title: Sunitinib--CLIO conjugate: a VEGFR/PDGFR-targeting active MR probe.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Chemistry, Sejong University, Seoul, 143-747, South Korea.
authors.forename: Gwang Tae
authors.initials: GT
authors.lastname: Noh
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Suh
authors.forename: Youngkyu
authors.initials: Y
authors.lastname: Song
authors.forename: Chang Kyung
authors.initials: CK
authors.lastname: Lee
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Baek
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Gyunggoo
authors.initials: G
authors.lastname: Cho
authors.forename: Eunju
authors.initials: E
authors.lastname: Kim
authors.forename: Young Ro
authors.initials: YR
authors.lastname: Kim
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Cho
authors.forename: Dongyeol
authors.initials: D
authors.lastname: Lim
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D046529:Microscopy, Electron, Transmission; D015335:Molecular Probes; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects*; D000077210:Sunitinib
chemical_list: D005290:Ferric Compounds; D007211:Indoles; D015335:Molecular Probes; D011758:Pyrroles; C000499:ferric oxide; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib