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Molecular design of radiocopper-labelled Affibody molecules
Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..ORCID iD: 0000-0002-6122-1734
Univ Turku, Turku PET Ctr, Turku, Finland.;Univ Turku, MediCity Res Lab, Turku, Finland.;Turku Univ Hosp, Dept Oncol & Radiotherapy, Turku, Finland..
Univ Turku, Turku PET Ctr, Turku, Finland.;Abo Akad Univ, Turku PET Ctr, Turku, Finland..
Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6542Article in journal (Refereed) Published
Abstract [en]

The use of long-lived positron emitters Cu-64 or Cu-61 for labelling of Affibody molecules may improve breast cancer patients' stratification for HER-targeted therapy. Previous animal studies have shown that the use of triaza chelators for Cu-64 labelling of synthetic Affibody molecules is suboptimal. In this study, we tested a hypothesis that the use of cross-bridged chelator, CB-TE2A, in combination with Gly-Glu-Glu-Glu spacer for labelling of Affibody molecules with radiocopper would improve imaging contrast. CB-TE2A was coupled to the N-terminus of synthetic Affibody molecules extended either with a glycine (designation CB-TE2A-G-ZHER2:342) or Gly-Glu-Glu-Glu spacer (CB-TE2A-GEEE-ZHER2:342). Biodistribution and targeting properties of Cu-64-CB-TE2A-G-ZHER2:342 and Cu-64-CB-TE2A-GEEE-ZHER2:342 were compared in tumor-bearing mice with the properties of Cu-64-NODAGA-ZHER2:S1, which had the best targeting properties in the previous study. Cu-64-CB-TE2A-GEEE-ZHER2:342 provided appreciably lower uptake in normal tissues and higher tumor-to-organ ratios than Cu-64-CB-TE2A-GZHER2:342 and Cu-64-NODAGA-ZHER2:S1. The most pronounced was a several-fold difference in the hepatic uptake. At the optimal time point, 6 h after injection, the tumor uptake of Cu-64-CB-TE2A-GEEE-ZHER2: 342 was 16 +/- 6% ID/g and tumor-to-blood ratio was 181 +/- 52. In conclusion, a combination of the cross-bridged CB-TE2A chelator and Gly-Glu-Glu-Glu spacer is preferable for radiocopper labelling of Affibody molecules and, possibly, other scaffold proteins having high renal re-absorption.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 6542
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-227766DOI: 10.1038/s41598-018-24785-2ISI: 000430795000041PubMedID: 29695813Scopus ID: 2-s2.0-85046069525OAI: oai:DiVA.org:kth-227766DiVA, id: diva2:1205485
Funder
Swedish Research Council, 2015-02353 2013-5135 2015-02509Swedish Cancer Society, CAN 2015/350 2014/474
Note

QC 20180514

Available from: 2018-05-14 Created: 2018-05-14 Last updated: 2018-05-14Bibliographically approved

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