@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{adelabu_ettedgui_joshi_nantogma_chowdhury_mcbride_theis_sabbasani_chandrasekhar_sail_et al._2022, title={Rapid C-13 Hyperpolarization of the TCA Cycle Intermediate alpha-Ketoglutarate via SABRE-SHEATH}, volume={9}, ISSN={["1520-6882"]}, url={https://doi.org/10.1021/acs.analchem.2c02160}, DOI={10.1021/acs.analchem.2c02160}, abstractNote={α-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-13C,5-12C,D4]α-ketoglutarate with the future goal of utilizing its [1-13C]-hyperpolarized state for real-time metabolic imaging of α-ketoglutarate analytes and its downstream metabolites in vivo. The signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) hyperpolarization technique was used to create 9.7% [1-13C] polarization in 1 minute in this isotopologue. The efficient 13C hyperpolarization, which utilizes parahydrogen as the source of nuclear spin order, is also supported by favorable relaxation dynamics at 0.4 μT field (the optimal polarization transfer field): the exponential 13C polarization buildup constant Tb is 11.0 ± 0.4 s whereas the 13C polarization decay constant T1 is 18.5 ± 0.7 s. An even higher 13C polarization value of 17.3% was achieved using natural-abundance α-ketoglutarate disodium salt, with overall similar relaxation dynamics at 0.4 μT field, indicating that substrate deuteration leads only to a slight increase (∼1.2-fold) in the relaxation rates for 13C nuclei separated by three chemical bonds. Instead, the gain in polarization (natural abundance versus [1-13C]-labeled) is rationalized through the smaller heat capacity of the "spin bath" comprising available 13C spins that must be hyperpolarized by the same number of parahydrogen present in each sample, in line with previous 15N SABRE-SHEATH studies. Remarkably, the C-2 carbon was not hyperpolarized in both α-ketoglutarate isotopologues studied; this observation is in sharp contrast with previously reported SABRE-SHEATH pyruvate studies, indicating that the catalyst-binding dynamics of C-2 in α-ketoglutarate differ from that in pyruvate. We also demonstrate that 13C spectroscopic characterization of α-ketoglutarate and pyruvate analytes can be performed at natural 13C abundance with an estimated detection limit of 80 micromolar concentration × *%P13C. All in all, the fundamental studies reported here enable a wide range of research communities with a new hyperpolarized contrast agent potentially useful for metabolic imaging of brain function, cancer, and other metabolically challenging diseases.}, number={39}, journal={ANALYTICAL CHEMISTRY}, author={Adelabu, Isaiah and Ettedgui, Jessica and Joshi, Sameer M. and Nantogma, Shiraz and Chowdhury, Md Raduanul H. and McBride, Stephen and Theis, Thomas and Sabbasani, Venkata R. and Chandrasekhar, Mushti and Sail, Deepak and et al.}, year={2022}, month={Sep} }