Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1
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). Radio...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/14/3589 |
| _version_ | 1797527443605553152 |
|---|---|
| author | Sergey M. Deyev Tianqi Xu Yongsheng Liu Alexey Schulga Elena Konovalova Javad Garousi Sara S. Rinne Maria Larkina Haozhong Ding Torbjörn Gräslund Anna Orlova Vladimir Tolmachev Anzhelika Vorobyeva |
| author_facet | Sergey M. Deyev Tianqi Xu Yongsheng Liu Alexey Schulga Elena Konovalova Javad Garousi Sara S. Rinne Maria Larkina Haozhong Ding Torbjörn Gräslund Anna Orlova Vladimir Tolmachev Anzhelika Vorobyeva |
| author_sort | Sergey M. Deyev |
| collection | DOAJ |
| description | 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 (<i>N</i>- or <i>C</i>-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an <i>N</i>- or <i>C</i>-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 <i>C</i>-terminus provided the best tumor-to-organ ratios. The non-residualizing [<sup>125</sup>I]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. |
| first_indexed | 2024-03-10T09:43:49Z |
| format | Article |
| id | doaj.art-30a2d0c61c974613acc33ff194aec89c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:43:49Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-30a2d0c61c974613acc33ff194aec89c2023-11-22T03:25:50ZengMDPI AGCancers2072-66942021-07-011314358910.3390/cancers13143589Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1Sergey M. Deyev0Tianqi Xu1Yongsheng Liu2Alexey Schulga3Elena Konovalova4Javad Garousi5Sara S. Rinne6Maria Larkina7Haozhong Ding8Torbjörn Gräslund9Anna Orlova10Vladimir Tolmachev11Anzhelika Vorobyeva12Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaMolecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, SwedenDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, SwedenResearch Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, RussiaDepartment of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, 114 17 Stockholm, SwedenDepartment of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, 114 17 Stockholm, 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, RussiaThe 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 (<i>N</i>- or <i>C</i>-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an <i>N</i>- or <i>C</i>-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 <i>C</i>-terminus provided the best tumor-to-organ ratios. The non-residualizing [<sup>125</sup>I]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.https://www.mdpi.com/2072-6694/13/14/3589radionuclideEpCAMDARPinPETSPECTimaging |
| spellingShingle | Sergey M. Deyev Tianqi Xu Yongsheng Liu Alexey Schulga Elena Konovalova Javad Garousi Sara S. Rinne Maria Larkina Haozhong Ding Torbjörn Gräslund Anna Orlova Vladimir Tolmachev Anzhelika Vorobyeva Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1 Cancers radionuclide EpCAM DARPin PET SPECT imaging |
| title | Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1 |
| title_full | Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1 |
| title_fullStr | Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1 |
| title_full_unstemmed | Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1 |
| title_short | Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1 |
| title_sort | influence of the position and composition of radiometals and radioiodine labels on imaging of epcam expression in prostate cancer model using the darpin ec1 |
| topic | radionuclide EpCAM DARPin PET SPECT imaging |
| url | https://www.mdpi.com/2072-6694/13/14/3589 |
| work_keys_str_mv | AT sergeymdeyev influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT tianqixu influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT yongshengliu influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT alexeyschulga influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT elenakonovalova influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT javadgarousi influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT sarasrinne influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT marialarkina influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT haozhongding influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT torbjorngraslund influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT annaorlova influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT vladimirtolmachev influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 AT anzhelikavorobyeva influenceofthepositionandcompositionofradiometalsandradioiodinelabelsonimagingofepcamexpressioninprostatecancermodelusingthedarpinec1 |