OBJECTIVETo prepare (99m)Tc-labeled Anti-VEGF mAb 5-FU loaded polylactic acid nanoparticles ((99m)Tc-Ab-5-FU-NPs) and investigate its biodistribution in human gastric carcinoma xenografts.

METHODS(99m)Tc-Ab-5-FU-NPs were prepared by labeling Ab-5-FU-NPs with (99m)Tc using improved Schwarz method. After isolation of (99m)Tc-Ab-5-FU-NPs using SephadexG250 column, the labeling ratio and radiochemical purity were determined using chromatography. The immunocompetence of (99m)Tc- Ab-5-FU-NPs was detected by ELISA and immunohistochemistry. (99m)Tc-Ab-5-FU-NPs were then injected via the tail vein into SCID mice bearing human gastric carcinoma, and (99m)Tc labeled mice-derived monoclonal IgG loaded polylactic acid nanoparticles were used as the control, followed by radioimmunoscintigraphic imaging at 2 and 6 h. The radioactive count and radioactive ratio of the tumor and non-tumor tissue (T/NT) in the animal models were calculated using ROI technique. After imaging at 24 h, SCID mice were sacrificed and the radioactive distribution, the %ID/g, as well as the T/NT radioactive ratio were examined, respectively. The concentrations of 5-FU in the tumor and blood were also detected using HPLC method.

RESULTSThe labeling ratio of (99m)Tc-Ab-5-FU-NPs was 90%-95%. (99m)Tc-Ab-5-FU-NPs were detected in the tumor tissues by radioimmunoimaging 2 h after the injection. ID%/g in the tumor tissues at 2 and 6 h were both significantly higher than that of the control group. Both the ID%/g in tumor tissues and radioactive ratio of tumor and blood at 6 h were higher than those at 2 h, and the concentration of 5-FU in experimental group increased continuously with time and was significantly higher than that in control group.

CONCLUSIONS(99m)Tc-Ab-5-FU-NPs prepared in this study can meet the demands of radioimmunoimaging, and the anti-VEGF monoclonal antibody possesses reliable immune targeting ability. Six hours after injection, (99m)Tc-Ab-5-FU-NPs can specifically accumulate in the tumor tissues in human gastric carcinoma xenografts at high concentration.