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

Autor: Nurmaya Effendi, Kazuhiro Shiba, Yoji Kitamura, Kenji Mishiro, Akira Odani, Takehiko Maeda, Kazuma Ogawa, Daisuke Yamada, Takeshi Takarada
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Biodistribution
Stereochemistry
medicine.drug_class
Cell Survival
Clinical Biochemistry
PDGFRβ
Pharmaceutical Science
Mice
Nude
Molecular imaging
Tyrosine kinase inhibitor
Biochemistry
Receptor tyrosine kinase
Tyrosine-kinase inhibitor
Iodine Radioisotopes
Receptor
Platelet-Derived Growth Factor beta
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
Growth factor receptor
Cell Line
Tumor
Drug Discovery
medicine
Animals
Humans
Tissue Distribution
Molecular Biology
Mice
Inbred BALB C
biology
Molecular Structure
Radiotracer
Chemistry
Organic Chemistry
Mammary Neoplasms
Experimental
Transmembrane protein
Imaging agent
030104 developmental biology
030220 oncology & carcinogenesis
Molecular Probes
biology.protein
MCF-7 Cells
Molecular Medicine
Female
Platelet-derived growth factor receptor
Zdroj: Bioorganic and Medicinal Chemistry. 25(20):5576-5585
ISSN: 0968-0896
Popis: 金沢大学新学術創成研究機構
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 1h 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. © 2017.
Embargo Period 12 months
Databáze: OpenAIRE
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