Assessment of tumor hypoxia and interstitial fluid pressure by gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging.

Abstract

Extensive hypoxia and high interstitial fluid pressure (IFP) in the primary tumor may cause resistance to radiation treatment and promote metastatic spread. The potential of gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the extent of hypoxia and the level of interstitial hypertension in tumors was investigated in this preclinical study. Twenty-three A-07 tumors were subjected to DCE-MRI and subsequent measurement of IFP and fraction of pimonidazole-positive hypoxic tissue (HF(Pim)). Parametric tumor images of K(trans), v(e), and V(b)(Tofts) (Tofts model) and of K(i) and V(b)(Patlak) (Patlak model) were produced by pharmacokinetic analyses of the DCE-MRI series. There was no correlation between IFP and HF(Pim) in the tumors. K(trans) and K(i) decreased significantly with increasing HF(Pim), whereas V(b)(Tofts) and V(b)(Patlak) increased significantly with increasing IFP. Information on both the extent of hypoxia and the level of interstitial hypertension in A-07 tumors can be derived from a single DCE-MRI series by using gadomelitol as contrast agent.