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Minerva Biotecnologica 2009 March;21(1):21-30

Copyright © 2009 EDIZIONI MINERVA MEDICA

lingua: Inglese

Update on Affibody molecules for in vivo imaging of targets for cancer therapy

Tolmachev V. 1, 2, 3, Orlova A. 1, 2

1 Unit of Biomedical Radiation Sciences, Rudbeck Laboratory Uppsala University, Sweden 2 Affibody AB, Bromma, Sweden 3 Unit of Nuclear Medicine, Department of Medical Sciences Uppsala University, Sweden


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An increasing specificity of the cancer treatment requires an accurate detection of cancer-associated molecular targets to avoid over- and undertreatment. Radionuclide molecular imaging is a promising way for visualisation of such targets. Affibody molecules (Affibody® molecules), small (7 kDa) robust scaffold proteins constitute a new promising class of high-affinity molecular probes for in vivo molecular imaging. Pre-clinical studies demonstrated a great potential of derivatives of ZHER2:342 Affibody molecule to visualise expression of HER2 in tumour xenografts. Robustness of the Affibody scaffold enabled labelling in harsh conditions without loosing specificity of the HER2-binding. This paper provides an overview of the recent development of Affibody molecules. During the recent year, an important achievement was the development of site-specific labelling of Affibody molecules providing well-characterised uniform conjugates with defined biodistribution and targeting properties. The site-specific labelling was obtained either by an incorporation of chelators during peptides synthesis of Affibody molecules or by an introduction of a single cysteine in the originally cysteine-free Affibody scaffold and the use of a thiol-directed coupling. A feasibility of modification of the biodistribution of Affibody molecules by different chelators was another interesting finding. This was demonstrated during development of mercaptoacetyl-containing peptide based chelators for 99mTc-labelling of Affibody molecules. Several positron-emitting labels enabled the use of advantages of PET for Affibody-mediated radionuclide imaging. It was demonstrated that the rapid targeting of Affibody molecules is compatible with the use of such labels as 68Ga and 18F.

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