New improved radiometabolite analysis method for [18F]FTHA from human plasma: a test-retest study with postprandial and fasting state

• Published in: EJNMMI research Vol. 14; no. 1; pp. 53 - 9
• Main Authors: Aarnio, Richard, Kirjavainen, Anna, Rajander, Johan, Forsback, Sarita, Kalliokoski, Kari, Nuutila, Pirjo, Milicevic, Zvonko, Coskun, Tamer, Haupt, Axel, Laitinen, Iina, Haaparanta-Solin, Merja
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 13.06.2024; Springer Nature B.V; SpringerOpen
• Subjects: [18F]FTHA; Blood plasma; Cardiac Imaging; Fasting; Imaging; Medicine; Medicine & Public Health; Metabolic imaging; Nuclear Medicine; Oncology; Original Research; Orthopedics; Parent fraction; Plasma; Radio-TLC; Radioactivity; Radiology; Radiometabolite analysis; Reproducibility; Thin layer chromatography; Parent fraction; Radio-TLC; Metabolic imaging; [; F]FTHA; Radiometabolite analysis; [18F]FTHA
• DOI: 10.1186/s13550-024-01114-5
• ISSN: 2191-219X

Background Fatty acid uptake can be measured using PET and 14-( R,S )‐[ 18 F]fluoro‐6‐thia‐heptadecanoic acid ([ 18 F]FTHA). However, the relatively rapid rate of [ 18 F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [ 18 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 [ 18 F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [ 18 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 [ 18 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. Results The new TLC method separated seven [ 18 F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [ 18 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 [ 18 F]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 [ 18 F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [ 18 F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [ 18 F]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 .