Mechanism of gadophrin-2 accumulation in tumor necrosis

The molecular mechanism by which gadophrin-2 targets necrotic tumor tissue was investigated. Biodistribution studies and magnetic resonance imaging (M RI) and histologic/autoradiographic correlation were performed in xenograft mouse models bearing human tumors (HT 29, WiDr. LX 1), Binding of gadophri n-2 to DNA, lipids, or proteins was determined by fluorescence spectrophoto metry, Protein binding was determined by dialysis and gel electrophoresis. Accumulation of gadophrin-2 was low (<0.7% injected dose/g tissue at 24 hou rs after injection) in viable tumor but higher in necrotic tumor regions an d was readily detectable by MRI, Within a given tumor, the agent preferenti ally localized in the periphery of necrotic areas. Within these regions gad ophrin-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, (C) 1999 Wiley-Liss, Inc.