Richard Aarnio, Anna Kirjavainen, Johan Rajander, Sarita Forsback, Kari Kalliokoski, Pirjo Nuutila, Zvonko Milicevic, Tamer Coskun, Axel Haupt, Iina Laitinen, Merja Haaparanta-Solin
{"title":"人体血浆中[18F]FTHA 的新改进放射性代谢物分析方法：餐后和空腹状态下的重复测试研究。","authors":"Richard Aarnio, Anna Kirjavainen, Johan Rajander, Sarita Forsback, Kari Kalliokoski, Pirjo Nuutila, Zvonko Milicevic, Tamer Coskun, Axel Haupt, Iina Laitinen, Merja Haaparanta-Solin","doi":"10.1186/s13550-024-01114-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Fatty acid uptake can be measured using PET and 14-(R,S)-[<sup>18</sup>F]fluoro-6-thia-heptadecanoic acid ([<sup>18</sup>F]FTHA). However, the relatively rapid rate of [<sup>18</sup>F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [<sup>18</sup>F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [<sup>18</sup>F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [<sup>18</sup>F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [<sup>18</sup>F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.</p><p><strong>Results: </strong>The new TLC method separated seven [<sup>18</sup>F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [<sup>18</sup>F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [<sup>18</sup>F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.</p><p><strong>Conclusions: </strong>The newly developed improved radio-TLC method for [<sup>18</sup>F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [<sup>18</sup>F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [<sup>18</sup>F]FTHA metabolic rate under different study settings.</p><p><strong>Trial registration: </strong>EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT05132335 .</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"53"},"PeriodicalIF":3.1000,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176130/pdf/","citationCount":"0","resultStr":"{\"title\":\"New improved radiometabolite analysis method for [<sup>18</sup>F]FTHA from human plasma: a test-retest study with postprandial and fasting state.\",\"authors\":\"Richard Aarnio, Anna Kirjavainen, Johan Rajander, Sarita Forsback, Kari Kalliokoski, Pirjo Nuutila, Zvonko Milicevic, Tamer Coskun, Axel Haupt, Iina Laitinen, Merja Haaparanta-Solin\",\"doi\":\"10.1186/s13550-024-01114-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Fatty acid uptake can be measured using PET and 14-(R,S)-[<sup>18</sup>F]fluoro-6-thia-heptadecanoic acid ([<sup>18</sup>F]FTHA). However, the relatively rapid rate of [<sup>18</sup>F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [<sup>18</sup>F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [<sup>18</sup>F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [<sup>18</sup>F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [<sup>18</sup>F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.</p><p><strong>Results: </strong>The new TLC method separated seven [<sup>18</sup>F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [<sup>18</sup>F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [<sup>18</sup>F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.</p><p><strong>Conclusions: </strong>The newly developed improved radio-TLC method for [<sup>18</sup>F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [<sup>18</sup>F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [<sup>18</sup>F]FTHA metabolic rate under different study settings.</p><p><strong>Trial registration: </strong>EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT05132335 .</p>\",\"PeriodicalId\":11611,\"journal\":{\"name\":\"EJNMMI Research\",\"volume\":\"14 1\",\"pages\":\"53\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-06-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176130/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13550-024-01114-5\",\"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/s13550-024-01114-5","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}
New improved radiometabolite analysis method for [18F]FTHA from human plasma: a test-retest study with postprandial and fasting state.
Background: Fatty acid uptake can be measured using PET and 14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). However, the relatively rapid rate of [18F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [18F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [18F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [18F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [18F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.
Results: The new TLC method separated seven [18F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [18F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [18F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.
Conclusions: The newly developed improved radio-TLC method for [18F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [18F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [18F]FTHA metabolic rate under different study settings.
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
