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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Thoracic Oncology

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1563030

This article is part of the Research TopicAdvancing Diagnostic Excellence in Early Lung Cancer DetectionView all articles

Elevated FDG Uptake in Non-Tumorous Lung Regions Does Not Predict Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer Patients

Provisionally accepted
Friederike VölterFriederike Völter1,2,3*Lukas WehlteLukas Wehlte4Blerina ResuliBlerina Resuli3,4Julia WalterJulia Walter3,4Lea DaisenbergerLea Daisenberger5Maria IngenerfMaria Ingenerf6Maurice HeimerMaurice Heimer6Matthias BrendelMatthias Brendel1,7,8Gabriel T SheikhGabriel T Sheikh1Lena M UnterrainerLena M Unterrainer1,10,9Diego Kauffmann-GuerreroDiego Kauffmann-Guerrero3,4Thomas PflugerThomas Pfluger1Lucie HeinzerlingLucie Heinzerling11,12Amanda TufmanAmanda Tufman3,4
  • 1Department of Nuclear Medicine, LMU University Hospital, Munich, Bavaria, Germany
  • 2Department of Medicine IV, Endocrinology, Diabetes and Metabolism, LMU University Hospital, Munich, Germany
  • 3German Center for Lung Research (DZL CPC-M), Munich, Germany
  • 4Department of Medicine V, LMU Munich University Hospital, Munich, Germany
  • 5Department of Dermatology and Allergy, LMU University Hospital, Munich, Germany
  • 6Department of Radiology, LMU Munich University Hospital, Munich, Bavaria, Germany
  • 7Munich Cluster of Systems Neurology (SyNergy), Munich, Bavaria, Germany
  • 8German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
  • 9Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
  • 10Bayerisches Zentrum für Krebsforschung (BZKF), partner site Munich, Munich, Germany
  • 11Comprehensive Cancer Center Erlangen-EMN (CCC), Erlangen, Bavaria, Germany
  • 12Department of Dermatology, University Hospital Erlangen, Comprehensive Cancer Center Erlangen – European Metropolitan Region Nürnberg, CCC Alliance WERA,, Erlangen, Germany

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Background: Predictors for checkpoint inhibitor-related pneumonitis (cinrPneumonitis) are desperately needed. This study aimed to investigate the pretreatment standardized uptake value (SUV) on [ 18 F]FDG-PET/CT of non-tumorous lung tissue as a predictive imaging marker for the development of cinrPneumonitis in 239 patients with lung cancer. Methods: All patients with lung cancer receiving [ 18 F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) prior to immune checkpoint inhibitor (ICI) therapy were included and retrospectively analyzed. Pretreatment SUVMEAN, SUVMAX, SUV95, SUV normalized by lean body mass (SULMEAN, SULMAX) and clinical variables were compared for patients with and without cinrPneumonitis. Logistic regression analyses were performed to identify the predictive value of pretreatment SUV for the development of cinrPneumonitis. Results: A total of 239 patients were included, of whom 41 (17.2%) developed cinrPneumonitis. The pretreatment radioligand uptake (SUVMEAN, SUVMAX, SUV95, SULMEAN and SULMAX) was not significantly elevated in patients who developed cinrPneumonitis. Logistic regression using sex, age, body mass index and chronic obstructive pulmonary disease as covariables additionally showed no significant association between pretreatment radioligand uptake and the risk of cinrPneumonitis. However, an increased likelihood of developing cinrPneumonitis (relative risk = 1.979; p = 0.027) was shown in patients who received thoracic radiation during ICI therapy. Conclusion: This is the largest study on the association of pretreatment radioligand uptake of the nontumorous lung and the risk of an cinrPneumonitis. Our results showed no significant association between elevated pretreatment radioligand uptake of non-tumorous lung tissue on FDG-PET/CT and the development of cinrPneumonitis.

Keywords: lung cancer, NSCLC, SCLC, [ 18 F]FDG-PET/CT, Standardized uptake value, Checkpoint inhibitor therapy, Checkpoint inhibitor-related pneumonitis, Immune-related adverse events

Received: 02 May 2025; Accepted: 20 Jul 2025.

Copyright: © 2025 Völter, Wehlte, Resuli, Walter, Daisenberger, Ingenerf, Heimer, Brendel, Sheikh, Unterrainer, Kauffmann-Guerrero, Pfluger, Heinzerling and Tufman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Friederike Völter, Department of Nuclear Medicine, LMU University Hospital, Munich, Bavaria, Germany

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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