Ketone bodies labelled with positron emitting radionuclides allows in vivo PET studies of ketone metabolism (Bouteldja et al., 2014).
[1-11C]Acetoacetate ([11C]AcAc) and R-β-[1-11C]hydroxybutyrate ([11C]β-HB) follow the same transport and metabolism pathway through acetyl-CoA as acetate, enabling the use of the same models as are used to analyse [11C]acetate PET studies (Tremblay et al., 2007; Bentourkia et al., 2009; Croteau et al., 2014). [11C]β-HB and [11C]AcAc even equilibrate rapidly in vivo, and both of these tracers, but mostly [11C]β-HB, will be present in blood after administration of either of those (Blomqvist et al., 2002; Bentourkia et al., 2009).
[11C]AcAc brain data has been usually collected for 10 min after administration, and analysed using Patlak plot (Roy et al., 2012; Nugent et al., 2014; Castellano et al., 2015; Courchesne-Loyer et al., 2017; Croteau et al., 2018; Fortier et al., 2019; Cuenoud et al., 2020). Bentourkia et al (2009) fitted a two-tissue compartment model to rat brain data, using Ki = K1*k3/(k2+k3) multiplied by plasma concentration of unlabelled acetoacetate as the outcome parameter.
Cerebral metabolic rate of AcAc can be calculated from the Patlak plot or compartmental model derived net influx rate Ki as:
, where CAcAc is the concentration of AcAc in plasma, and LC is the lumped constant. LC=1.0, because [11C]AcAc is chemically identical to the native acetoacetate. Since [11C]AcAc is reversibly converted to β-HB in the body, the plasma concentration of β-HB may need to be included in CAcAc (Bentourkia et al., 2009). Based on the work of Blomqvist et al (1995), the cerebral metabolic rate of ketones could be estimates as the combined metabolic rates of AcAc and β-HB:
The ketone uptake in the liver, kidneys, and heart muscle has been assessed in humans with SUV method (Cuenoud et al., 2020). Myocardial data from rats has been analyzed using the same two-tissue compartment model as the brain data (Bentourkia et al., 2009).
[11C]AcAc may have some potential use in cancer studies. PET study in mouse models showed that uptake in tumours was clearly higher than in skeletal muscle, and slightly higher than the uptake of [11C]acetate (Authier et al., 2008).
Arterial input function
Arterial blood sampling is recommended, but image-derived input from left myocardial cavity and internal carotid arteries have also been used (Bentourkia et al., 2009; Roy et al., 2012; Nugent et al., 2014; Castellano et al., 2015). Blood TAC needs to be converted to plasma TAC. Plasma-to-blood ratio in a [11C]AcAc mice study (Authier et al., 2008, tables 2 and 3) was about 1.41 at 5 min p.i., and the ratio then stayed at the same level at 15 min and 30 min, and decreased to ∼1.25 at 60 min, suggesting that unchanged [11C]AcAc and its possible first radioactive metabolites stay in plasma, and only late metabolites can penetrate the red blood cell membrane.
The main radioactive metabolite in [11C]AcAc studies is [11C]CO2. Bentourkia et al (2009) applied an empiric two-parameter exponential function to correct for the fraction of metabolites in the plasma, and fitted these parameters with the compartmental model fit to the PET data. Nugent et al (2014) and Castellano et al (2015) corrected the estimate of the metabolic rate for the loss of [11C]CO2 from tissue with the assumption that it is the same as in [1-11C]β-HB study (Blomqvist et al., 1995).
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Updated at: 2023-08-24
Created at: 2017-06-28
Written by: Vesa Oikonen