TY - JOUR
T1 - Radiolabeled γ-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging
AU - Sano, Kohei
AU - Iwamiya, Yuriko
AU - Kurosaki, Tomoaki
AU - Ogawa, Mikako
AU - Magata, Yasuhiro
AU - Sasaki, Hitoshi
AU - Ohshima, Takashi
AU - Maeda, Minoru
AU - Mukai, Takahiro
N1 - Funding Information:
This research was supported by the Grant-in-Aid for Scientific Research (B) ( 24390294 ) and for Research Activity Start-up ( 21890179 ) from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) . We would like to thank Nihon Medi-Physics, Tokyo, Japan, for donating the 111 InCl 3 . The mouse macrophage cell line, RAW264 (RCB0535), was provided by the RIKEN BRC.
Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2014/11/28
Y1 - 2014/11/28
N2 - We established a ternary anionic complex constructed with polyamidoamine dendrimer (4th generation; G4) modified with chelating agents (diethylenetriamine pentaacetic acid (DTPA) derivative), polyethyleneimine (PEI), and γ-polyglutamic acid (PGA) as a safe nano-platform for molecular imaging. We prepared indium-111-labeled DTPA-G4/PEI/γ-PGA, and evaluated the effectiveness as a nuclear imaging probe for sentinel lymph node (LN), the first LN that drains the primary tumor. 111In-DTPA-G4/PEI with strong cationic charge agglutinated with erythrocytes and showed extremely high cytotoxicity. By contrast, the anionic 111In-DTPA-G4/PEI/γ-PGA had little agglutination activity with erythrocytes and no cytotoxicity, indicating their high biocompatibility. 111In-DTPA-G4/PEI/γ-PGA was highly taken up by macrophage cells (high populations in LNs) comparable to 111In-DTPA-G4/PEI. The uptake mechanisms of 111In-DTPA-G4/PEI/γ-PGA were suggested to be both phagocytosis and γ-PGA-specific pathway. Upon administration of each 111In-labeled nano-platform into rat footpads intradermally, significantly higher radioactivity of 111In-DTPA-G4/PEI/γ-PGA was observed in the first draining popliteal LN when compared with that of 111In-DTPA-G4/PEI. Moreover, 111In-DTPA-G4/PEI/γ-PGA clearly visualized the sentinel LN with single photon emission computed tomography (SPECT) compared with 111In-DTPA-G4/PEI. Thus, 111In-DTPA-G4/PEI/γ-PGA can be useful as a nano-platform for molecular imaging including sentinel LN imaging.
AB - We established a ternary anionic complex constructed with polyamidoamine dendrimer (4th generation; G4) modified with chelating agents (diethylenetriamine pentaacetic acid (DTPA) derivative), polyethyleneimine (PEI), and γ-polyglutamic acid (PGA) as a safe nano-platform for molecular imaging. We prepared indium-111-labeled DTPA-G4/PEI/γ-PGA, and evaluated the effectiveness as a nuclear imaging probe for sentinel lymph node (LN), the first LN that drains the primary tumor. 111In-DTPA-G4/PEI with strong cationic charge agglutinated with erythrocytes and showed extremely high cytotoxicity. By contrast, the anionic 111In-DTPA-G4/PEI/γ-PGA had little agglutination activity with erythrocytes and no cytotoxicity, indicating their high biocompatibility. 111In-DTPA-G4/PEI/γ-PGA was highly taken up by macrophage cells (high populations in LNs) comparable to 111In-DTPA-G4/PEI. The uptake mechanisms of 111In-DTPA-G4/PEI/γ-PGA were suggested to be both phagocytosis and γ-PGA-specific pathway. Upon administration of each 111In-labeled nano-platform into rat footpads intradermally, significantly higher radioactivity of 111In-DTPA-G4/PEI/γ-PGA was observed in the first draining popliteal LN when compared with that of 111In-DTPA-G4/PEI. Moreover, 111In-DTPA-G4/PEI/γ-PGA clearly visualized the sentinel LN with single photon emission computed tomography (SPECT) compared with 111In-DTPA-G4/PEI. Thus, 111In-DTPA-G4/PEI/γ-PGA can be useful as a nano-platform for molecular imaging including sentinel LN imaging.
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U2 - 10.1016/j.jconrel.2014.08.025
DO - 10.1016/j.jconrel.2014.08.025
M3 - Article
C2 - 25238958
AN - SCOPUS:84907701019
VL - 194
SP - 310
EP - 315
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -