Tumor imaging using a picomolar affinity HER2 binding affibody molecule

Cancer Research
Anna OrlovaFredrik Y Nilsson

Abstract

The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could be provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, Z(HER2:342) showed a >2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue ...Continue Reading

References

Mar 15, 1990·International Journal of Cancer. Journal International Du Cancer·P G NataliA Ullrich
Sep 1, 1996·Journal of Molecular Recognition : JMR·J NilssonM Uhlén
Jul 3, 1999·Physiological Reviews·C C Michel, F E Curry
Nov 11, 1999·Protein Engineering·E GunneriussonP Nygren
Nov 4, 2000·Biochimica Et Biophysica Acta·A Skerra
Nov 28, 2000·International Journal of Cancer. Journal International Du Cancer·C T KuanD D Bigner
Mar 17, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R C BastUNKNOWN American Society of Clinical Oncology Tumor Markers Expert Panel
Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Akiko KoideShohei Koide
Feb 28, 2002·Journal of Immunological Methods·Jenny RönnmarkPer-Ake Nygren
Mar 29, 2002·International Journal of Cancer. Journal International Du Cancer·Virna Cortez-RetamozoHilde Revets
Jun 6, 2002·European Journal of Biochemistry·Jenny RönnmarkPer-Ake Nygren
Aug 15, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D GancbergD Larsimont
Sep 3, 2002·Chemistry & Biology·Lihui XuDasa Lipovsek
Dec 17, 2002·Current Opinion in Biotechnology·Surinder K BatraDavid Colcher
Oct 3, 2003·Journal of Cellular Biochemistry·Linda A Landon, Susan L Deutscher
Oct 24, 2003·Trends in Biotechnology·Lucy J HoltIan M Tomlinson
Apr 21, 2004·Nature Biotechnology·H Kaspar BinzAndreas Plückthun
May 11, 2004·Nature Biotechnology·Peter M Smith-JonesSteven M Larson
Jun 23, 2004·Protein Engineering, Design & Selection : PEDS·M WikmanS Ståhl
Jul 21, 2004·Journal of Immunological Methods·Per-Ake Nygren, Arne Skerra
Feb 22, 2005·Nature Biotechnology·Yi LiJonathan M Boulter
Jul 2, 2005·Cancer Biotherapy & Radiopharmaceuticals·Ann-Charlott SteffenJörgen Carlsson
Oct 8, 2005·Nature Biotechnology·H Kaspar BinzAndreas Plückthun
Mar 16, 2006·European Journal of Nuclear Medicine and Molecular Imaging·Ann-Charlott SteffenJörgen Carlsson

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Citations

Dec 1, 2011·Applied Microbiology and Biotechnology·Chung-Jen ChiangYun-Peng Chao
Jun 8, 2006·European Journal of Nuclear Medicine and Molecular Imaging·Giovanni Lucignani
Dec 6, 2006·European Journal of Nuclear Medicine and Molecular Imaging·Torun EngfeldtVladimir Tolmachev
Jun 15, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Torun EngfeldtVladimir Tolmachev
Sep 12, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Weibo CaiXiaoyuan Chen
Dec 25, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Gabriela Kramer-MarekJacek Capala
Jan 15, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Ann-Charlott SteffenJörgen Carlsson
Jul 3, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Torun EkbladVladimir Tolmachev
Dec 11, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Vladimir TolmachevAnna Orlova
Sep 23, 2009·European Journal of Nuclear Medicine and Molecular Imaging·Anna OrlovaVladimir Tolmachev
Jul 16, 2011·European Journal of Nuclear Medicine and Molecular Imaging·Zheng MiaoZhen Cheng
Dec 16, 2011·European Journal of Nuclear Medicine and Molecular Imaging·Daniel RosikVladimir Tolmachev
Feb 23, 2010·Amino Acids·Zheng MiaoZhen Cheng
Mar 17, 2010·Amino Acids·Xin LinXiaoyuan Chen
Jul 5, 2012·Clinical & Experimental Metastasis·Alain P PeckingJean Louis Alberini
May 16, 2008·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Mohammad NamavariSanjiv S Gambhir
Jun 27, 2009·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Helena WållbergAnna Orlova
Jan 18, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hanna LindbergVladimir Tolmachev
Feb 9, 2011·Bioconjugate Chemistry·Susan HoppmannZhen Cheng
Apr 9, 2013·Journal of the American Chemical Society·Alexander M SpokoynyBradley L Pentelute
Jan 19, 2008·Nature Reviews. Cancer·Kevin Brindle
Oct 14, 2009·Molecular BioSystems·Raphael AlfordHisataka Kobayashi
Aug 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Charles EigenbrotTorleif Härd
Jan 1, 2010·Biotechnology & Genetic Engineering Reviews·R Cochran, Frank Cochran
Nov 6, 2007·Cancer Biotherapy & Radiopharmaceuticals·Anna OrlovaVladimir Tolmachev
Mar 2, 2010·Cancer Biotherapy & Radiopharmaceuticals·Robert M SharkeyDavid M Goldenberg
Dec 24, 2010·Protein Engineering, Design & Selection : PEDS·Nina KronqvistJohn Löfblom
Aug 9, 2013·Protein Engineering, Design & Selection : PEDS·Malin LindborgTorleif Härd
Jul 16, 2010·Journal of Virology·Natalya BelousovaVictor Krasnykh
May 7, 2013·Annual Review of Biomedical Engineering·Scott BantaOren Shur
Jun 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sang Bong LeeJacek Capala
Jan 6, 2009·Breast Cancer Research : BCR·David A Mankoff

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