Papers

Peer-reviewed International journal
Oct 15, 2017

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.

Bioorganic & medicinal chemistry
  • Nurmaya Effendi
  • ,
  • Kazuma Ogawa
  • ,
  • Kenji Mishiro
  • ,
  • Takeshi Takarada
  • ,
  • Daisuke Yamada
  • ,
  • Yoji Kitamura
  • ,
  • Kazuhiro Shiba
  • ,
  • Takehiko Maeda
  • ,
  • Akira Odani

Volume
25
Number
20
First page
5576
Last page
5585
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1016/j.bmc.2017.08.025
Publisher
PERGAMON-ELSEVIER SCIENCE LTD

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.

Link information
DOI
https://doi.org/10.1016/j.bmc.2017.08.025
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28838832
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000413402100040&DestApp=WOS_CPL
ID information
  • DOI : 10.1016/j.bmc.2017.08.025
  • ISSN : 0968-0896
  • eISSN : 1464-3391
  • Pubmed ID : 28838832
  • Web of Science ID : WOS:000413402100040

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