Evaluation of an antibody-PNA conjugate as a clearing agent for antibody-based PNA-mediated radionuclide pretargeting
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Published:2020-11-27
Issue:1
Volume:10
Page:
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ISSN:2045-2322
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Container-title:Scientific Reports
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language:en
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Short-container-title:Sci Rep
Author:
Myrhammar Anders,Vorobyeva Anzhelika,Westerlund Kristina,Yoneoka Shuichiro,Orlova Anna,Tsukahara Takehiko,Tolmachev Vladimir,Karlström Amelie Eriksson,Altai Mohamed
Abstract
AbstractRadionuclide molecular imaging of cancer-specific targets is a promising method to identify patients for targeted antibody therapy. Radiolabeled full-length antibodies however suffer from slow clearance, resulting in high background radiation. To overcome this problem, a pretargeting system based on complementary peptide nucleic acid (PNA) probes has been investigated. The pretargeting relies on sequential injections of primary, PNA-tagged antibody and secondary, radiolabeled PNA probe, which are separated in time, to allow for clearance of non-bound primary agent. We now suggest to include a clearing agent (CA), designed for removal of primary tumor-targeting agent from the blood. The CA is based on the antibody cetuximab, which was conjugated to PNA and lactosaminated by reductive amination to improve hepatic clearance. The CA was evaluated in combination with PNA-labelled trastuzumab, T-ZHP1,for radionuclide HER2 pretargeting. Biodistribution studies in normal mice demonstrated that the CA cleared ca. 7 times more rapidly from blood than unmodified cetuximab. Injection of the CA 6 h post injection of the radiolabeled primary agent [131I]I-T-ZHP1gave a moderate reduction of the radioactivity concentration in the blood after 1 h from 8.5 ± 1.8 to 6.0 ± 0.4%ID/g. These proof-of-principle results could guide future development of a more efficient CA.
Funder
Vetenskapsrådet VINNOVA Cancerfonden Svenska Sällskapet för Medicinsk Forskning Kungliga Tekniska Hogskolan
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
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