Mol Imaging Biol. 2014 Jun;16(3):340-9 doi: 10.1007/s11307-013-0697-9. 2013 Nov 02.

Sunitinib--CLIO conjugate: a VEGFR/PDGFR-targeting active MR probe

Noh GT, Kim MH, Suh JY, Song Y, Lee CK, Baek JH, Lee YS, Cho G, Kim E, Kim YR, Cho HJ, Lim D, Kim JK.

Abstract

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.

PMID: 24185817