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RGD peptide-conjugated multimodal NaGdF4:Yb3+/Er3+ nanophosphors for upconversion luminescence, MR, and PET imaging of tumor angiogenesis.

Authors
Lee, J; Lee, TS; Ryu, J; Hong, S; Kang, M; Im, K; Kang, JH; Lim, SM; Park, S; Song, R
Citation
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 54(1):96-103, 2013
Journal Title
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
ISSN
0161-55051535-5667
Abstract
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 Er(3+)/Yb(3+) co-doped NaGdF(4) 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 NaGdF(4):Yb(3+)/Er(3+) UCNPs along with polyethylene glycol molecules and was consecutively radiolabeled with (124)I. 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 (124)I-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. (124)I-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 (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)I-labeled RGD-functionalized UCNPs have high specificity for α(v)β(3) 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.
MeSH terms
AnimalsCell Line, TumorDimerizationErbium/*chemistryFeasibility StudiesFluorides/*chemistryGadolinium/*chemistryGlioblastoma/*blood supply/diagnosis/pathology/radionuclide imagingHumansIntegrin alphaVbeta3/metabolismIodine Radioisotopes/diagnostic useLuminescent Agents/chemistryLuminescent MeasurementsMagnetic Resonance ImagingMiceMolecular Imaging/*methodsNanostructures/*diagnostic use/toxicityNeovascularization, PathologicOligopeptides/*chemistry/*diagnostic use/toxicityPolyethylene Glycols/chemistryPositron-Emission TomographyYtterbium/*chemistry
DOI
10.2967/jnumed.112.108043
PMID
23232276
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
박, 선
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