUVmax, 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.https://doi.org/10.1186/s13550-025-01225-718F-FLT PETPD-1 inhibitorLung cancerSpleenBone marrowProliferation
spellingShingle Masayuki Sato
Yukihiro Umeda
Tetsuya Tsujikawa
Tetsuya Mori
Akikazu Shimada
Tomoaki Sonoda
Makiko Yamaguchi
Chisato Honjo
Yuko Waseda
Yasushi Kiyono
Tamotsu Ishizuka
Hidehiko Okazawa
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
EJNMMI Research
18F-FLT PET
PD-1 inhibitor
Lung cancer
Spleen
Bone marrow
Proliferation
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic 18F-FLT PET
PD-1 inhibitor
Lung cancer
Spleen
Bone marrow
Proliferation
url https://doi.org/10.1186/s13550-025-01225-7
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