The position of 99mTc-HYNIC and the molecular design of the DARPin G3 constructs influence the selection of an imaging tracer to detect expression in HER2-expressing tumors; Journal of Radioanalytical and Nuclear Chemistry; Vol. 335

Bibliographic Details
Parent link:	Journal of Radioanalytical and Nuclear Chemistry.— .— New York: Springer Science+Business Media LLC. Vol. 335.— 2026.— P. 1945–1959
Other Authors:	Larkina M. S. Mariya Sergeevna, Varvashenya R. N. Ruslan Nikolaevich, Prach A. A. Anastasiya Aleksandrovna, Plotnikov E. V. Evgeny Vladimirovich, Tretyakova (Tretjyakova) M. S. Maria Sergeevna, Eskova D. D. Darjya Dmitrievna, Bodenko V. V. Vitalina Vasiljevna, Yanovich G. Gleb, Shulga (Schulga) A. A. Aleksey Anatolievich, Konovalova E. V. Elena Valerjevna, Ziganshin R. Rustam, Belousov M. V. Mikhail Valerievich, Chernov V. I. Vladimir Ivanovich, Tolmachev V. M. Vladimir Maksimilianovich, Deev S. M. Sergey Mikhaylovich
Summary:	Title screen Purpose The objective of the present study was to test the hypothesis that the position of the HYNIC chelator in DARPin G3 variants affects in vivo biodistribution and to select the most effective variant as a 99mTc imaging agent for HER2-expressing tumors. Methods This study evaluated the labelling, affinity, cellular processing, biodistribution, and in vivo targeting specificity of novel N- and C-terminal DARPin G3-HYNIC constructs. In addition, amino acid sequences containing E3C or (G3S)3C at the N- and C-terminus of the protein were used as linkers for HYNIC binding to DARPin G3 to enrich the molecular design of constructs in this study. Results The results demonstrated that the position of the HYNIC chelating group in DARPin G3 constructs did not affect the binding properties of the target in vitro and in vivo. At the same time, the position of HYNIC was found to strongly influence the biodistribution of labelled DARPin G3 constructs in CD1 mice, showing increased accumulation in the kidneys and decreased levels in the liver, spleen, and lungs when HYNIC was added to the N-terminus of the protein variants. Conclusion New N- and C-terminal constructs of DARPin G3-HYNIC were generated for HER2 targeting. It is evident that changing the position of the chelator in DARPin G3-HYNIC leads to differences in pharmacokinetic behaviour. The biodistribution of HYNIC variants attached to the N- or C-terminus of DARPin G3 was not significantly altered by different amino acid linkers. Therefore, variants with HYNIC positioned at the N-terminus are more useful for selecting a 99mTc-DARPin G3 imaging tracer. The [99mTc]Tc-HYNIC-C(G3S)3-G3 variant exhibited enhanced biodistribution compared to [99mTc]Tc-HYNIC-CE3-G3, particularly regarding reduced uptake in the liver AM_Agreement
Language:	English
Published:	2026
Subjects:	труды учёных ТПУ электронный ресурс Designed ankyrin repeat proteins HER2 Imaging HYNIC 99mTc
Online Access:	https://doi.org/10.1007/s10967-026-10739-w
Format:	Electronic Book Chapter
KOHA link:	https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=686120