Measurements of human breast cancer using magnetic resonance spectroscopy: a review of clinical measurements and a report of localized31P measurements of response to treatment

Abstract

A review of the literature has shown that in human breast tumours, large signals from phosphomonoesters (PME) and phosphodiesters (PDE) are evident. In serial measurements in 19 patients with breast cancer, a decrease in PME was significantly associated with a stable or responding disease (p = 0.017), and an increase in PME was associated with disease progression. Extract studies have shown PME to comprise of phosphoethanolamine (PEth) and phosphocholine (PCho), with the PEth to PCho ratio ranging from 1.3 to 12. The PCho content of high grade tumours was found to be higher than low grade tumours. In some animal models, changes in PCho have been shown to correlate with indices of cellular proliferation, and spheroid studies have shown a decrease in PCho content in spheroids with smaller growth fractions. A serial study of 25 patients with advanced primary breast tumours undergoing hormone, chemotherapy or radiotherapy treatments, showed that in this heterogenous group there were significant changes in metabolites that were seen during the first 3 weeks (range 2–4 weeks) of treatment, that correlated with volume change over this period, employed here as a measure of response. Changes in PME (p = 0.003), total phosphate (TP) (p = 0.008) and total nucleoside tri‐phosphate (TNTP) (p = 0.02) over 3 (±1) weeks were significantly associated with response, as were the levels of PME (p < 0.001), PDE (p = 0.01), TP (p = 0.001) and TNTP (p = 0.007) at week 3 (±1). PME at week 3 (±1) was also significantly associated with the best volume response to treatment (p = 0.03). A reproducibility analysis of results from the observation of normal breast metabolism in four volunteers showed a mean coefficient of variation of 25%, after correcting for changes resulting from the menstrual cycle. Reproducibility studies in four patients with breast cancer showed a mean coefficient of variation of 33%, with the reproducibility being better in patients measured on different days (difference in TP was −6%) compared with those measured on the same day (difference in TP was −29%). © 1998 John Wiley & Sons, Ltd.

Evaluation of total choline from in-vivo volume localized proton MR spectroscopy and its response to neoadjuvant chemotherapy in locally advanced breast cancer

“…The post-therapy histopathological investigations of Group III patients correlated well (~80% -11 out of 14 showed concordance) with the presence or absence of choline (Tables 3 and 4). Rapid decrease of phosphomonoesters (one of these is phosphocholine) has been observed in 31 P MRS study of breast carcinoma during effective chemotherapy (Glaholm et al, 1989;Leach et al, 1998).…”

“…The phosphocholine (PC) and phosphoethanolamine (PE) are the precursors in the synthesis of phosphatidylcholine (PCho) and phosphatidylethanolamine (PEth), respectively, and are also degradation products of phospholipid breakdown by phospholipase C. Several NMR studies have revealed high concentrations of phosphomonoesters (PC and PE) in human breast tumors (Sijens et al, 1988;Merchant et al, 1988;Glaholm et al, 1989;Degani, 1994;Katz-Brull et al, 1998;Leach et al, 1998). Smith et al (1991) have shown a strong association between the proliferation rate of a rat mammary tumour and the PC and GPC content of the tumour.…”

Metabolic assessment of the action of targeted cancer therapeutics using magnetic resonance spectroscopy

“…High levels of PMEs, PDEs and total choline (tCho) are observed in tumours by in vivo 31 P-and 1 H-MRS, which are characteristic metabolic features of cancer (Negendank, 1992;Leach et al, 1998). These changes are often reversed on successful treatment with chemo-or radiotherapy and are now being explored as biomarkers for tumour diagnosis, staging and clinical response monitoring Shah et al, 2006).…”

Changes in choline metabolism as potential biomarkers of phospholipase Cγ1 inhibition in human prostate cancer cells

“…Compared with normal tissues, tumors commonly display larger signals from phosphomonoesters (comprising phosphocholine and phosphoethanolamine) as detected by 31 P MRS and total choline (comprising choline + phosphocholine + glycerophosphocholine) as detected by 1 H MRS (22)(23)(24)(25).…”

“…The altered profiles of choline metabolites have been observed in many in vitro and in vivo experimental models (cells, tissues, and tumor xenografts) and in patients (22)(23)(24)(25)(26)(27)(28)(29). They are believed to be a consequence of increased rates of choline transport and phosphorylation and/or changes in levels of phospholipid metabolizing enzymes occurring in cancer relative to normal cells (30)(31)(32)(33).…”