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SABRE hyperpolarized anticancer agents for use in 1 H MRI
Author(s) -
Fear Elizabeth J.,
Kennerley Aneurin J.,
Rayner Peter J.,
Norcott Philip,
Roy Soumya S.,
Duckett Simon B.
Publication year - 2022
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.29166
Subject(s) - hyperpolarization (physics) , spin isomers of hydrogen , chemistry , nuclear magnetic resonance spectroscopy , nuclear magnetic resonance , polarization (electrochemistry) , hydrogen , physics , stereochemistry , organic chemistry
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 ‐H 2 ) 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‐ d 4 solvent facilitated polarization transfer from p ‐H 2 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 T 1 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.