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

Shalaby, Nourhan; Kelly, John J.; Martínez, Francisco Martínez; Fox, Matthew S.; Qi, Qi; Thiessen, Jonathan D.; Hicks, Justin; Scholl, Timothy J.; Ronald, John A.

doi:10.1007/s11307-021-01697-8

Cited by 11 publications

(8 citation statements)

References 55 publications

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“…An important advantage of OATP1B3 is its human origin and the accompanying clinically approved Gd-EOB-DTPA agent, making this reporter system highly compatible in humans by minimizing the potential risk for causing immunogenic reactions compared to HSV1-TK. Our group has previously described combining OATP1B3 for MRI with the human sodium iodine symporter for PET to track stem cells ( 57 ), and we envision our SynNotch system could incorporate these two human reporters to harness the combined strength of both clinical modalities.…”

Section: Discussionmentioning

confidence: 99%

Visualizing cell–cell communication using synthetic notch activated MRI

Wang

Chen

Nyström

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Cell–cell communication plays a fundamental role in multicellular organisms. Cell-based cancer immunotherapies rely on the ability of innate or engineered receptors on immune cells to engage specific antigens on cancer cells to induce tumor kill. To improve the development and translation of these therapies, imaging tools capable of noninvasively and spatiotemporally visualizing immune-cancer cell interactions would be highly valuable. Using the synthetic Notch (SynNotch) system, we engineered T cells that upon interaction with a chosen antigen (CD19) on neighboring cancer cells induce the expression of optical reporter genes and the human-derived, magnetic resonance imaging (MRI) reporter gene organic anion transporting polypeptide 1B3 (OATP1B3). Administration of engineered T cells induced the antigen-dependent expression of all our reporter genes in mice bearing CD19-positive tumors but not CD19-negative tumors. Notably, due to the high spatial resolution and tomographic nature of MRI, contrast-enhanced foci within CD19-positive tumors representing OATP1B3-expressing T cells were clearly visible and their distribution was readily mapped. We then extended this technology onto human natural killer-92 (NK-92) cells, observing similar CD19-dependent reporter activity in tumor-bearing mice. Furthermore, we show that when delivered intravenously, engineered NK-92 cells can be detected via bioluminescence imaging in a systemic cancer model. With continued work, this highly modular imaging strategy could aid in the monitoring of cell therapies in patients and, beyond this, augment our understanding of how different cell populations interact within the body during normal physiology or disease.

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Section: Discussionmentioning

confidence: 99%

Visualizing cell–cell communication using synthetic notch activated MRI

Wang

Chen

Nyström

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…In previous studies, cells were incubated for just 60 min before assessing relaxation rate changes at 3.0 T. In these past experiments, we saw no significant uptake of agent into control cells. 12,13,50 We propose that the additional 30 min incubation may have facilitated the large concentration gradient between the intra-and extracellular compartments to drive Mn(II) into the control cells, providing an inaccurate picture of the OATP-mediated transport of the novel Mn(II) agents. This could also be the result of probes interacting with the outer cell membrane through electrostatic or lipophilic interactions though this work did not explore this theory with measurements.…”

Section: ■ Discussion and Conclusionmentioning

confidence: 99%

“…Most recently human OATPs (OATP1B3 and OATP1B1) have been expressed in cancer cells to perform longitudinal, 3D tracking of engineered cells in vivo (Figure ). − …”

Section: Introductionmentioning

confidence: 99%

Development of a Suite of Gadolinium-Free OATP1-Targeted Paramagnetic Probes for Liver MRI

McRae,

Cleary,

DeRoche

et al. 2023

J. Med. Chem.

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Five amphiphilic, anionic Mn(II) complexes were synthesized as contrast agents targeted to organic anion transporting polypeptide transporters (OATP) for liver magnetic resonance imaging (MRI). The Mn(II) complexes are synthesized in three steps, each from the commercially available trans-1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid (CDTA) chelator, with T 1-relaxivity of complexes ranging between 2.3 and 3.0 mM–1 s–1 in phosphate buffered saline at an applied field strength of 3.0 T. Pharmacokinetics were assessed in female BALB/c mice by acquiring T 1-weighted images dynamically for 70 min after agent administration and determining contrast enhancement and washout in various organs. Uptake of Mn(II) complexes in human OATPs was investigated through in vitro assays using MDA-MB-231 cells engineered to express either OATP1B1 or OATP1B3 isoforms. Our study introduces a new class of Mn-based OATP-targeted contrast that can be broadly tuned via simple synthetic protocols.

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“…Among all the modalities, reporter genes expressing PET tracers have progressed quickly and are considered most valuable for clinical translation. Notably, the combination of PET and MRI reporter genes exhibits translational potential with superiority in both specificity and localization [ 94 ].…”

Section: Opportunities and Challengesmentioning

confidence: 99%

Reporter Genes for Brain Imaging Using MRI, SPECT and PET

Gao

Wang

Gong

et al. 2022

IJMS

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The use of molecular imaging technologies for brain imaging can not only play an important supporting role in disease diagnosis and treatment but can also be used to deeply study brain functions. Recently, with the support of reporter gene technology, optical imaging has achieved a breakthrough in brain function studies at the molecular level. Reporter gene technology based on traditional clinical imaging modalities is also expanding. By benefiting from the deeper imaging depths and wider imaging ranges now possible, these methods have led to breakthroughs in preclinical and clinical research. This article focuses on the applications of magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) reporter gene technologies for use in brain imaging. The tracking of cell therapies and gene therapies is the most successful and widely used application of these techniques. Meanwhile, breakthroughs have been achieved in the research and development of reporter genes and their imaging probe pairs with respect to brain function research. This paper introduces the imaging principles and classifications of the reporter gene technologies of these imaging modalities, lists the relevant brain imaging applications, reviews their characteristics, and discusses the opportunities and challenges faced by clinical imaging modalities based on reporter gene technology. The conclusion is provided in the last section.

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

Cited by 11 publications

References 55 publications

Visualizing cell–cell communication using synthetic notch activated MRI

Visualizing cell–cell communication using synthetic notch activated MRI

Development of a Suite of Gadolinium-Free OATP1-Targeted Paramagnetic Probes for Liver MRI

Reporter Genes for Brain Imaging Using MRI, SPECT and PET

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