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Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9643Article in journal (Refereed) Published
Abstract [en]

Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide Lu-177 extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe Z(HER2:342)SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. (68)GaHP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted Lu-177-HP2. The uptake of both Ga-68-Z(HER2:342)SR-HP1 and Ga-68-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of Ga-68-HP2 correlated better with the uptake of Lu-177-HP2 than the uptake of Ga-68 Z(HER2:342) SR-HP1. The use of Ga-68-HP2 as a theranostics counterpart would be preferable approach for clinical translation.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 9643
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Radiology, Nuclear Medicine and Medical Imaging
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URN: urn:nbn:se:uu:diva-360010DOI: 10.1038/s41598-018-27886-0ISI: 000436078500006PubMedID: 29942011OAI: oai:DiVA.org:uu-360010DiVA, id: diva2:1247903
Funder
Swedish Research Council, 2015-02353Swedish Research Council, 2015-02509Swedish Research Council, 2016-05207VINNOVA, 2015-02509Swedish Cancer Society, CAN 2015/350Swedish Cancer Society, 2014/474Swedish Society for Medical Research (SSMF)Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2018-09-13Bibliographically approved

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Vorobyeva, AnzhelikaMitran, BogdanAltai, MohamedRinne, SaraSörensen, JensOrlova, AnnaTolmachev, Vladimir

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