h13C MRI Detects Stimulation of Distal Tumor Glycolytic Flux From Hepatic Ablation in a Breast Metastasis Model
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Goodwin, J. Scott
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CitationGoodwin, J. Scott. 2020. h13C MRI Detects Stimulation of Distal Tumor Glycolytic Flux From Hepatic Ablation in a Breast Metastasis Model. Doctoral dissertation, Harvard Medical School.
AbstractThermal ablation is an effective therapy for liver tumors, however there is evidence that it can stimulate tumor growth at distant sites via the HFG/c-Met pathway, which is also linked to tumor metabolism. We evaluated this effect in vivo using hyperpolarized 13C-pyruvate MRI.
Fisher rats were implanted with R3230 rat breast adenocarcinoma cells (n=28) and assigned to either: sham surgery, hepatic radiofrequency ablation (RFA), or hepatic RFA + adjuvant c-Met inhibition with PHA-665752 (single IP dose, 0.83 mg/kg at 24h post-RFA). MRI was performed 24h before and 72h after treatment, and the conversion of 13C-pyruvate into 13C-lactate within each tumor was quantified as lactate:pyruvate ratio (LPR).
Hepatic RFA alone resulted in increased growth of the distant tumor compared to sham (0.50±0.13 mm/day and 0.11±0.07 mm/day, respectively; p<0.0001). In the hepatic RFA + adjuvant PHA group, tumor growth rate declined immediately following PHA administration, with a post-treatment growth rate (0.06±0.13 mm/day) similar to the sham group (p=0.28). A significant increase in LPR was seen following hepatic RFA (p=0.02), while LPR was unchanged in the sham (p=0.10) and RFA+PHA (p=0.90) arms.
In vivo h13C-pyruvate MRI can detect hepatic RFA-induced increases in lactate conversion within a distant R3230 tumor, which is coupled with relatively increased tumor growth. Adjuvant inhibition of c-Met suppresses these off-target effects. The results highlight the potential for h13C-pyruvate MRI as a potential in vivo tool to detect lesions at risk for off-target RFA stimulation and suggest a possible role for adjuvant c-Met inhibition in such cases.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37365204