An automated liquid chromatographic plasma analysis of amino acids used in combination with positron emission tomography (PET) for determination of in vivo plasma kinetics.
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 beta-[11C]-L-5-hydroxy-tryptophan ([11C]-L-5-HTP), beta-[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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Uppsala University PET Centre, Sweden.
K J
KJ
Lindner
P
P
Hartvig
N
N
Tyrefors
C
C
Hedlund
B
B
Långström
D006916:5-Hydroxytryptophan / Q000097:blood; D000596:Amino Acids / Q000097:blood* / Q000493:pharmacokinetics; D001322:Autoanalysis; D001798:Blood Proteins / Q000737:chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007202:Indicators and Reagents; D007980:Levodopa / Q000097:blood; D008715:Methionine / Q000031:analogs & derivatives / Q000097:blood; D008970:Molecular Weight; D012371:Robotics; D014055:Tomography, Emission-Computed
D000596:Amino Acids; D001798:Blood Proteins; D007202:Indicators and Reagents; D007980:Levodopa; D008715:Methionine; C038344:methionine methyl ester; D006916:5-Hydroxytryptophan