Total-body Dynamic Imaging and Kinetic Modeling of 18 F-AraG in Healthy Individuals and a Non-Small Cell Lung Cancer Patient Undergoing Anti-PD-1 Immunotherapy.

Autor:	Omidvari N; Department of Biomedical Engineering, University of California Davis, Davis, CA, USA., Levi J; CellSight Technologies Inc., San Francisco, CA, USA., Abdelhafez YG; Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA.; Radiotherapy and Nuclear Medicine Department, South Egypt Cancer Institute, Assiut University, Egypt., Wang Y; Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA.; Department of Biomedical Engineering, University of California Davis, Davis, CA, USA., Nardo L; Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA., Daly ME; Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center School of Medicine, Sacramento, CA, USA., Wang G; Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA., Cherry SR; Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.; Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Nov 01. Date of Electronic Publication: 2023 Nov 01.
DOI:	10.1101/2023.09.22.23295860
Abstrakt:	Immunotherapies, especially the checkpoint inhibitors such as anti-PD-1 antibodies, have transformed cancer treatment by enhancing immune system's capability to target and kill cancer cells. However, predicting immunotherapy response remains challenging. 18 F-AraG is a molecular imaging tracer targeting activated T cells, which may facilitate therapy response assessment by non-invasive quantification of immune cell activity within tumor microenvironment and elsewhere in the body. The aim of this study was to obtain preliminary data on total-body pharmacokinetics of 18 F-AraG, as a potential quantitative biomarker for immune response evaluation. Methods: The study consisted of 90-min total-body dynamic scans of four healthy subjects and one non-small cell lung cancer (NSCLC) patient, scanned before and after anti-PD-1 immunotherapy. Compartmental modeling with Akaike information criterion model selection were employed to analyze tracer kinetics in various organs. Additionally, seven sub-regions of the primary lung tumor and four mediastinal lymph nodes were analyzed. Practical identifiability analysis was performed to assess reliability of kinetic parameter estimation. Correlations of SUVmean, SUVR (tissue-to-blood ratio), and Logan plot slope K L o g a n with total volume-of-distribution V T were calculated to identify potential surrogates for kinetic modeling. Results: Strong correlations were observed between K L o g a n and SUVR values with V T , suggesting that they can be used as promising surrogates for V T , especially in organs with low blood-volume fraction. Moreover, the practical identifiability analysis suggests that the dynamic 18 F-AraG PET scans could potentially be shortened to 60 minutes, while maintaining quantification accuracy for all organs-of-interest. The study suggests that although 18 F-AraG SUV images can provide insights on immune cell distribution, kinetic modeling or graphical analysis methods may be required for accurate quantification of immune response post-therapy. While SUVmean showed variable changes in different sub-regions of the tumor post-therapy, the SUVR, K L o g a n , and V T showed consistent increasing trends in all analyzed sub-regions of the tumor with high practical identifiability. Conclusion: Our findings highlight the promise of 18 F-AraG dynamic imaging as a non-invasive biomarker for quantifying the immune response to immunotherapy in cancer patients. The promising total-body kinetic modeling results also suggest potentially wider applications of the tracer in investigating the role of T cells in the immunopathogenesis of diseases. Competing Interests: DISCLAIMER Jelena Levi is employed by CellSight Technologies. CellSight Technologies Inc. is commercializing 18F-AraG. No other potential conflict of interest relevant to this article was reported.
Databáze:	MEDLINE
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