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

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Oncology

Background:

• Vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) are key targets in cancer therapy.
• Developing specific and active magnetic resonance (MR) probes for these receptors is crucial for effective cancer diagnosis and treatment monitoring.

Purpose of the Study:

• To evaluate the feasibility of using a sunitinib-cross-linked iron-oxide (CLIO) conjugate as a specific MR probe for VEGFR/PDGFR.
• To assess the active targeting capability and quantify VEGFR/PDGFR expression using this novel MR probe.

Main Methods:

• Synthesized a sunitinib-CLIO conjugate targeting VEGFR/PDGFR.
• Estimated conjugate-driven ΔR2 in VEGFR/PDGFR-positive (U118MG) and negative (HT29) cells and tumors, using CLIO as a control.
• Quantified tumor-binding conjugates using Prussian-blue staining.

Main Results:

• Sunitinib-CLIO demonstrated significantly higher ΔR2 in VEGFR/PDGFR-positive U118MG cells (2.1/s) and tumors (11.2/s) compared to negative HT29 cells (1.0/s) and tumors (5.9/s).
• Tumor binding was independent of the enhanced permeability and retention effect, as indicated by a lack of correlation with Gd-DTPA enhancement.
• Prussian-blue staining confirmed greater conjugate binding in U118MG tumors (8.5%) versus HT29 tumors (1.4%).

Conclusions:

• Sunitinib-CLIO conjugate functions as an active MR probe for quantifying VEGFR/PDGFR.
• This conjugate offers a specific and effective method for molecular imaging of VEGFR/PDGFR expression in tumors.