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báo cáo hóa học: " In vitro and in vivo pre-clinical analysis of a F(ab’)2 fragment of panitumumab for molecular imaging and therapy of HER1-positive cancers"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: In vitro and in vivo pre-clinical analysis of a F(ab’)2 fragment of panitumumab for molecular imaging and therapy of HER1-positive cancers | Wong et al. EJNMMI Research 2011 1 1 http www.ejnmmires.eom content 1 1 1 9 EJNMMI Research a SpringerOpen Journal RESEARCH Open Access In vitro and in vivo pre-clinical analysis of a F ab 2 fragment of panitumumab for molecular imaging and therapy of HER1-positive cancers 1 2 2 2 2 Karen J Wong Kwamena E Baidoo Tapan K Nayak Kayhan Garmestani Martin W Brechbiel and Diane E Milenic 2 Abstract Background The objective of this study was to characterize the in vitro and in vivo properties of the F ab 2 fragment of panitumumab and to investigate its potential for imaging and radioimmunotherapy. Methods The panitumumab F ab 2 was generated by enzymatic pepsin digestion. After the integrity and immunoreactivity of the F ab 2 was evaluated the fragment was radiolabeled. In vivo studies included direct quantitation of tumor targeting and normal organ distribution of the radiolabeled panitumumab F ab 2 as well as planar g-scintigraphy and PET imaging. Results The panitumumab F ab 2 was successfully produced by peptic digest. The F ab 2 was modified with the CHX-A -DTPA chelate and efficiently radiolabeled with either 111In or 86Y. In vivo tumor targeting was achieved with acceptable uptake of radioactivity in the normal organs. The tumor targeting was validated by both imaging modalities with good visualization of the tumor at 24 h. Conclusions The panitumumab F ab 2 fragment is a promising candidate for imaging of HER1-positive cancers. Background Monoclonal antibodies mAb have been used in medicine for nearly three decades for purposes including imaging and therapy due to their selectivity for specific targets 1 . While intact monoclonal antibody molecules are still most commonly used they may not necessarily be the most efficient or desired molecular form depending on the application. Because of their relatively large size approximately 150 kD intact mAbs tend to have unfavorable imaging kinetics relatively poor tumor penetration and present with the potential for .