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Targeted multimodal nano-reporters for pre-procedural MRI and intra-operative image-guidance

Lee, Joonseok, Gordon, Andrew C., Kim, Hacksung, Park, Wooram, Cho, Soojeong, Lee, Byeongdu, Larson, Andrew C., Rozhkova, Elena A., Kim, Dong-Hyun
Biomaterials 2016 v.109 pp. 69-77
animal models, antibodies, hepatoma, image analysis, luminescence, magnetic resonance imaging, nanoparticles, planning, rats, resection, tissues
Multimodal-imaging probes offer a novel approach, which can provide detail diagnostic information for the planning of image-guided therapies in clinical practice. Here we report targeted multimodal Nd3+-doped upconversion nanoparticle (UCNP) imaging reporters, integrating both magnetic resonance imaging (MRI) and real-time upconversion luminescence imaging (UCL) capabilities within a single platform. Nd3+-doped UCNPs were synthesized as a core–shell structure showing a bright visible emission upon excitation at the near infrared (minimizing biological overheating and increasing tissue penetration depth) as well as providing strong MRI T2 contrast (high r2/r1 ratio). Transcatheter intra-arterial infusion of Nd3+-doped UCNPs conjugated with anti-CD44-monoclonal antibody allowed for high performance in vivo multimodal UCL and MR imaging of hepatocellular carcinoma (HCC) in an orthotopic rat model. The resulted in vivo multimodal imaging of Nd3+ doped core-shell UCNPs combined with transcatheter intra-arterial targeting approaches successfully discriminated liver tumors from normal hepatic tissues in rats for surgical resection applications. The demonstrated multimodal UCL and MRI imaging capabilities of our multimodal UCNPs reporters suggest strong potential for in vivo visualization of tumors and precise surgical guidance to fill the gap between pre-procedural imaging and intraoperative reality.