PURPOSE: This study was conducted to evaluate feasibility of sunitinib-CLIO conjugate as a vascular endothelial growth factor receptor/platelet-derived growth factor receptor (VEGFR/PDGFR)-specific magnetic resonance (MR) probe. PROCEDURE: VEGFR/PDGFR-targeting MR probe was synthesized by conjugating cross-linked iron-oxide (CLIO) with tyrosine-kinase inhibitor (sunitinib). In VEGFR/PDGFR-positive (U118MG) and VEGFR/PDGFR-negative (HT29) cells and tumor models, conjugate-driven ΔR 2 was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates. RESULTS: ΔR 2 between sunitinib-CLIO-treated and non-treated cells was greater in U118MG (mean, 2.1/s) than in HT29 cells (1.0/s). In in vivo study, conjugate induced a greater ΔR 2 in U118MG (11.2/s) than HT29 tumors (5.9/s). Conjugate-induced R 2 changes were not correlated with degree of Gd-DTPA enhancement, demonstrating that tumor binding of sunitinib-CLIO was independent of enhanced permeability and retention effect. % area of Prussian-blue staining was greater in U118MG (8.5 %) than in HT29 (1.4 %). CONCLUSIONS: Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR.
PURPOSE: This study was conducted to evaluate feasibility of sunitinib-CLIO conjugate as a vascular endothelial growth factor receptor/platelet-derived growth factor receptor (VEGFR/PDGFR)-specific magnetic resonance (MR) probe. PROCEDURE: VEGFR/PDGFR-targeting MR probe was synthesized by conjugating cross-linked iron-oxide (CLIO) with tyrosine-kinase inhibitor (sunitinib). In VEGFR/PDGFR-positive (U118MG) and VEGFR/PDGFR-negative (HT29) cells and tumor models, conjugate-driven ΔR 2 was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates. RESULTS: ΔR 2 between sunitinib-CLIO-treated and non-treated cells was greater in U118MG (mean, 2.1/s) than in HT29 cells (1.0/s). In in vivo study, conjugate induced a greater ΔR 2 in U118MG (11.2/s) than HT29 tumors (5.9/s). Conjugate-induced R 2 changes were not correlated with degree of Gd-DTPA enhancement, demonstrating that tumor binding of sunitinib-CLIO was independent of enhanced permeability and retention effect. % area of Prussian-blue staining was greater in U118MG (8.5 %) than in HT29 (1.4 %). CONCLUSIONS:Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR.
Authors: Olga Potapova; A Douglas Laird; Michelle A Nannini; Angela Barone; Guangmin Li; Katherine G Moss; Julie M Cherrington; Dirk B Mendel Journal: Mol Cancer Ther Date: 2006-05 Impact factor: 6.261
Authors: Samit K Bhattacharya; Eric D Cox; John C Kath; Alan M Mathiowetz; Joel Morris; James D Moyer; Leslie R Pustilnik; Kris Rafidi; Daniel T Richter; Chunyan Su; Matthew D Wessel Journal: Biochem Biophys Res Commun Date: 2003-07-25 Impact factor: 3.575
Authors: Martin A Funovics; Barbara Kapeller; Christoph Hoeller; Henry S Su; Rainer Kunstfeld; Stephan Puig; Karin Macfelda Journal: Magn Reson Imaging Date: 2004-07 Impact factor: 2.546