Pharmacokinetics And Biodistribution Of SPIO-shRNA Dual Functional Molecular Probe In Vivo

PART1 Pharmacokinetics and MR Imaging of SPIO-sh RNADual Functional Molecular Probe in VivoObjective: The research aimed to investigate the pharmacokinetics and the the main organ distribution of SPIO-shRNA dual functional molecular probe by MRI in vivo.Methods: Eighteen newZealand white rabbits who randomly divided into 3 groups were injected with different doses of SPIO-shRNA molecular probe, respectively, blood samples were taken to measure iron content 30 min before and different time points post injection, the pharmacokinetic parameters were calculated. Twenty four Kun Ming(KM) mice were randomly divided into 4 groups: the control group were injected with phys iological saline 200 μL per mice via the tail vein, the other 3 groups were injected with different doses of SPIO-ShRNA molecular probe, respectively. MRI was performed at 24 hours after intravenous administration of SPIO-ShRNA dual functional molecular probe to mice, then the liver, spleen, kidney, brain and muscle of mice were obtained. Sections were maded and stained with Prussian blue staining for iron. The main organ distribution of the SPIO-shRNA molecular probe were observed.Results: Results showed that the pharmacokinetics of the molecular probe complied with two-compartment model, the blood half-life more than 3 hours; the probe main in the liver and spleen could be detected by MRI, the signal intensity of liver and spleen reduced with the increase of probe’s doses, it was confirmed with Prussian blue staining of tissue sections and a great many of probe can escape the phagocytosis of mononuclear phagocyte system also.Conclusion: The present investigation highlithts the pharmacokinetic parameters of SPIO-shRNA molecular probe and it’s main organ distribution, it provides an important reference value for the time and dose of probe at tumor by MRI in vivo.PART2 Magnetic Resonance Imaging Tracing the Biodist ribution of SPIO-shRNA Dual F unctional Molecular P robe in VivoObjective: To investigate the biodistribution of SPIO-shRNA molecular probe by MRI in vivo.Methods: 6 new Zealand white rabbits were injected intravenously with SPIO-shRNA molecular probe(9.6 mg Fe/kg). The blood samples were taken to analyse the pharmacokinetic parameters through measuring the iron content by AAS at 30 min before and different time points until 24 h after the injection. 6 Kun Ming(KM) mice were injected intravenously with SPIO-shRNA molecular probe(4.8 mg Fe/kg). The biodistribution of SPIO-shRNA molecular probe was traced by MRI in vivo. 96 KM mice were randomly divided into 2 control group and 14 experimental groups: each mouse in experimental group was injected intravenously with SPIO-shRNA molecular probe(4.8 mg Fe/kg). The iron content of liver, spleen, kidney, brain and muscle were measured by AAS method and Prussian blue staining at 1, 3, 5, 7, 9, 11 and 14 d after the injection in order to observe the distribution of the SPIO-shRNA molecular probe in the main organ.Results: The pharmacokinetics of the molecular probe complied with two-compartment model, and the blood half-life is(3.692±0.196) h. The datas of MRI showed the probe were distributed in liver and spleen, and the signal intensity were reduced in accord with the increase of probe’s doses in liver and spleen. The probe’s metabolism was slow, and the probe was cleared from liver and spleen at 2 weeks after the injection. The results of AAS and Prussian blue staining further testified the results of MRI.Conclusion: Our data showed the biodistribution of SPIO-shRNA molecular probe in main organ can be traced by MRI in vivo. Meanwhile, it provides important information for the effectiveness of the probe by MRI at tumor in vivo.