August 13, 2008

Integrin-Targeting With RGD4C-TNF Fusion Protein

By Anonymous

Wang et al. from the Stanford University School of Medicine (CA) reported in the May issue of Molecular Cancer Therapeutics (2008;7:1044-1053) on the use of integrin alpha^sub v^beta^sub 3^ as a target for tumor-specific delivery of tumor necrosis factor-alpha (TNF). Cell reptor binding assay and microPET imaging verified that the fusion protein RGD4C-TNF bound specifically to alpha^sub v^beta^sub 3^. ^sup 64^Cu-DOTA-RGD4C-TNF was found to have significantly higher activity accumulation in integrin-positive tumors than ^sup 64^Cu-DOTA-TNF. The authors also found that tumor accumulation of ^sup 64^Cu-DOTA-RGD4C-TNF was effectively blocked by c(RGDyK) peptide in alpha^sub v^beta^sub 3^-positive tumor models, suggesting the alpha^sub v^beta^sub 3^ specificity of RGD4C-TNF fusion protein in vivo. RGD4C-TNF was also significantly more potent than TNF in inhibiting orthotopic MDA-MB-435 tumor growth. Ex vivo tissue staining confirmed the specific cytotoxicity of RGD4C-TNF against integrin-positive tumor cells and tumor vasculature. Molecular Cancer Therapeutics

Copyright Society of Nuclear Medicine Jul 2008

(c) 2008 Journal of Nuclear Medicine, The. Provided by ProQuest LLC. All rights Reserved.