RESUMO
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.
