000 04023nlm1a2200505 4500
001 662557
005 20231030041825.0
035 _a(RuTPU)RU\TPU\network\33712
035 _aRU\TPU\network\5872
090 _a662557
100 _a20200902a2020 k y0engy50 ba
101 0 _aeng
135 _adrcn ---uucaa
181 0 _ai
182 0 _ab
200 1 _aInfluence of Residualizing Properties of the Radiolabel on Radionuclide Molecular Imaging of HER3 Using Affibody Molecules
_fM. V. Bukkel, S. S. Rinne, Xu Tianqi [et al.]
203 _aText
_celectronic
320 _a[References: 60 tit.]
330 _aHuman epidermal growth factor receptor type 3 (HER3) is an emerging therapeutic target in several malignancies. To select potential responders to HER3-targeted therapy, radionuclide molecular imaging of HER3 expression using affibody molecules could be performed. Due to physiological expression of HER3 in normal organs, high imaging contrast remains challenging. Due to slow internalization of affibody molecules by cancer cells, we hypothesized that labeling (HE)3-ZHER3:08698-DOTAGA affibody molecule with non-residualizing [125I]-N-succinimidyl-4-iodobenzoate (PIB) label would improve the tumor-to-normal organs ratios compared to previously reported residualizing radiometal labels. The [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA was compared side-by-side with [111In]In-(HE)3-ZHER3:08698-DOTAGA. Both conjugates demonstrated specific high-affinity binding to HER3-expressing BxPC-3 and DU145 cancer cells. Biodistribution in mice bearing BxPC-3 xenografts at 4 and 24?h pi showed faster clearance of the [125I]I-PIB label compared to the indium-111 label from most tissues, except blood. This resulted in higher tumor-to-organ ratios in HER3-expressing organs for [125I]I-PIB-(HE)3-ZHER3:08698-DOTAGA at 4 h, providing the tumor-to-liver ratio of 2.4 ± 0.3. The tumor uptake of both conjugates was specific, however, it was lower for the [125I]I-PIB label. In conclusion, the use of non-residualizing [125I]I-PIB label for HER3-targeting affibody molecule provided higher tumor-to-liver ratio than the indium-111 label, however, further improvement in tumor uptake and retention is needed.
461 _tInternational Journal of Molecular Sciences
463 _tVol. 21, iss. 4
_v[1312, 16 p. ]
_d2020
610 1 _aтруды учёных ТПУ
610 1 _aэлектронный ресурс
610 1 _aHER3
610 1 _aaffibody
610 1 _aradionuclide
610 1 _amolecular imaging
610 1 _aiodine
610 1 _aPIB
610 1 _aрадионуклиды
610 1 _aвизуализация
610 1 _aиод
701 1 _aBukkel
_bM. V.
701 1 _aRinne
_bS. S.
_gSara
701 0 _aXu Tianqi
701 1 _aLeitao
_bCh. D.
_gCharles Dahlsson
701 1 _aStahl
_bS.
_gStefan
701 1 _aLofblom
_bJ.
_gJohn
701 1 _aOrlova
_bA. M.
_cspecialist in the field of medical technology
_cSenior Researcher, Oncoteranostika Research Center, Ph.D
_f1960-
_gAnna Markovna
_2stltpush
_3(RuTPU)RU\TPU\pers\46554
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 _aVorobjeva (Vorobyeva)
_bA. G.
_cspecialist in the field of medical technology
_cSenior Researcher, Oncoteranostika Research Center, Ph.D
_f1990-
_gAnzhelika Grigorjevna
_2stltpush
_3(RuTPU)RU\TPU\pers\46556
712 0 2 _aНациональный исследовательский Томский политехнический университет
_bИсследовательская школа химических и биомедицинских технологий
_bНаучно-исследовательский центр "Онкотераностика"
_h8442
_2stltpush
_3(RuTPU)RU\TPU\col\27561
801 2 _aRU
_b63413507
_c20200902
_gRCR
856 4 _uhttps://doi.org/10.3390/ijms21041312
942 _cCF