In Vivo Tracking of Adenoviral-transduced Iron Oxide-labeled Bone Marrow-derived Dendritic Cells Using Magnetic Particle Imaging

Overview

Journal Eur Radiol Exp

Date 2023 Aug 14

PMID 37580614

Authors

Corby Fink

Julia J Gevaert

John W Barrett

Jimmy D Dikeakos

Paula J Foster

Gregory A Dekaban

Affiliations

Soon will be listed here.

Abstract

Background: Despite 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.

Methods: Adenovirus (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.

Results: No 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.

Conclusion: We 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 Statement: Tracking 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.

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References

Graeser M, Knopp T, Szwargulski P, Friedrich T, von Gladiss A, Kaul M . Towards Picogram Detection of Superparamagnetic Iron-Oxide Particles Using a Gradiometric Receive Coil. Sci Rep. 2017; 7(1):6872. PMC: 5537232. DOI: 10.1038/s41598-017-06992-5. View

Blalock L, Landsberg J, Messmer M, Shi J, Pardee A, Haskell R . Human dendritic cells adenovirally-engineered to express three defined tumor antigens promote broad adaptive and innate immunity. Oncoimmunology. 2012; 1(3):287-357. PMC: 3382861. DOI: 10.4161/onci.18628. View

Knopp T, Gdaniec N, Moddel M . Magnetic particle imaging: from proof of principle to preclinical applications. Phys Med Biol. 2017; 62(14):R124-R178. DOI: 10.1088/1361-6560/aa6c99. View

Dadfar S, Roemhild K, Drude N, von Stillfried S, Knuchel R, Kiessling F . Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications. Adv Drug Deliv Rev. 2019; 138:302-325. PMC: 7115878. DOI: 10.1016/j.addr.2019.01.005. View

Damjanovic D, Zhang X, Mu J, Medina M, Xing Z . Organ distribution of transgene expression following intranasal mucosal delivery of recombinant replication-defective adenovirus gene transfer vector. Genet Vaccines Ther. 2008; 6:5. PMC: 2259349. DOI: 10.1186/1479-0556-6-5. View

Liu C, Lou Y, Lizee G, Qin H, Liu S, Rabinovich B . Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J Clin Invest. 2008; 118(3):1165-75. PMC: 2230660. DOI: 10.1172/JCI33583. View

Nejadnik H, Jung K, Theruvath A, Kiru L, Liu A, Wu W . Instant labeling of therapeutic cells for multimodality imaging. Theranostics. 2020; 10(13):6024-6034. PMC: 7255004. DOI: 10.7150/thno.39554. View

Gevaert J, Fink C, Dikeakos J, Dekaban G, Foster P . Magnetic Particle Imaging Is a Sensitive In Vivo Imaging Modality for the Detection of Dendritic Cell Migration. Mol Imaging Biol. 2022; 24(6):886-897. DOI: 10.1007/s11307-022-01738-w. View

Fink C, Smith M, Sehl O, Gaudet J, Meagher T, Sheikh N . Quantification and characterization of granulocyte macrophage colony-stimulating factor activated human peripheral blood mononuclear cells by fluorine-19 cellular MRI in an immunocompromised mouse model. Diagn Interv Imaging. 2020; 101(9):577-588. DOI: 10.1016/j.diii.2020.02.004. View

10.

Gonzales C, Yoshihara H, Dilek N, Leignadier J, Irving M, Mieville P . In-Vivo Detection and Tracking of T Cells in Various Organs in a Melanoma Tumor Model by 19F-Fluorine MRS/MRI. PLoS One. 2016; 11(10):e0164557. PMC: 5063406. DOI: 10.1371/journal.pone.0164557. View

11.

Yang X, Shao G, Zhang Y, Wang W, Qi Y, Han S . Applications of Magnetic Particle Imaging in Biomedicine: Advancements and Prospects. Front Physiol. 2022; 13:898426. PMC: 9285659. DOI: 10.3389/fphys.2022.898426. View

12.

Mendell J, Al-Zaidy S, Rodino-Klapac L, Goodspeed K, Gray S, Kay C . Current Clinical Applications of In Vivo Gene Therapy with AAVs. Mol Ther. 2020; 29(2):464-488. PMC: 7854298. DOI: 10.1016/j.ymthe.2020.12.007. View

13.

Simonetta F, Alam I, Lohmeyer J, Sahaf B, Good Z, Chen W . Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET. Clin Cancer Res. 2020; 27(4):1058-1068. PMC: 7887027. DOI: 10.1158/1078-0432.CCR-20-2770. View

14.

Mercier S, Gahery-Segard H, Monteil M, Lengagne R, Guillet J, Eloit M . Distinct roles of adenovirus vector-transduced dendritic cells, myoblasts, and endothelial cells in mediating an immune response against a transgene product. J Virol. 2002; 76(6):2899-911. PMC: 136003. DOI: 10.1128/jvi.76.6.2899-2911.2002. View

15.

Datta J, Terhune J, Lowenfeld L, Cintolo J, Xu S, Roses R . Optimizing dendritic cell-based approaches for cancer immunotherapy. Yale J Biol Med. 2014; 87(4):491-518. PMC: 4257036. View

16.

Sun Q, Zhao X, Peng C, Hao Y, Zhao Y, Jiang N . Immunotherapy for Lewis lung carcinoma utilizing dendritic cells infected with CK19 gene recombinant adenoviral vectors. Oncol Rep. 2015; 34(5):2289-95. PMC: 4583529. DOI: 10.3892/or.2015.4231. View

17.

de Vries I, Lesterhuis W, Barentsz J, Verdijk P, van Krieken J, Boerman O . Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol. 2005; 23(11):1407-13. DOI: 10.1038/nbt1154. View

18.

de Chickera S, Willert C, Mallet C, Foley R, Foster P, Dekaban G . Cellular MRI as a suitable, sensitive non-invasive modality for correlating in vivo migratory efficiencies of different dendritic cell populations with subsequent immunological outcomes. Int Immunol. 2011; 24(1):29-41. DOI: 10.1093/intimm/dxr095. View

19.

Liu C, Zhang Z, Ping Y, Qin G, Zhang K, Maimela N . Comprehensive Analysis of PD-1 Gene Expression, Immune Characteristics and Prognostic Significance in 1396 Glioma Patients. Cancer Manag Res. 2020; 12:4399-4410. PMC: 7294103. DOI: 10.2147/CMAR.S238174. View

20.

Dekaban G, Hamilton A, Fink C, Au B, de Chickera S, Ribot E . Tracking and evaluation of dendritic cell migration by cellular magnetic resonance imaging. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013; 5(5):469-83. DOI: 10.1002/wnan.1227. View