@article{macculloch_browning_bedoya_mcbride_abdulmojeed_dedesma_goodson_rosen_chekmenev_yen_et al._2023, title={Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo}, volume={16-17}, ISSN={["2666-4410"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85168097895&partnerID=MN8TOARS}, DOI={10.1016/j.jmro.2023.100129}, abstractNote={Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. Biocompatible formulations of hyperpolarized [1-13C]pyruvate in, both, methanol-water mixtures, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe, and scalable molecular imaging.}, journal={JOURNAL OF MAGNETIC RESONANCE OPEN}, author={Macculloch, Keilian and Browning, Austin and Bedoya, David O. Guarin and Mcbride, Stephen J. and Abdulmojeed, Mustapha B. and Dedesma, Carlos and Goodson, Boyd M. and Rosen, Matthew S. and Chekmenev, Eduard Y. and Yen, Yi-Fen and et al.}, year={2023}, month={Dec} }
 @article{macculloch_browning_tomhon_lehmkuhl_chekmenev_theis_2023, title={Parahydrogen in Reversible Exchange Induces Long-Lived 15N Hyperpolarization of Anticancer Drugs Anastrozole and Letrozole}, volume={5}, ISSN={["1520-6882"]}, url={https://doi.org/10.1021/acs.analchem.2c04817}, DOI={10.1021/acs.analchem.2c04817}, abstractNote={Hyperpolarization modalities overcome the sensitivity limitations of NMR and unlock new applications. Signal amplification by reversible exchange (SABRE) is a particularly cheap, quick, and robust hyperpolarization modality. Here, we employ SABRE for simultaneous chemical exchange of parahydrogen and nitrile-containing anticancer drugs (letrozole or anastrozole) to enhance 15N polarization. Distinct substrates require unique optimal parameter sets, including temperature, magnetic field, or a shaped magnetic field profile. The fine tuning of these parameters for individual substrates is demonstrated here to maximize 15N polarization. After optimization, including the usage of pulsed μT fields, the 15N nuclei on common anticancer drugs, letrozole and anastrozole, can be polarized within 1-2 min. The hyperpolarization can exceed 10%, corresponding to 15N signal enhancement of over 280,000-fold at a clinically relevant magnetic field of 1 T. This sensitivity gain enables polarization studies at naturally abundant 15N enrichment level (0.4%). Moreover, the nitrile 15N sites enable long-lasting polarization storage with [15N]T1 over 9 min, enabling signal detection from a single hyperpolarization cycle for over 30 min.}, number={20}, journal={ANALYTICAL CHEMISTRY}, author={MacCulloch, Keilian and Browning, Austin and TomHon, Patrick and Lehmkuhl, Soeren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2023}, month={May} }
 @article{browning_macculloch_tomhon_mandzhieva_chekmenev_goodson_lehmkuhl_theis_2023, title={Spin dynamics of [1,2-C-13(2)]pyruvate hyperpolarization by parahydrogen in reversible exchange at micro Tesla fields}, volume={25}, ISSN={["1463-9084"]}, url={https://doi.org/10.1039/D3CP00843F}, DOI={10.1039/d3cp00843f}, abstractNote={Hyperpolarization of 13C-pyruvate via Signal Amplificaton By Reversibble Exchange (SABRE) is an important recent discovery because of both the relative simplicity of hyperpolarization and the central biological relevance of pyruvate as a biomolecular probe for in vitro or in vivo studies. Here, we analyze the [1,2-13C2]pyruvate-SABRE spin system and its field dependence theoretically and experimentally. We provide first-principles analysis of the governing 4-spin dihydride-13C2 Hamiltonian and numerical spin dynamics simulations of the 7-spin dihydride-13C2-CH3 system. The analytical and the numerical results are compared to matching systematic experiments. With these methods we unravel the observed spin state mixing of singlet states and triplet states at microTesla fields and we also analyze the dynamics during transfer from micro-Tesla field to high field for detection to understand the resulting spectra from the [1,2-13C2]pyruvate-SABRE system.}, number={24}, journal={PHYSICAL CHEMISTRY CHEMICAL PHYSICS}, author={Browning, Austin and Macculloch, Keilian and TomHon, Patrick and Mandzhieva, Iuliia and Chekmenev, Eduard Y. and Goodson, Boyd M. and Lehmkuhl, Soeren and Theis, Thomas}, year={2023}, month={Jun}, pages={16446–16458} }
