Two-step in vivo tumor targeting by biotin- Conjugated antibodies and superparamagnetic nanoparticles assessed by magnetic resonance imaging at 1.5 T

Purpose: The purpose of this study was to assess two-step in vivo tumor targeting by specific biotin-conjugated antibodies and ultrasmall superparamagnetic iron oxide (USPIO)-anti-biotin nanoparticles as contrast agents for magnetic resonance imaging (MRI) at 1.5 T. Procedures: D430B human lymphoma cells, expressing the CD70 surface antigen, were injected either s.c. or i.v. to induce pseudo-metastases in NOD/SCID mice. Thirty micrograms of biotin-conjugated monoclonal anti-CD70 was injected i.v., followed 4 h later by 8 μmol Fe/Kg USPIO-anti-biotin. After 24 h, MRI was performed on T2* and b-FFE sequences. Signal intensity (SI) was calculated before and after USPIO-anti-biotin administration. Results: Subcutaneous xenografts showed a dishomogeneous 30% decrease in SI on T2* with anti-CD70+USPIO-anti-biotin treatment. Pseudo-metastatic xenografts showed a slight reduction in SI on T2*, but a 60% decrease in SI on b-FFE-weighted sequences. Prussian blue staining confirmed the presence of iron nanoparticles in the excised tumors. Conclusion: MRI at 1.5 T can detect tumors by a two-step in vivo biotin-based protocol, which may allow the targeting of any cell surface antigen.