Comparative evaluation of 111In-labeled NOTA-conjugated affibody molecules for visualization of HER3 expression in malignant tumors

Ken G. Andersson, Maria Rosestedt, Zohreh Varasteh, Magdalena Malm, Mattias Sandström, Vladimir Tolmachev, John Löfblom, Stefan Ståhl, Anna Orlova

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium?111 (111In) and assessed in vitro and in vivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with 111In provided stable conjugates. In vitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT?474 breast carcinoma cells. In mice bearing BT?474 xenografts, the tumor uptake of the two conjugates was receptor?specific. Direct in vivo comparison of 111In-HEHEHE-Z08698-NOTA and 111In-HEHEHE-Z08699?NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for 111In-HEHEHE-Z08698-NOTA [12±3 vs. 8±1, 4 h post injection (p.i.)] due to more efficient blood clearance. 111In-HEHEHEZ08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.

Original languageEnglish
Pages (from-to)1042-1048
Number of pages7
JournalOncology Reports
Volume34
Issue number2
DOIs
Publication statusPublished - 1 Aug 2015
Externally publishedYes

Keywords

  • Affibody molecules
  • HER3
  • Indium-111
  • Molecular imaging
  • NOTA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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