Details

Autor(en) / Beteiligte

• Andersson, Ken G
• Rosestedt, Maria
• Varasteh, Zohreh
• Malm, Magdalena
• Sandstrom, Mattias
• Tolmachev, Vladimir
• Lofblom, John
• Stahl, Stefan
• Orlova, Anna

Titel

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

Ist Teil von

• Oncology reports, 2015-08, p.1042

Ort / Verlag

Spandidos Publications

Erscheinungsjahr

2015

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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-Z08699NOTA HER3-specific affibody molecules were labeled with indium-111 ([sup.111]In) 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 [sup.111]In 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 [sup.111]In-HEHEHE-Z08698-NOTA and [sup.111]In-HEHEHE-Z08699-NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for [sup.111]In-HEHEHE-Z08698-NOTA [12 ± 3 vs. 8 ± 1, 4 h post injection (p.i.)] due to more efficient blood clearance. [sup.111]In-HEHEHEZ0869-8-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. Key words: NOTA, indium-111, affibody molecules, HER3, molecular imaging