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":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"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\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"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\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13550-024-01114-5\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13550-024-01114-5","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","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.
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