In vivo tracking of adenoviral-transduced iron oxide-labeled bone marrow-derived dendritic cells using magnetic particle imaging

European Radiology Experimental

Original Article

Corby Fink¹  Gregory A. Dekaban¹  Julia J. Gevaert²  Paula J. Foster²  Jimmy D. Dikeakos³  John W. Barrett⁴ 

[1] Biotherapeutics Research Laboratory, Robarts Research Institute, London, ON, Canada;Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada;Cellular and Molecular Imaging Group, Robarts Research Institute, London, ON, Canada;Department of Medical Biophysics, University of Western Ontario, London, ON, Canada;Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada;Department of Otolaryngology–Head and Neck Surgery, University of Western Ontario, London, ON, Canada;

关键词: Adenoviridae;    Cell tracking;    Immunotherapy;    Magnetic iron oxide nanoparticles;    Mice (inbred C57BL/6);   

DOI  :  10.1186/s41747-023-00359-4

 received in 2023-03-07, accepted in 2023-05-30,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDespite widespread study of dendritic cell (DC)-based cancer immunotherapies, the in vivo postinjection fate of DC remains largely unknown. Due in part to a lack of quantifiable imaging modalities, this is troubling as the amount of DC migration to secondary lymphoid organs correlates with therapeutic efficacy. Magnetic particle imaging (MPI) has emerged as a suitable modality to quantify in vivo migration of superparamagnetic iron oxide (SPIO)-labeled DC. Herein, we describe a popliteal lymph node (pLN)-focused MPI scan to quantify DC in vivo migration accurately and consistently.MethodsAdenovirus (Ad)-transduced SPIO+ (Ad SPIO+) and SPIO+ C57BL/6 bone marrow-derived DC were generated and assessed for viability and phenotype, then fluorescently labeled and injected into mouse hind footpads (n = 6). Two days later, in vivo DC migration was quantified using whole animal, pLN-focused, and ex vivo pLN MPI scans.ResultsNo significant differences in viability, phenotype and in vivo pLN migration were noted for Ad SPIO+ and SPIO+ DC. Day 2 pLN-focused MPI quantified DC migration in all instances while whole animal MPI only quantified pLN migration in 75% of cases. Ex vivo MPI and fluorescence microscopy confirmed that pLN MPI signal was due to originally injected Ad SPIO+ and SPIO+ DC.ConclusionWe overcame a reported limitation of MPI by using a pLN-focused MPI scan to quantify pLN-migrated Ad SPIO+ and SPIO+ DC in 100% of cases and detected as few as 1000 DC (4.4 ng Fe) in vivo. MPI is a suitable preclinical imaging modality to assess DC-based cancer immunotherapeutic efficacy.Relevance statementTracking the in vivo fate of DC using noninvasive quantifiable magnetic particle imaging can potentially serve as a surrogate marker of therapeutic effectiveness.Key points• Adenoviral-transduced and iron oxide-labeled dendritic cells are in vivo migration competent.• Magnetic particle imaging is a suitable modality to quantify in vivo dendritic cell migration.• Magnetic particle imaging focused field of view overcomes dynamic range limitation.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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