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- W2092942893 abstract "Imaging of expression of human epidermal growth factor receptor type 2 (HER2) in breast carcinomas may help to select patients eligible for trastuzumab therapy. The Affibody molecule ZHER2:342 is a small (7-kDa) non-immunoglobulin affinity protein, which binds to HER2 with a picomolar affinity. Previously, a benzyl-DTPA conjugate of ZHER2:342 was labeled with 111In and demonstrated good targeting in murine xenografts. We considered that the use of the macrocyclic chelator DOTA could increase the label stability and enhance a choice of nuclides, which could be used as a label for ZHER2:342. The goal of this study was the preparation and pre-clinical evaluation of the indium-111- labeled DOTA-derivative of ZHER2:342. Isothiocyanate-benzyl-DOTA was coupled to recombinant ZHER2:342, and the conjugate was efficiently labeled with 111In at 60° C. The specificity of 111In-benzyl-DOTA-ZHER2:342 binding to HER2 was confirmed in vitro using HER2-expressing breast carcinoma BT474 and ovarian carcinoma SKOV-3 cell lines. Biodistribution of 111In-benzyl-DOTA-ZHER2:342 was performed in nude mice bearing LS174T xenografts and compared directly with the biodistribution of 111In-benzyl-DTPA-ZHER2:342. In vivo, 111In-benzyl-DOTA-ZHER2:342 demonstrated quick clearance from blood and non-specific organs except the kidneys. Four hours post injection (pi), the tumor uptake of 111In-benzyl-DOTA-ZHER2:342 (4.4±1.0% IA/g) was specific and the tumor-to-blood ratio was 23. The use of benzyl-DTPA provided higher tumor-to-blood and tumor-to-liver ratios. γ-camera imaging showed clear visualization of HER2-expressing xenografts using 111In-benzyl-DOTA-ZHER2:342. 111In-benzyl-DOTA-ZHER2:342 has a potential for imaging of HER2 expression in malignant tumors." @default.
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- W2092942893 date "2007-09-01" @default.
- W2092942893 modified "2023-10-16" @default.
- W2092942893 title "Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors" @default.
- W2092942893 doi "https://doi.org/10.3892/ijmm.20.3.397" @default.
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