The lactate dehydrogenase-A gene (LDH-A), whose product catalyzes the inter-conversion of pyruvate and lactate, is a known c-MYC-responsive gene¹. We used hyperpolarized [1-¹³C]pyruvate imaging to monitor tumor progression and regression in a murine breast cancer model that conditionally expresses the human c-MYC transgene in a doxycycline switchable manner. Previously, it was shown that this model could develop a secondary tumor even after the primary tumor regresses nearly fully following c-MYC deinduction². Hence, the purpose of this project was to monitor altered glycolytic metabolism by hyperpolarized metabolic MRI in this multi-stage mammary tumorigenesis animal model.Tumor grafts derived from a human c-MYC transgenic mouse were transplanted into one of the mammary glands of normal female FVB mice. Following the transplant, the mice were fed with chows containing doxycycline (doxy-chow) for deregulated c-MYC expression from the onset. After the formation of palpable tumors, we performed a baseline [1-¹³C]pyruvate imaging study and removed the doxy-chow from the diet (off-doxy) for tumor regression. In the span of 7 weeks, follow up studies were performed at multiple time points (4, 16, 33, 49 days after the baseline). ¹H images were also acquired to monitor morphological changes and to spatially register the ¹³C data. Changes in tumor volume over time were measured from the proton images.1) Morphological regression of the tumor (50% decrease in volume from the baseline) was observed as soon as 4 days after off-doxy (c-MYC deinduction) together with a 80% decreased lactate-to-pyruvate ratio (Figure 1). Lactate production further decreased until the 16^th day as shown in the ¹³C spectra and the lac/pyr image. Then, on the 33^rd day after off-doxy, an increase in the lactate-to-pyruvate ratio was observed, eventhough there were no apparent changes in the tumor volume at this point. Subsequently, a recurrent solid tumor mass was observed after 49 days post off-doxy with dramatically increased lactate production. 2) From a different animal, we observed a possible metastatic lesion forming in the mouse liver (44 days post off-doxy) together with a recurrent tumor in its primary tumor site (Figure 2). The ¹³C data showed high levels of alanine production only in the liver voxels.1) An increase in lactate-to-pyruvate ratio as measured by hyperpolarized [1-¹³C]pyruvate imaging was observed weeks before the formation of a secondary tumor, which recurred in a doxycycline independent manner. This observation suggets that when there is a secondary genetic mutation, of which LDH-A is a downstream target, then hyperpolarized metabolic MRI can detect the tumor recurrence much faster than conventional ¹H anatomical imaging. 2) Previously, a high rate of conversion from pyruvate to alanine has been observed in pre-tumor stage of c-MYC-induced liver cancer mice³. Our data suggests that hyperpolarized [1-¹³C]pyruvate imaging is capable of detecting possible liver metastasis even when conventional ¹H anatomical imaging fails to reveal the pathogenic lesions.We observed that hyperpolarized [1-¹³C]pyruvate metabolic imaging could detect the in vivo glycolytic alterations that occur following c-MYC transgene induction/deinduction at different stages of mammary tumor formation.