Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics
The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron em...
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MDPI AG
2025-01-01
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| Online Access: | https://www.mdpi.com/1420-3049/30/2/212 |
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| author | Lorraine Gaenaelle Gé Mathias Bogetoft Danielsen Aaraby Yoheswaran Nielsen Mathias Lander Skavenborg Niels Langkjær Helge Thisgaard Christine J. McKenzie |
| author_facet | Lorraine Gaenaelle Gé Mathias Bogetoft Danielsen Aaraby Yoheswaran Nielsen Mathias Lander Skavenborg Niels Langkjær Helge Thisgaard Christine J. McKenzie |
| author_sort | Lorraine Gaenaelle Gé |
| collection | DOAJ |
| description | The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (<sup>58m</sup>Co) and the Positron Emission Tomography-isotope cobalt-55 (<sup>55</sup>Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co<sup>2+</sup> and Co<sup>3+</sup>. With cobalt-57 (<sup>57</sup>Co) serving as a surrogate radionuclide for <sup>55/58m</sup>Co, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [<sup>57</sup>Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of <sup>57</sup>Co from the complex. In conclusion, [<sup>57</sup>Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR. |
| format | Article |
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| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-ab74bc03a6f04ca987a71a6af2e6f3402025-01-24T13:43:08ZengMDPI AGMolecules1420-30492025-01-0130221210.3390/molecules30020212Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted TheranosticsLorraine Gaenaelle Gé0Mathias Bogetoft Danielsen1Aaraby Yoheswaran Nielsen2Mathias Lander Skavenborg3Niels Langkjær4Helge Thisgaard5Christine J. McKenzie6Department of Nuclear Medicine, Odense University Hospital, Kloevervaenget 47, 5000 Odense C, DenmarkDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, DenmarkDepartment of Nuclear Medicine, Odense University Hospital, Kloevervaenget 47, 5000 Odense C, DenmarkDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, DenmarkDepartment of Nuclear Medicine, Odense University Hospital, Kloevervaenget 47, 5000 Odense C, DenmarkDepartment of Nuclear Medicine, Odense University Hospital, Kloevervaenget 47, 5000 Odense C, DenmarkDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, DenmarkThe overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (<sup>58m</sup>Co) and the Positron Emission Tomography-isotope cobalt-55 (<sup>55</sup>Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co<sup>2+</sup> and Co<sup>3+</sup>. With cobalt-57 (<sup>57</sup>Co) serving as a surrogate radionuclide for <sup>55/58m</sup>Co, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [<sup>57</sup>Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of <sup>57</sup>Co from the complex. In conclusion, [<sup>57</sup>Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR.https://www.mdpi.com/1420-3049/30/2/212theranosticsCo isotopes (<sup>58m</sup>Co<sup>57</sup>Co and <sup>55</sup>Co)polypyridyl chelatorGE11EGFR targeting |
| spellingShingle | Lorraine Gaenaelle Gé Mathias Bogetoft Danielsen Aaraby Yoheswaran Nielsen Mathias Lander Skavenborg Niels Langkjær Helge Thisgaard Christine J. McKenzie Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics Molecules theranostics Co isotopes (<sup>58m</sup>Co <sup>57</sup>Co and <sup>55</sup>Co) polypyridyl chelator GE11 EGFR targeting |
| title | Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics |
| title_full | Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics |
| title_fullStr | Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics |
| title_full_unstemmed | Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics |
| title_short | Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics |
| title_sort | radiocobalt labeling of a polypyridylamine chelate conjugated to ge11 for egfr targeted theranostics |
| topic | theranostics Co isotopes (<sup>58m</sup>Co <sup>57</sup>Co and <sup>55</sup>Co) polypyridyl chelator GE11 EGFR targeting |
| url | https://www.mdpi.com/1420-3049/30/2/212 |
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