Imaging of HER3-expressing xenografts in mice using a 99mTc(CO) 3-HEHEHE-ZHER3:08699 affibody molecule

Anna Orlova, Magdalena Malm, Maria Rosestedt, Zohreh Varasteh, Ken Andersson, Ram Kumar Selvaraju, Mohamed Altai, Hadis Honarvar, Joanna Strand, Stefan Ståhl, Vladimir Tolmachev, John Löfblom

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Purpose: Human epidermal growth factor receptor type 3 (HER3) is a transmembrane receptor tyrosine kinase belonging to the HER (ErbB) receptor family. Membranous expression of HER3 is associated with trastuzumab resistance in breast cancer and the transition to androgen independence in prostate cancer. Imaging of HER3 expression in malignant tumors may provide important diagnostic information that can influence patient management. Affibody molecules with low picomolar affinity to HER3 were recently selected. The aim of this study was to investigate the feasibility of HER3 imaging using radiolabeled Affibody molecules. Methods: A HER3-binding Affibody molecule, Z08699, with a HEHEHE-tag on N-terminus was labeled with 99mTc(CO)3 using an IsoLink kit. In vitro and in vivo binding specificity and the cellular processing of the labeled binder were evaluated. Biodistribution of 99mTc(CO)3-HEHEHE-Z08699 was studied over time in mice bearing HER3-expressing xenografts. Results: HEHEHE-Z08699 was labeled with 99mTc(CO)3 with an isolated yield of >80 % and a purity of >99 %. Binding of 99mTc(CO) 3-HEHEHE-Z08699 was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of the receptor/Affibody molecule complex (70 % of cell-associated radioactivity was internalized after 24 h). The tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor-mediated uptake was also found in the liver, lung, stomach, intestine, and salivary glands. At 4 h pi, tumor-to-blood ratios were 7±3 for BT474, and 6±2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. Conclusions: The results of this study suggest the feasibility of HER3-imaging in malignant tumors using Affibody molecules.

Original languageEnglish
Pages (from-to)1450-1459
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume41
Issue number7
DOIs
Publication statusPublished - Jul 2014
Externally publishedYes

Keywords

  • Affibody molecule
  • HER3
  • Molecular imaging
  • Molecular targeting
  • Technetium-99 m

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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