 @article{nantogma_eriksson_adelabu_mandzhieva_browning_tomhon_warren_theis_goodson_chekmenev_2022, title={Interplay of Near-Zero-Field Dephasing, Rephasing, and Relaxation Dynamics and [1-C-13]Pyruvate Polarization Transfer Efficiency in Pulsed SABRE-SHEATH}, volume={11}, ISSN={["1520-5215"]}, url={https://doi.org/10.1021/acs.jpca.2c07150}, DOI={10.1021/acs.jpca.2c07150}, abstractNote={Hyperpolarized [1-13C]pyruvate is a revolutionary molecular probe enabling ultrafast metabolic MRI scans in 1 min. This technology is now under evaluation in over 30 clinical trials, which employ dissolution Dynamic Nuclear Polarization (d-DNP) to prepare a batch of the contrast agent; however, d-DNP technology is slow and expensive. The emerging SABRE-SHEATH hyperpolarization technique enables fast (under 1 min) and robust production of hyperpolarized [1-13C]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes. Here, we study the application of microtesla pulses to investigate their effect on C-13 polarization efficiency, compared to that of conventional SABRE-SHEATH employing a static field (∼0.4 μT), to provide the matching conditions of polarization transfer from parahydrogen-derived hydrides to the 13C-1 nucleus. Our results demonstrate that using square-microtesla pulses with optimized parameters can produce 13C-1 polarization levels of up to 14.8% (when detected, averaging over all resonances), corresponding to signal enhancement by over 122,000-fold at the clinically relevant field of 1.4 T. We anticipate that our results can be directly translated to other structurally similar biomolecules such as [1-13C]α-ketoglutarate and [1-13C]α-ketoisocaproate. Moreover, other more advanced pulse shapes can potentially further boost heteronuclear polarization attainable via pulsed SABRE-SHEATH.}, number={48}, journal={JOURNAL OF PHYSICAL CHEMISTRY A}, author={Nantogma, Shiraz and Eriksson, Shannon L. and Adelabu, Isaiah and Mandzhieva, Iuliia and Browning, Austin and TomHon, Patrick and Warren, Warren S. and Theis, Thomas and Goodson, Boyd M. and Chekmenev, Eduard Y.}, year={2022}, month={Nov} }
 @article{macculloch_tomhon_browning_akeroyd_lehmkuhl_chekmenev_theis_2021, title={Hyperpolarization of common antifungal agents with SABRE}, volume={6}, ISSN={["1097-458X"]}, url={https://doi.org/10.1002/mrc.5187}, DOI={10.1002/mrc.5187}, abstractNote={Signal amplification by reversible exchange (SABRE) is a robust and inexpensive hyperpolarization (HP) technique to enhance nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) signals using parahydrogen (pH2 ). The substrate scope of SABRE is continually expanding. Here, we present the polarization of three antifungal drugs (voriconazole, clotrimazole and fluconazole) and elicit the detailed HP mechanisms for 1 H and 15 N nuclei. In this exploratory work, 15 N polarization values of ~1% were achieved using 50% pH2 in solution of 3 mM catalyst and 60 mM substrate in perdeuterated methanol. All hyperpolarized 15 N sites exhibited long T1 in excess of 1 minute at a clinically relevant field of 1 T. Hyperpolarizing common drugs is of interest due to their potential biomedical applications as MRI contrast agents or to enable studies on protein dynamics at physiological concentrations. We optimize the polarization with respect to temperature and the polarization transfer field (PTF) for 1 H nuclei in the millitesla regime and for 15 N nuclei in the microtesla regime, which provides detailed insights into exchange kinetics and spin evolution. This work broadens the SABRE substrate scope and provides mechanistic and kinetic insights into the HP process.}, number={12}, journal={MAGNETIC RESONANCE IN CHEMISTRY}, publisher={Wiley}, author={MacCulloch, Keilian and Tomhon, Patrick and Browning, Austin and Akeroyd, Evan and Lehmkuhl, Soren and Chekmenev, Eduard Y. and Theis, Thomas}, year={2021}, month={Jun} }