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Comparative Evaluation of Two DARPin Variants: Effect of Affinity, Size, and Label on Tumor Targeting Properties
Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow, Russia;Natl Res Tomsk Polytech Univ, Tomsk, Russia;Natl Res Nucl Univ MEPhI, Inst Engn Phys Biomed PhysBio, Bionanophoton Lab, Moscow, Russia.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.ORCID-id: 0000-0002-4778-3909
Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow, Russia.
Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow, Russia.
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2019 (engelsk)Inngår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 16, nr 3, s. 995-1008Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins that can be selected for binding to desirable molecular targets. High affinity and small size of DARPins render them promising probes for radionuclide molecular imaging. However, detailed knowledge on many factors influencing their imaging properties is still lacking. We have evaluated two human epidermal growth factor 2 (HER2)-specific DARPins with different size and binding properties. DARPins 9_29-H-6 and G3-H-6 were radiolabeled with iodine-125 and tricarbonyl technetium-99m and evaluated in vitro. A side-by-side comparison of biodistribution and tumor targeting was performed. HER2-specific tumor accumulation of G3-H-6 was demonstrated. A combination of smaller size and higher affinity resulted in a higher tumor uptake of G3-H-6 in comparison to 9_29-H6. Technetium-99m labeled G3-H-6 demonstrated a better biodistribution profile than 9_29-H-6, with several-fold lower uptake in liver. Radioiodinated G3-H-6 showed the best tumor-to-organ ratios. The combined effect of affinity, molecular weight, scaffold composition, and nonresidualizing properties of iodine label provided radioiodinated G3-H-6 with high clinical potential for imaging of HER2.

sted, utgiver, år, opplag, sider
AMER CHEMICAL SOC , 2019. Vol. 16, nr 3, s. 995-1008
Emneord [en]
DARPin, targeting, radionuclide, imaging, I-12S, Tc-99m
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Identifikatorer
URN: urn:nbn:se:uu:diva-380491DOI: 10.1021/acs.molpharmaceut.8b00922ISI: 000460600400008PubMedID: 30608701OAI: oai:DiVA.org:uu-380491DiVA, id: diva2:1299833
Forskningsfinansiär
Swedish Research Council, 2015-02353Swedish Research Council, 2015-02509Vinnova, 2016-04060Swedish Cancer Society, CAN 2015/350Swedish Cancer Society, 2017/425Swedish Society for Medical Research (SSMF)Tilgjengelig fra: 2019-03-28 Laget: 2019-03-28 Sist oppdatert: 2019-03-28bibliografisk kontrollert

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