Synthesis and Bioevaluation of Iodine-131 Directly Labeled Cyclic RGD-PEGylated Gold Nanorods for Tumor-Targeted Imaging

Abstract

Introduction Radiolabeled gold nanoparticles play an important role in biomedical application. The aim of this study was to prepare iodine-131 (131I)-labeled gold nanorods (GNRs) conjugated with cyclic RGD and evaluate its biological characteristics for targeted imaging of integrin αvβ3-expressing tumors. Methods HS-PEG(5000)-COOH molecules were applied to replace CTAB covering the surface of bare GNRs for better biocompatibility, and c(RGDfK) peptides were conjugated onto the carboxyl terminal of GNR-PEG-COOH via EDC/NHS coupling reactions. The nanoconjugate was characterized, and 131I was directly tagged on the surface of GNRs via AuI bonds for SPECT/CT imaging. We preliminarily studied the characteristics of the probe and its feasibility for tumor-targeting SPECT/CT imaging. Results The [131I]GNR-PEG-cRGD probe was prepared in a simple and rapid manner and was stable in both PBS and fetal bovine serum. It targeted selectively and could be taken up by tumor cells mainly via integrin αvβ3-receptor-mediated endocytosis. In vivo imaging, biodistribution, and autoradiography results showed evident tumor uptake in integrin αvβ3-expressing tumors. Conclusions These promising results showed that this smart nanoprobe can be used for angiogenesis-targeted SPECT/CT imaging. Furthermore, the nanoprobe possesses a remarkable capacity for highly efficient photothermal conversion in the near-infrared region, suggesting its potential as a multifunctional theranostic agent.

Gold Nanoparticles and Nanorods in Nuclear Medicine: A Mini Review

“…The cellular in vitro uptake of 131 I-AuNRs conjugated with cyclic RGD (namely, a peptide targeting a cell adhesion molecule integrin α v β 3 ) in B16F10 mouse malignant melanoma cells (positive for integrin α v β 3 ) and MCF-7 human breast cancer cells (negative for integrin α v β 3 ) has been studied. The result shows a strong uptake in the first ones compared to the last ones, and this confirms that the internalization occurs through receptor-mediated endocytosis [91].…”

“…PEG-modified AuNRs show a nearly neutral surface and have little in vivo cytotoxicity. The application of AuNRs in nuclear medicine has attracted great interest in the last few years [91,95,114].…”

“…Zhang et al conjugated 131 I-labeled AuNRs with cyclic arginine-glycine-aspartic acid (RGD) and investigated its biological characteristics for the targeted imaging of integrin α V β 3 -expressing tumors [91]. The 131 I-labeled AuNRs-PEG-cRGD probe targeted selectively and could be taken up by tumor cells mainly via integrin α-receptor-mediated endocytosis.…”

“…In vivo imaging, biodistribution, and autoradiography studies showed tumor uptake in integrin α V β 3 -expressing tumors. For better investigation of inflammation, Shao et al designed inflammation targeting nuclear and optical dual-modality contrast agents prepared by the 125 I radiolabeling of AuNRs conjugated with anti-intercellular adhesion molecule 1 (ICAM-1) Ab [91]. The success of the targeted delivery of AuNRs inflammatory tissue enabled both nuclear and optical imaging of inflammation at the molecular or cellular level.…”

“…Several radionuclides have been proposed to label AuNPs: 198 Au, 125 I, 111 In, 64 Cu, 68 Ga, and 99m Tc [31]. Depending on the physical properties of the radionuclide, the diagnostic imaging has different characteristics: γ-emitting radionuclides provide single-photon emission computed tomography (SPECT) imaging [87,91,97,134,135], while β+-emitting radionuclides provide positron emission tomography (PET) imaging [41,88] or Cerenkov luminescence imaging [81]. When a β-emitting radionuclide is used, its application is "radiometabolic therapy".…”