Affibody-mediated Tumour Targeting of HER-2 Expressing Xenografts in Mice

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2006 Mar 16

PMID 16538504

Citations 24

Authors

Ann-Charlott Steffen

Anna Orlova

Maria Wikman

Fredrik Y Nilsson

Stefan Stahl

Gregory P Adams

Vladimir Tolmachev

Jorgen Carlsson

Affiliations

Soon will be listed here.

Abstract

Purpose: Targeted delivery of radionuclides for diagnostic and therapeutic applications has until recently largely been limited to receptor ligands, antibodies and antibody-derived molecules. Here, we present a new type of molecule, a 15-kDa bivalent affibody called (Z(HER2:4))(2), with potential for such applications. The (Z(HER2:4))(2) affibody showed high apparent affinity (K (D)=3 nM) towards the oncogene product HER-2 (also called p185/neu or c-erbB-2), which is often overexpressed in breast and ovarian cancers. The purpose of this study was to investigate the in vivo properties of the new targeting agent.

Methods: The biodistribution and tumour uptake of the radioiodinated (Z(HER2:4))(2) affibody was studied in nude mice carrying tumours from xenografted HER-2 overexpressing SKOV-3 cells.

Results: The radioiodinated (Z(HER2:4))(2) affibody was primarily excreted through the kidneys, and significant amounts of radioactivity were specifically targeted to the tumours. The blood-borne radioactivity was, at all times, mainly in the macromolecular fraction. A tumour-to-blood ratio of about 10:1 was obtained 8 h post injection, and the tumours could be easily visualised with a gamma camera at this time point.

Conclusion: The results indicate that the (Z(HER2:4))(2) affibody is an interesting candidate for applications in nuclear medicine, such as radionuclide-based tumour imaging and therapy.

Citing Articles

Advances in the Application of Radionuclide-Labeled HER2 Affibody for the Diagnosis and Treatment of Ovarian Cancer.

Hu X, Li D, Fu Y, Zheng J, Feng Z, Cai J Front Oncol. 2022; 12:917439.

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Novel EBV LMP1 C-terminal domain binding affibody molecules as potential agents for in vivo molecular imaging diagnosis of nasopharyngeal carcinoma.

Kamara S, Guo Y, Mao S, Ye X, Li Q, Zheng M Appl Microbiol Biotechnol. 2021; 105(19):7283-7293.

PMID: 34505914 DOI: 10.1007/s00253-021-11559-6.

Mammalian Expression and Biotinylation of Extracellular Protein Targets for Directed Evolution.

Grindel B, Engel B, Hall C, Kelderhouse L, Lucci A, Zacharias N ACS Omega. 2020; 5(39):25440-25455.

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Arming HSV-Based Oncolytic Viruses with the Ability to Redirect the Host's Innate Antiviral Immunity to Attack Tumor Cells.

Fu X, Tao L, Wu W, Zhang X Mol Ther Oncolytics. 2020; 19:33-46.

PMID: 33024817 PMC: 7530262. DOI: 10.1016/j.omto.2020.09.002.

Affibody Molecules as Targeting Vectors for PET Imaging.

Tolmachev V, Orlova A Cancers (Basel). 2020; 12(3).

PMID: 32168760 PMC: 7139392. DOI: 10.3390/cancers12030651.

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