title: Nitroxyl radicals-modified dendritic poly(l-lysine) as a contrast agent for Overhauser-enhanced MRI.
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 PR25-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.
authors.affiliation: a Department of Applied Chemistry and Biochemistry , Graduate School of Science and Technology, Kumamoto University , 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555 , Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.forename: Risa
authors.initials: R
authors.lastname: Gokuden
authors.forename: Kazuto
authors.initials: K
authors.lastname: Watanabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Naganuma
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology*; D061848:Optical Imaging; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D005609:Free Radicals; D011107:Polylysine; D011092:Polyethylene Glycols
keywords: dendritic poly(l-lysine); free radicals; overhauser-enhanced MRI; polyethyleneglycol; tumor imaging