Sunitinib-CLIO Conjugate: A VEGFR/PDGFR-Targeting Active MR Probe
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- Sunitinib-CLIO Conjugate: A VEGFR/PDGFR-Targeting Active MR Probe
- Noh, Gwang Tae; Kim, Mi-Hyun; Suh, Ji-Yeon; Song, Youngkyu; Lee, Chang Kyung; Baek, Jin Hee; Lee, Yong Seok; Cho, Gyunggoo; Kim, Eunju; Kim, Young Ro; Cho, Hyungjoon; Lim, Dongyeol; Kim, Jeong Kon
- Angiogenesis; Iron oxide; MR probe; PDGFR; VEGFR
- Issue Date
- MOLECULAR IMAGING AND BIOLOGY, v.16, no.3, pp.340 - 349
- 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.
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 Delta R (2) was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates.
Delta R (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 Delta R (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 %).
Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR.
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