title: Radiolabeled γ-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging.
abstract: 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. (111)In-DTPA-G4/PEI with strong cationic charge agglutinated with erythrocytes and showed extremely high cytotoxicity. By contrast, the anionic (111)In-DTPA-G4/PEI/γ-PGA had little agglutination activity with erythrocytes and no cytotoxicity, indicating their high biocompatibility. (111)In-DTPA-G4/PEI/γ-PGA was highly taken up by macrophage cells (high populations in LNs) comparable to (111)In-DTPA-G4/PEI. The uptake mechanisms of (111)In-DTPA-G4/PEI/γ-PGA were suggested to be both phagocytosis and γ-PGA-specific pathway. Upon administration of each (111)In-labeled nano-platform into rat footpads intradermally, significantly higher radioactivity of (111)In-DTPA-G4/PEI/γ-PGA was observed in the first draining popliteal LN when compared with that of (111)In-DTPA-G4/PEI. Moreover, (111)In-DTPA-G4/PEI/γ-PGA clearly visualized the sentinel LN with single photon emission computed tomography (SPECT) compared with (111)In-DTPA-G4/PEI. Thus, (111)In-DTPA-G4/PEI/γ-PGA can be useful as a nano-platform for molecular imaging including sentinel LN imaging.
authors.affiliation: Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.affiliation: Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Iwamiya
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Photon Medical Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Photon Medical Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohshima
authors.affiliation: Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyama Kitamachi, Higashinada-ku, Kobe 658-8558, Japan. Electronic address: tmukai@kobepharma-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000187:drug effects; D007205:Indium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000000981:diagnostic imaging*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D004369:Pentetic Acid / Q000737:chemistry; D010587:Phagocytosis / Q000187:drug effects; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D004369:Pentetic Acid
keywords: Molecular imaging; Nanoparticle; Self assembly; Sentinel lymph node; γ-Polyglutamic acid