Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3

Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3

Bibliographic Details
Parent link:Scientific Reports
Vol. 9.— 2019.— [9405, 11 p.]
Other Authors: Vorobjeva (Vorobyeva) A. G. Anzhelika Grigorjevna, Shulga (Schulga) A. A. Aleksey Anatolievich, Konovalova E. V. Elena Valerjevna, Guler R. Rezan, Lofblom J. John, Sandstrom M. Mattias, Garousi J. Javad, Chernov V. I. Vladimir Ivanovich, Bragina O. D. Olga Dmitrievna, Orlova A. M. Anna Markovna, Tolmachev V. M. Vladimir Maksimilianovich, Deev S. M. Sergey Mikhaylovich
Summary:Title screen
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.
Language:English
Published: 2019
Subjects:
электронный ресурс
труды учёных ТПУ
Online Access:https://doi.org/10.1038/s41598-019-45795-8
Format: Electronic Book Chapter
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=664818

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