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Robust surface coating for a fast, facile fluorine-18 labeling of iron oxide nanoparticles for PET/MR dual-modality imaging.

ABSTRACT: Grafting a robust organic shell around inorganic nanoparticles can optimize their colloidal features to dramatically improve their physicochemical properties. Here, we have developed a polymer coating procedure for providing colloidal stability to the nanoparticles and, more importantly, for applying a fast, facile fluorine-18 labeling of iron oxide nanoparticles (IONPs) for positron emission tomography (PET)/magnetic resonance (MR) dual-modality imaging. The structure of the amphiphilic polymer is based on a backbone of polyacrylic acid, conjugated with multiple oleylamines to form a comb-like branched structure. The dense polymer shell provides high colloidal stability to the IONPs against harsh conditions such as high temperature, low pH value, and high ion strength. By incorporating a 1,4,7-triazacyclononane (NOTA) chelator to the comb-like amphiphilic polymer for the chelation of aluminum fluoride ions, we applied a one-step radiolabeling approach for a fast, facile radiofluorination of magnetic nanoparticles. The new strategy can significantly reduce the procedure time and radiation exposure. The PET/MR dual modality imaging was successfully achieved in living subjects by using 18F labeled magnetic nanoparticles.

SUBMITTER: Sun Z

PROVIDER: S-EPMC5154751 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Robust surface coating for a fast, facile fluorine-18 labeling of iron oxide nanoparticles for PET/MR dual-modality imaging.

Sun Ziyan Z Cheng Kai K Wu Fengyu F Liu Hongguang H Ma Xiaowei X Su Xinhui X Liu Yang Y Xia Liming L Cheng Zhen Z

Nanoscale 20161201 47

Grafting a robust organic shell around inorganic nanoparticles can optimize their colloidal features to dramatically improve their physicochemical properties. Here, we have developed a polymer coating procedure for providing colloidal stability to the nanoparticles and, more importantly, for applying a fast, facile fluorine-18 labeling of iron oxide nanoparticles (IONPs) for positron emission tomography (PET)/magnetic resonance (MR) dual-modality imaging. The structure of the amphiphilic polymer ...[more]

PMID: 27858030

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Project description:RG7388 (Idasanutlin) is a potent inhibitor of oncoprotein murine double minute 2 (MDM2). Herein we investigated the feasibility of developing 18F-labeled RG7388 as a radiotracer for imaging MDM2 expression in tumors with positron emission tomography (PET). Two fluorinated analogues of RG7388, 6 and 7, were synthesized by attaching a fluoronicotinyl moiety to RG7388 via a polyethylene glycol (PEG3) or a propyl linker. The inhibitory potency (IC50) of 6 and 7 against MDM2 was determined by a fluorescence polarization (FP)-based assay. Next, compound 6 was labeled with 18F using a trimethylammonium triflate precursor to obtain [18F]FN-PEG3-RG7388 ([18F]6), and its properties were evaluated in MDM2 expressing wild-type p53 tumor cell lines (SJSA-1 and HepG2) in vitro and in tumor xenografts in vivo. The FP assays revealed an IC50 against MDM2 of 119 nM and 160 nM for 6 and 7, respectively. 18F-labeling of 6 was achieved in 50.3 ± 7.5% radiochemical yield. [18F]6 exhibited a high uptake (∼70% of input dose) and specificity in SJSA-1 and HepG2 cell lines. Saturation binding assays revealed a binding affinity (Kd) of 128 nM for [18F]6 on SJSA-1 cells. In mice, [18F]6 showed fast clearance from blood with a maximum tumor uptake of 3.80 ± 0.85% injected dose per gram (ID/g) in HepG2 xenografts at 30 min postinjection (p.i.) and 1.32 ± 0.32% ID/g in SJSA-1 xenografts at 1 h p.i. Specificity of [18F]6 uptake in tumors was demonstrated by pretreatment of mice with SJSA-xenografts with a blocking dose of RG7388 (35 mg/kg body weight, i.p.). In vivo stability studies in mice using HPLC showed ∼60% and ∼30% intact [18F]6 remaining in plasma at 30 min and 1 h p.i., respectively, with the remaining activity attributed to polar peaks. Our results suggest that RG7388 is a promising molecular scaffold for 18F-labeled probe development for MDM2. Additional labeling strategies and functionalizing locations on RG7388 are under development to improve binding affinity and in vivo stability of the 18F-labeled compound to make it more amenable for PET imaging of MDM2 in vivo.

Project description:PurposeThe trend towards faster acquisition protocols in whole-body positron emission tomography/magnetic resonance (PET/MR) arises the question of whether short PET data acquisition protocols in a whole-body multi-station context allow for reduced PET acquisition times while providing adequate PET image quality and accurate quantification parameters. The study goal is to investigate how reducing PET acquisition times affects PET image quality and quantification in whole-body PET/MR in patients with oncologic findings.MethodsFifty-one patients with different oncologic findings underwent a clinical whole-body 18F-Fluorodeoxyglucose PET/MR examination. PET data was reconstructed with 4, 3, 2, and 1 min/bed time intervals for each patient to simulate the effect of reduced PET acquisition times. The 4-minute PET reconstructions served as reference standard. All whole-body PET data sets were analyzed regarding image quality, lesion detectability, PET quantification and standardized uptake values.ResultsA total of 91 lesions were detected in the 4-minute PET reconstructions. The same number of congruent lesions was also noticed in the 3 and 2 minutes-per-bed (mpb) reconstructed images. A total of 2 lesions in 2 patients was not detected in the 1 minute PET data reconstructions due to poor image quality. Image noise in the blood pool increased from 22.2% (4 mpb) to 42.1% (1 mpb). Signal-to-noise ratio declined with shorter timeframes from 13.1 (4 mpb) to 9.3 (1 mpb). SUVmean and SUVmax showed no significant changes between 4 and 1 mpb reconstructed timeframes.ConclusionsReconstruction of PET data with different time intervals has shown that 2 minutes acquisition time per bed position instead of 4 minutes is sufficient to provide accurate lesion detection and adequate image quality in a clinical setting, despite the trends to lower image quality with shorter PET acquisition times. This provides latitude for potential reduction of PET acquisition times in fast PET/MR whole-body examinations.

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Dataset Information

Robust surface coating for a fast, facile fluorine-18 labeling of iron oxide nanoparticles for PET/MR dual-modality imaging.

Publications

Robust surface coating for a fast, facile fluorine-18 labeling of iron oxide nanoparticles for PET/MR dual-modality imaging.

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