Quantification of [11C]MTO PET

Etomidate is an imidazole-based potent inhibitor of steroid 11β-hydroxylase (mitochondrial cytochrome P450 11B1, CYP11B1) and aldosterone synthase (hydroxylase cytochrome P450, CYT11B2), which are key enzymes in the biosynthesis of cortisol and aldosterone (Mendichovszky et al., 2016). It is used as a short-acting intravenous sedative and anaesthetic agent, because it can modulate GABAA receptors at low concentrations, and functions as an allosteric agonist at higher concentrations. Bergström et al (1998) labelled etomidate and its methylated version with 11C and found that the methylated version, [O-methyl-11C]metomidate ([11C]MTO), is easier to synthesize and gives better image contrast in the adrenal cortex than the labelled etomidate.

In the adrenal cortex, steroid 11β-hydroxylase is expressed in zona glomerulosa and zona fasciculata, and aldosterone synthase is expressed in zona glomerulosa. Since [11C]MTO binds both of these enzymes, new aldosterone synthase specific radiopharmaceuticals have been developed, including [18F]CDP2230 and [18F]AldoView.

PET imaging with [O-methyl-11C]metomidate can be used in quantification of adrenal masses and to discriminate tumours of adrenal cortical origin from non-cortical lesions (Bergström et al., 2000; Khan et al., 2003; Zettinig et al., 2004). [11C]MTO is useful in imaging of adrenal incidentalomas (Minn et al., 2004). [11C]MTO is not optimal for subtype diagnosis in primary aldosteronism (Conn's syndrome) (Soinio et al., 2020).

Etomidate and its close analogue (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[18F]fluoroethylester (FETO) were shown to have potential to bind to GABAARs (Mitterhauser et al., 2003); same applies to [11C]MTO. GABA receptors are upregulated in hepatocellular carcinoma (HCC), but [11C]MTO did not show sufficient sensitivity for a clinical application (Roivainen et al., 2013).

Quantification of [11C]MTO PET

In both normal adrenals and adrenal adenomas plateau radioactivity is reached in ∼10 min after [11C]MTO administration, and kinetics thereafter remain rather stable up to 40 min (Minn et al., 2004).

Methods for quantification of [11C]MTO:

A strong relationship between SUV and Ki has been seen for all tumour types and normal adrenal glands (Minn et al., 2004). Thus a static PET scan without blood sampling is sufficient for clinical [11C]MTO PET.

Plasma data

Usually, arterial or arterialized venous blood samples are collected manually to measure the concentration of total radioactivity in plasma.

If radioactivity concentration is measured in blood instead of plasma (for example, image-derived input), the blood TACs must be converted to plasma before any further analysis.

Parent tracer is highly protein bound, while the metabolites dominate the protein free plasma; yet the plasma-to-blood ratio was about 1.2 during the 80-min study (Bergström et al., 2000). This suggests that parent tracer and its metabolites are distributed equally to the water space in the plasma and RBC.

Metabolite correction

Metomidate and etomidate are metabolized by hepatic and plasma esterases.

There are two major [11C]MTO metabolites in plasma. The rate of their appearance varies considerably between individual patients (Minn et al., 2004). In order to calculate Patlak plot (or FUR), the plasma radioactivity concentrations must be corrected for metabolites, and unchanged fractions must be individually measured (Minn et al., 2004). Without metabolite correction, Patlak plots are not usable, and replacing plasma input with spleen as reference tissue also leads to slightly curved plots (Bergström et al., 2000).

Correction for time delay

For Patlak or FUR analysis, correction for time delay is not required.

PET data

ROIs can be drawn and calculated from dynamic and parametric images as usual.


Literature

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Updated at: 2023-02-03
Created at: 2008-03-27
Written by: Vesa Oikonen