Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy
Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratification of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies, thereby making treatment personalized and more effici...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15181 |
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| author | Vladimir Tolmachev Vitalina Bodenko Maryam Oroujeni Sergey Deyev Elena Konovalova Alexey Schulga Sarah Lindbo Sophia Hober Olga Bragina Anna Orlova Anzhelika Vorobyeva |
| author_facet | Vladimir Tolmachev Vitalina Bodenko Maryam Oroujeni Sergey Deyev Elena Konovalova Alexey Schulga Sarah Lindbo Sophia Hober Olga Bragina Anna Orlova Anzhelika Vorobyeva |
| author_sort | Vladimir Tolmachev |
| collection | DOAJ |
| description | Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratification of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies, thereby making treatment personalized and more efficient. Clinical evaluation in a phase I study demonstrated that injections of two scaffold protein-based imaging probes, [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 and [<sup>99m</sup>Tc]Tc-ADAPT6, are safe, well-tolerated and cause a low level of radioactivity in healthy tissue. The goal of this preclinical study was to select the best probe for stratification of patients and response monitoring. Biodistribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 expression or MDA-MB-468 xenografts with very low expression. Changes in accumulation of the probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [<sup>99m</sup>Tc]Tc-ADAPT6 and [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 permitted high contrast imaging of HER2-expressing tumors and a clear discrimination between tumors with high and low HER2 expression. However, [<sup>99m</sup>Tc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 is capable of detecting the decrease of HER2 expression on response to trastuzumab therapy only 24 h after injection of the loading dose. This indicates that the [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 tracer would be better for monitoring early response to such treatment. The results of this study should be considered in planning of further clinical development of HER2 imaging probes. |
| first_indexed | 2024-03-09T17:44:12Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:12Z |
| publishDate | 2022-12-01 |
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| spelling | doaj.art-1993c20ee1914f64be505194cea7d5522023-11-24T11:14:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231518110.3390/ijms232315181Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab TherapyVladimir Tolmachev0Vitalina Bodenko1Maryam Oroujeni2Sergey Deyev3Elena Konovalova4Alexey Schulga5Sarah Lindbo6Sophia Hober7Olga Bragina8Anna Orlova9Anzhelika Vorobyeva10Department of Immunology, Genetics and Pathology, Uppsala University, 752 37 Uppsala, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 37 Uppsala, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaDepartment of Protein Science, KTH Royal Institute of Technology, 100 44 Stockholm, SwedenDepartment of Protein Science, KTH Royal Institute of Technology, 100 44 Stockholm, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 37 Uppsala, SwedenNon-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratification of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies, thereby making treatment personalized and more efficient. Clinical evaluation in a phase I study demonstrated that injections of two scaffold protein-based imaging probes, [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 and [<sup>99m</sup>Tc]Tc-ADAPT6, are safe, well-tolerated and cause a low level of radioactivity in healthy tissue. The goal of this preclinical study was to select the best probe for stratification of patients and response monitoring. Biodistribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 expression or MDA-MB-468 xenografts with very low expression. Changes in accumulation of the probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [<sup>99m</sup>Tc]Tc-ADAPT6 and [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 permitted high contrast imaging of HER2-expressing tumors and a clear discrimination between tumors with high and low HER2 expression. However, [<sup>99m</sup>Tc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 is capable of detecting the decrease of HER2 expression on response to trastuzumab therapy only 24 h after injection of the loading dose. This indicates that the [<sup>99m</sup>Tc]Tc-(HE)<sub>3</sub>-G3 tracer would be better for monitoring early response to such treatment. The results of this study should be considered in planning of further clinical development of HER2 imaging probes.https://www.mdpi.com/1422-0067/23/23/15181radionuclide molecular imagingHER2scaffold proteinsDARPinADAPT6technetium-99m |
| spellingShingle | Vladimir Tolmachev Vitalina Bodenko Maryam Oroujeni Sergey Deyev Elena Konovalova Alexey Schulga Sarah Lindbo Sophia Hober Olga Bragina Anna Orlova Anzhelika Vorobyeva Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy International Journal of Molecular Sciences radionuclide molecular imaging HER2 scaffold proteins DARPin ADAPT6 technetium-99m |
| title | Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy |
| title_full | Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy |
| title_fullStr | Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy |
| title_full_unstemmed | Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy |
| title_short | Direct In Vivo Comparison of <sup>99m</sup>Tc-Labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy |
| title_sort | direct in vivo comparison of sup 99m sup tc labeled scaffold proteins darpin g3 and adapt6 for visualization of her2 expression and monitoring of early response for trastuzumab therapy |
| topic | radionuclide molecular imaging HER2 scaffold proteins DARPin ADAPT6 technetium-99m |
| url | https://www.mdpi.com/1422-0067/23/23/15181 |
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