Seweryn Krajewski, Lukasz Steczek, Karina Gotowicz, Urszula Karczmarczyk, Joanna Towpik, Ewa Witkowska-Patena, Krzysztof Łyczko, Maciej Mazur, Przemysław Kozanecki, Joanna Włostowska, Juhani Knuuti, Mirosław Dziuk, Piotr Garnuszek, Cezary Kozanecki
{"title":"用于 PET 心肌灌注成像的新型放射性同位素 [18F]SYN1 和 [18F]SYN2 的临床前评估。","authors":"Seweryn Krajewski, Lukasz Steczek, Karina Gotowicz, Urszula Karczmarczyk, Joanna Towpik, Ewa Witkowska-Patena, Krzysztof Łyczko, Maciej Mazur, Przemysław Kozanecki, Joanna Włostowska, Juhani Knuuti, Mirosław Dziuk, Piotr Garnuszek, Cezary Kozanecki","doi":"10.1186/s13550-024-01122-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Positron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the <sup>18</sup>F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [<sup>18</sup>F]SYN1 and [<sup>18</sup>F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer.</p><p><strong>Results: </strong>The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [<sup>18</sup>F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [<sup>18</sup>F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [<sup>18</sup>F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [<sup>18</sup>F]SYN1 and 0.0109 mSv/MBq for [<sup>18</sup>F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [<sup>18</sup>F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M<sub>1</sub> and M<sub>2</sub> receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule.</p><p><strong>Conclusion: </strong>[<sup>18</sup>F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [<sup>18</sup>F]SYN2 in clinical studies.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"63"},"PeriodicalIF":3.1000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231114/pdf/","citationCount":"0","resultStr":"{\"title\":\"Preclinical evaluation of [<sup>18</sup>F]SYN1 and [<sup>18</sup>F]SYN2, novel radiotracers for PET myocardial perfusion imaging.\",\"authors\":\"Seweryn Krajewski, Lukasz Steczek, Karina Gotowicz, Urszula Karczmarczyk, Joanna Towpik, Ewa Witkowska-Patena, Krzysztof Łyczko, Maciej Mazur, Przemysław Kozanecki, Joanna Włostowska, Juhani Knuuti, Mirosław Dziuk, Piotr Garnuszek, Cezary Kozanecki\",\"doi\":\"10.1186/s13550-024-01122-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Positron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the <sup>18</sup>F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [<sup>18</sup>F]SYN1 and [<sup>18</sup>F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer.</p><p><strong>Results: </strong>The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [<sup>18</sup>F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [<sup>18</sup>F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [<sup>18</sup>F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [<sup>18</sup>F]SYN1 and 0.0109 mSv/MBq for [<sup>18</sup>F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [<sup>18</sup>F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M<sub>1</sub> and M<sub>2</sub> receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule.</p><p><strong>Conclusion: </strong>[<sup>18</sup>F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [<sup>18</sup>F]SYN2 in clinical studies.</p>\",\"PeriodicalId\":11611,\"journal\":{\"name\":\"EJNMMI Research\",\"volume\":\"14 1\",\"pages\":\"63\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231114/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13550-024-01122-5\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13550-024-01122-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Preclinical evaluation of [18F]SYN1 and [18F]SYN2, novel radiotracers for PET myocardial perfusion imaging.
Background: Positron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the 18F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [18F]SYN1 and [18F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer.
Results: The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [18F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [18F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [18F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [18F]SYN1 and 0.0109 mSv/MBq for [18F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [18F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M1 and M2 receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule.
Conclusion: [18F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [18F]SYN2 in clinical studies.
EJNMMI ResearchRADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-
CiteScore
5.90
自引率
3.10%
发文量
72
审稿时长
13 weeks
期刊介绍：
EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies.
The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
