期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 14, 期 -, 页码 2591-2605出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S195223
关键词
superparamagnetic iron oxide nanoparticles; trimethyl chitosan; bombesin; gallium-68; PET/MRI
资金
- International Atomic Energy Agency (IAEA) [F22064]
- Tehran University of Medical Sciences, Tehran, Iran [26985]
Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions. Methods: In this work, N,N)V-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs) conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) as a radioisotope chelator and bombesin (BN) as a targeting peptide (DOTA-BNTMC-MNPs) were prepared and validated using fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and powder X-ray diffraction (PXRD) tests. Final NPs were radiolabeled with gallium-68 (Ga-68) and evaluated in vitro and in vivo as a potential PET/MRI probe for breast cancer (BC) detection. Results: The DOTA-BN-TMC-MNPs with a particle size between 20 and 30 run were efficiently labeled with Ga-68 (radiochemical purity higher than 98% using thin layer chromatography (TLC)). The radiolabeled NPs showed insignificant toxicity (>74% cell viability) and high affinity (IC50=8.79 mu g/mL) for the gastrin-releasing peptide (GRP)-avid BC T-47D cells using competitive binding assay against Tc-99m-hydrazinonicotinamide (HYNIC)-gamma-aminobutyric acid (GABA)-BN (7-14). PET and MRI showed visible uptake of NPs by T-47D tumors in xenograft mouse models. Conclusion: Ga-68-DOTA-BN-TMC-MNPs could be a potential diagnostic probe to detect BC using PET/MRI technique.
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