biostudies-literatureNantogma SDivision of ChemistryBundesministerium für Bildung und ForschungNIBIB NIH HHSDeutsche ForschungsgemeinschaftB.E.S.T. Fluidsysteme GmbH I Swagelok StuttgartDeutschen Konsortium für Translationale KrebsforschungBiological and Environmental ResearchCouncil on grants of the President of the Russian FederationWayne State UniversityRussian Science FoundationAlbert-Ludwigs-Universität FreiburgNational Institute of Biomedical Imaging and Bioengineering770-780https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922715biostudies-literatureUnknown9(2)¹³C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of ¹³C nuclear spins that also need to be synchronized with MRI field gradient pulses. Here, we demonstrate sensing of hyperpolarized allyl [1-¹³C]pyruvate via the stimulated emission of radiation that mitigates the requirements currently blocking broader adoption. Specifically, ¹³C Radiofrequency Amplification by Stimulated Emission of Radiation (¹³C RASER) was obtained after pairwise addition of parahydrogen to a pyruvate precursor, detected in a commercial inductive detector with a quality factor (<i>Q</i>) of 32 for sample concentrations as low as 0.125 M with ¹³C polarization of 4%. Moreover, parahydrogen-induced polarization allowed for the preparation of a mixture of ketone and hemiketal forms of hyperpolarized allyl [1-¹³C]pyruvate, which are separated by 10 ppm in ¹³C NMR spectra. This is a good model system to study the simultaneous ¹³C RASER signals of multiple ¹³C species. This system models the metabolic production of hyperpolarized [1-¹³C]lactate from hyperpolarized [1-¹³C]pyruvate, which has a similar chemical shift difference. Our results show that ¹³C RASER signals can be obtained from both species simultaneously when the emission threshold is exceeded for both species. On the other hand, when the emission threshold is exceeded only for one of the hyperpolarized species, ¹³C stimulated emission is confined to this species only, therefore enabling the background-free detection of individual hyperpolarized ¹³C signals. The reported results pave the way to novel sensing approaches of ¹³C hyperpolarized pyruvate, potentially unlocking hyperpolarized ¹³C MRI on virtually any MRI system─an attractive vision for the future molecular imaging and diagnostics.ACS sensorsCarbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-&lt;sup&gt;13&lt;/sup&gt;C]Pyruvate.PMC10922715MK-2826.2022.1.3SCHM 3694/2-1R21 EB033872SFB147921-73-10105R01 EB029829R01EB029829CHE-1904780DE-SC0023334R21EB025313R21 EB02531313N16448SCHM 3694/1-122-43-04426R21EB033872Chukanov NVde Maissin HNelson CAdelabu IAbdurraheem AKoptyug IVTheis TSalnikov OGChekmenev EYNantogma SSchmidt ABAppelt SLehmkuhl SfalseCarbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-&lt;sup&gt;13&lt;/sup&gt;C]Pyruvate.¹³C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of ¹³C nuclear spins that also need to be synchronized with MRI field gradient pulses. Here, we demonstrate sensing of hyperpolarized allyl [1-¹³C]pyruvate via the stimulated emission of radiation that mitigates the requirements currently blocking broader adoption. Specifically, ¹³C Radiofrequency Amplification by Stimulated Emission of Radiation (¹³C RASER) was obtained after pairwise addition of parahydrogen to a pyruvate precursor, detected in a commercial inductive detector with a quality factor (<i>Q</i>) of 32 for sample concentrations as low as 0.125 M with ¹³C polarization of 4%. Moreover, parahydrogen-induced polarization allowed for the preparation of a mixture of ketone and hemiketal forms of hyperpolarized allyl [1-¹³C]pyruvate, which are separated by 10 ppm in ¹³C NMR spectra. This is a good model system to study the simultaneous ¹³C RASER signals of multiple ¹³C species. This system models the metabolic production of hyperpolarized [1-¹³C]lactate from hyperpolarized [1-¹³C]pyruvate, which has a similar chemical shift difference. Our results show that ¹³C RASER signals can be obtained from both species simultaneously when the emission threshold is exceeded for both species. On the other hand, when the emission threshold is exceeded only for one of the hyperpolarized species, ¹³C stimulated emission is confined to this species only, therefore enabling the background-free detection of individual hyperpolarized ¹³C signals. The reported results pave the way to novel sensing approaches of ¹³C hyperpolarized pyruvate, potentially unlocking hyperpolarized ¹³C MRI on virtually any MRI system─an attractive vision for the future molecular imaging and diagnostics.2024-01-01T00:00:00Z2024 Feb2025-04-04T08:51:23.124Z2025-04-04T08:51:23.124ZS-EPMC109227153819870910.1021/acssensors.3c02075