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Article

Indirect Radioiodination of DARPin G3 Using N-succinimidyl-Para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging

1
Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden
2
Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
3
Department of Medicinal Chemistry, Uppsala University, 75123 Uppsala, Sweden
4
Science for Life Laboratory, Uppsala University, 75123 Uppsala, Sweden
5
Bio-Nanophotonic Lab, Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University ‘MEPhI’, 115409 Moscow, Russia
6
Nuclear Medicine Department, Cancer Research Institute, Tomsk National Research Medical Center Russian Academy of Sciences, 634050 Tomsk, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(12), 3047; https://doi.org/10.3390/ijms20123047
Received: 13 June 2019 / Revised: 17 June 2019 / Accepted: 19 June 2019 / Published: 21 June 2019
(This article belongs to the Section Molecular Pharmacology)
Radionuclide molecular imaging of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal cancer might be used to stratify patients for HER2-targeted therapy as well as monitor treatment response and disease progression. Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins with favorable properties for molecular imaging. Herein we compared two methods for labeling the anti-HER2 DARPin (HE)3-G3, direct and indirect radioiodination. We hypothesized that the use of N-succinimidyl-para-iodobenzoate (SPIB) for radioiodination would facilitate the clearance of radiometabolites and improve the contrast of imaging. Both radiolabeled (HE)3-G3 variants preserved their binding specificity and high affinity to HER2-expressing cells. The specificity of tumor targeting in vivo was also demonstrated. A biodistribution comparison of [125I]I-(HE)3-G3 and [125I]I-PIB-(HE)3-G3, in mice bearing HER2 expressing SKOV3 xenografts, showed rapid clearance of [125I]I-PIB-(HE)3-G3 from normal organs and tissues and low accumulation of activity in organs with NaI-symporter expression. Both radiolabeled (HE)3-G3 variants had equal tumor uptake. Consequently, the indirect label provided higher tumor-to-blood and tumor-to-organ ratios compared with the direct label. Comparative Single Photon Emission Computed Tomography (SPECT)/CT imaging of HER2 expression in SKOV3 xenografts, using both radiolabeled DARPins, demonstrated the superior imaging contrast of the indirect label. Indirect radioiodination of (HE)3-G3 using SPIB could be further applied for SPECT and PET imaging with iodine-123 and iodine-124. View Full-Text
Keywords: DARPin; HER2; imaging; radionuclide; iodine; radioiodination DARPin; HER2; imaging; radionuclide; iodine; radioiodination
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MDPI and ACS Style

Vorobyeva, A.; Schulga, A.; Rinne, S.S.; Günther, T.; Orlova, A.; Deyev, S.; Tolmachev, V. Indirect Radioiodination of DARPin G3 Using N-succinimidyl-Para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging. Int. J. Mol. Sci. 2019, 20, 3047. https://doi.org/10.3390/ijms20123047

AMA Style

Vorobyeva A, Schulga A, Rinne SS, Günther T, Orlova A, Deyev S, Tolmachev V. Indirect Radioiodination of DARPin G3 Using N-succinimidyl-Para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging. International Journal of Molecular Sciences. 2019; 20(12):3047. https://doi.org/10.3390/ijms20123047

Chicago/Turabian Style

Vorobyeva, Anzhelika, Alexey Schulga, Sara S. Rinne, Tyran Günther, Anna Orlova, Sergey Deyev, and Vladimir Tolmachev. 2019. "Indirect Radioiodination of DARPin G3 Using N-succinimidyl-Para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging" International Journal of Molecular Sciences 20, no. 12: 3047. https://doi.org/10.3390/ijms20123047

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