Fear, Elizabeth J, Kennerley, Aneurin J orcid.org/0000-0002-7599-7461, Rayner, Peter J orcid.org/0000-0002-6577-4117 et al. (3 more authors) (2022) SABRE hyperpolarized anticancer agents for use in 1 H MRI. Magnetic Resonance in Medicine. pp. 11-27. ISSN 1522-2594
Abstract
PURPOSE: Enabling drug tracking (distribution/specific pathways) with magnetic resonance spectroscopy requires manipulation (via hyperpolarization) of spin state populations and targets with sufficiently long magnetic lifetimes to give the largest possible window of observation. Here, we demonstrate how the proton resonances of a group of thienopyridazines (with known anticancer properties), can be amplified using the para-hydrogen (p-H2 ) based signal amplification by reversible exchange (SABRE) hyperpolarization technique. METHODS: Thienopyridazine isomers, including a 2 H version, were synthesized in house. Iridium-based catalysts dissolved in a methanol-d4 solvent facilitated polarization transfer from p-H2 gas to the target thienopyridazines. Subsequent SABRE 1 H responses of hyperpolarized thienopyridazines were completed (400 MHz NMR). Pseudo-singlet state approaches were deployed to extend magnetic state lifetimes. Proof of principle spectral-spatial images were acquired across a range of field strengths (7T-9.4T MRI). RESULTS: 1 H-NMR signal enhancements of -10,130-fold at 9.4T (~33% polarization) were achieved on thieno[2,3-d]pyridazine (T[2,3-d]P), using SABRE under optimal mixing/field transfer conditions. 1 H T1 lifetimes for the thienopyridazines were ~18-50 s. Long-lived state approaches extended the magnetic lifetime of target proton sites in T[2,3-d]P from an average of 25-40 seconds. Enhanced in vitro imaging (spatial and chemical shift based) of target T[2,3-d]P was demonstrated. CONCLUSION: Here, we demonstrate the power of SABRE to deliver a fast and cost-effective route to hyperpolarization of important chemical motifs of anticancer agents. The SABRE approach outlined here lays the foundations for realizing continuous flow, hyperpolarized tracking of drug delivery/pathways.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 15 Mar 2022 09:40 |
Last Modified: | 02 Dec 2024 01:15 |
Published Version: | https://doi.org/10.1002/mrm.29166 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/mrm.29166 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:184773 |
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Filename: Magnetic_Resonance_in_Med_2022_Fear_SABRE_hyperpolarized_anticancer_agents_for_use_in_1H_MRI_1_.pdf
Description: Magnetic Resonance in Med - 2022 - Fear - SABRE hyperpolarized anticancer agents for use in 1H MRI (1)
Licence: CC-BY 2.5