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Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.ORCID iD: 0000-0003-4334-9360
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, 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 177Lu 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 ZHER2:342-SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide 68Ga. 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. 68Ga-HP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted 177Lu-HP2. The uptake of both 68Ga-ZHER2:342-SR-HP1 and 68Ga-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of 68Ga-HP2 correlated better with the uptake of 177Lu-HP2 than the uptake of 68Ga-ZHER2:342-SR-HP1. The use of 68Ga-HP2 as a theranostics counterpart would be preferable approach for clinical translation. 

Place, publisher, year, edition, pages
Nature Publishing Group , 2018. Vol. 8, no 1, article id 9643
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Chemical Sciences
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URN: urn:nbn:se:kth:diva-236553DOI: 10.1038/s41598-018-27886-0ISI: 000436078500006Scopus ID: 2-s2.0-85049217625OAI: oai:DiVA.org:kth-236553DiVA, id: diva2:1266149
Funder
Swedish Cancer Society, CAN 2015/350 2014/474Swedish Research Council, 2015-02353 2015-02509 2016-05207VINNOVA, 2015-02509Swedish Society for Medical Research (SSMF)
Note

QC 20181127

Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2018-11-27Bibliographically approved

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Westerlund, KristinaEriksson Karlström, Amelie

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