Detection of Transferrin Receptor Over-Expression in a Rodent Model of Myocardial Ischemia/Reperfusion Injury Using Novel 99mTc Transferrin Conjugates: A Pilot Study

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.

Evaluation of the Radioimmunotherapy Using I-131 Labeled Vascular Endothelial Growth Factor Receptor2 Antibody in Melanoma Xenograft Murine Model / 핵의학분자영상

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.