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Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy.


ABSTRACT: 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.

SUBMITTER: Vorobyeva A 

PROVIDER: S-EPMC6018533 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy.

Vorobyeva Anzhelika A   Westerlund Kristina K   Mitran Bogdan B   Altai Mohamed M   Rinne Sara S   Sörensen Jens J   Orlova Anna A   Tolmachev Vladimir V   Karlström Amelie Eriksson AE  

Scientific reports 20180625 1


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 <sup>177</sup>Lu extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In th  ...[more]

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