99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-$ HT_{7} $ receptors
Background The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-$ HT_{7} $R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-$ HT_{7} $R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-$ HT_{7} $R imaging agents. Methods Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[99mTc(CO)3($ H_{2} $O)3]+ and 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were applied for in vivo imaging in U-87 MG Xenografted models. Results Specific binding study indicates that 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can recognize 5-$ HT_{7} $R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99mTc(CO)3-[6] and 99mTc(CO)3-[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor’s radiotracer uptake, indicating the binding of these radiotracers to the 5-$ HT_{7} $R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99mTc(CO)3-[6] and 99mTc(CO)3-[7] at 60 min was 3.33 and 3.88, respectively. Conclusions 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can visualize tumor in the U87-MG xenograft model due to their affinity toward 5-$ HT_{7} $R. Graphical abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Annals of nuclear medicine - 38(2023), 2 vom: 30. Nov., Seite 139-153 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mardanshahi, Alireza [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
5-HT |
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| Anmerkungen: |
© The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s12149-023-01885-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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SPR054553326 |
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| 520 | |a Background The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-$ HT_{7} $R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-$ HT_{7} $R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-$ HT_{7} $R imaging agents. Methods Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[99mTc(CO)3($ H_{2} $O)3]+ and 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were obtained with high radiochemical purity (RCP > 94%). The stability of the radiotracers was evaluated in both saline and mouse serum. Specific binding on different cell lines including U-87 MG, MCF-7, SKBR3, and HT-29 was performed. The biodistribution of these radiotracers was evaluated in normal and U-87 MG Xenografted models. Finally, 99mTc(CO)3-[6] and 99mTc(CO)3-[7] were applied for in vivo imaging in U-87 MG Xenografted models. Results Specific binding study indicates that 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can recognize 5-$ HT_{7} $R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of 99mTc(CO)3-[6] and 99mTc(CO)3-[7] is the highest at 30 min post-injection (0.8 ± 0.25 and 0.64 ± 0.18%ID/g, respectively). The data of the biodistribution study in the U87-MG xenograft model revealed that these radiotracers could accumulate in the tumor site, and the highest tumor uptake was observed at 60 min post-injection (3.38 ± 0.65 and 3.27 ± 0.5%ID/g, respectively). The injection of pimozide can block the tumor’s radiotracer uptake, indicating the binding of these radiotracers to the 5-$ HT_{7} $R. The imaging study in the xenograft model also confirms the biodistribution data. The acquired images clearly show the tumor site, and the tumor-to-muscle ratio for 99mTc(CO)3-[6] and 99mTc(CO)3-[7] at 60 min was 3.33 and 3.88, respectively. Conclusions 99mTc(CO)3-[6] and 99mTc(CO)3-[7] can visualize tumor in the U87-MG xenograft model due to their affinity toward 5-$ HT_{7} $R. Graphical abstract | ||
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