Synthesis and evaluation of radioiodinated 1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging

Publication date: Available online 16 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Nurmaya Effendi, Kazuma Ogawa, Kenji Mishiro, Takeshi Takarada, Daisuke Yamada, Yoji Kitamura, Kazuhiro Shiba, Takehiko Maeda, Akira Odani
Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane tyrosine kinase receptor and it is upregulated in various malignant tumors. Radiolabeled PDGFRβ inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRβ. In this study, [¹²⁵I]-1-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl)quinoline-8-yl}piperidin-4-amine ([¹²⁵I]IIQP) and [¹²⁵I]-N-3-iodobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([¹²⁵I]IB-IQP) were designed and synthesized, and their potential as PDGFRβ imaging agents was evaluated. In cellular uptake experiments, [¹²⁵I]IIQP and [¹²⁵I]IB-IQP showed higher uptake by PDGFRβ-positive cells than by PDGFRβ-negative cells, and the uptake in PDGFRβ-positive cells was inhibited by co-culture with PDGFRβ ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRβ-positive), the tumor uptake of radioactivity at 1 h after the injection of [¹²⁵I]IIQP was significantly higher than that after the injection of [¹²⁵I]IB-IQP. These results indicated that [¹²⁵I]IIQP can be a suitable PDGFRβ imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRβ-targeted imaging agent with a higher signal / noise ratio.

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