Lactate MRSI and DCE MRI as surrogate markers of prostate tumor aggressiveness

Abstract

Longitudinal studies of lactate MR spectroscopic imaging (MRSI) and dynamic contrast-enhanced MR imaging (DCE-MRI) were performed at 4.7 T in two prostate tumor models grown in rats, the Dunning R3327-AT (AT) and Dunning H (H), to determine the potential of lactate and the perfusion/permeability parameter Akep as markers of tumor aggressiveness. Subcutaneous AT (n = 12) and H (n = 6) tumors were studied at different volumes between 100 and 2900 mm3 (Groups 1 to 5). Lactate concentration was determined from Selective Multiple Quantum Coherence (Sel-MQC) MRSI using phantom substitution method. Tumor enhancement after administration of Gd-DTPA was analyzed using the Brix-Hoffmann model and the Akep parameter was used as a measure of tumor perfusion/permeability. Lactate was not detected in the smallest AT tumors (Group 1; 100–270 mm3). In larger AT tumors, lactate concentration increased from 2.8 ± 1.0 mM (Group 2; 290–700 mm3) to 8.4 ± 2.9 mM (Group 3; 1000–1340 mm3), 8.2 ± 2.2 mM (Group 4; 1380–1750 mm3), and then decreased to 5.0 ± 1.7 mM (Group 5; 1900–2500 mm3) and was consistently higher in the tumor core than in the rim. Lactate was not detected in any of the Dunning H tumors. The mean tumor Akep values decreased with increasing volume in both tumor types, but were significantly higher in H tumors. In AT tumors, the Akep values were significantly higher in the rim than in the core. Histological hypoxic and necrotic fractions in AT tumors increased with volume from 0% in Group 1 to about 20% and 30%, respectively, in Group 5. Minimal amounts of hypoxia and necrosis were found in H tumors of all sizes. Thus the presence of lactate and heterogeneous perfusion/permeability are signatures of aggressive, metabolically deprived Dunning R3327-AT tumor, but not the slow-growing Dunning H tumor.

Catabolism of Exogenous Lactate Reveals It as a Legitimate Metabolic Substrate in Breast Cancer

“…A recent study measuring lactate accumulation and spatial distribution in prostate cancer compared the aggressive, anaplastic, fast-growing Dunning R3327-AT to the parental, well-differentiated, slow-growing Dunning R3327-H in animal models [86]. Similar to the findings in human solid tumors, the more aggressive AT tumor line showed significantly more lactate accumulation and necrosis, specifically in the tumor core [86].…”

Magic Angle Spinning NMR-Based Metabolic Profiling of Head and Neck Squamous Cell Carcinoma Tissues

“…49 Elevated level of alanine, which is also another important end product of glycolysis/glutaminolysis, was found in HNSCC and metastatic tissues and it has been found to be a major source of energy in tumor proliferation and growth. Recent studies reported that the change in lactate and alanine can act as an important parameter for monitoring tumor aggressiveness in prostate cancer 50 and prognosis for lung cancer. 51 We believe that monitoring the changes of these two metabolites could also be used as in-vivo diagnostic/prognostic marker in HNSCC.…”

Metabolic Imaging: A Link between Lactate Dehydrogenase A, Lactate, and Tumor Phenotype

“…The 1-dimensional (1D) lactate spectra from the 5-mm thick center slice were processed by a 1D Fourier transform, similar to our previous methodology (31). The absolute magnitude of the echo signal from the slice was fitted by a home-written program using Matlab® (The MathWorks) and normalized to the slice volume.…”

“…The sections were then stained with CD31 antibody (endothelial cell marker) and adjacent tumor sections were processed for H&E staining. Images of the sections were processed using Matlab® to estimate the fraction of tumor necrosis (31). …”