Fractions of unchanged tracer in plasma
Background
Injected radioligand is metabolized in the body, and for most PET tracers, one or more of their metabolites still contain the isotope label and are released to the blood. The fractions of radioactive plasma metabolites must be measured and subtracted from plasma time-activity curve (TAC), because in the model calculations only parent tracer concentration can be used as model input.
If reference tissue input models can be used to analyze the results, there is no need to measure plasma or blood TACs nor the fractions of unchanged tracer and metabolites in the plasma.
Where the fraction data comes from?
For measuring the fractions of authentic tracer and labeled metabolites in the plasma, separate arterial or (usually) venous blood samples are taken following a predetermined timing schedule during the PET study. The blood samples are immediately placed in ice or mixed with an inhibitor to prevent further metabolism in the sample tube. Plasma is separated from the blood sample using a refrigerated centrifuge. The realtive fractions of the parent tracer and its labelled metabolite in each metabolite sample are determined withHPLC or TLC or other chromatographic methods either in the blood laboratory (Anne Roivainen) or in the MediCity laboratory (Merja Haaparanta).
The chemist or biochemist responsible for the metabolite analysis provides a list of measured fractions or percentages at the specific times, either on paper or by email, and currently in the PETO system.
In [15O]O2 studies, the only labeled metabolite in blood is [15O]H2O. Plasma curve is measured from separate blood samples, and used for the metabolite correction. The plasma curve is processed as usual.
How the fractions should be saved for further processing?
With any text editor (e.g. Textpad or Wordpad in Windows and Text Editor in Solaris), write an ASCII file (MSDOS text file format) containing one line per each sample time in minutes and corresponding fraction (not percentage) of the authentic tracer, separated by space(s) or tab(s). Use decimal point (not comma) as decimal separator. The fractions of the metabolite(s) need not to be written, but it can be done, if also the metabolite curve is needed in the analysis (e.g. [18F]FDOPA compartmental model analysis).
For example, a file uo0171ap.rat contains the fractions of authentic [11C]choline in plasma:
# Uo0171 # Time Choline fraction 1 1.00 5 0.79 10 0.51 15 0.40 20 0.36 25 0.28
As in the example, any number of comment lines starting with '#' can be included in the file.
Usually the measured fractions are not used in the metabolite correction as such, but only after fitting a mathematical function to the fractions.
