Radiolabeled γ-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging

Kohei Sano, Yuriko Iwamiya, Tomoaki Kurosaki, Mikako Ogawa, Yasuhiro Magata, Hitoshi Sasaki, Takashi Ohshima, Minoru Maeda, Takahiro Mukai

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)310-315
Number of pages6
JournalJournal of Controlled Release
Volume194
DOIs
Publication statusPublished - Nov 28 2014

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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