Nitroxyl radicals-modified dendritic poly(l -lysine) as a contrast agent for Overhauser-enhanced MRI

Takuro Niidome, Risa Gokuden, Kazuto Watanabe, Takeshi Mori, Tatsuya Naganuma, Hideo Utsumi, Kazuhiro Ichikawa, Yoshiki Katayama

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    Overhauser-enhanced magnetic resonance imaging (OMRI), which is a double resonance technique, creates images of free radical distribution in animals by enhancing the water proton signal intensity by the overhauser effect. In this study, we constructed a contrast agent by combining PROXYL groups that have nitroxyl radicals with PEG-modified dendritic poly(l-lysine) that accumulates in the tumor by enhanced permeability and retention (EPR) effect. Addition of the PROXYL groups at the PEG chains termini on KG6 was advantageous in OMRI, because the ESR signal of the nitroxyl radical was maintained without decay caused by mobility restriction, even if the PROXYL groups were attached at 25 mol% on one molecule. After intramuscular injection of the molecule modified at 25 mol%, that is, PR25-PEG-KG6, a significant OMRI signal was observed at the injected site. However, no signal was detected in the tumor after intravenous injection of PR25-PEG-KG6 to a tumor-bearing mouse, although PR 25-PEG-KG6 itself accumulated in the tumor. The reason was that the nitroxyl radicals were immediately reduced in the blood after the injection, suggesting that use of stable nitroxyl radicals will enable detection of tumors by OMRI after intravenous injection.

    Original languageEnglish
    Pages (from-to)1425-1439
    Number of pages15
    JournalJournal of Biomaterials Science, Polymer Edition
    Volume25
    Issue number13
    DOIs
    Publication statusPublished - Sep 2 2014

    All Science Journal Classification (ASJC) codes

    • Biophysics
    • Bioengineering
    • Biomaterials
    • Biomedical Engineering

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