الملخص
PURPOSE: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of 131I labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and METHODS: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to 200-250 mm3 in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of 131I-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), 131I-DC101 50 microgram/mouse (group 2), non-labeled DC101 50 microgram/mouse (group 3), 131I-DC101 30 microgram/mouse (group 4) and 15 microgram/mouse (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. RESULTS: In gamma camera images, the uptake of 131I-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of 131I-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. CONCLUSION: These results indicated that delivery of 131I to tumor using Flk-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.
الموضوعات
Animals , Mice , Capillary Permeability , Gamma Cameras , Melanoma , Mice, Nude , Radioactivity , Radioimmunotherapy , Thyroid Gland , Transplantation, Heterologous , Tumor Burden , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2الملخص
BACKGROUND AND OBJECTIVES: Reperfusion of ischemic myocardium is necessary to salvage tissue from eventual death. However, new pathophysiological changes are initiated after reperfusion. The aim of this study was to investigate one of the mechanisms of ischemia/reperfusion (I/R) injury, and we focused on transferrin. MATERIALS AND METHODS: Male Spragre-Dawley (SD) rats were used for the I/R model. Myocardial ischemia was produced by occlusion of the left anterior descending coronary artery for 30 minutes. 99mTc Transferrin-Chitosan-hydrazino nicotinate hydrochloride (HYNIC) (Tfc) (/37 MBq/mL) was injected once after the reperfusion was finished. Autoradiography, hematoxylin and eosin (H & E) staining and determination of the tissue myeloperoxidase (MPO) activity were performed. RESULTS: Autoradiography showed remarkable 99mTc-Tfc uptake in the left ventricular myocardium at the reperfusion period from 0 to 1.5 hours, whereas no uptake was demonstrated at 3 hours. The uptake was increased again at 6 and 24 hours. Western blotting showed that the transferrin receptor (TfR) proteins were increased at 0 to 1.5 hours compared with that of the control; this expression of TfR disappeared at 3 hours, and it showed up for the second time at 6 and 24 hours. The MPO activity only at 24 hours was significantly higher than that of the control and those MPO activities at 0 to 6 hours (p=0.001). CONCLUSION: In the rodent model of 30 minutes occlusion and reperfusion, our study revealed, with using 99mTc-Tfc, that the TfR expression increased in the myocardium till 3 hours after reperfusion. TfR-mediated entry of iron into the cardiomyocytes may represent that this process plays a role in the I/R injury during the early reperfusion period.
الموضوعات
Animals , Humans , Male , Rats , Autoradiography , Blotting, Western , Coronary Vessels , Eosine Yellowish-(YS) , Hematoxylin , Iron , Myocardial Ischemia , Myocardium , Myocytes, Cardiac , Niacin , Peroxidase , Pilot Projects , Proteins , Receptors, Transferrin , Reperfusion , Reperfusion Injury , Rodentia , Transferrinالملخص
The aim of this study was to ascertain the folate receptor (FR) targetability by an in vitro study and to acquire FR-targeted images in vivo models by using synthetic folate conjugates. PEG-folate was synthesized and labeled with (99m)Tc and fluorescein isothiocynate (FITC). Cell uptake studies were carried out in KB cells (FR-positive) and A549 cells (FR-negative) using FITC- and the (99m)Tc-labeled conjugates. The radiolabeled conjugate was intravenously injected to KB tumor xenografted mice. After it was injected, gamma images were recorded at 30 min, 1, 2, 3 and 4 hr. Cell uptake studies showed a difference between the KB cells and the A549 cells by flow cytometry analysis and gamma counting. On in vivo images, the tumor-tonormal muscle ratio was greater than 4. It ascertained that the PEG-folate conjugate specifically binds to the FR expressed on tumor cells in vitro. Moreover, it was possible to acquire the FR-targeted gamma images using PEG-folate conjugates in tumor models.