Imaging breast cancer using hyperpolarized carbon-13 MRI

Abstract

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Intratumoral Distribution of Lactate and the Monocarboxylate Transporters 1 and 4 in Human Glioblastoma Multiforme and Their Relationships to Tumor Progression-Associated Markers

“…Furthermore, our findings indicate a possible connection between the distinct regional gene expression patterns of MCT1, EMT, stemness and dormancy markers with the regional lactate concentration. Recent examinations using hyperpolarized carbon-13 MRSI could also show a significant correlation between the lactate to pyruvate ratio and MCT1 expression in breast cancer [ 43 ]. Definitely, an exclusive contemplation of the regional lactate concentration will not allow any conclusion to be drawn concerning the molecular features of the tumor.…”

Tensor image enhancement and optimal multichannel receiver combination analyses for human hyperpolarized 13C MRSI

“…Figure 4B shows a data set from a brain tumor case (oligoastrocytoma) with relatively low raw SNR due to a long injection delay (114 s). Employing TRI with the optimum rank of (13,7,11,8) from a data matrix size (59, 10, 18, 24) resulted in an 8-fold aSNR gain, sufficient to recover the bicarbonate signal, which was at noise level in the absence of TRI.…”

Hyperpolarized 13C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer

“…The lactate and pyruvate SNR and the Lac/Pyr ratio in this patient at baseline were included in a previous feasibility study (12). therapy is frequently associated with pathologic complete response (20,21).…”