TY - JOUR
T1 - Affibody-mediated tumour targeting of HER-2 expressing xenografts in mice
AU - Steffen, Ann Charlott
AU - Orlova, Anna
AU - Wikman, Maria
AU - Nilsson, Fredrik Y.
AU - Ståhl, Stefan
AU - Adams, Gregory P.
AU - Tolmachev, Vladimir
AU - Carlsson, Jörgen
N1 - Funding Information:
Acknowledgements. The authors thank Charles Widström at the department of Nuclear Medicine at Uppsala University Hospital for help with the gamma camera. Thanks also to Kenneth Wester and Veronika Asplund Eriksson for help with the immunohistochemistry, autoradiography and photographic procedures. The work was financially supported by grant no 0980-B04-17XCC (040171) from the Swedish Cancer Society.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2006/6
Y1 - 2006/6
N2 - 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 (ZHER2:4)2, with potential for such applications. The (ZHER2:4)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 (ZHER2:4) 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.
AB - 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 (ZHER2:4)2, with potential for such applications. The (ZHER2:4)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 (ZHER2:4) 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.
KW - Affibody
KW - HER-2
KW - Imaging
KW - SKOV-3
KW - Tumour
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U2 - 10.1007/s00259-005-0012-3
DO - 10.1007/s00259-005-0012-3
M3 - Article
C2 - 16538504
AN - SCOPUS:33646259546
VL - 33
SP - 631
EP - 638
JO - European Journal of Nuclear Medicine
JF - European Journal of Nuclear Medicine
SN - 1619-7070
IS - 6
ER -