Bright Ferritin—a Reporter Gene Platform for On-Demand, Longitudinal Cell Tracking on MRI

Szulc, Daniel A.; Lee, Xavier A.; Cheng, Hai-Ying Mary; Cheng, Hai‐Ling Margaret

doi:10.1016/j.isci.2020.101350

Cited by 11 publications

(1 citation statement)

References 46 publications

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“…Using endogenous biomolecules for molecular imaging also inspires many innovations in developing exogenous imaging probes. For example, using iron-storage proteins (e.g., ferritin) for T 2 * imaging or QSM quantification for iron in vivo led to the development of MRI reporter genes that can be incorporated into the therapeutic cells for MRI tracking of the cell transplants and other cell-based therapies. , On the other hand, many drugs and therapeutic agents are inherently CEST contrast agents, including some already entering the phases of clinical trials . Thus, these compounds can be used as theranostic agents that can include image-guided drug delivery in their clinical applications to improve the efficacy and timely assess treatment responses, as demonstrated in a number of previous studies. − …”

Section: Future Development and Perspectives Of Label-free Molecular Mrimentioning

confidence: 99%

Label-Free Chemically and Molecularly Selective Magnetic Resonance Imaging

Liu

Thamizhchelvan

et al. 2023

Chemical & Biomedical Imaging

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Biomedical imaging, especially molecular imaging, has been a driving force in scientific discovery, technological innovation, and precision medicine in the past two decades. While substantial advances and discoveries in chemical biology have been made to develop molecular imaging probes and tracers, translating these exogenous agents to clinical application in precision medicine is a major challenge. Among the clinically accepted imaging modalities, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) exemplify the most effective and robust biomedical imaging tools. Both MRI and MRS enable a broad range of chemical, biological and clinical applications from determining molecular structures in biochemical analysis to imaging diagnosis and characterization of many diseases and image-guided interventions. Using chemical, biological, and nuclear magnetic resonance properties of specific endogenous metabolites and native MRI contrast-enhancing biomolecules, label-free molecular and cellular imaging with MRI can be achieved in biomedical research and clinical management of patients with various diseases. This review article outlines the chemical and biological bases of several label-free chemically and molecularly selective MRI and MRS methods that have been applied in imaging biomarker discovery, preclinical investigation, and image-guided clinical management. Examples are provided to demonstrate strategies for using endogenous probes to report the molecular, metabolic, physiological, and functional events and processes in living systems, including patients. Future perspectives on label-free molecular MRI and its challenges as well as potential solutions, including the use of rational design and engineered approaches to develop chemical and biological imaging probes to facilitate or combine with label-free molecular MRI, are discussed.

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Section: Future Development and Perspectives Of Label-free Molecular Mrimentioning

confidence: 99%

Label-Free Chemically and Molecularly Selective Magnetic Resonance Imaging

Liu

Thamizhchelvan

et al. 2023

Chemical & Biomedical Imaging

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A Dual‐Gene Reporter‐Amplifier Architecture for Enhancing the Sensitivity of Molecular MRI by Water Exchange

Huang,

Chen,

Zhu

et al. 2024

ChemBioChem

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The development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in vivo. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction of cells express the reporter. To overcome this limitation, we developed an approach for amplifying the sensitivity of molecular MRI by combining a chemogenetic contrast mechanism with a biophysical approach to increase water diffusion through the co‐expression of a dual‐gene construct comprising an organic anion transporting polypeptide, Oatp1b3, and a water channel, Aqp1. We first show that the expression of Aqp1 amplifies MRI contrast in cultured cells engineered to express Oatp1b3. We demonstrate that the contrast amplification is caused by Aqp1‐driven increase in water exchange, which provides the gadolinium ions internalized by Oatp1b3‐expressing cells with access to a larger water pool compared with exchange‐limited conditions. We further show that our methodology allows cells to be detected using approximately 10‐fold lower concentrations of gadolinium than that in the Aqp1‐free scenario. Finally, we show that our approach enables the imaging of mixed‐cell cultures containing a low fraction of Oatp1b3labeled cells that are undetectable on the basis of Oatp1b3 expression alone.

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