English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Our objective was to compare  111 In- or  64 Cu-DOTA-trastuzumab Fab fragments for imaging small or large s.c. 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  111 In or  64 Cu by conjugation to 1,4,7,10-tetraazacyclododecane N, N', N'', N'''-tetraacetic acid (DOTA). The purity of  111 In- and  64 Cu-DOTA-trastuzumab Fab was measured by SDS-PAGE and HPLC. HER2 binding affinity was determined in saturation radioligand binding assays using SKBR-3 cells (1.3 × 10 6  HER2/cell). MicroSPECT/CT and microPET/CT were performed in athymic mice bearing s.c. BT-20 and MDA-MB-231 xenografts with low (0.5 to 1.6 × 10 5  receptors/cell), MDA-MB-361 tumors with intermediate (5.1 × 10 5  receptors/cell) or SKOV-3 xenografts with high HER2 expression (1.2 × 10 6  receptors/cell) at 24 h p.i. of 70 MBq (10 μg) of  111 In-DOTA-trastuzumab Fab or 22 MBq (10 μg) of  64 Cu-DOTA-trastuzumab Fab or irrelevant  111 In- or  64 Cu-DOTA-rituximab Fab. Tumor and normal tissue uptake were quantified in biodistribution studies.    Results   111 In- and  64 Cu-DOTA-trastuzumab were > 98% radiochemically pure and bound HER2 with high affinity ( K  d  = 20.4 ± 2.5 nM and 40.8 ± 3.5 nM, respectively). MDA-MB-361 and SKOV-3 tumors were most clearly imaged using  111 In- and  64 Cu-DOTA-trastuzumab Fab. Significantly higher tumor/blood ( T / B ) ratios were found for  111 In-DOTA-trastuzumab Fab than  111 In-DOTA-rituximab Fab for BT-20, MDA-MB-231 and MDA-MB-361 xenografts, and there was a direct association between  T / B  ratios and HER2 expression. In contrast, tumor uptake of  64 Cu-DOTA-trastuzumab Fab was significantly higher than  64 Cu-DOTA-rituximab Fab in MDA-MB-361 tumors but no direct association with HER2 expression was found. Both  111 In- and  64 Cu-DOTA-trastuzumab Fab imaged small (5 to 10 mm) or larger (10 to 15 mm) MDA-MB-361 tumors. Higher blood, liver, and spleen radioactivity were observed for  64 Cu-DOTA-trastuzumab Fab than  111 In-DOTA-trastuzumab Fab.    Conclusions  We conclude that  111 In-DOTA-trastuzumab Fab was more specific than  64 Cu-DOTA-trastuzumab Fab for imaging HER2-positive tumors, especially those with low receptor density. This was due to higher levels of circulating radioactivity for  64 Cu-DOTA-trastuzumab Fab which disrupted the relationship between HER2 density and  T / B  ratios. Use of alternative chelators that more stably bind  64 Cu may improve the association between  T / B  ratios and HER2 density for  64 Cu-labeled trastuzumab Fab.

ejnmmi research

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