Measurement of tumor interstitial volume fraction: method and implication for drug delivery

It is important to evaluate the tumor interstitial volume fraction that is accessible for drug accumulation during the distribution phase in order to determine the potential efficacy of cancer chemotherapy. In this study, we performed simulations of magnetic resonance imaging (MRI) signal intensity using a two-compartment tissue model for quantitative analyses of absolute interstitial volume measurements while we experimentally characterized a mouse tumor model with a dual MR contrast-agent method. Previously, consecutive intravenous injections of a strictly intravascular T1 contrast agent followed by an extravasating agent were used as a strategy for the quantification of both relative blood volume (Rel_BV) and relative interstitial volume (Rel_ITST) (Weissleder et al. Eur J Cancer 1998;34:1448-1454; Bogdanov et al. Neoplasia 1991;1:438-435). In the current study, we demonstrate that this approach can be further improved, and that it enables one to accurately evaluate both relative and absolute interstitial volumes. The animal data indicated that a significant difference exists between the absolute interstitial volume fractions of subcutaneously implanted MDA PCa 2b tumor and skeletal muscle tissue (27.5 +/- 9.1% and 15.9 +/- 0.7%, respectively (P < 0.05)), while only a minor difference was found for the absolute blood volumes (Abs_BV) (Kim et al. Magn Reson Med 2002;47:1110-1120) of these tissues.