000 | 04244nam1a2200445 4500 | ||
---|---|---|---|
001 | 664818 | ||
005 | 20231030041942.0 | ||
035 | _a(RuTPU)RU\TPU\network\36003 | ||
035 | _aRU\TPU\network\35410 | ||
090 | _a664818 | ||
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.] |
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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 |
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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 |
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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 |