Abstract

Understanding tumor vascular physiology is critically important for developing non-invasive, molecularly targeted diagnostic agents and therapies. In this study, using three different human prostate cancer xenografts (MDA PCa 2b, PC3, and LnCap), structural and physiological parameters of neoplastic vasculature and interstitum were explored with a widely available magnetic resonance imaging (MRI) pulse sequence (3D SPGR: spoiled gradient echo). Using dual injection technique employing two T1 contrast agents of different molecular masses (Weissleder, R., Cheng, H. C., Marecos, E., Kwong, K. K., Bogdanov, A., Jr. Eur. J. Cancer 34, 1448-1454 (1998).), steady state (SS) MRI measurements and dynamic contrast agent enhancement (DCE) MRI measurements were simultaneously acquired and analyzed using a two-compartment model for calculating parameters reflecting tumoral architecture and physiology. In particular, interstitial volume and vascular permeability were independently quantified using these two different MRI techniques. Relative vascular water exchange rate, calculated by the flip angle (FA) dependence of measured blood volume using SS technique, and vascular permeability of contrast agent, extrapolated from DCE MRI, were compared. It was found that the SS and DCE techniques were comparable and yielded similar qualitative results for extravascular compartment (interstitial volume). However, the permeability (water exchange rate and contrast agent vascular permeability) values were in disagreement. The results of MR studies are important for interpreting optical imaging results obtained using long-circulating of tumor-associated enzymatic activity.