TY - JOUR
T1 - New improved radiometabolite analysis method for [ 18F]FTHA from human plasma
T2 - a test-retest study with postprandial and fasting state
AU - Aarnio, Richard
AU - Kirjavainen, Anna
AU - Rajander, Johan
AU - Forsback, Sarita
AU - Kalliokoski, Kari
AU - Nuutila, Pirjo
AU - Milicevic, Zvonko
AU - Coskun, Tamer
AU - Haupt, Axel
AU - Laitinen, Iina
AU - Haaparanta-Solin, Merja
N1 - © 2024. The Author(s).
PY - 2024/6/13
Y1 - 2024/6/13
N2 - 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. TRIAL REGISTRATION: EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.CLINICALTRIALS: gov/ct2/show/NCT05132335 .
AB - 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. TRIAL REGISTRATION: EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.CLINICALTRIALS: gov/ct2/show/NCT05132335 .
KW - Metabolic imaging
KW - Parent fraction
KW - Radio-TLC
KW - Radiometabolite analysis
KW - [f-18]ftha
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=aboakademi&SrcAuth=WosAPI&KeyUT=WOS:001249172700001&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1186/s13550-024-01114-5
DO - 10.1186/s13550-024-01114-5
M3 - Article
C2 - 38869780
SN - 2191-219X
VL - 14
JO - EJNMMI Research
JF - EJNMMI Research
IS - 1
M1 - 53
ER -