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Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I

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...

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Autores principales: Tolmachev, Vladimir, Bodenko, Vitalina, Orlova, Anna, Schulga, Alexey, Deyev, Sergey M., Vorobyeva, Anzhelika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713777/
https://www.ncbi.nlm.nih.gov/pubmed/36478911
http://dx.doi.org/10.3892/ol.2022.13598
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author Tolmachev, Vladimir
Bodenko, Vitalina
Orlova, Anna
Schulga, Alexey
Deyev, Sergey M.
Vorobyeva, Anzhelika
author_facet Tolmachev, Vladimir
Bodenko, Vitalina
Orlova, Anna
Schulga, Alexey
Deyev, Sergey M.
Vorobyeva, Anzhelika
author_sort Tolmachev, Vladimir
collection PubMed
description 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-[(125)I]iodobenzoyl ([(125)I]PIB) groups. Both the (125)I-labelled EVD ((125)I-EVD) and (99m)Tc-labelled EVD ((99m)Tc-EVD) bound specifically to EpCAM-expressing SK-RC-52 renal carcinoma cells. The binding affinity (K(D) value) of (99m)Tc-EVD to SK-RC-52 cells was 400±28 pM. The tracers' uptake in SK-RC-52 ×enografts at 3 h after injection was 5.2±1.4%ID/g for (125)I-EVD and 6.0±1.4%ID/g for (99m)Tc-EVD (no significant difference). These uptake values in SK-RC-52 ×enografts 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 (99m)Tc-EVD (25±6) compared with that of (125)I-EVD (14±3). However, (125)I-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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spelling pubmed-97137772022-12-06 Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I Tolmachev, Vladimir Bodenko, Vitalina Orlova, Anna Schulga, Alexey Deyev, Sergey M. Vorobyeva, Anzhelika Oncol Lett Articles 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-[(125)I]iodobenzoyl ([(125)I]PIB) groups. Both the (125)I-labelled EVD ((125)I-EVD) and (99m)Tc-labelled EVD ((99m)Tc-EVD) bound specifically to EpCAM-expressing SK-RC-52 renal carcinoma cells. The binding affinity (K(D) value) of (99m)Tc-EVD to SK-RC-52 cells was 400±28 pM. The tracers' uptake in SK-RC-52 ×enografts at 3 h after injection was 5.2±1.4%ID/g for (125)I-EVD and 6.0±1.4%ID/g for (99m)Tc-EVD (no significant difference). These uptake values in SK-RC-52 ×enografts 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 (99m)Tc-EVD (25±6) compared with that of (125)I-EVD (14±3). However, (125)I-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. D.A. Spandidos 2022-11-17 /pmc/articles/PMC9713777/ /pubmed/36478911 http://dx.doi.org/10.3892/ol.2022.13598 Text en Copyright: © Tolmachev et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Tolmachev, Vladimir
Bodenko, Vitalina
Orlova, Anna
Schulga, Alexey
Deyev, Sergey M.
Vorobyeva, Anzhelika
Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I
title Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I
title_full Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I
title_fullStr Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I
title_full_unstemmed Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I
title_short Visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein Ec1 labelled with (99m)Tc and (125)I
title_sort visualization of epithelial cell adhesion molecule-expressing renal cell carcinoma xenografts using designed ankyrin repeat protein ec1 labelled with (99m)tc and (125)i
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713777/
https://www.ncbi.nlm.nih.gov/pubmed/36478911
http://dx.doi.org/10.3892/ol.2022.13598
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