Repurposing Clinical Agents for Chemical Exchange Saturation Transfer Magnetic Resonance Imaging: Current Status and Future Perspectives

Chen, Zelong; Zheng, Han; Liu, Guanshu

doi:10.3390/ph14010011

Cited by 23 publications

(20 citation statements)

References 166 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While endogenous CEST contrast demonstrated uniqueness in imaging brain tumors, other non-metallic CEST contrast agents have been exploited to further enhance the contrast of specific molecular alterations in tumors [50,78,[122][123][124][125]. Compared to endogenous molecules, the administration of contrast agents could provide a relatively high local concentration.…”

Section: Non-metallic Cest Contrast Agents For Brain Tumor Imagingmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Imaging of Brain Tumors and Drug Delivery Using CEST MRI: Promises and Challenges

et al. 2022

View full text Add to dashboard Cite

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) detects molecules in their natural forms in a sensitive and non-invasive manner. This makes it a robust approach to assess brain tumors and related molecular alterations using endogenous molecules, such as proteins/peptides, and drugs approved for clinical use. In this review, we will discuss the promises of CEST MRI in the identification of tumors, tumor grading, detecting molecular alterations related to isocitrate dehydrogenase (IDH) and O-6-methylguanine-DNA methyltransferase (MGMT), assessment of treatment effects, and using multiple contrasts of CEST to develop theranostic approaches for cancer treatments. Promising applications include (i) using the CEST contrast of amide protons of proteins/peptides to detect brain tumors, such as glioblastoma multiforme (GBM) and low-grade gliomas; (ii) using multiple CEST contrasts for tumor stratification, and (iii) evaluation of the efficacy of drug delivery without the need of metallic or radioactive labels. These promising applications have raised enthusiasm, however, the use of CEST MRI is not trivial. CEST contrast depends on the pulse sequences, saturation parameters, methods used to analyze the CEST spectrum (i.e., Z-spectrum), and, importantly, how to interpret changes in CEST contrast and related molecular alterations in the brain. Emerging pulse sequence designs and data analysis approaches, including those assisted with deep learning, have enhanced the capability of CEST MRI in detecting molecules in brain tumors. CEST has become a specific marker for tumor grading and has the potential for prognosis and theranostics in brain tumors. With increasing understanding of the technical aspects and associated molecular alterations detected by CEST MRI, this young field is expected to have wide clinical applications in the near future.

show abstract

Section: Non-metallic Cest Contrast Agents For Brain Tumor Imagingmentioning

confidence: 99%

“…One of the widely studied non-metallic CEST contrast agents for brain tumor imaging is D-glucose [123]. Glucose (C 6 H 12 O 6 ) is a hexose with five hydroxyl (-OH) protons which can be detected by CEST MRI (Figure 2).…”

Section: Non-metallic Cest Contrast Agents For Brain Tumor Imagingmentioning

confidence: 99%

Molecular Imaging of Brain Tumors and Drug Delivery Using CEST MRI: Promises and Challenges

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Few of the already known clinical agents have also been repurposed as diaCEST CAs. 22 , 23 However, even then the sensitivity or efficiency of diaCEST CAs remains an ongoing challenge.…”

Section: Introductionmentioning

confidence: 99%

“…The quest for efficient diaCEST CA has prompted testing of almost all classes of organic compounds containing labile protons in the slow to medium exchange regime, including endogenous CAs such as glucose, glycogens, glycosaminoglycan, protamine, glutamate, urea, nucleic acids, peptides, and so forth present inside the human body. Few of the already known clinical agents have also been repurposed as diaCEST CAs. , However, even then the sensitivity or efficiency of diaCEST CAs remains an ongoing challenge.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Hydrothermal Carbon Quantum Dots as a Contrast Amplifying Technique for the diaCEST MRI Contrast Agents

Pandey

Ghosh

2022

ACS Omega

View full text Add to dashboard Cite

The discovery of exogenous contrast agents (CAs) is one of the key factors behind the success and widespread acceptability of MRI as an imaging tool. To the long list of CAs, the newest addition is the chemical exchange saturation transfer (CEST)-based CAs. Among them, the diaCEST CAs are the safer metal-free option constituted by a large pool of organic and macromolecules, but the tradeoff comes in terms of smaller natural offset. Another major challenge for the CEST CAs is that they need to operate in the tens of millimolar concentration range to produce any meaningful contrast. The quest for high efficiency diaCEST agents has led to a number of strategies such as use of hydrogen bonding, use of equivalent protons, and use of diatropic ring current. Here, we present carbon quantum dot formation using hydrothermal treatment as a new strategy to amplify diaCEST contrast efficiency. We show that while the well-known analgesic drug lidocaine hydrochloride when repurposed as a diaCEST CA produces no contrast at the physiological pH and temperature, the carbon dots prepared from it elevate the physiological contrast to a sizable 11%. Also, the maximum efficiency at an acidic pH gets amplified by a factor of 2 to 46%. The study showed that the enhancement in CEST efficiency is reproducible and the pH response of these carbon dots is tunable through variation in synthesis conditions such as temperature, duration, and precursor concentration.

show abstract

“…This imaging technology has attracted a number of preclinical and clinical research studies [ 4 , 5 ], becoming a promising molecular imaging tool that is available in the clinic [ 6 , 7 ]. Particularly, CEST imaging has been explored in assessing tumor metabolism, pH microenvironment, and histological types [ 4 , 5 , 6 ]. Like other MR techniques, CEST has been intensively investigated for characterizing brain tumors, with several dedicated reviews [ 6 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

Gao

Zou

et al. 2021

IJMS

View full text Add to dashboard Cite

Chemical exchange saturation transfer (CEST) MRI is a promising molecular imaging tool which allows the specific detection of metabolites that contain exchangeable amide, amine, and hydroxyl protons. Decades of development have progressed CEST imaging from an initial concept to a clinical imaging tool that is used to assess tumor metabolism. The first translation efforts involved brain imaging, but this has now progressed to imaging other body tissues. In this review, we summarize studies using CEST MRI to image a range of tumor types, including breast cancer, pelvic tumors, digestive tumors, and lung cancer. Approximately two thirds of the published studies involved breast or pelvic tumors which are sites that are less affected by body motion. Most studies conclude that CEST shows good potential for the differentiation of malignant from benign lesions with a number of reports now extending to compare different histological classifications along with the effects of anti-cancer treatments. Despite CEST being a unique ‘label-free’ approach with a higher sensitivity than MR spectroscopy, there are still some obstacles for implementing its clinical use. Future research is now focused on overcoming these challenges. Vigorous ongoing development and further clinical trials are expected to see CEST technology become more widely implemented as a mainstream imaging technology.

show abstract

Repurposing Clinical Agents for Chemical Exchange Saturation Transfer Magnetic Resonance Imaging: Current Status and Future Perspectives

Cited by 23 publications

References 166 publications

Molecular Imaging of Brain Tumors and Drug Delivery Using CEST MRI: Promises and Challenges

Molecular Imaging of Brain Tumors and Drug Delivery Using CEST MRI: Promises and Challenges

Preparation of Hydrothermal Carbon Quantum Dots as a Contrast Amplifying Technique for the diaCEST MRI Contrast Agents

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

Contact Info

Product

Resources

About