The use of yttrium in medical imaging and therapy : historical background and future perspectives

Yttrium is a chemically versatile rare earth element that finds use in a range of applications including lasers and superconductors. In medicine, yttrium-based materials are used in medical lasers and biomedical implants. This is extended through the array of available yttrium isotopes to enable roles for 90Y complexes as radiopharmaceuticals and 86Y tracers for positron emission tomography (PET) imaging. The naturally abundant isotope 89Y is proving to be suitable for nuclear magnetic resonance investigations, where initial reports in the emerging field of hyperpolarised magnetic resonance imaging (MRI) are promising. In this review we explore the coordination and radiochemical properties of yttrium, and its role in drugs for radiotherapy, PET imaging agents and perspectives for applications in hyperpolarised MRI. This journal i

Advancing homogeneous catalysis for parahydrogen-derived hyperpolarisation and its NMR applications

Abstract Parahydrogen-induced polarisation (PHIP) is a nuclear spin hyperpolarisation technique employed to enhance NMR signals for a wide range of molecules. This is achieved by exploiting the chemical reactions of parahydrogen (para-H₂), the spin-0 isomer of H₂. These reactions break the molecular symmetry of para-H₂ in a way that can produce dramatically enhanced NMR signals for reaction products, and are usually catalysed by a transition metal complex. In this review, we discuss recent advances in novel homogeneous catalysts that can produce hyperpolarised products upon reaction with para-H₂. We also discuss hyperpolarisation attained in reversible reactions (termed signal amplification by reversible exchange, SABRE) and focus on catalyst developments in recent years that have allowed hyperpolarisation of a wider range of target molecules. In particular, recent examples of novel ruthenium catalysts for trans and geminal hydrogenation, metal-free catalysts, iridium sulfoxide-containing SABRE systems, and cobalt complexes for PHIP and SABRE are reviewed. Advances in this catalysis have expanded the types of molecules amenable to hyperpolarisation using PHIP and SABRE, and their applications in NMR reaction monitoring, mechanistic elucidation, biomedical imaging, and many other areas, are increasing

Toward optimizing and understanding reversible hyperpolarization of lactate esters relayed from para-hydrogen

Abstract The SABRE-Relay hyperpolarization method is used to enhance the ¹H and ¹³C NMR signals of lactate esters, which find use in a wide range of medical, pharmaceutical, and food science applications. This is achieved by the indirect relay of magnetization from para-hydrogen, a spin isomer of dihydrogen, to OH-containing lactate esters via a SABRE-hyperpolarized NH intermediary. This delivers ¹H and ¹³C NMR signal enhancements as high as 245- and 985-fold, respectively, which makes the lactate esters far more detectable using NMR. DFT-calculated J-couplings and spin dynamics simulations indicate that, while polarization can be transferred from the lactate OH to other ¹H nuclei via the J-coupling network, incoherent mechanisms are needed to polarize the ¹³C nuclei at the 6.5 mT transfer field used. The resulting sensitivity boost is predicted to be of great benefit for the NMR detection and quantification of low concentrations (<mM) of lactate esters and could provide a useful precursor for the production of hyperpolarized lactate, a key metabolite

Ultrafast Laplace NMR to study metal–ligand interactions in reversible polarisation transfer from parahydrogen

Abstract Laplace Nuclear Magnetic Resonance (NMR) can determine relaxation parameters and diffusion constants, giving valuable information about molecular structure and dynamics. Information about relaxation times (T₁ and T₂) and the self-diffusion coefficient (D) can be extracted from exponentially decaying NMR signals by performing a Laplace transform, which is a different approach to traditional NMR involving Fourier transform of a free induction decay. Ultrafast Laplace NMR uses spatial encoding to collect the entire data set in just a single scan which provides orders of magnitude time savings. In this work we use ultrafast Laplace NMR D–T₂ correlation sequences to measure key relaxation (T₂) and diffusion (D) parameters of methanolic solutions containing pyridine. For the first time we combine this technique with the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE), which employs an iridium catalyst to reversibly transfer polarisation from parahydrogen, to boost the ¹H NMR signals of pyridine by up to 300-fold. We demonstrate use of ultrafast Laplace NMR to monitor changes in pyridine T₂ and D associated with ligation to the iridium SABRE catalyst and kinetic isotope exchange reactions. The combined 1440-fold reduction in experiment time and 300-fold ¹H NMR signal enhancement allow the determination of pyridine D coefficients and T₂ values at 25 mM concentrations in just 3 seconds using SABRE hyperpolarised ultrafast Laplace NMR

Reversible hyperpolarization of ketoisocaproate using sulfoxide‐containing polarization transfer catalysts

Abstract The substrate scope of sulfoxide‐containing magnetisation transfer catalysts is extended to hyperpolarize α‐ketoisocaproate and α‐ketoisocaproate‐1‐[¹³C]. This is achieved by forming [Ir(H)₂(κ²‐ketoisocaproate)(N‐heterocyclic carbene)(sulfoxide)] which transfers latent magnetism from p‐H₂ via the signal amplification by reversible exchange (SABRE) process. The effect of polarization transfer field on the formation of enhanced ¹³C magnetization is evaluated. Consequently, performing SABRE in a 0.5 μT field enabled most efficient magnetisation transfer. ¹³C NMR signals for α‐ketoisocaproate‐1‐[¹³C] in methanol‐d⁴ are up to 985‐fold more intense than their traditional Boltzmann derived signal intensity (0.8 % ¹³C polarisation). Single crystal X‐ray diffraction reveals the formation of the novel catalyst decomposition products [Ir(μ‐H)(H)₂(IMes)(SO(Ph)(Me)₂)]₂ and [(Ir(H)₂(IMes)(SO(Me)₂))₂(μ‐S)] when the sulfoxides methylphenylsulfoxide and dimethylsulfoxide are used respectively

Hyperpolarised NMR to aid molecular profiling of electronic cigarette aerosols

Abstract Signal amplification by reversible exchange (SABRE) hyperpolarisation is used to enhance the NMR signals of nicotine and acrolein in methanol-d₄ solutions of electronic cigarette aerosols. Consequently, detection of 74 μM nicotine is possible in just a single scan ¹H NMR spectrum. The first example of an aldehyde hyperpolarised using SABRE is demonstrated and we work towards novel real-world applications of SABRE-hyperpolarised NMR for chemical analysis