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Comparative Evaluation of Radioiodine and Technetium-Labeled DARPin 9_29 for Radionuclide Molecular Imaging of HER2 Expression in Malignant Tumors
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
Russian Acad Sci, Canc Res Inst, Nucl Med Dept, Tomsk Natl Res Med Ctr, Tomsk, Russia.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
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2018 (engelsk)Inngår i: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, artikkel-id 6930425Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

High expression of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal carcinomas is a predictive biomarker for treatment using HER2-targeted therapeutics (antibodies trastuzumab and pertuzumab, antibody-drug conjugate trastuzumab DM1, and tyrosine kinase inhibitor lapatinib). Radionuclide molecular imaging of HER2 expression might permit stratification of patients for HER2-targeting therapies. In this study, we evaluated a new HER2-imaging probe based on the designed ankyrin repeat protein (DARPin) 9_29. DARPin 9_29 was labeled with iodine-125 by direct radioiodination and with [Tc-99m] Tc(CO)(3) using the C-terminal hexahistidine tag. DARPin 9_29 preserved high specificity and affinity of binding to HER2-expressing cells after labeling. Uptake of [I-125] I-DARPin 9_29 and [Tc-99m] Tc(CO)(3)-DARPin 9_29 in HER2-positive SKOV-3 xenografts in mice at 6 h after injection was 3.4 +/- 0.7 % ID/g and 2.9 +/- 0.7 % ID/g, respectively. This was significantly (p < 0.00005) higher than the uptake of the same probes in HER2-negative Ramos lymphoma xenografts, 0.22 +/- 0.09 % ID/g and 0.30 +/- 0.05 % ID/g, respectively. Retention of [I-125] I-DARPin 9_29 in the lung, liver, spleen, and kidneys was appreciably lower compared with [Tc-99m] Tc(CO)(3)-DARPin 9_29, which resulted in significantly (p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by SPECT/CT imaging. In conclusion, radioiodine is a preferable label for DARPin 9_29.

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WILEY-HINDAWI , 2018. artikkel-id 6930425
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URN: urn:nbn:se:uu:diva-359679DOI: 10.1155/2018/6930425ISI: 000435897100001PubMedID: 29977173OAI: oai:DiVA.org:uu-359679DiVA, id: diva2:1245986
Forskningsfinansiär
Swedish Research Council, 2015-02353Swedish Research Council, 2015-02509VINNOVA, 2016-04060Swedish Cancer Society, 2015/350Swedish Cancer Society, 2017/425Swedish Society for Medical Research (SSMF)Tilgjengelig fra: 2018-09-06 Laget: 2018-09-06 Sist oppdatert: 2018-09-06bibliografisk kontrollert

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