Radyoişaretli bevacizumab'ın radyofarmasötik potansiyelinin incelenmesi
Investigation of radiopharmaceutical potential of radiolabeled bevacizumab
Yazar: İLKNUR DEMİR
Danışman: DOÇ. DR. F. ZÜMRÜT BİBER MÜFTÜLER
Ege Üniversitesi / Fen Bilimleri Enstitüsü / Nükleer Bilimler Ana Bilim Dalı
Derece: Yüksek Lisans, 2009
Konu: Onkoloji = Oncology ; Radyoloji ve Nükleer Tıp = Radiology and Nuclear Medicine

Özet:
Anjiogenezis, tümör gelişimini içeren bir çok fizyolojik ve patolojik proseslerde önemli bir rol oynamaktadır. Vaskular endotelyal büyüme faktörü (VEGF); tümör hücreleri ile ilişkili tümör anjiogenezisde önemli bir büyüme faktörüdür. Bevacizumab (BevMab) VEGF'ye karşı geliştirilmiş hümanize monoklonal antikor olup, VEGF'nin endotel hücre yüzey reseptörlerine bağlanmasını inhibe eder. Food and Drug Administration (FDA) tarafından önerilen çeşitli solid tümörlerinin tedavisinde kullanılan ilk antianjiogenik ilaçtır.Bu çalışmanın esası VEGF'yi in vivo olarak görüntülemede kullanılabilecek 99mTc ile işaretli bir antianjiogenik ajan geliştirmektir.Bu amaçla BevMab; hidrofilik bir grup olan dietilentriamin pentaasetik asit (DTPA) ile konjuge edilip, yapı hidrofilik hale getirilerek 99mTc radyonüklidi ile kalay klorür indirgeme yöntemine göre işaretlenmiştir.Radyoişaretli bileşiğin kalite kontrol çalışmaları İnce Tabaka Radyo Kromatografi (TLRC) ve Yüksek Performanslı Sıvı Radyo Kromatografi yöntemleri kullanılarakyapılmış ve bağlanma verimi % 95'in üzerinde belirlenmiştir. Biyodağılım çalışmaları dişi ve erkek Albino Wistar sıçanlar üzerinde gerçekleştirilmiş gram doku başına enjekte edilen doz değerleri hesaplanarak zamanla değişimi incelenmiştir. Tüm deneysel veriler SPSS 13 programı kullanılarak istatistiksel değerlendirme yapılmıştır.99mTc-BevMab-DTPA bileşiğinin in vivo olarak VEGF'yi görüntülemede bir antianjiogenik konjugat olarak kullanılabilirliği sonucuna varılmıştır.

Abstract:
Angiogenesis plays a crucial role in many physiological and pathologic processes including tumor growth. Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. Bevacizumab (BevMab), a humanized monoclonal antibody against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. It is the first antiangiogenic treatment in various solid tumors approved by the American Food and Drug Administration.The goal of this study is to develope an antiangiogenic agent radiolabeled with 99mTc and to be used for in vivo imaging of VEGF.For this purpose, BevMab was conjugated with the hydrophilic group diethylenetriamine pentaacetic acid (DTPA) and the product was labeled with 99mTc using stannous chloride reducing method.The quality control studies of radiolabeled compound (99mTc-BevMab-DTPA) were done with Thin Layer Radio Chromatography (TLRC) and High Performance Liquid Radio Chromatography (HPLRC) methods (% 95 ? ) to confirm labeling efficiency. The biodistribution studies are performed on female and male Albino Wistar rats. The injected dose per gram tissue is calculated and time-activity curves are examined. All the experimental data are evaluated using statistical SPSS 13 program.99mTc-BevMab-DTPA may be used for in vivo VEGF imaging agent as an antiangiogenic congugate.Angiogenesis plays a crucial role in many physiological and pathologic processes including tumor growth. Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. Bevacizumab (BevMab), a humanized monoclonal antibody against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. It is the first antiangiogenic treatment in various solid tumors approved by the American Food and Drug Administration.The goal of this study is to develope an antiangiogenic agent radiolabeled with 99mTc and to be used for in vivo imaging of VEGF.For this purpose, BevMab was conjugated with the hydrophilic group diethylenetriamine pentaacetic acid (DTPA) and the product was labeled with 99mTc using stannous chloride reducing method.The quality control studies of radiolabeled compound (99mTc-BevMab-DTPA) were done with Thin Layer Radio Chromatography (TLRC) and High Performance Liquid Radio Chromatography (HPLRC) methods (% 95 ? ) to confirm labeling efficiency. The biodistribution studies are performed on female and male Albino Wistar rats. The injected dose per gram tissue is calculated and time-activity curves are examined. All the experimental data are evaluated using statistical SPSS 13 program.99mTc-BevMab-DTPA may be used for in vivo VEGF imaging agent as an antiangiogenic congugate.Angiogenesis plays a crucial role in many physiological and pathologic processes including tumor growth. Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. Bevacizumab (BevMab), a humanized monoclonal antibody against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. It is the first antiangiogenic treatment in various solid tumors approved by the American Food and Drug Administration.The goal of this study is to develope an antiangiogenic agent radiolabeled with 99mTc and to be used for in vivo imaging of VEGF.For this purpose, BevMab was conjugated with the hydrophilic group diethylenetriamine pentaacetic acid (DTPA) and the product was labeled with 99mTc using stannous chloride reducing method.The quality control studies of radiolabeled compound (99mTc-BevMab-DTPA) were done with Thin Layer Radio Chromatography (TLRC) and High Performance Liquid Radio Chromatography (HPLRC) methods (% 95 ? ) to confirm labeling efficiency. The biodistribution studies are performed on female and male Albino Wistar rats. The injected dose per gram tissue is calculated and time-activity curves are examined. All the experimental data are evaluated using statistical SPSS 13 program.99mTc-BevMab-DTPA may be used for in vivo VEGF imaging agent as an antiangiogenic congugate.