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

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 gamma-polyglutamic acid (PGA) as a safe nano-platform for molecular imaging. We prepared indium-111-labeled DTPA-G4/PEI/gamma-PGA, and evaluated the effectiveness as a nuclear imaging probe for sentinel lymph node (LN), the first LN that drains the primary tumor. In-111-DTPA-G4/PEI with strong cationic charge agglutinated with erythrocytes and showed extremely high cytotoxicity. By contrast, the anionic In-111-DTPA-G4/PEI/gamma-PGA had little agglutination activity with erythrocytes and no cytotoxicity, indicating their high biocompatibility. In-111-DTPA-G4/PEI/gamma-PGA was highly taken up by macrophage cells (high populations in LNs) comparable to In-111-DTPA-G4/PEI. The uptake mechanisms of In-111-DTPA-G4/PEI/gamma-PGA were suggested to be both phagocytosis and gamma-PGA-specific pathway. Upon administration of each In-111-labeled nano-platform into rat footpads intradermally, significantly higher radioactivity of In-111-DTPA-G4/PEI/gamma-PGA was observed in the first draining popliteal LN when compared with that of In-111-DTPA-G4/PEI. Moreover, In-111-DTPA-G4/PEI/gamma-PGA clearly visualized the sentinel LN with single photon emission computed tomography (SPECT) compared with In-111-DTPA-G4/PEI. Thus, In-111-DTPA-G4/PEI/gamma-PGA can be useful as a nano-platform for molecular imaging including sentinel LN imaging. (C) 2014 Elsevier B.V. All rights reserved.