Abstract: |
Longitudinal studies of lactate MRSI and dynamic contrast-enhanced MRI were performed at 4.7T 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 Ak ep as markers of tumor aggressiveness. Subcutaneous AT (n=12) and H (n=6) tumors were studied at different volumes between 100 and 2900mm 3 (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 Ak ep parameter was used as a measure of tumor perfusion/permeability. Lactate was not detected in the smallest AT tumors (Group 1; 100-270mm 3). In larger AT tumors, the lactate concentration increased from 2.8±1.0mm (Group 2; 290-700mm 3) to 8.4±2.9mm (Group 3; 1000-1340mm 3) and 8.2±2.2mm (Group 4; 1380-1750mm 3), and then decreased to 5.0±1.7mm (Group 5; 1900-2500mm 3), 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 Ak ep values decreased with increasing volume in both tumor types, but were significantly higher in H tumors. In AT tumors, the Ak ep 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. © 2011 John Wiley & Sons, Ltd. |