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A Human-derived Dual MRI/PET Reporter Gene System with High Translational Potential for Cell Tracking

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Abstract

Purpose

Reporter gene imaging has been extensively used to longitudinally report on whole-body distribution and viability of transplanted engineered cells. Multi-modal cell tracking can provide complementary information on cell fate. Typical multi-modal reporter gene systems often combine clinical and preclinical modalities. A multi-modal reporter gene system for magnetic resonance imaging (MRI) and positron emission tomography (PET), two clinical modalities, would be advantageous by combining the sensitivity of PET with the high-resolution morphology and non-ionizing nature of MRI.

Procedures

We developed and evaluated a dual MRI/PET reporter gene system composed of two human-derived reporter genes that utilize clinical reporter probes for engineered cell detection. As a proof-of-concept, breast cancer cells were engineered to co-express the human organic anion transporter polypeptide 1B3 (OATP1B3) that uptakes the clinical MRI contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), and the human sodium iodide symporter (NIS) which uptakes the PET tracer, [18F] tetrafluoroborate ([18F] TFB).

Results

T1-weighted MRI results in mice exhibited significantly higher MRI signals in reporter-gene-engineered mammary fat pad tumors versus contralateral naïve tumors (p < 0.05). No differences in contrast enhancement were observed at 5 h after Gd-EOB-DTPA administration using either intravenous or intraperitoneal injection. We also found significantly higher standard uptake values (SUV) in engineered tumors in comparison to the naïve tumors in [18F]TFB PET images (p < 0.001). Intratumoral heterogeneity in signal enhancement was more conspicuous in relatively higher resolution MR images compared to PET images.

Conclusions

Our study demonstrates the ability to noninvasively track cells engineered with our human-derived dual MRI/PET reporter system, enabling a more comprehensive evaluation of transplanted cells. Future work is focused on applying this tool to track therapeutic cells, which may one day enable the broader application of cell tracking within the healthcare system.

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Acknowledgements

This study was funded by the Ontario Institute for Cancer Research (IA-028) National Institutes of Health (1UH2EB028907-01), Translational Breast Cancer Research Unit, and the National Science and Engineering Research Council of Canada.

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Authors and Affiliations

  1. Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Canada

    Nourhan Shalaby, Qi Qi, Timothy J. Scholl & John A. Ronald

  2. Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Canada

    John Kelly, Francisco Martinez, Jonathan Thiessen, Justin Hicks, Timothy J. Scholl & John A. Ronald

  3. Lawson Health Research Institute, London, Canada

    Mathew Fox, Justin Hicks & John A. Ronald

  4. Saint Joseph’s Health Care, Toronto, Canada

    Mathew Fox & Jonathan Thiessen

  5. Lawson Cyclotron and Radiochemistry Facility, London, Canada

    Jonathan Thiessen & Justin Hicks

  6. Ontario Institute for Cancer Research, Toronto, Canada

    Timothy J. Scholl

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  1. Nourhan Shalaby
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  2. John Kelly
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All authors contributed to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work. All authors contributed to drafting the work or revising it critically for important intellectual content. All authors approved the final version of the manuscript to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Shalaby, N., Kelly, J., Martinez, F. et al. A Human-derived Dual MRI/PET Reporter Gene System with High Translational Potential for Cell Tracking. Mol Imaging Biol 24, 341–351 (2022). https://doi.org/10.1007/s11307-021-01697-8

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