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

Corby Fink; Julia J Gevaert; John W Barrett; Jimmy D Dikeakos; Paula J Foster; Gregory A Dekaban

doi:10.1186/s41747-023-00359-4

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

Eur Radiol Exp. 2023 Aug 15;7(1):42. doi: 10.1186/s41747-023-00359-4.

Authors

Corby Fink^{1

2}, Julia J Gevaert^{3

4}, John W Barrett⁵, Jimmy D Dikeakos², Paula J Foster^{3

4}, Gregory A Dekaban^{6

7}

Affiliations

¹ Biotherapeutics Research Laboratory, Robarts Research Institute, London, ON, Canada.
² Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
³ Cellular and Molecular Imaging Group, Robarts Research Institute, London, ON, Canada.
⁴ Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.
⁵ Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, ON, Canada.
⁶ Biotherapeutics Research Laboratory, Robarts Research Institute, London, ON, Canada. dekaban@uwo.ca.
⁷ Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada. dekaban@uwo.ca.

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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae
Animals
Bone Marrow*
Cell Movement
Dendritic Cells
Magnetic Phenomena
Magnetic Resonance Imaging* / methods
Mice
Mice, Inbred C57BL

Substances

ferric oxide

Grants and funding

CIHR/Canada