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- Bragina, O. D., et al.
(author)
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A direct comparison of the diagnostic efficacy of alternative scaffold- based radiopharmaceuticals [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 in patients with HER2-positive breast cancer
- 2023
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In: BYULLETEN SIBIRSKOY MEDITSINY. - 1682-0363 .- 1819-3684. ; 22:3, s. 6-13
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Journal article (peer-reviewed)abstract
- Aim. To perform a direct comparison of the diagnostic efficacy of [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 in HER2-positive breast cancer patients before the systemic treatment.Materials and methods. The study included 11 patients with HER2-positive breast cancer (T1-4N0-2M0-1) before the initiation of systemic treatment. All patients underwent a radionuclide examination with [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 with the interval of 3-4 days. Single-photon emission computed tomography (SPECT) /computed tomography (CT) was performed 2 and 4 hours after [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 administration, respectively.Results. The analysis of [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 distribution showed their high uptake in the kidneys and liver. Breast tumors were visualized in all cases. The average tumor uptake of [(99)mTc]Tc-ADAPT6 was 4.7 +/- 2.1, which was significantly higher than in the [(99)mTc]Tc-(HE)3-G3 injection (3.5 +/- 1.7) (p < 0.005, paired t-test). The tumor-to-background ratio (15.2 +/- 7.4 and 19.6 +/- 12.4, respectively) had no statistical differences in both cases (p > 0.05, paired t -test). Liver metastases were visualized in patients 1 and 5 and corresponded to the projection of metastases according to contrast-enhanced abdominal CT. The accumulation of [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 in the projection of metastases in both cases was significantly higher compared to the primary tumor (1.3 and 1.7 times higher in patient 1; 2.2 and 3.5 times higher in patient 5, respectively).Conclusion. Both [(99)mTc]Tc-ADAPT6 and [(99)mTc]Tc-(HE)3-G3 demonstrated the diagnostic efficacy in visualizing a primary HER2-positive tumor in breast cancer patients. However, [(99)mTc]Tc-ADEPT6 had higher accumulation values, which makes it a more promising diagnostic agent.
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- Bragina, O. D., et al.
(author)
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Clinical possibilities of HER2-positive breast cancer diagnosis using alternative scaffold proteins
- 2022
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In: BYULLETEN SIBIRSKOY MEDITSINY. - : Siberian State Medical University. - 1682-0363 .- 1819-3684. ; 21:3, s. 132-139
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Journal article (peer-reviewed)abstract
- HER2-positive breast cancer occurs in 15-20% of breast cancer patients and is associated primarily with a poor prognosis of the disease and the need for highly specific targeted therapy. Despite the clinical importance of determining HER2/neu, traditional diagnostic methods have their disadvantages and require the study of new additional research techniques. The information presented in this review makes it possible to consider current trends in the radionuclide diagnosis of HER2-positive breast cancer using the latest class of alternative scaffold proteins and to consider various aspects of their use in clinical practice.
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- Bragina, O. D., et al.
(author)
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Possibilities of predicting the HER2 / neu status in a primary tumor in breast cancer patients using (99)mTc-DARPinG3
- 2022
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In: BYULLETEN SIBIRSKOY MEDITSINY. - : SIBERIAN STATE MEDICAL UNIV. - 1682-0363 .- 1819-3684. ; 21:4, s. 6-12
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Journal article (peer-reviewed)abstract
- Aim: To determine informative prognostic criteria for assessing the HER2 / neu status in primary breast cancer using 99mTc-DARPinG3.Materials and methods; The study included 10 patients with breast cancer (T1-4N0-2M0) before systemic therapy, who underwent a radionuclide study using 99mTc-DARPinG3 at a dose of 3,000 & mu;g. Five patients were characterized by HER2 / neu overexpression in primary breast cancer, whereas 5 patients were HER2-negative. For all patients, morphological and immunohistochemical studies and fluorescence in situ hybridization (FISH) of the primary tu-mor nodule were carried out. Single-photon emission computed tomography (SPECT) of the chest was performed for all patients 4 hours after the injection of 99mTc-DARPinG3.Results: The total activity of 99mTc-DARPinG3 was 522.4 & PLUSMN; 341.8 MBq. The comparative analysis showed that higher uptake of the labeled protein in HER2-positive breast cancer was significant (p = 0.0159, Mann - Whitney U test). The analysis of the ratios showed significant differences in the tumor-to-background ratios in patients with HER2-positive breast cancer (p < 0.0159, Mann - Whitney U test). Based on the logistic regression analysis, a mathematical model was developed to predict the status of HER2 / neu in primary breast cancer patients (specificity and sensitivity 100%; p = 0.0004) using 99mTc-DARPinG3 at a dose of 3,000 mcg 4 hours after the injection of the radiopharmaceutical.Conclusion: The results of the study allow to consider the tumor-to-background ratio 4 hours after the injection of 99mTc-DARPinG3 as an additional prognostic parameter for determining the HER2 / neu status in primary breast cancer.
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- Deyev, Sergey M., et al.
(author)
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Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:14
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Journal article (peer-reviewed)abstract
- Simple Summary Metastasis-targeting therapy might improve outcomes in oligometastatic prostate cancer. Epithelial cell adhesion molecule (EpCAM) is overexpressed in 40-60% of prostate cancer cases and might be used as a target for specific delivery of toxins and drugs. Radionuclide molecular imaging could enable non-invasive detection of EpCAM and stratification of patients for targeted therapy. Designed ankyrin repeat proteins (DARPins) are scaffold proteins, which can be selected for specific binding to different targets. The DARPin Ec1 binds strongly to EpCAM. To determine an optimal design of Ec1-based probes, we labeled Ec1 at two different positions with four different nuclides (Ga-68, In-111, Co-57 and I-125) and investigated the impact on Ec1 biodistribution. We found that the C-terminus is the best position for labeling and that In-111 and I-125 provide the best imaging contrast. This study might be helpful for scientists developing imaging probes based on scaffold proteins. The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40-60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an N- or C-terminal cysteine, were produced, site-specifically conjugated to a DOTA chelator and labeled with cobalt-57, gallium-68 or indium-111. Site-specific radioiodination was performed using ((4-hydroxyphenyl)-ethyl)maleimide (HPEM). Biodistribution of eight radiolabeled Ec1-probes was measured in nude mice bearing PCa DU145 xenografts. In all cases, positioning of a label at the C-terminus provided the best tumor-to-organ ratios. The non-residualizing [I-125]I-HPEM label provided the highest tumor-to-muscle and tumor-to-bone ratios and is more suitable for EpCAM imaging in early-stage PCa. Among the radiometals, indium-111 provided the highest tumor-to-blood, tumor-to-lung and tumor-to-liver ratios and could be used at late-stage PCa. In conclusion, label position and composition are important for the DARPin Ec1.
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