tailieunhanh - Chan et al. EJNMMI Research 2011, 1:15 http://www.ejnmmires.com/content/1/1/15 ORIGINAL

Chan et al. EJNMMI Research 2011, 1:15 ORIGINAL RESEARCH Open Access A comparison of 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging subcutaneous HER2positive tumor xenografts in athymic mice using microSPECT/CT or microPET/CT Conrad Chan1, Deborah A Scollard1, Kristin McLarty1, Serena Smith1 and Raymond M Reilly1,2,3* Abstract Background: Our objective was to compare 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging small or large . tumor xenografts in athymic mice that display a wide range of human epidermal growth factor receptor2 (HER2) expression using microSPECT/CT or microPET/CT. Methods: Trastuzumab Fab were labeled with 111In or 64Cu by conjugation to 1,4,7,10-tetraazacyclododecane N, N’, N’’, N’’’-tetraacetic acid (DOTA). The. | Chan et al. EJNMMI Research 2011 1 15 http content 1 1 15 9 EJNMMI Research a SpringerOpen Journal ORIGINAL RESEARCH Open Access A comparison of 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging subcutaneous HER2-positive tumor xenografts in athymic mice using microSPECT CT or microPET CT Conrad Chan1 Deborah A Scollard1 Kristin McLarty1 Serena Smith1 and Raymond M Reilly1 2 3 Abstract Background Our objective was to compare 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging small or large . tumor xenografts in athymic mice that display a wide range of human epidermal growth factor receptor-2 HER2 expression using microSPECT CT or microPET CT. Methods Trastuzumab Fab were labeled with 111In or 64Cu by conjugation to 1 4 7 10-tetraazacyclododecane N N N N -tetraacetic acid DOTA . The purity of 111In- and 64Cu-DOTA-trastuzumab Fab was measured by SDS-PAGE and HPLC. HER2 binding affinity was determined in saturation radioligand binding assays using SKBR-3 cells X 106 HER2 cell . MicroSPECT CT and microPET CT were performed in athymic mice bearing . BT-20 and MDA-MB-231 xenografts with low to X 105 receptors cell MDA-MB-361 tumors with intermediate X 105 receptors cell or SKOV-3 xenografts with high HER2 expression X 106 receptors cell at 24 h . of 70 MBq 10 qg of 111In-DOTA-trastuzumab Fab or 22 MBq 10 qg of 64Cu-DOTA-trastuzumab Fab or irrelevant 111In- or 64Cu-DOTA-rituximab Fab. Tumor and normal tissue uptake were quantified in biodistribution studies. Results 111In- and 64Cu-DOTA-trastuzumab were 98 radiochemically pure and bound HER2 with high affinity Kd nM and nM respectively . MDA-MB-361 and SKOV-3 tumors were most clearly imaged using 111In- and 64Cu-DOTA-trastuzumab Fab. Significantly higher tumor blood T B ratios were found for 111In-DOTA-trastuzumab Fab than 111In-DOTA-rituximab Fab for BT-20 MDA-MB-231 and MDA-MB-361 xenografts and there was a direct association between T B .