PET imaging of enzyme activity

Enzyme activity

Molar concentration of enzymes cannot be measured in vivo, and in medical imaging the quantification of the activity of an enzyme is more useful than the mass of enzyme protein. Biochemists have traditionally defined the enzyme activity as the amount of enzyme that catalyses the transformation of 1 µmol of substrate into products in 1 min under standard conditions. The corresponding SI unit katal (kat) is defined as the amount of activity sufficient to catalyse the transformation of 1 mol of substrate into products in 1 s under standard conditions (Cornish-Bowden, 1995).

In vitro the rate of catalysis (rate of substrate consumption or product formation) can be quantified by chromatographic, spectroscopic or fluorescence methods. Optimal probes for in vivo studies have a product which is trapped within the site of the enzyme activity. Alternatively, the concentration of the enzyme can be measured using probes which are bound to the active site of the enzyme but are not catalysed (reversible or irreversible inhibitors), using quantification techniques similar to the receptor binding assays. Third option is to label enzyme activators/inhibitors which have a binding pocket separate from the active site in the enzyme molecule, for example glucokinase activators for imaging glucokinase enzyme in the pancreas and liver.

Quantification using PET

In in vivo PET studies the original substrate (radiopharmaceutical) and the product can only be separated mathematically from the kinetic radioactivity concentration curves.

The most commonly used PET radiopharmaceutical [18F]FDG is a probe depicting mainly the activity of hexokinase enzyme, based on the trapping of the product. [18F]FDOPA is used to quantify the activity of aromatic L-amino acid decarboxylase in the brain. Rempel et al (2017) have reviewed the PET (and SPECT) radiopharmaceuticals developed for imaging of hydrolytic enzyme activities. Imaging of aromatase was reviewed by Biegon (2016).

PET could be used to monitor enzyme replacement therapy (Phenix et al., 2010).

See also:


Cornish-Bowden A. Fundamentals of Enzyme Kinetics. Revised edition, Portland Press, 1995.

Cumming P, Vasdev N. The assay of enzyme activity by positron emission tomography. Neuromethods 2012; 71: 111-135. doi: 10.1007/7657_2012_53.

Hagberg GE, Torstenson R, Marteinsdottir I, Fredrikson M, Långström B, Blomqvist G. Kinetic compartment modeling of [11C]-5-hydroxy-L-tryptophan for positron emission tomography assessment of serotonin synthesis in human brain. J Cereb Blood Flow Metab. 2002; 22: 1352-1366. doi: 10.1097/01.WCB.0000040946.89393.9d.

Hicks JW. Discovery and preclinical evaluation of novel enzyme targeting radiotracers for positron emission tomography. Thesis. Institute of Medical Science, University of Toronto, 2015.

Holland JP, Cumming P, Vasdev N. PET radiopharmaceuticals for probing enzymes in the brain. Am J Nucl Med Mol Imaging 2013; 3(3): 194-216. PMID: 23638333.

Rempel BP, Price EW, Phenix CP. Molecular imaging of hydrolytic enzymes using PET and SPECT. Mol Imaging 2017; 16: 1536012117717852. doi: 10.1177/1536012117717852.


Updated at: 2019-03-07
Created at: 2015-08-03
Written by: Vesa Oikonen