Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors

  • Authors:
    • Anna Orlova
    • Thuy Tran
    • Charles Widström
    • Torun Engfeldt
    • Amelie Eriksson Karlström
    • Vladimir Tolmachev
  • View Affiliations

  • Published online on: September 1, 2007     https://doi.org/10.3892/ijmm.20.3.397
  • Pages: 397-404
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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.

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September 2007
Volume 20 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Orlova A, Tran T, Widström C, Engfeldt T, Eriksson Karlström A and Tolmachev V: Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors. Int J Mol Med 20: 397-404, 2007
APA
Orlova, A., Tran, T., Widström, C., Engfeldt, T., Eriksson Karlström, A., & Tolmachev, V. (2007). Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors. International Journal of Molecular Medicine, 20, 397-404. https://doi.org/10.3892/ijmm.20.3.397
MLA
Orlova, A., Tran, T., Widström, C., Engfeldt, T., Eriksson Karlström, A., Tolmachev, V."Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors". International Journal of Molecular Medicine 20.3 (2007): 397-404.
Chicago
Orlova, A., Tran, T., Widström, C., Engfeldt, T., Eriksson Karlström, A., Tolmachev, V."Pre-clinical evaluation of [111In]-benzyl-DOTA-ZHER2:342, a potential agent for imaging of HER2 expression in malignant tumors". International Journal of Molecular Medicine 20, no. 3 (2007): 397-404. https://doi.org/10.3892/ijmm.20.3.397