A simplified analysis of [18F]3′-deoxy-3′-fluorothymidine metabolism and retention
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- Shields, A.F., Briston, D.A., Chandupatla, S. et al. Eur J Nucl Med Mol Imaging (2005) 32: 1269. doi:10.1007/s00259-005-1813-0
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Purpose: [18F]3′-deoxy-3′-fluorothymidine (FLT) is a thymidine analog developed for imaging tumor proliferation with positron emission tomography (PET). To quantitatively assess images, the blood activities of FLT and its glucuronidated metabolite were measured and its kinetics analyzed. This study sought to limit the number of blood samples needed to measure FLT retention.
Methods: Total FLT activity was measured from 18 venous samples obtained over the first hour and dynamic imaging performed on 33 patients (average dose 350 MBq/mmol). The 5-, 10-, 30- and 60-min samples were analyzed to measure the fraction of activity in FLT and its glucuronide. HPLC analysis was compared against a two-step column (Sep-Pak) and metabolic rates measured using full and limited sampling. Probenecid (2 g, oral) was given to two patients to determine whether imaging of the liver improved.
Results: At 60 min, 74% of the blood activity was unmetabolized (range 57–85%). HPLC and Sep-Pak gave comparable results (r=0.97; average difference 2.1%). For kinetic analysis, eight venous samples were sufficient to accurately measure total activity; for metabolite analysis, a single sample at 60 min yielded data with mean errors of 2.2%. The metabolic rate correlated with average SUV (r2=0.85; p=0.0002). An aorta input function gave kinetic results comparable to venous blood (r2= 0.82). Probenecid did not improve imaging of the liver.
Conclusion: Dynamic measurements of FLT retention can be used to calculate metabolic rates using a limited set of samples and correction for metabolites measured in a single sample obtained at 60 min.