Comparative Preclinical Evaluation of the Tumor-Targeting Properties of Radioiodine and Technetium-Labeled Designed Ankyrin Repeat Proteins for Imaging of Epidermal Growth Factor Receptor Expression in Malignant Tumors; International Journal of Molecular Sciences; Vol. 26, iss. 21

Comparative Preclinical Evaluation of the Tumor-Targeting Properties of Radioiodine and Technetium-Labeled Designed Ankyrin Repeat Proteins for Imaging of Epidermal Growth Factor Receptor Expression in Malignant Tumors

Bibliographic Details
Parent link:	International Journal of Molecular Sciences.— .— Basel: MDPI AG Vol. 26, iss. 21.— 2025.— Article number 10609, 22 p.
Other Authors:	Larkina M. S. Mariya Sergeevna, Yanovich G. Gleb, Hasnowo L. A. Lutfi Aditya (Hasnowo Lutfi Aditya, Varvashenya R. N. Ruslan Nikolaevich, Yuldasheva F. Sh. Feruza Sherzod kizi, Tretyakova (Tretjyakova) M. S. Maria Sergeevna, Plotnikov E. V. Evgeny Vladimirovich, Zelchan (Zeltchan) R. V. Roman Vladimirovich, Shulga (Schulga) A. A. Aleksey Anatolievich, Konovalova E. V. Elena Valerjevna, Ziganshin R. Rustam, Belousov M. V. Mikhail Valerievich, Tolmachev V. Vladimir, Deev S. M. Sergey Mikhaylovich
Summary:	Title screen Radionuclide molecular imaging of epidermal growth factor receptor (EGFR) expression might permit the selection of patients for EGFR-targeting therapies. Designed ankyrin repeat protein (DARPin) E01 with a high affinity to the ectodomain III of the EGFR is a possible EGFR imaging probe. The goal of this study was to evaluate the potential of radiolabeled DARPin E01 for in vivo imaging of EGFR. DARPin E01 containing the (HE)3-tag was site-specifically labeled with a residualizing 99mTc (using 99mTc]Tc(CO)3). Two methods providing non-residualizing 123I labels, direct electrophilic radioiodination and indirect radioiodination using [123I]I-para-iodobenzoate (PIB), were tested. [99mTc]Tc-(HE)3-E01 and [123I]I-(HE)3-E01-PIB preserved specific binding to EGFR-expressing cells and affinity in the single-digit nanomolar range. Direct labeling with 123I resulted in a substantial loss of binding. In vitro cellular processing studies showed that both [99mTc]Tc-(HE)3-E01 and [123I]I-(HE)3-E01-PIB had rapid binding and relatively slow internalization. Evaluation of [99mTc]Tc-(HE)3-E01 biodistribution in normal CD1 mice showed that its hepatic uptake was non-saturable, suggesting that this tracer does not bind to murine EGFR. A side-by-side comparison of biodistribution and tumor targeting of [99mTc]Tc-(HE)3-E01 and [123I]I-(HE)3-E01-PIB was performed in Nu/j mice bearing EGFR-positive A-431 and EGFR-negative Ramos human cancer xenografts. Both radiolabeled DARPins demonstrated EGFR-specific tumor uptake. However, [123I]I-(HE)3-E01-PIB had appreciably lower uptake in normal organs compared to [99mTc]Tc-(HE)3-E01, which provided significantly (p < 0.05) higher tumor-to-organ ratios. Gamma-camera imaging confirmed that [123I]I-(HE)3-E01-PIB demonstrated a higher imaging contrast in preclinical models than [99mTc]Tc-(HE)3-E01. In conclusion, DARPin (HE)3-E01 labeled using a non-residualizing [123I]I-para-iodobenzoate (PIB) label is the preferred radiotracer for in vivo imaging of EGFR expression in cancer Текстовый файл
Language:	English
Published:	2025
Subjects:	EGFR imaging DARPin E01 radiolabeling technetium-99m iodine-123 residualizing label non-residualizing label tumor targeting biodistribution SPECT imaging электронный ресурс труды учёных ТПУ
Online Access:	https://doi.org/10.3390/ijms262110609
Format:	Electronic Book Chapter
KOHA link:	https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=684383

Internet

https://doi.org/10.3390/ijms262110609