ArticleJournal of the American Chemical Society2013
Transforming thymidine into a magnetic resonance imaging probe for monitoring gene expression.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Quantifying Transmembrane Water Exchange by Diffusion NMR Methods: From Yeast Cells to Optic Nerve Ex Vivo.NMR in biomedicine · 2026Article
- Novel non‑metal‑based contrast agents for MR imaging: Emerging approaches and clinical perspectives (Review).International journal of oncology · 2025Review
- Noninvasive Imaging of Transgene Expression in Neurons Using Chemical Exchange Saturation Transfer MRI.NMR in biomedicine · 2025Article
- Going Above and Beyond: Achieving High Contrast and Higher Offset through Carbon Dot-Based diaCEST MRI Contrast Agent.Chemical & biomedical imaging · 2025Article
- Visualization of Unconjugated Bilirubin In Vivo with a Novel Approach Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging in a Rat Model.ACS chemical neuroscience · 2024Article
- Design Chemical Exchange Saturation Transfer Contrast Agents and Nanocarriers for Imaging Proton ExchangeACS nano · 2024Review
- A Genetically Engineered Reporter System Designed forJournal of the American Chemical Society · 2024Article
- Intramolecular Hydrogen Bonding Based CEST MRI Contrast Agents As an Emerging Design Strategy: A Mini-Review.ACS omega · 2024Review
- Theranostics - a sure cure for cancer after 100 years?Theranostics · 2024Review
- A putative design for the electromagnetic activation of split proteins for molecular and cellular manipulation.Frontiers in bioengineering and biotechnology · 2024Article
- Development of a synthetic biosensor for chemical exchange MRI utilizing in silico optimized peptides.NMR in biomedicine · 2023Article
- Protein and peptide engineering for chemical exchange saturation transfer imaging in the age of synthetic biology.NMR in biomedicine · 2023Review
- A Genetic Programming Approach to Engineering MRI Reporter Genes.ACS synthetic biology · 2023Article
- Development of a Synthetic Biosensor for Chemical Exchange MRI UtilizingbioRxiv : the preprint server for biology · 2023Article
- Preparation of Hydrothermal Carbon Quantum Dots as a Contrast Amplifying Technique for the diaCEST MRI Contrast Agents.ACS omega · 2022Article
- Computationally designed dual-color MRI reporters for noninvasive imaging of transgene expression.Nature biotechnology · 2022Article
- In vivo tracking of unlabelled mesenchymal stromal cells by mannose-weighted chemical exchange saturation transfer MRI.Nature biomedical engineering · 2022Article
- Paracetamol and other acetanilide analogs as inter-molecular hydrogen bonding assisted diamagnetic CEST MRI contrast agents.RSC advances · 2021Article
- Repurposing Clinical Agents for Chemical Exchange Saturation Transfer Magnetic Resonance Imaging: Current Status and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Redesigned reporter gene for improved proton exchange-based molecular MRI contrast.Scientific reports · 2020Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
Abstract
Synthetic chemistry has revolutionized the understanding of many biological systems. Small compounds that act as agonists and antagonists of proteins, and occasionally as imaging probes, have contributed tremendously to the elucidation of many biological pathways. Nevertheless, the function of thousands of proteins is still elusive, and designing new imaging probes remains a challenge. Through screening and characterization, we identified a thymidine analogue as a probe for imaging the expression of herpes simplex virus type-1 thymidine kinase (HSV1-TK). To detect the probe, we used chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI), in which a dynamic exchange process between an exchangeable proton and the surrounding water protons is used to amplify the desired contrast. Initially, five pyrimidine-based molecules were recognized as putative imaging agents, since their exchangeable imino protons resonate at 5-6 ppm from the water proton frequency and their detection is therefore less affected by endogenous CEST contrast or confounded by direct water saturation. Increasing the pK(a) value of the imino proton by reduction of its 5,6-double bond results in a significant reduction of the exchange rate (k(ex)) between this proton and the water protons. This reduced k(ex) of the dihydropyrimidine nucleosides fulfills the "slow to intermediate regime" condition for generating high CEST-MRI contrast. Consequently, we identified 5-methyl-5,6-dihydrothymidine as the optimal probe and demonstrated its feasibility for in vivo imaging of HSV1-TK. In light of these findings, this new approach can be generalized for designing specific probes for the in vivo imaging of a variety of proteins and enzymes.
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