Comparative Evaluation of Radioiodine and Technetium-Labeled DARPin 9-29 for Radionuclide Molecular Imaging of HER2 Expression in Malignant Tumors

Anzhelika Vorobyeva, Olga Bragina, Mohamed Altai, Bogdan Mitran, Anna Orlova, Alexey Shulga, Galina Proshkina, Vladimir Chernov, Vladimir Tolmachev, Sergey Deyev

Research output: Contribution to journalArticle

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Abstract

High expression of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal carcinomas is a predictive biomarker for treatment using HER2-targeted therapeutics (antibodies trastuzumab and pertuzumab, antibody-drug conjugate trastuzumab DM1, and tyrosine kinase inhibitor lapatinib). Radionuclide molecular imaging of HER2 expression might permit stratification of patients for HER2-targeting therapies. In this study, we evaluated a new HER2-imaging probe based on the designed ankyrin repeat protein (DARPin) 9-29. DARPin 9-29 was labeled with iodine-125 by direct radioiodination and with [99mTc]Tc(CO)3 using the C-terminal hexahistidine tag. DARPin 9-29 preserved high specificity and affinity of binding to HER2-expressing cells after labeling. Uptake of [125I]I-DARPin 9-29 and [99mTc]Tc(CO)3-DARPin 9-29 in HER2-positive SKOV-3 xenografts in mice at 6 h after injection was 3.4 ± 0.7 %ID/g and 2.9 ± 0.7 %ID/g, respectively. This was significantly (p<0.00005) higher than the uptake of the same probes in HER2-negative Ramos lymphoma xenografts, 0.22 ± 0.09 %ID/g and 0.30 ± 0.05 %ID/g, respectively. Retention of [125I]I-DARPin 9-29 in the lung, liver, spleen, and kidneys was appreciably lower compared with [99mTc]Tc(CO)3-DARPin 9-29, which resulted in significantly (p<0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by SPECT/CT imaging. In conclusion, radioiodine is a preferable label for DARPin 9-29.

Original languageEnglish
Article number6930425
JournalContrast Media and Molecular Imaging
Volume2018
DOIs
Publication statusPublished - 1 Jan 2018

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Ankyrin Repeat
Molecular Imaging
Technetium
Radionuclide Imaging
Neoplasms
Proteins
Carbon Monoxide
His-His-His-His-His-His
Heterografts
human ERBB2 protein
Antibodies
Iodine
Protein-Tyrosine Kinases
Lymphoma
Therapeutics
Spleen
Biomarkers
Breast Neoplasms
Kidney
Lung

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Comparative Evaluation of Radioiodine and Technetium-Labeled DARPin 9-29 for Radionuclide Molecular Imaging of HER2 Expression in Malignant Tumors. / Vorobyeva, Anzhelika; Bragina, Olga; Altai, Mohamed; Mitran, Bogdan; Orlova, Anna; Shulga, Alexey; Proshkina, Galina; Chernov, Vladimir; Tolmachev, Vladimir; Deyev, Sergey.

In: Contrast Media and Molecular Imaging, Vol. 2018, 6930425, 01.01.2018.

Research output: Contribution to journalArticle

Vorobyeva, Anzhelika ; Bragina, Olga ; Altai, Mohamed ; Mitran, Bogdan ; Orlova, Anna ; Shulga, Alexey ; Proshkina, Galina ; Chernov, Vladimir ; Tolmachev, Vladimir ; Deyev, Sergey. / Comparative Evaluation of Radioiodine and Technetium-Labeled DARPin 9-29 for Radionuclide Molecular Imaging of HER2 Expression in Malignant Tumors. In: Contrast Media and Molecular Imaging. 2018 ; Vol. 2018.
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abstract = "High expression of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal carcinomas is a predictive biomarker for treatment using HER2-targeted therapeutics (antibodies trastuzumab and pertuzumab, antibody-drug conjugate trastuzumab DM1, and tyrosine kinase inhibitor lapatinib). Radionuclide molecular imaging of HER2 expression might permit stratification of patients for HER2-targeting therapies. In this study, we evaluated a new HER2-imaging probe based on the designed ankyrin repeat protein (DARPin) 9-29. DARPin 9-29 was labeled with iodine-125 by direct radioiodination and with [99mTc]Tc(CO)3 using the C-terminal hexahistidine tag. DARPin 9-29 preserved high specificity and affinity of binding to HER2-expressing cells after labeling. Uptake of [125I]I-DARPin 9-29 and [99mTc]Tc(CO)3-DARPin 9-29 in HER2-positive SKOV-3 xenografts in mice at 6 h after injection was 3.4 ± 0.7 {\%}ID/g and 2.9 ± 0.7 {\%}ID/g, respectively. This was significantly (p<0.00005) higher than the uptake of the same probes in HER2-negative Ramos lymphoma xenografts, 0.22 ± 0.09 {\%}ID/g and 0.30 ± 0.05 {\%}ID/g, respectively. Retention of [125I]I-DARPin 9-29 in the lung, liver, spleen, and kidneys was appreciably lower compared with [99mTc]Tc(CO)3-DARPin 9-29, which resulted in significantly (p<0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by SPECT/CT imaging. In conclusion, radioiodine is a preferable label for DARPin 9-29.",
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AU - Vorobyeva, Anzhelika

AU - Bragina, Olga

AU - Altai, Mohamed

AU - Mitran, Bogdan

AU - Orlova, Anna

AU - Shulga, Alexey

AU - Proshkina, Galina

AU - Chernov, Vladimir

AU - Tolmachev, Vladimir

AU - Deyev, Sergey

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AB - High expression of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal carcinomas is a predictive biomarker for treatment using HER2-targeted therapeutics (antibodies trastuzumab and pertuzumab, antibody-drug conjugate trastuzumab DM1, and tyrosine kinase inhibitor lapatinib). Radionuclide molecular imaging of HER2 expression might permit stratification of patients for HER2-targeting therapies. In this study, we evaluated a new HER2-imaging probe based on the designed ankyrin repeat protein (DARPin) 9-29. DARPin 9-29 was labeled with iodine-125 by direct radioiodination and with [99mTc]Tc(CO)3 using the C-terminal hexahistidine tag. DARPin 9-29 preserved high specificity and affinity of binding to HER2-expressing cells after labeling. Uptake of [125I]I-DARPin 9-29 and [99mTc]Tc(CO)3-DARPin 9-29 in HER2-positive SKOV-3 xenografts in mice at 6 h after injection was 3.4 ± 0.7 %ID/g and 2.9 ± 0.7 %ID/g, respectively. This was significantly (p<0.00005) higher than the uptake of the same probes in HER2-negative Ramos lymphoma xenografts, 0.22 ± 0.09 %ID/g and 0.30 ± 0.05 %ID/g, respectively. Retention of [125I]I-DARPin 9-29 in the lung, liver, spleen, and kidneys was appreciably lower compared with [99mTc]Tc(CO)3-DARPin 9-29, which resulted in significantly (p<0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by SPECT/CT imaging. In conclusion, radioiodine is a preferable label for DARPin 9-29.

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