Application of 188Re-labeled BaGdF5-PEG nanoparticles on the growth inhibition of hepatoma cells and the SPECT imaging in rabbit models

Abstract

Objective To investigate the inhibitory effect of 188Re-labeled BaGdF5-poly(ethylene glycol)(PEG) nanoparticles (NPs) on hepatoma cells, and explore the application of the radiolabeled NPs for SPECT imaging. Methods BaGdF5-PEG NPs were synthesized by hydrothermal method, and were further radiolabeled with 188Re using diethylene triamine pentaacetic acid (DTPA) as a coupling agent. The human hepatoma cells SMCC 7721 were treated with different concentrations of BaGdF5-PEG NPs, 188ReO4- or 188Re-DTPA-BaGdF5 NPs (14.8, 74.0, 370.0×104 Bq/ml) for 24 h, and then the cell proliferation rates were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. 188ReO4- and 188Re-DTPA-BaGdF5 NPs were administrated into normal rabbits via the ear vein, respectively. For the former, static SPECT/CT imaging were performed at 30, 60 min post-injection, and for the latter, dynamic SPECT images were captured within 10 min, and static SPECT/CT images at 30, 60, 120 min post-injection. The rabbit VX2 tumor model was established, and a microcatheter was inserted into hepatic artery via the rabbit femoral artery, and then the mixture of 188Re-DTPA-BaGdF5 NPs and lipiodol was injected into the tumor region. SPECT/CT imaging for VX2 tumor was performed at 30 min later. Data were analyzed by two-sample t test. Results The BaGdF5-PEG NPs were nearly square and the particle size was about 10 nm. The labeling yield of 188Re-DTPA-BaGdF5 was 94.1% at the optimum conditions. Moreover, it showed high stability in vitro and in vivo. In vitro, BaGdF5-PEG NPs did not exhibit obvious cytotoxicity even at a high concentration. Both 188ReO4- and 188Re-DTPA-BaGdF5 could inhibit the proliferation of SMCC 7721 cells, but 188Re-DTPA-BaGdF5 showed a significantly stronger inhibitory effect at the doses of 74.0 and 370.0×104 Bq/ml (t values: 4.21, 4.09, both P<0.01). In vivo,188ReO4- was absorbed by maxillary glands and was quickly eliminated from blood via the kidneys. The 188Re-DTPA-BaGdF5 NPs mainly accumulated in the liver and spleen. In addition, retention and accumulation of 188Re-DTPA-BaGdF5 NPs in the liver tumor could be achieved by using transarterial intervention technique for drug delivery. Conclusion 188Re-DTPA-BaGdF5 NPs have certain killing effects on hepatoma cells in vitro, and with the help of transarterial intervention technique, the NPs can be aggregated within liver tumor, where they not only can be used for SPECT imaging, but also have potential therapeutic effects. Key words: Liver neoplasms; Tumor cells, cultured; Nanoparticles; Rhenium; Tomography, emission-computed, single-photon; Tomography, X-ray computed; Rabbits