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Synthetic Affibody Molecules: A Novel Class of Affinity Ligands for Molecular Imaging of HER2-Expressing Malignant Tumors

¹ Affibody AB, Bromma, Sweden; ² Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University; and ³ Department of Hospital Physics, Uppsala University Hospital, Uppsala, Sweden

Requests for reprints: Joachim Feldwisch, Affibody AB, Voltavägen 13, P.O. Box 20137, SE-16102 Bromma, Sweden. Phone: 46-859883852; Fax: 46-859883801; E-mail: joachim.feldwisch{at}affibody.com.

The Affibody molecule Z_{HER2:342-pep2}, site-specifically and homogeneously conjugated with a 1,4,7,10-tetra-azacylododecane-N,N',N'',N'''-tetraacetic acid (DOTA) chelator, was produced in a single chemical process by peptide synthesis. DOTA-Z_{HER2:342-pep2} folds spontaneously and binds HER2 with 65 pmol/L affinity. Efficient radiolabeling with >95% incorporation of ¹¹¹In was achieved within 30 min at low (room temperature) and high temperatures (up to 90°C). Tumor uptake of ¹¹¹In-DOTA-Z_{HER2:342-pep2} was specific for HER2-positive xenografts. A high tumor uptake of 23% injected activity per gram tissue, a tumor-to-blood ratio of >7.5, and high-contrast gamma camera images were obtained already 1 h after injection. Pretreatment with Herceptin did not interfere with tumor targeting, whereas degradation of HER2 using the heat shock protein 90 inhibitor 17-allylamino-geldanamycin before administration of ¹¹¹In-DOTA-Z_{HER2:342-pep2} obliterated the tumor image. The present results show that radiolabeled synthetic DOTA-Z_{HER2:342-pep2} has the potential to become a clinically useful radiopharmaceutical for in vivo molecular imaging of HER2-expressing carcinomas. [Cancer Res 2007;67(5):2178–86]

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