Comparative evaluation of tumor targeting using the anti-HER2 ADAPT scaffold protein labeled at the C-terminus with indium-111 or technetium-99m

Scientific Reports. 2017;7(1):1-11 DOI 10.1038/s41598-017-15366-w

 

Journal Homepage

Journal Title: Scientific Reports

ISSN: 2045-2322 (Online)

Publisher: Nature Publishing Group

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS

Javad Garousi (Institute for Immunology, Genetics and Pathology, Uppsala University)
Sarah Lindbo (School of Biotechnology, Division of Protein Technology, KTH Royal Institute of Technology)
Bogdan Mitran (Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University)
Jos Buijs (Institute for Immunology, Genetics and Pathology, Uppsala University)
Anzhelika Vorobyeva (Institute for Immunology, Genetics and Pathology, Uppsala University)
Anna Orlova (Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University)
Vladimir Tolmachev (Institute for Immunology, Genetics and Pathology, Uppsala University)
Sophia Hober (School of Biotechnology, Division of Protein Technology, KTH Royal Institute of Technology)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 20 weeks

 

Abstract | Full Text

Abstract ABD-Derived Affinity Proteins (ADAPTs) is a novel class of engineered scaffold proteins derived from an albumin-binding domain of protein G. The use of ADAPT6 derivatives as targeting moiety have provided excellent preclinical radionuclide imaging of human epidermal growth factor 2 (HER2) tumor xenografts. Previous studies have demonstrated that selection of nuclide and chelator for its conjugation has an appreciable effect on imaging properties of scaffold proteins. In this study we performed a comparative evaluation of the anti-HER2 ADAPT having an aspartate-glutamate-alanine-valine-aspartate-alanine-asparagine-serine (DEAVDANS) N-terminal sequence and labeled at C-terminus with 99mTc using a cysteine-containing peptide based chelator, glycine-serine-serine-cysteine (GSSC), and a similar variant labeled with 111In using a maleimido derivative of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator. Both 99mTc-DEAVDANS-ADAPT6-GSSC and 111In-DEAVDANS-ADAPT6-GSSC-DOTA accumulated specifically in HER2-expressing SKOV3 xenografts. The tumor uptake of both variants did not differ significantly and average values were in the range of 19–21%ID/g. However, there was an appreciable variation in uptake of conjugates in normal tissues that resulted in a notable difference in the tumor-to-organ ratios. The 111In-DOTA label provided 2–6 fold higher tumor-to-organ ratios than 99mTc-GSSC and is therefore the preferable label for ADAPTs.