Open Access

Visualization of epithelial cell adhesion molecule‑expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with 99mTc and 125I

  • Authors:
    • Vladimir Tolmachev
    • Vitalina Bodenko
    • Anna Orlova
    • Alexey Schulga
    • Sergey M. Deyev
    • Anzhelika Vorobyeva
  • View Affiliations

  • Published online on: November 17, 2022     https://doi.org/10.3892/ol.2022.13598
  • Article Number: 12
  • Copyright: © Tolmachev et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The upregulation of epithelial cell adhesion molecule (EpCAM) expression, found in a substantial fraction of renal cell carcinomas (RCCs), renders it a potential molecular target for the treatment of disseminated RCC. However, the heterogeneous expression of EpCAM necessitates first identifying the patients with sufficiently high expression of EpCAM in tumors. Using the specific radionuclide‑based visualization of EpCAM might enable such identification. The designed ankyrin repeat protein, Ec1, is a small (molecular weight, 18 kDa) targeting protein with a subnanomolar affinity to EpCAM. Using a modified Ec1, a tracer was developed for the radionuclide‑based visualization of EpCAM in vivo, i.e., an EpCAM‑visualizing designed ankyrin repeat protein (EVD). EVD was labelled with either technetium‑99m using technetium tricarbonyl or with iodine‑125 (as a surrogate for iodine‑123) by coupling it to para‑[125I]iodobenzoyl ([125I]PIB) groups. Both the 125I‑labelled EVD (125I‑EVD) and 99mTc‑labelled EVD (99mTc‑EVD) bound specifically to EpCAM‑expressing SK‑RC‑52 renal carcinoma cells. The binding affinity (KD value) of 99mTc‑EVD to SK‑RC‑52 cells was 400±28 pM. The tracers' uptake in SK‑RC‑52 xenografts at 3 h after injection was 5.2±1.4%ID/g for 125I‑EVD and 6.0±1.4%ID/g for 99mTc‑EVD (no significant difference). These uptake values in SK‑RC‑52 xenografts were significantly higher (P<0.001) than those in Ramos lymphoma xenografts (used as EpCAM‑negative control). The tumor‑to‑blood uptake ratio was significantly higher for 99mTc‑EVD (25±6) compared with that of 125I‑EVD (14±3). However, 125I‑EVD was associated with higher tumor‑to‑liver, tumor‑to‑salivary gland, tumor‑to‑spleen and tumor‑to‑intestinal wall ratios. This makes it the preferable tracer for visualizing EpCAM expression levels in the frequently occurring abdominal metastases of RCC.
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January-2023
Volume 25 Issue 1

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Spandidos Publications style
Tolmachev V, Bodenko V, Orlova A, Schulga A, Deyev SM and Vorobyeva A: Visualization of epithelial cell adhesion molecule‑expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with <sup>99m</sup>Tc and <sup>125</sup>I. Oncol Lett 25: 12, 2023
APA
Tolmachev, V., Bodenko, V., Orlova, A., Schulga, A., Deyev, S.M., & Vorobyeva, A. (2023). Visualization of epithelial cell adhesion molecule‑expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with <sup>99m</sup>Tc and <sup>125</sup>I. Oncology Letters, 25, 12. https://doi.org/10.3892/ol.2022.13598
MLA
Tolmachev, V., Bodenko, V., Orlova, A., Schulga, A., Deyev, S. M., Vorobyeva, A."Visualization of epithelial cell adhesion molecule‑expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with <sup>99m</sup>Tc and <sup>125</sup>I". Oncology Letters 25.1 (2023): 12.
Chicago
Tolmachev, V., Bodenko, V., Orlova, A., Schulga, A., Deyev, S. M., Vorobyeva, A."Visualization of epithelial cell adhesion molecule‑expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with <sup>99m</sup>Tc and <sup>125</sup>I". Oncology Letters 25, no. 1 (2023): 12. https://doi.org/10.3892/ol.2022.13598