{"title":"99mTc(CO)3标记的1-(2-吡啶基)哌嗪衍生物作为5-HT7受体的放射性配体。","authors":"Alireza Mardanshahi, Samaneh Vaseghi, Seyed Jalal Hosseinimehr, Seyed Mohammad Abedi, Sajjad Molavipordanjani","doi":"10.1007/s12149-023-01885-2","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT<sub>7</sub>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<sub>7</sub>R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT<sub>7</sub>R imaging agents. </p><h3>Methods</h3><p>Compounds <b>6</b> and <b>7</b> as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with <i>fac</i>-[<sup>99m</sup>Tc(CO)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>]<sup>+</sup> and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] 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, <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] were applied for in vivo imaging in U-87 MG Xenografted models.</p><h3>Results</h3><p>Specific binding study indicates that <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] can recognize 5-HT<sub>7</sub>R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] 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<sub>7</sub>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 <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] at 60 min was 3.33 and 3.88, respectively. </p><h3>Conclusions</h3><p><sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] can visualize tumor in the U87-MG xenograft model due to their affinity toward 5-HT<sub>7</sub>R.</p><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8007,"journal":{"name":"Annals of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-HT7 receptors\",\"authors\":\"Alireza Mardanshahi, Samaneh Vaseghi, Seyed Jalal Hosseinimehr, Seyed Mohammad Abedi, Sajjad Molavipordanjani\",\"doi\":\"10.1007/s12149-023-01885-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT<sub>7</sub>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<sub>7</sub>R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT<sub>7</sub>R imaging agents. </p><h3>Methods</h3><p>Compounds <b>6</b> and <b>7</b> as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with <i>fac</i>-[<sup>99m</sup>Tc(CO)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>]<sup>+</sup> and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] 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, <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] were applied for in vivo imaging in U-87 MG Xenografted models.</p><h3>Results</h3><p>Specific binding study indicates that <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] can recognize 5-HT<sub>7</sub>R of U87-MG cell line. The biodistribution study in normal mice indicates that the brain uptake of <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] 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<sub>7</sub>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 <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] at 60 min was 3.33 and 3.88, respectively. </p><h3>Conclusions</h3><p><sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>6</b>] and <sup>99m</sup>Tc(CO)<sub>3</sub>-[<b>7</b>] can visualize tumor in the U87-MG xenograft model due to their affinity toward 5-HT<sub>7</sub>R.</p><h3>Graphical abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":8007,\"journal\":{\"name\":\"Annals of Nuclear Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-11-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Nuclear Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12149-023-01885-2\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Nuclear Medicine","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12149-023-01885-2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5-HT7 receptors
Background
The 5-hydroxytryptamine receptor (5-HTR) family includes seven classes of receptors. The 5-HT7R is the newest member of this family and contributes to different physiological and pathological processes. As a pathology, glioblastoma multiform (GBM) overexpresses 5-HT7R; hence, this study aims to develop radiolabeled aryl piperazine derivatives as 5-HT7R imaging agents.
Methods
Compounds 6 and 7 as 1-(3-nitropyridin-2-yl)piperazine derivatives were radiolabeled with fac-[99mTc(CO)3(H2O)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-HT7R 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-HT7R. 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-HT7R.
期刊介绍：
Annals of Nuclear Medicine is an official journal of the Japanese Society of Nuclear Medicine. It develops the appropriate application of radioactive substances and stable nuclides in the field of medicine.
The journal promotes the exchange of ideas and information and research in nuclear medicine and includes the medical application of radionuclides and related subjects. It presents original articles, short communications, reviews and letters to the editor.
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