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WE‐D‐L100J‐01: In Vivo PET Imaging of Angiogenesis in Tumor Mice Model with 64Cu Labeled Avastin
Author(s) -
Chang T,
Wang Z
Publication year - 2007
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1118/1.2761538
Subject(s) - dota , in vivo , angiogenesis , conjugate , bevacizumab , chemistry , medicine , nuclear medicine , cancer research , chemotherapy , mathematical analysis , microbiology and biotechnology , mathematics , biology
Purpose: Using angiogenesis principle to develop a new PET contrast agent for tumor detection with higher tumor specificity and decrease the background spots shown in 18 FDG imaging. Method and Materials: Bevacizumab (Avastin; Genentech) is the antibody of the vascular endothelial growth factor (VEGF), an angiogenesis factor. Avastin was conjugated to a macrocyclic ligand (DOTA) and labeled with a positron emitter,64 Cu . Briefly, 1,4,7,10‐tetraazacyclododecane‐N, N′,N″,N‴‐tetraacetic acid mono‐N‐hydroxysuccinimide ester (DOTA‐NHS‐ester) was reacted with Avastin in 0.1 M Na 2HPO 4buffer of pH 7.5 at 4°C for 12 h. After conjugation, the reaction mixture was centrifuged repeatedly through an YM‐30 centricon with 50 mM ammonium citrate buffer of pH 6.5 in order to remove small molecules. The Avastin‐DOTA conjugate was labeled with64 Cu at 43°C for 1h and purified with Bio‐Spin 6 column. The microPET/CT imaging was conducted on xenograft models of pancreatic adenocarcinoma established from MiaPaca2 cell line.64 Cu ‐Avastin was administered i.v. at a dose of 240μCi/40μg Ab into a xenograft pancreatic cancer model. The mouse was imaged with microPET/CT scanner (Gamma Medica Ideas, Inc.) at 1h, 4h and 24h post‐injection. Results: The radiolabeling of Avastin was successfully carried out in our lab which gave a radiochemical purity of >92%. The serum challenge studies have demonstrated that 85% of radiolabeled antibody was still intact, even at 24 hour. The images confirmed high accumulation of radiolabeled64 Cu ‐DOTA‐Avastin conjugate in tumors located in the both left and right flank of animal as well as in the head and neck. The image also shows that the conventional hot spots of 18 FDG image such as, brain, kidneys and bladder do not appear on the image. Conclusion:64 Cu ‐DOTA‐Avastin can be used as a tumor detection agent for PET scan and effectively decrease the background spots in image compared to 18 FDG image.