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To date, however, most studies have used [1\u2010\n 1<\/jats:sup>\n 3<\/jats:sup>\n C]pyruvate and dynamic nuclear polarization (dDNP). Here, we establish efficient hyperpolarization (HP) of protio and partially\u2010deuterated [1\u2010\n 1<\/jats:sup>\n 3<\/jats:sup>\n C]ketoisocaproate (KIC) using Spin\u2010Lock\u2010Induced\u2010Crossing\u2010Signal Amplification by Reversible Exchange (SLIC\u2010SABRE), a high\u2010throughput, uncomplex and low\u2010cost method based on parahydrogen. We demonstrate\n 13<\/jats:sup>\n C polarization up to \u224828% and T\n 1<\/jats:sub>\n relaxation times > 200 s at 1 T in methanol\u2010d\n 4<\/jats:sub>\n . A rapid purification procedure allowed us to obtain biocompatible formulations with \u224811%\n 13<\/jats:sup>\n C polarization at the time of injection, sufficient for in cellulo and in vivo studies. We found that branched\u2010chain\u2010amino\u2010acid transaminase (BCAT) activity leads to HP [1\u2010\n 1<\/jats:sup>\n 3<\/jats:sup>\n C]leucine formation exclusively in BCAT1\u2010high MDA\u2010MB231 breast\u2010cancer cells, but not in BCAT1\u2010low MCF7 or PyB6 cells. In a proof\u2010of\u2010concept in vivo experiment,\n 13<\/jats:sup>\n C magnetic resonance spectroscopy imaging of the healthy mouse brain detected [1\u2010\n 13<\/jats:sup>\n C]leucine formation after intravenous injection of SABRE [1\u2010\n 13<\/jats:sup>\n C]KIC\u2010d\n 2<\/jats:sub>\n . Our results demonstrate that [1\u2010\n 13<\/jats:sup>\n C]KIC\u2010d\n 2<\/jats:sub>\n provides a sensitive readout of BCAT1\u2010dependent metabolism and that SLIC\u2010SABRE can rapidly generate this probe for\n 13<\/jats:sup>\n C MRI, extending accessible parahydrogen\u2010based hyperpolarization to amino\u2010acid pathways relevant to cancer biology and chemoresistance.\n <\/jats:p>","DOI":"10.1002\/advs.76213","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:40:03Z","timestamp":1782211203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hyperpolarization of [1\u2010\n 13<\/sup>\n C]Ketoisocaproate\u2010d\n 2<\/sub>\n by Reversible Exchange with Parahydrogen Enables Profiling of Branched\u2010Chain\u2010Amino\u2010Acid Metabolism in Cellulo and in 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