Mechanism of gadophrin-2 accumulation in tumor necrosis

Abstract

The molecular mechanism by which gadophrin‐2 targets necrotic tumor tissue was investigated. Biodistribution studies and magnetic resonance imaging (MRI) and histologic/autoradiographic correlation were performed in xenograft mouse models bearing human tumors (HT 29, WiDr, LX 1). Binding of gadophrin‐2 to DNA, lipids, or proteins was determined by fluorescence spectrophotometry. Protein binding was determined by dialysis and gel electrophoresis. Accumulation of gadophrin‐2 was low (<0.7% injected dose/g tissue at 24 hours after injection) in viable tumor but higher in necrotic tumor regions and was readily detectable by MRI. Within a given tumor, the agent preferentially localized in the periphery of necrotic areas. Within these regions gadophrin‐2 was bound to interstitial albumin and not other proteins, lipids, or DNA. Tumoral accumulation of gadophrin‐2 most likely occurs through its binding to plasma albumin and subsequent slow extravasation into the tumor interstitium.J. Magn. Reson. Imaging 1999;9:336–341.