Diversity of RGD radiotracers in monitoring antiangiogenesis of flavopiridol and paclitaxel in ovarian cancer xenograft-bearing mice |
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| Institution: | 1. Department of Nuclear Medicine, Qilu Hospital, Shandong University, Jinan, China;2. Biomedical Isotope Research Center, School of Medicine, Shandong University, Jinan, China;1. Department of Medical Imaging, University of Arizona, Tucson, AZ, USA;2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA;3. AmProtein Cooperation, San Gabriel, CA, USA;1. School of Health Sciences, Purdue University, IN 47907, USA;2. Department of Nuclear Medicine, China-Japan Friendship Hospital, Beijing, 100029, China;1. The MR Research Centre, Aarhus University hospital, and Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark;2. Department of Cardiology, Aarhus University hospital, and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark;3. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark;4. Department of Neurology, the first affiliated hospital of Zhengzhou University, Zhengzhou, China;5. Aarhus School of Engineering, Aarhus University, Aarhus, Denmark;6. Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark;7. Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark;1. Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China;2. Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China |
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| Abstract: | IntroductionAlthough encouraging results had been shown in antiangiogenesis therapy monitoring, the underlying mechanism of RGD radiotracer accumulation needs to be further illustrated. This study was aimed to investigate the diversity of RGD radiotracers in monitoring antiangiogenic agent's effects and the underlying mechanism in ovarian cancer-bearing mice with a new agent flavopiridol compared with paclitaxel.MethodsOvarian cancer SKOV-3 xenograft-bearing mice were established and divided into three groups, flavopiridol, paclitaxel and control. Flavopiridol (5 mg/kg body weight) and paclitaxel (20 mg/kg body weight) were administered every 3 days for 16 days. Tumor growth and proliferation were monitored by caliper measurements and immunofluorescence staining. Antiangiogenic effects were determined by tumor microvessel density (MVD) in vivo and by endothelial cell tube formation assay in vitro, respectively. 99mTc-3P-RGD2 was prepared, and its biodistribution studies were carried out. The effect of antiangiogenesis therapy on integrin αvβ3 expression was studied by immunohistochemical staining and flow cytometry.ResultsBoth paclitaxel and flavopiridol therapy could apparently inhibit tumor growth and proliferation, and antiangiogenic effects of therapy were validated in vivo and in vitro. However, compared with the control group, ID%/g tumor uptake of 99mTc-3P-RGD2 showed a significant decrease at 2 hours (by 39.96% ± 8.23%, P = 0.044) and at 4 hours (by 35.76% ± 11.42%, P = 0.024) post injection in the paclitaxel-treated group, but a slight increase of tumor uptake in the flavopiridol-treated group at 2 hours (by 4.42% ± 0.24%, p = 0.898) and at 4 hours (by 12.2% ± 1.84%, P = 0.702). The further studies indicated flavopiridol therapy has a dual-effect, reducing integrin αvβ3 expression on endothelial cells due to the reduction of tumor MVD and up-regulating the integrin αvβ3 expression on tumor cells.ConclusionsThere is diversity in evaluating antiangiogenic response when using 99mTc-3P-RGD2, which may be an important reminder in future clinical applications of RGD radiotracers as a strategy for antiangiogenesis therapy response monitoring. |
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