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Recently, we have shown that not only the amount of lactate produced, as a consequence of the Warburg effect, but also its efflux out of the cell, is a critical marker of RCC aggressiveness and differentiating RCCs from benign renal tumors. Enzymatic conversions can now be measured in situ with hyperpolarized (HP) <jats:sup>13<\/jats:sup>C magnetic resonance (MR) on a sub\u2010minute time scale. Using RCC models, we have shown that this technology can interrogate in real time both lactate production and compartmentalization, which are associated with tumor aggressiveness. The dynamic HP MR data have enabled us to robustly characterize parameters that have been elusive to measure directly in intact living cells and murine tumors thus far. Specifically, we were able to measure the same intracellular lactate longitudinal relaxation time in three RCC cell lines of 16.42 s, and lactate efflux rate ranging from 0.14 to 0.8 s<jats:sup>\u22121<\/jats:sup> in the least to the most aggressive RCC cell lines and correlate it to monocarboxylate transporter isoform 4 expression. We also analyzed dynamic HP lactate and pyruvate data from orthotopic murine RCC tumors using a simplified one\u2010compartment model, and showed comparable apparent pyruvate to lactate conversion rate (<jats:italic>k<\/jats:italic><jats:sub><jats:italic>PL<\/jats:italic><\/jats:sub>) values with those measured in vitro. This kinetic modeling was then extended to characterize the lactate dynamics in patient\u2010derived living RCC tissue slices; and even without direct measurement of the extracellular lactate signal the efflux parameter was still assessed and was distinct between the benign renal tumors and RCCs. Across all these preclinical models, the rate parameters of <jats:italic>k<\/jats:italic><jats:sub><jats:italic>PL<\/jats:italic><\/jats:sub> and lactate efflux correlated to cancer aggressiveness, demonstrating the validity of our modeling approach for noninvasive assessment of RCC aggressiveness.<\/jats:p>","DOI":"10.1002\/nbm.4467","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T21:51:11Z","timestamp":1610488271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Modeling hyperpolarized lactate signal dynamics in cells, patient\u2010derived tissue slice cultures and murine models"],"prefix":"10.1002","volume":"34","author":[{"given":"Fayyaz","family":"Ahamed","sequence":"first","affiliation":[{"name":"University of California, Berkeley  Berkeley California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Van 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