Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3 / A. G. Vorobjeva (Vorobyeva), A. A. Shulga, E. M. Konovalova [et al.]

Уровень набора: Scientific ReportsАльтернативный автор-лицо: Vorobjeva (Vorobyeva), A. G., specialist in the field of medical technology, Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D, 1990-, Anzhelika Grigorjevna;Shulga, A. A., biologist, Researcher, Tomsk Polytechnic University, Candidate of Biological Sciences, 1960-, Aleksey Anatolievich;Konovalova, E. M., Elena Mikhaylovna;Guler, R., Rezan;Lofblom, J., John;Sandstrom, M., Mattias;Garousi, J., Javad;Chernov, V. I., specialist in the field of medical technology, lead engineer of Tomsk Polytechnic University, doctor of medical sciences, 1962-, Vladimir Ivanovich;Bragina, O. D., specialist in the field of medical technology, Senior Researcher of the Tomsk Polytechnic University, Candidate of medical Sciences, 1986-, Olga Dmitrievna;Orlova, A. P., Anna Petrovna;Tolmachev, V. M., specialist in the field of medical technology, Director of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D, 1961-, Vladimir Maksimilianovich;Deev, S. M., biologist, Leading Researcher, Tomsk Polytechnic University, Doctor of Biological Sciences, 1951-, Sergey MikhaylovichКоллективный автор (вторичный): Национальный исследовательский Томский политехнический университет, Физико-технический институт, Лаборатория № 31 ядерного реактораЯзык: английский.Резюме или реферат: Radionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARPin G3, a small (14?kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE)3) of histidine-containing tags would influence the biodistribution of [99mTc]Tc(CO)3-labeled DARPin G3. To test the hypothesis, G3 variants containing tags at N-terminus (H6-G3 and (HE)3-G3) or at C-terminus (G3-H6 and G3-(HE)3) were labeled with [99mTc]Tc(CO)3. Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [99mTc]Tc(CO)3-labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [99mTc]Tc(CO)3-(HE)3-G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [99mTc]Tc(CO)3-(HE)3-G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites..Примечания о наличии в документе библиографии/указателя: [References: 42 tit.].Тематика: электронный ресурс | труды учёных ТПУ Ресурсы он-лайн:Щелкните здесь для доступа в онлайн
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[References: 42 tit.]

Radionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARPin G3, a small (14?kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE)3) of histidine-containing tags would influence the biodistribution of [99mTc]Tc(CO)3-labeled DARPin G3. To test the hypothesis, G3 variants containing tags at N-terminus (H6-G3 and (HE)3-G3) or at C-terminus (G3-H6 and G3-(HE)3) were labeled with [99mTc]Tc(CO)3. Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [99mTc]Tc(CO)3-labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [99mTc]Tc(CO)3-(HE)3-G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [99mTc]Tc(CO)3-(HE)3-G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites.

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