CXCL12 Targeted Ultrasound Contrsat Agent Combined With Ovarian Cancer In Vitro And In Vivo

Objective: CXCL12 antibody targeting ultrasound microbubble contrast agent was prepared and its targeted adhesion was tested in vitro,and the characteristics of CXCL12 targeted ultrasound contrast agent in the recognition of ovarian cancer transplanted tumor in nude mice were discussed.Methods: Common lipid ultrasound contrast agent and biotinylated lipid ultrasound contrast agent were prepared by mechanical shock method.Antibodies were connected to lipid ultrasound contrast agent by biotin-streptomycin method to make CXCL12 targeted lipid microbubbles.The connection between antibodies and microbubbles was detected by immunofluorescence method and the common lipid microbubbles were used as control.The binding of CXCL12 targeted lipid microbubbles to human ovarian cancer SKOV3 cells was observed under a general optical microscope,and the ultrasound contrast agent microspheres without CXCL12 were used as the control group.Subcutaneously implanted human ovarian cancer cell line SKOV3 was used to construct a nude mouse model of tumor transplantation.Ordinary and targeted ultrasound contrast agents were injected respectively for contrast-enhanced ultrasonography.The TIC parameters of each group were analyzed.Results:Immunofluorescence showed that CXCL12 antibody can be specifically attached to the surface of microvesicles.In vitro cell target finding experiments showed that SKOV3 cells were extensively bound to the targeted contrast agent under the ordinary optical microscope,while no significant specific binding was observed in the ordinary contrast agent group.The time intensity curve(TIC)of the targeted group and the general contrast agent groupwas analyzed as follows:The peak intensity of the targeted group is73.33(62.33,83.54)was higher than that in general contrast agent group 67.98(60.39,80.17)dB(P < 0.05),the peak reaching time of the targeted group was 32.06(24.98,41.23)shorter than that in general contrast agent group39.51(22.09,48.63)(P < 0.05),and the average transit time of the targeted groupis502.28(411.25,563.86)was longer than that in the general contrast agent group372.49(314.58,513.22)(P < 0.05).Conclusions: CXCL12 targeted lipid microbubble contrast agent prepared by biotin-streptavidin method can effectively bind human ovarian cancer SKOV3 cells in vitro.The imaging results showed that the targeted contrast agent could better evaluate the transplanted tumor of ovarian cancer in nude mice than the non-targeted contrast agent,which was of certain value for the early diagnosis of ovarian cancer.