TY - JOUR T1 - RGD Peptide–Conjugated Multimodal NaGdF<sub>4</sub>:Yb<sup>3+</sup>/Er<sup>3+</sup> Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 96 LP - 103 DO - 10.2967/jnumed.112.108043 VL - 54 IS - 1 AU - Junghan Lee AU - Tae Sup Lee AU - Jiyoung Ryu AU - Sukmin Hong AU - Moonsik Kang AU - Kangbin Im AU - Joo Hyun Kang AU - Sang Moo Lim AU - Sun Park AU - Rita Song Y1 - 2013/01/01 UR - http://jnm.snmjournals.org/content/54/1/96.abstract N2 - Multimodal nanoparticles have been extensively studied for target-specific imaging and therapy of various diseases, including cancer. In this study, radiolabeled arginine-glycine-aspartic acid (RGD)–functionalized Er3+/Yb3+ co-doped NaGdF4 upconversion nanophosphors (UCNPs) were synthesized and evaluated as a multimodal PET/MR/optical probe with tumor angiogenesis–specific targeting properties. Methods: A dimeric cyclic RGDyk ((cRGDyk)2) peptide was conjugated to polyacrylic acid–coated NaGdF4:Yb3+/Er3+ UCNPs along with polyethylene glycol molecules and was consecutively radiolabeled with 124I. In 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 ± 8 nm and 32 ± 9 nm, respectively. (cRGDyk)2-UCNPs have a low cytotoxic effect on cells. Upconversion luminescence signals of (cRGDyk)2-UCNP were specifically localized on the surface of U87MG cells. 124I-c(RGDyk)2-UCNPs specifically accumulated in U87MG tumors (2.8 ± 0.8 vs. 1.3 ± 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 124I-c(RGDyk)2-UCNPs was confirmed by inductively coupled plasma mass spectrometry and biologic transmission electron microscopy analysis. Conclusion: These results suggest that 124I-labeled RGD–functionalized UCNPs have high specificity for αvβ3 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. ER -