Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues

Abstract

The goal of this study was to investigate the use of lactate and alanine as metabolic biomarkers of prostate cancer using (1)H high-resolution magic angle spinning (HR-MAS) spectroscopy of snap-frozen transrectal ultrasound (TRUS)-guided prostate biopsy tissues. A long-echo-time rotor-synchronized Carr-Purcell-Meiboom-Gill (CPMG) sequence including an electronic reference to access in vivo concentrations (ERETIC) standard was used to determine the concentrations of lactate and alanine in 82 benign and 16 malignant biopsies (mean 26.5% +/- 17.2% of core). Low concentrations of lactate (0.61 +/- 0.28 mmol/kg) and alanine (0.14 +/- 0.06 mmol/kg) were observed in benign prostate biopsies, and there was no significant difference between benign predominantly glandular (N = 54) and stromal (N = 28) biopsies between patients with (N = 38) and without (N = 44) a positive clinical biopsy. In biopsies containing prostate cancer there was a highly significant (P < 0.0001) increase in lactate (1.59 +/- 0.61 mmol/kg) and alanine (0.26 +/- 0.07 mmol/kg), and minimal overlap with lactate concentrations in benign biopsies. This study demonstrates for the first time very low concentrations of lactate and alanine in benign prostate biopsy tissues. The significant increase in the concentration of both lactate and alanine in biopsy tissue containing as little as 5% cancer could be exploited in hyperpolarized (13)C spectroscopic imaging (SI) studies of prostate cancer patients.

Figures

FIG. 1

Representative 1H HR-MAS spectra and corresponding histopathologic sections of (a) benign predominantly glandular (40% glandular, 60% stroma) and (b) prostate cancer (70% Gleason 3+3) biopsy tissues. The major metabolites, TSP, and ERETIC resonances are shown. Lactate to alanine regions from 144-ms CPMG spectra are shown inset.

FIG. 2

a: Lactate concentrations in benign and malignant prostate biopsy tissues. Minimal overlap (15/82) was observed between benign and cancer tissues. b: Alanine concentrations in benign and malignant prostate biopsy tissues. Moderate overlap (39/82) was observed between benign and cancer tissue.