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

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

Tolmachev, Vladimir (author): Uppsala universitet,Cancerprecisionsmedicin,Natl Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Uppsala Univ, Dept Immunol Genet & Pathol, Dag Hammarskjolds vag 20, S-75185 Uppsala, Sweden.

Bodenko, Vitalina (author): Natl Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia.

Orlova, Anna, 1960- (author): Uppsala universitet,Theranostics,Natl Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.

Schulga, Alexey (author): Natl Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.

Deyev, Sergey M. (author): Natl Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia.;Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.

Vorobyeva, Anzhelika (author): Uppsala universitet,Cancerprecisionsmedicin

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2022-11-17
2023
English.
In: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 25:1

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Journal article (peer-reviewed)

Abstract Subject headings

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-[I-125]iodobenzoyl ([I-125]PIB) groups. Both the I-125-labelled EVD (I-125-EVD) and Tc-99m-labelled EVD (Tc-99m-EVD) bound specifically to EpCAM-expressing SK-RC-52 renal carcinoma cells. The binding affinity (K-D value) of Tc-99m-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 I-125-EVD and 6.0 +/- 1.4%ID/g for Tc-99m-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 Tc-99m-EVD (25 +/- 6) compared with that of I-125-EVD (14 +/- 3). However, I-125-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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Keyword

RCC
EpCAM
radionuclide molecular imaging
SPECT
I-125
Tc-99m
DARPin Ec1
ESP

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