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Synthesis and evaluation of 99mTc-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5HT7 receptors.
Karimi, Maryam; Mardanshahi, Alireza; Irannejad, Hamid; Mohammad Abedi, Seyed; Molavipordanjani, Sajjad.
Afiliación
  • Karimi M; Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • Mardanshahi A; Department of Radiology and Nuclear Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • Irannejad H; Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • Mohammad Abedi S; Department of Radiology and Nuclear Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • Molavipordanjani S; Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: sajjad.molavi@gmail.com.
Bioorg Chem ; 135: 106486, 2023 06.
Article en En | MEDLINE | ID: mdl-36965286
Glioblastoma multiform (GBM) is one of the most aggressive tumors of the central nervous system in humans. GBM overexpresses serotonin-7 receptors (5-HT7Rs); hence, this study aims to develop 5-HT7R targeted radiotracers. Aryl piperazine derivatives can act as ligands for 5-HT7R. Therefore, compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were synthesized and radiolabeled with 99mTcN2+ core. Radiolabeled 6 and 7 (99mTcN-[6] and 99mTcN-[7]) were prepared with high radiochemical purity (RCP > 96%). They displayed high affinity toward U-87 MG cell line 5-HT7R. The calculated Ki for 99mTcN-[7] was lower than that of 99mTcN-[6] (14.85 ± 0.32 vs 22.57 ± 0.73 nM) which indicates the higher affinity of 99mTcN-[7] toward 5-HT7R. A molecular docking study also confirmed the binding of these radiotracers to 5-HT7R. The biodistribution study in normal mice revealed that 99mTcN-[7] has the highest brain accumulation at 30 min post-injection (0.54 ± 0.12 %ID/g) while the uptake of 99mTcN-[6] is much lower (0.14 ± 0.02 %ID/g). The biodistribution study in the xenograft model confirms that the radiotracers recognize the tumor site. 99mTcN-[6], and 99mTcN-[7] showed the highest tumor uptake at 1-hour post-injection (5.44 ± 0.58 vs 4.94 ± 1.65 %ID/g) and tumor-to-muscle ratios were (4.61 vs. 5.61). The injection of pimozide blocks the receptors and significantly reduces the tumor-to-muscle ratios at 1-hour post-injection to 0.81 and 0.31, respectively. In correlation with in vitro study, 99mTcN-[6] and 99mTcN-[7] visualize the tumor site in U-87 MG glioma xenografted nude mice and display the tumor-to-muscle ratios of 7.05 and 6.03.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Organotecnecio / Glioma Límite: Animals / Humans Idioma: En Revista: Bioorg Chem Año: 2023 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Organotecnecio / Glioma Límite: Animals / Humans Idioma: En Revista: Bioorg Chem Año: 2023 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Estados Unidos