Monitoring mammary tumor progression and effect of tamoxifen treatment in MMTV-PymT using MRI and magnetic resonance spectroscopy with hyperpolarized [1-13C]pyruvate

Abstract

Purpose: To use dynamic magnetic resonance spectroscopy (MRS) of hyperpolarized 13C-pyruvate to follow the progress over time in vivo of breast cancer metabolism in the MMTVPymT model, and to follow the response to the anti-estrogen drug tamoxifen. Methods: Tumor growth was monitored by anatomical MRI by measuring tumor volumes. Dynamic MRS of hyperpolarized 13C was used to measure an "apparent" pyruvate-to-lactate rate constant (kp) of lactate dehydrogenase (LDH) in vivo. Further, ex vivo pathology and in vitro LDH initial reaction velocity were evaluated. Results: Tamoxifen significantly halted the tumor growth measured as tumor volume by MRI. In the untreated animals, kp correlated with tumor growth. The kP was somewhat but not significantly lower in the treated group. Studies in vitro confirmed the effects of tamoxifen on tumor growth, and here the LDH reaction velocity was reduced significantly in the treated group. Conclusion: These hyperpolarized 13C MRS findings indicate that tumor metabolic changes affects kP. The measured kp did not relate to treatment response to the same extent as did tumor growth, histological evaluation, and in vitro determination of LDH activity.