Abstract
Quantification of physiological processes measured with positron emission tomography (PET) requires an “input” function which can be the concentration of administered radio-tracer in plasma. Radioactive nuclides used in PET have short half lives (2–20 min) and a limited time is available for the PET investigation including analysis of the composition of the radioactive signal in plasma. Therefore, an automated method for the analysis and separation of β-[ 11C]- l-5-hydroxy-tryptophan ([ 11C]- l-5-HTP), β-[ 11C]- l-3,4-dihydroxy-phenylalanine ([ 11C]- l-DOPA) and l-[methyl- 11C]-methionine and their respective metabolites in plasma was developed. A size exclusion column was used for isolation of the low molecular weight fraction. In the case of [ 11C]- l-5-HTP and [ 11C]- l-DOPA, the low molecular weight fraction was injected onto a liquid chromatographic system for separation of radioactive tracer from in vivo formed radio-labelled metabolites. The elution volume from the size exclusion column was 7.0, 5.0 and 3.5 ml for [ 11C]- l-5-HTP, [ 11C]- l-DOPA and l-[methyl- 11C]-methionine, respectively. An interaction with the column matrix and the solutes was observed for both [ 11C]- l-5-HTP and [ 11C]- l-DOPA. The yield in the isolation step was >98%. Separation of [ 11C]- l-5-HTP and [ 11C]- l-DOPA from their respective metabolites was performed with high-performance liquid chromatography with automated collection of fractions of the eluate corresponding to those of administered tracer and metabolites. The fractions were measured for radioactivity in a well counter. Inter- and intraday variation in retention were less than 3% RSD. Fortyfive minutes after injection of [ 11C]- l-5-HTP or [ 11C]- l-DOPA the radioactivity in the [ 11C]- l-5-HTP or [ 11C]- l-DOPA fraction was 58.5 ± 6.4 (RSD, n = 4) and 31.0 ± 2.7 (RSD, n = 3), respectively. High and low molecular weight fractions from plasma after injection of l-[methyl- 11C]-methionine were collected and measured for radioactivity. An incorporation of [ 11C]- l-methionine in plasma proteins, i.e. the high molecular weight fraction, was observed but with large inter-individual differences.
Published Version
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