Author/Authors :
Vorobyeva, Anzhelika Department of Immunology - Genetics and Pathology - Uppsala University - Uppsala, Sweden , Bragina, Olga Nuclear Medicine Department - Cancer Research Institute - Tomsk National Research Medical Center Russian Academy of Sciences - Tomsk, Russia , Altai, Mohamed Department of Immunology - Genetics and Pathology - Uppsala University - Uppsala, Sweden , Mitran, Bogdan Department of Medicinal Chemistry - Uppsala University - Uppsala, Sweden , Orlova, Anna Department of Medicinal Chemistry - Uppsala University - Uppsala, Sweden , Shulga, Alexey Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences - Moscow, Russia , Proshkina, Galina Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences - Moscow, Russia , Chernov, Vladimir Nuclear Medicine Department - Cancer Research Institute - Tomsk National Research Medical Center Russian Academy of Sciences - Tomsk, Russia , Tolmachev, Vladimir Department of Immunology - Genetics and Pathology - Uppsala University - Uppsala, Sweden , Deyev, Sergey Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry - Russian Academy of Sciences - Moscow, Russia
Abstract :
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 [99mTc]Tc(CO)3
using the C-terminal hexahistidine tag. DARPin 9_29 preserved high specificity and aflnity of binding to HER2-expressing cells after
labeling. Uptake of [125I]I-DARPin 9_29 and [99mTc]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. is 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 [125I]IDARPin 9_29 in the lung, liver, spleen, and kidneys was appreciably lower compared with [99mTc]Tc(CO)3-DARPin 9_29, which
resulted in significantly (p < 0.05) higher tumor-to-organ ratios. e biodistribution data were confirmed by SPECT/CT imaging. In
conclusion, radioiodine is a preferable label for DARPin 9_29.
