L-[11C]methionine PET

L-Methionine

Methionine (Met) is a naturally occurring essential amino acid in humans. Methione is an intermediate in the biosynthesis of cysteine, carnitine, taurine, and phospholipids. It is used in protein synthesis, and as S-adenosyl-L-methionine in enzymatic transmethylation reactions. When S-adenosylmethione has lost its methyl group, the resulting S-adenosylhomocusteine may be converted to homocysteine. Homocysteine can be used to regenerate methionine or cysteine, the only other sulfur-containing amino acid.

L-Methionine is transported into cells via the L-type amino acid transporter 1 (LAT1). In tumours, the demand for L-methionine increases, with increased protein and phospholipid synthesis (Stern et al., 1984; Leskinen-Kallio et al., 1991).

Radioligands

L-Methionine can be labelled with the positron emitting radionuclide 11C to obtain the chemically identical PET tracer. 11C has been attached to the methyl and carboxylic group, producing L-[methyl-11C]methionine and L-[1-11C]methionine, respectively.

When L-methionine is labelled to the methyl group, the radionuclide will follow the methyl group in transmethylation reactions into various small and large molecules. Transmethylation reactions of carboxylic-labelled L-methionine leads to formation of S-adenosyl-L-[1-11C]methionine, and further to S-adenosyl-L-[1-11C]homocysteine, which is again precursor of protein and methionine synthesis (Ishiwata et al., 1988). Decarboxylation reactions lead to formation of [11C]CO2, which, in addition to pulmonary clearance, can be incorporated into nonvolatile compounds such as [11C]urea, [11C]glucose, and [11C]lactate.

In tumours, the total uptake rates of the two L-methionines are similar, but in healthy tissues, especially in the liver the uptake kinetics and the labelled compounds are different (Ishiwata et al., 1988).

L-[11C]methionine tracers are mainly used to detect malignant tumours, especially in head and neck cancer, and inflammation, since L-methionine accumulates also in tissues with active inflammation and during tissue repair. The high L-[11C]methionine uptake in salivary glands and nasal epithelium may hamper the tumour imaging, but that is a common problem with tracers that target increasing metabolism. S-[11C]-methyl-L-cysteine does not accumulate in the salivary glands, but its uptake in healthy brain is higher than that of L-[11C]methionine (Parente et al., 2018).

In clinical use, the L-[methyl-11C]methionine PET data is usually analyzed using simple SUV or SUV ratio methods. Horsager et al. (2017) analyzed pig liver L-[methyl-11C]methionine data using extended Patlak plot, including kloss to account for the loss of 11C-proteins and 11C-metabolites from the liver. The flux (metabolic rate) of methionine from plasma to liver was calculated by multiplying Ki by plasma L-methionine concentration. About 17 min p.i. the plasma 11C-protein concentration increased linearly, and the slope was reported as the appearance rate of 11C-proteins in plasma, Rprot.

Syrota et al (1979 and 1981) and Takasu et al. (2001) proposed using L-[methyl-11C]methionine for measurement of exocrine pancreatic function.


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References:

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Created at: 2017-06-27
Updated at: 2018-05-14
Written by: Vesa Oikonen