# Correction of plasma TAC for metabolites

It is common that the PET tracer is metabolized in the liver, kidneys or other parts of the body already during the PET scan, and one or more of the metabolites is still carrying the isotope label. If labeled metabolites are found in the plasma in significant amounts, their proportion has to be subtracted from the plasma curve, because only the concentration of parent tracer can be used as input function in quantitative analysis of the tracer kinetics.

In brain studies the radioactive metabolites, that usually are
more polar than the authentic tracer, do not usually pass the
blood-brain barrier (BBB), but in other tissues,
especially in oncological studies, marked uptake of radioactive metabolite(s) can be observed.
In those cases the plasma concentrations of both the parent tracer and the radioactive metabolite
may have to included in the compartmental model or spectral analysis
(Tomasi et al., 2012;
Ichise et al., 2016).
Small polar radiometabolites, such as [^{11}C]formaldehyde and
[^{11}C]CO_{2} can pass even the
BBB, and substantially affect the brain tissue concentrations and reduce the signal-to-background
ratio (Johansen et al., 2018).
^{18}F-labelled radioligands are often defluorinated during the PET study; free
[^{18}F]F^{-} and other bone-seeking
isotopes, such as Zr^{4+}, may hamper brain PET studies by
causing high activity in the skull bone next to the brain cortex.

## Metabolite correction in TPC

The fractions of authentic (parent) tracer in plasma must be written in an ASCII file (fraction data). A mathematical function can be fitted to these fractions. Total radioactivity in plasma (PTAC) is measured from arterial plasma samples. With that and the fitted parent fractions, metabolite corrected plasma curve can be calculated using metabcor. TACs of radioactive metabolites in plasma can also be saved, if necessary.

## Alternative metabolite correction methods

### Mathematical metabolite correction

For references, see Burger and Buck (1996), and Sanabria-Bohórquez et al. (2000).

### Population based methods

Ideally, fractions of plasma metabolites should be measured for each person participating in
a PET study. However, the measured fraction curves are sometimes noisy, or there are missing samples.
One alternative is to calculate population average curve of
the fractions of parent tracer in the plasma, if the inter-individual variation in the rate of
metabolism is small. Population average must be determined from a group that is comparable to the
study population by their age, sex, and body weight. For example, for rate of metabolism of
[^{18}F]FDPN a significant gender difference has been found
(Henriksen et al., 2006).

The population average fraction curve can be fitted to a function, for example to the “Hill-type” or power or exponential functions, if there were only few samples or if the fraction curve must be extrapolated. In the fitting, use the weights that were written in the mean fraction curve.

## See also:

- Fractions of authentic tracer in plasma
- Converting percentage values to fractions in plasma parent fraction files
- Processing input data
- [
^{15}O]O_{2}metabolite correction - [
^{11}C]CO_{2}as a metabolite - Blood sampling

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Henriksen G, Spilker ME, Sprenger T, Hauser AI, Platzer S, Boecker H, Toelle TR, Schwaiger M,
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Nagar S, Argikar UA, Tweedie DJ (eds). *Enzyme Kinetics in Drug Metabolism - Fundamentals and
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Tags: Input function, Metabolite correction, Parent fraction, Plasma

Updated at: 2019-01-05

Created at: 2008-03-02

Written by: Vesa Oikonen