Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

vitro cytotoxicity testing was performed for 3 d. Upconversion luminescence imaging of (cRGDyk)2-UCNP was performed on U87MG cells with a laboratory-made confocal microscope. In vivo small-animal PET and clinical 3-T T1-weighted MR imaging of 124I-labeled RGD–functionalized UCNPs was acquired with or without blocking of cyclic RGD peptide in a U87MG tumor model. Inductively coupled plasma mass spectrometry and biologic transmission electron microscopy were done to evaluate gadolinium concentration and UCNP localization, respectively. Results: Polymer-coated UCNPs and dimeric RGD–conjugated UCNPs were monodispersely synthesized, and those of hydrodynamic size were 30 6 8n m and 326 9 nm, respectively. (cRGDyk)2UCNPs have a low cytotoxic effect on cells. Upconversion luminescence signals of (cRGDyk)2-UCNP were specifically localized on the surface of U87MG cells. 124 I-c(RGDyk)2-UCNPs specifically accumulated in U87MG tumors (2.8 6 0.8 vs. 1.3 6 0.4 percentage injected dose per gram in the blocking experiment), and T1-weighted MR images showed significant positive contrast enhancement in U87MG tumors. Tumor localization of 124 I-c(RGDyk) 2-UCNPs was confirmed by inductively coupled plasma mass spectrometry and biologic transmission electron microscopy analysis. Conclusion: These results suggest that 124 Ilabeled RGD–functionalized UCNPs have high specificity for avb3 integrin–expressing U87MG tumor cells and xenografted tumor models. Multimodal UCNPs can be used as a platform nanoparticle with multimodal imaging for cancer-specific diagnoses.