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.

• Authors: B Hofmann, A Bogdanov Jr, E Marecos, W Ebert, W Semmler, R Weissleder
• Journal: Journal of magnetic resonance imaging : JMRI (J Magn Reson Imaging) Vol. 9 Issue 2 Pg. 336-41 (Feb 1999) ISSN: 1053-1807 [Print] United States
• PMID: 10077034 (Publication Type: Journal Article)

Chemical References

• Mesoporphyrins
• Metalloporphyrins
• gadophrin-2

Topics

• Animals
• Humans
• Image Processing, Computer-Assisted
• Magnetic Resonance Imaging (methods)
• Mesoporphyrins (pharmacokinetics)
• Metalloporphyrins (pharmacokinetics)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms, Experimental (pathology)
• Tissue Distribution