Preparation and biodistribution study of 131I-BEV-PTX-SPIONs

Abstract

Background131I-BEV-PTX-SPIONs is a type of nanoparticle used in cancer therapy. It is composed of four components: a radioactive isotope of iodine (131I), a chemotherapy drug called paclitaxel (PTX), a type of nanoparticle called superparamagnetic iron oxide nanoparticles (SPIONs), and a molecule called bevacizumab (BEV) which is an antibody that targets and blocks the growth of blood vessels that supply tumors.PurposeThis study aims to investigate the preparation and biological distribution of 131I-BEV-PTX-SPIONs.MethodsFirst of all, 131I-BEV-PTX-SPIONs were prepared, synthetized and identified. The transmission electron microscope (TEM) were employed to observe the particle characteristics. Then, 30 tumor-burdened nude mice were divided into the single targeting group and the dual targeting group for evaluation of 131I-BEV-PTX-SPIONs distribution in these nude mice, each group was divided into five sub-groups based on time points of 2 h, 6 h, 12 h, 24 h and 48 h, 3 in each sub-group. Finally, 131I-BEV-PTX-SPIONs were injected into the caudal vein of these mice, and experiments of biological distribution in vivo and SPECT imaging were carried out, and results were analyzed using GraphPad Prism 8.3 software.ResultsThe nanospheres in prepared 131I-BEV-PTX-SPIONs are obtained in good mono dispersion with a diameter of approximately 220 nm by TEM observation. 131I-BEV-PTX-SPIONs obtained in a high radiolabeling yield is about 81.4% with the radiochemical purity of over 99% and good stability shown in the 0.2 mol·L-1 PB buffer. And it could attain sustained PTX release in vitro. Comparing with the cellular uptake of 131I, a higher uptake and sustained PTX release in vitro are shown for 131I-BEV-PTX-SPIONs. Biodistribution experimental results show: After the injection of 131I-BEV-PTX-SPIONs, with the extension of time, the radiation count of the tumor is relatively higher, at 12 h reaching the peak. And the T/NT ratio increased gradually, and it reaches 7.8±0.50 at 48 h. The counts and the ratios at 6 h, 12 h, 24 h and 48 h are notably higher in the dual targeting group than the single targeting group (P<0.05), and over time the differences are more significant. SPECT examination results show: At 2 h after the injection of 131I-BEV-PTX-SPIONs, the tumor site has a radioactive build-up. With the extension of time, the accumulation of radioactivity increased and remained stable, and the T/NT ratio rises steadily.ConclusionsThese results demonstrated the potential of 131I-BEV-PTX-SPIONs in the diagnosis and treatment of lung cancer, and it was worthy of further study.

Keywords

• superparamagnetic iron oxide nanoparticles
• paclitaxel
• 131i
• bevacizumab
• tumor bearing nude mice
• lung cancer