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

Abstract

B reast cancer is the most common cancer in women, accounting for over 2 million new cases annually worldwide (1). Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancers and is defined by low or absent expression of hormone receptors and lack of amplification or overexpression of human epidermal growth factor receptor type 2 (HER2). Therefore, TNBC lacks any established targeted treatment options, such as endocrine or anti-HER2 therapy. Compared with other subtypes of breast cancer, TNBC has an adverse overall outcome, but it often shows good response to neoadjuvant chemotherapy (2). In contrast to adjuvant chemotherapy, neoadjuvant chemotherapy allows assessment of treatment response in situ and downstaging of the tumor prior to surgery (2). Furthermore, complete pathologic response after neoadjuvant chemotherapy is an important prognostic factor in patients with TNBC, as it is indicative of longer event-free and overall survival (3,4). Early prediction of pathologic complete response at imaging would assist patient care and has been demonstrated using several approaches, including multiparametric proton MRI, but it remains challenging owing to the low accuracy of these techniques (5,6). The delayed identification of nonresponders results in increased patient morbidity from side effects as well as a risk of metastases from chemoresistant cells; it also has substantial economic implications (7).

Non-invasive Differentiation of M1 and M2 Activation in Macrophages using Hyperpolarized13C MRS of Pyruvate and DHA at 1.47 Tesla

“…The power of dynamic metabolic probing using HP 13 C MR is compelling, as it allows measuring previously inaccessible metabolic reactions non-invasively. HP 13 C metabolic imaging is a rapidly growing field, and is now being used in multiple clinical trials across the globe, targeting several organs including brain, heart, prostate and kidney [46][47][48][49][50][51][52][53][54][55][56][57] . It is very likely that, given the constant improvements reported both on the acquisition and processing sides, this methodology will soon approach feasibility for widespread clinical adoption.…”

The use of hyperpolarised 13C-MRI in clinical body imaging to probe cancer metabolism

“… 50 The first study investigating hyperpolarised 13 C-MRI in different types of breast cancer and early response assessment in triple-negative breast cancer (TNBC) used IDEAL spiral CSI at a temporal resolution of 4 seconds for dynamic metabolic imaging. 43 , 56 Spectral-spatial excitation is increasingly being used in clinical hyperpolarised 13 C-MRI of the prostate and brain as it increases the signal-to-noise ratio for downstream metabolites that are less abundant than pyruvate, while preserving polarisation of the 13 C-pyruvate, and can be combined with echo-planar or spiral k-space trajectories. 57 – 59 …”

“… 14 , 68 Preliminary evidence exists for a reduction in lactate labelling in conjunction with a successful response to treatment in human prostate cancer, following androgen ablation and chemotherapy and in breast cancer after a single cycle of neoadjuvant chemotherapy. 56 , 69 …”

Comparison of 13C MRI of hyperpolarized [1‐13C]pyruvate and lactate with the corresponding mass spectrometry images in a murine lymphoma model

“…Hyperpolarized [1- 13 C]pyruvate has been used clinically with promising applications, such as disease staging in prostate cancer, 3,4 and for detecting tumor treatment response. 5,6 However, the transient nature of the hyperpolarization means that only relatively rapid metabolic reactions can be studied, and it is difficult to relate signal intensity to concentration, which means that typically only apparent first-order rate constants describing isotope flux are quoted rather than metabolically relevant fluxes. 7 Mass spectrometry imaging (MSI) of excised tissue sections acquires a mass spectrum for each pixel of the image.…”