| Title: |
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. |
| Authors: |
Larkina, Mariia; Yanovich, Gleb; Hasnowo, Lutfi Aditya; Varvashenya, Ruslan; Yuldasheva, Feruza; Tretyakova, Maria; Plotnikov, Evgenii; Zelchan, Roman; Schulga, Alexey; Konovalova, Elena; Ziganshin, Rustam; Belousov, Mikhail V; Tolmachev, Vladimir M.; Deyev, Sergey M |
| Publisher Information: |
Uppsala universitet, Institutionen för immunologi, genetik och patologi |
| Publication Year: |
2025 |
| Collection: |
Uppsala University: Publications (DiVA) |
| Subject Terms: |
DARPin E01; EGFR imaging; SPECT imaging; biodistribution; iodine-123; non-residualizing label; radiolabeling; residualizing label; technetium-99m; tumor targeting; Pharmacology and Toxicology; Farmakologi och toxikologi |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
International Journal of Molecular Sciences, 1661-6596, 2025, 26:21; PMID 41226646; ISI:001615224900001 |
| DOI: |
10.3390/ijms262110609 |
| Availability: |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-573428; https://doi.org/10.3390/ijms262110609 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.8B42CBA2 |
| Database: |
BASE |