Assessment of microvascular density, extracellular volume fraction, and radiobiological hypoxia in human melanoma xenografts by dynamic contrast-enhanced MRI.
OBJECTIVE
To investigate whether gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may be a useful method for assessing fraction of radiobiologically hypoxic cells in tumors.


METHODS
A-07 and R-18 human melanoma xenografts were used as preclinical tumor models. DCE-MRI was performed at a voxel size of 0.23 x 0.47 x 2.0 mm(3). Tumor images of E . F (E is the initial extraction fraction of Gd-DTPA and F is blood perfusion) and lambda (the partition coefficient of Gd-DTPA) were produced by subjecting DCE-MRI series to Kety analysis. Microvascular density and extracellular volume fraction (ECVF) were determined by analysis of histological preparations. The fraction of radiobiologically hypoxic cells was measured by the paired survival curve method.


RESULTS
E . F correlated with microvascular density, and lambda correlated with ECVF. The fraction of hypoxic cells was approximately 6.5-fold higher in R-18 tumors than in A-07 tumors, consistent with the observation that A-07 tumors showed higher values for E . F and microvascular density and lower cell density (i.e., higher values for lambda and ECVF) than R-18 tumors.


CONCLUSIONS
E . F and lambda images obtained by Kety analysis of DCE-MRI series contain information that may be utilized to estimate the extent of radiobiological hypoxia in tumors.
Vestvik
Ida K
IK
Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
Egeland
Tormod A M
TA
Gaustad
Jon-Vidar
JV
Mathiesen
Berit
B
Rofstad
Einar K
EK
D000818:Animals; D002470:Cell Survival; D003287:Contrast Media / Q000494:pharmacology*; D005260:Female; D019786:Gadolinium DTPA / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008545:Melanoma / Q000098:blood supply* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology
D003287:Contrast Media; D019786:Gadolinium DTPA