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 language | English |
|---|---|
| Pages (from-to) | 1425-1439 |
| Number of pages | 15 |
| Journal | Journal of Biomaterials Science, Polymer Edition |
| Volume | 25 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - Sep 2 2014 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Bioengineering
- Biomaterials
- Biomedical Engineering
Cite this
Nitroxyl radicals-modified dendritic poly(l -lysine) as a contrast agent for Overhauser-enhanced MRI. / Niidome, Takuro; Gokuden, Risa; Watanabe, Kazuto; Mori, Takeshi; Naganuma, Tatsuya; Utsumi, Hideo; Ichikawa, Kazuhiro; Katayama, Yoshiki.
In: Journal of Biomaterials Science, Polymer Edition, Vol. 25, No. 13, 02.09.2014, p. 1425-1439.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitroxyl radicals-modified dendritic poly(l -lysine) as a contrast agent for Overhauser-enhanced MRI
AU - Niidome, Takuro
AU - Gokuden, Risa
AU - Watanabe, Kazuto
AU - Mori, Takeshi
AU - Naganuma, Tatsuya
AU - Utsumi, Hideo
AU - Ichikawa, Kazuhiro
AU - Katayama, Yoshiki
PY - 2014/9/2
Y1 - 2014/9/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84906306601&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906306601&partnerID=8YFLogxK
U2 - 10.1080/09205063.2014.943538
DO - 10.1080/09205063.2014.943538
M3 - Article
C2 - 25088777
AN - SCOPUS:84906306601
VL - 25
SP - 1425
EP - 1439
JO - Journal of Biomaterials Science, Polymer Edition
JF - Journal of Biomaterials Science, Polymer Edition
SN - 0920-5063
IS - 13
ER -