title: Lactate MRSI and DCE MRI as surrogate markers of prostate tumor aggressiveness.
abstract: 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 Ak(ep) as markers of tumor aggressiveness. Subcutaneous AT (n = 12) and H (n = 6) tumors were studied at different volumes between 100 and 2900 mm(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; 100-270 mm(3) ). In larger AT tumors, the lactate concentration increased from 2.8 ± 1.0 mm (Group 2; 290-700 mm(3)) to 8.4 ± 2.9 mm (Group 3; 1000-1340 mm(3)) and 8.2 ± 2.2 mm (Group 4; 1380-1750 mm(3) ), and then decreased to 5.0 ± 1.7 mm (Group 5; 1900-2500 mm(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.
authors: Department of Medical Physics, New York, NY, United States.
authors: J
authors: J
authors: Yaligar
authors: Department of Medical Physics, New York, NY, United States.|Department of Radiology, New York, NY, United States.
authors: S B
authors: SB
authors: Thakur
authors: Department of Medical Physics, New York, NY, United States.
authors: L
authors: L
authors: Bokacheva
authors: Department of Medical Physics, New York, NY, United States.
authors: S
authors: S
authors: Carlin
authors: Department of Epidemiology and Biostatistics, New York, NY, United States.
authors: H T
authors: HT
authors: Thaler
authors: Department of Medical Physics, New York, NY, United States.
authors: A
authors: A
authors: Rizwan
authors: Department of Medical Physics, New York, NY, United States.
authors: M E
authors: ME
authors: Lupu
authors: Department of Medical Physics, New York, NY, United States.
authors: Y
authors: Y
authors: Wang
authors: Department of Radiology, New York, NY, United States.
authors: C C
authors: CC
authors: Matei
authors: Department of Medical Physics, New York, NY, United States.|Department of Radiology, New York, NY, United States.
authors: K L
authors: KL
authors: Zakian
authors: Department of Medical Physics, New York, NY, United States.|Department of Radiology, New York, NY, United States.|Department of Medicine Memorial Sloan-Kettering Cancer Center, New York, NY, United States.
authors: J A
authors: JA
authors: Koutcher
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