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100 _a20210520a2019 k y0engy50 ba
101 0 _aeng
135 _adrcn ---uucaa
181 0 _ai
182 0 _ab
200 1 _aOptimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3
_fA. G. Vorobjeva (Vorobyeva), A. A. Shulga, E. M. Konovalova [et al.]
203 _aText
_celectronic
300 _aTitle screen
320 _a[References: 42 tit.]
330 _aRadionuclide 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.
461 _tScientific Reports
463 _tVol. 9
_v[9405, 11 p.]
_d2019
610 1 _aэлектронный ресурс
610 1 _aтруды учёных ТПУ
701 1 _aVorobjeva (Vorobyeva)
_bA. G.
_cspecialist in the field of medical technology
_cSenior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D
_f1990-
_gAnzhelika Grigorjevna
_2stltpush
_3(RuTPU)RU\TPU\pers\46556
701 1 _aShulga
_bA. A.
_cbiologist
_cResearcher, Tomsk Polytechnic University, Candidate of Biological Sciences
_f1960-
_gAleksey Anatolievich
_2stltpush
_3(RuTPU)RU\TPU\pers\46796
701 1 _aKonovalova
_bE. M.
_gElena Mikhaylovna
701 1 _aGuler
_bR.
_gRezan
701 1 _aLofblom
_bJ.
_gJohn
701 1 _aSandstrom
_bM.
_gMattias
701 1 _aGarousi
_bJ.
_gJavad
701 1 _aChernov
_bV. I.
_cspecialist in the field of medical technology
_clead engineer of Tomsk Polytechnic University, doctor of medical sciences
_f1962-
_gVladimir Ivanovich
_2stltpush
_3(RuTPU)RU\TPU\pers\34191
701 1 _aBragina
_bO. D.
_cspecialist in the field of medical technology
_cSenior Researcher of the Tomsk Polytechnic University, Candidate of medical Sciences
_f1986-
_gOlga Dmitrievna
_2stltpush
_3(RuTPU)RU\TPU\pers\35943
701 1 _aOrlova
_bA. P.
_gAnna Petrovna
701 1 _aTolmachev
_bV. M.
_cspecialist in the field of medical technology
_cDirector of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D
_f1961-
_gVladimir Maksimilianovich
_2stltpush
_3(RuTPU)RU\TPU\pers\46552
701 1 _aDeev
_bS. M.
_cbiologist
_cLeading Researcher, Tomsk Polytechnic University, Doctor of Biological Sciences
_f1951-
_gSergey Mikhaylovich
_2stltpush
_3(RuTPU)RU\TPU\pers\39299
712 0 2 _aНациональный исследовательский Томский политехнический университет
_bФизико-технический институт
_bЛаборатория № 31 ядерного реактора
_h6471
_2stltpush
_3(RuTPU)RU\TPU\col\20054
801 2 _aRU
_b63413507
_c20210520
_gRCR
856 4 _uhttps://doi.org/10.1038/s41598-019-45795-8
942 _cBK