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

• Published in: NMR in biomedicine Vol. 25; no. 1; pp. 113 - 122
• Main Authors: Yaligar, J., Thakur, S. B., Bokacheva, L., Carlin, S., Thaler, H. T., Rizwan, A., Lupu, M. E., Wang, Y., Matei, C. C., Zakian, K. L., Koutcher, J. A.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2012
• Subjects: Animals; Biomarkers, Tumor - metabolism; Cell Hypoxia; Contrast Media; DCE MRI; Dunning R3327-AT; Dunning R3327-H; Immunohistochemistry; lactate; Lactic Acid - metabolism; Magnetic Resonance Imaging - methods; Magnetic Resonance Spectroscopy - methods; Male; MRSI; Necrosis; Neoplasm Invasiveness; prostate; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Rats; Sel-MQC; Tumor Burden
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.1723

Longitudinal studies of lactate MRSI and dynamic contrast‐enhanced MRI were performed at 4.7 T in two prostate tumor models grown in rats, Dunning R3327‐AT (AT) and Dunning R3327‐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 1–5). Lactate concentration was determined using selective multiple quantum coherence MRSI with the phantom substitution method. Tumor enhancement after the administration of gadolinium diethylenetriaminepenta‐acetic acid 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, the 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) and 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 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 tumors. Copyright © 2011 John Wiley & Sons, Ltd. Lactate is not detected in small Dunning R3327‐AT tumors, but increases with growth and subsequently decreases. The spatial distribution of lactate is very heterogeneous in R3327‐AT tumors. This increase in lactate in R3327‐AT tumors occurs with a concomitant decrease in Akep and evolving differences in perfusion between the rim and core, indicating poorer perfusion. Lactate is not detected in slow‐growing Dunning R3327‐H tumors, suggesting that it is a potential marker of aggressive tumors.