RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 96
OP 103
DO 10.2967/jnumed.112.108043
VO 54
IS 1
A1 Lee, Junghan
A1 Lee, Tae Sup
A1 Ryu, Jiyoung
A1 Hong, Sukmin
A1 Kang, Moonsik
A1 Im, Kangbin
A1 Kang, Joo Hyun
A1 Lim, Sang Moo
A1 Park, Sun
A1 Song, Rita
YR 2013
UL http://jnm.snmjournals.org/content/54/1/96.abstract
AB 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.