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 language | English |
|---|---|
| Article number | 6930425 |
| Journal | Contrast Media and Molecular Imaging |
| Volume | 2018 |
| DOIs | |
| Publication status | Published - 1 Jan 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Comparative Evaluation of Radioiodine and Technetium-Labeled DARPin 9-29 for Radionuclide Molecular Imaging of HER2 Expression in Malignant Tumors
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
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85049219946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049219946&partnerID=8YFLogxK
U2 - 10.1155/2018/6930425
DO - 10.1155/2018/6930425
M3 - Article
AN - SCOPUS:85049219946
VL - 2018
JO - Contrast Media and Molecular Imaging
JF - Contrast Media and Molecular Imaging
SN - 1555-4309
M1 - 6930425
ER -