Quantification [18F]DPA-714 PET studies

DPA-714 (and previous molecule DPA-713) is a selective ligand for the translocator protein (TSPO), formerly known as peripheral benzodiazepine receptor (PBR). In human brain [11C]DPA-713 has much higher specific binding than the most used TSPO radioligand [11C]-(R)-PK11195 (Kobayashi et al., 2018).

James et al. (2008) performed [18F]DPA-714 PET studies with rats and a baboon (P. hamadryas). Studies have shown rapid brain uptake, good retention, and effective displacement (James et al., 2008). Spinal cord has been studied in rats (Abourbeh et al., 2012) and mice (Gargiulo et al., 2016).

Chauveau et al. (2009) compared F-18 labelled DPA-714 to C-11 labelled DPA-713 and to the classical (but not optimal) TSPO tracer [11C]-(R)-PK11195 in a rat model of acute neuroinflammation, and found that the highest binding potential (BP) and ipsilaterial-to-contralateral ratio were achieved with [18F]DPA-714. Displacement studies provided additional support for the usefulness of this tracer.

Lavisse et al. (2015a) studied cynomolgus monkeys, healthy and with induced neurodegeneration. Results also support the usefulness of [18F]DPA-714. Saba et al (2017) studied baboons, and noticed increased binding after acute alcohol exposure. In rat model, nalmefene prevents the increase of [18F]DPA-714 binding caused by binge-like ethanol exposure (Tournier et al., 2021).

Longitudinal [18F]DPA-714 PET imaging in transgenic mouse model of Alzheimer's disease could demonstrate increased neuroinflammation (Takkinen et al., 2017). In a mouse model of focal TBI [18F]DPA-714 has shown chronic neuroinflammation in regions remote from the initial site of injury (Hosomi et al., 2018). Depletion and repopulation of microglia can be tracked with [18F]DPA-714 PET in mice (Barca et al., 2022; Foray et al., 2022).

[18F]DPA-714 may be suitable for following development of inflammation in skeletal muscle (Wu et al., 2014). [124I]DPA-713 could be used for imaging macrophage-associated inflammation (Foss et al., 2018).

TSPO ligands shown promise in detecting brown adipose tissue because of its high content of mitochondria, and [18F]DPA-714 has shown promise in this respect (Wang et al., 2017; Niu et al., 2020).


[18F]DPA-714 and related radioligands contain the 18F on terminal position of an alkoxy chain, bonded to an aromatic moiety through oxygen atom, which has been shown to lead to appearance of radiometabolites in the plasma (Peyronneau et al., 2013). Radiometabolite formation could be reduced by attaching 18F directly to the aromatic ring (Keller et al., 2018).

In rats and baboons, [18F]DPA-714 is rapidly metabolized into at least three radiometabolites that are less lipophilic than the native radioligand (Peyronneau et al., 2013). Carboxylic acid derivative represents 15% of rat brain uptake 2 h after administration, but uptake is not specific and less than concentration in the plasma (Peyronneau et al., 2013). Chauveau et al. (2009) could detect only native radioligand in the brain 60 min after injection, and one radiometabolite in the plasma. Parent tracer fractions were 75%, 63% and 14% at 20, 40 and 60 min after injection (Chauveau et al., 2009). Similar results were obtained with [11C]DPA-713 (Boutin et al., 2007). In baboons the initial metabolism seems to be faster, with native tracer fractions of about 60% and 40% at 20 and 40 min (Peyronneau et al., 2013), but at 60 min the native tracer fraction is 30-40%, higher than in rats (Peyronneau et al., 2013; Saba et al., 2017).

Radiometabolites of [18F]DPA-714 are mainly excreted into urine, while parent radioligand is eliminated via the hepatobiliary route (Peyronneau et al., 2013).

Hill function has been fitted to plasma parent fractions (Van Weehaeghe et al., 2020).

Published analysis methods

Chauveau et al. (2009) analysed [18F]DPA-714 rat brain studies with SRTM, using contralateral ROI as reference input curve. PET scan duration was 70 min. BP was 3.08 ± 0.67. R1 was higher (1.64 ± 0.27) than with [11C]PK11195 (1.10 ± 0.06) or [11C]DPA-713 (1.30 ± 0.27). Wang et al. (2014) calculated simple lesion-to-normal ratio in rat brain injury model, and confirmed the result with displacement. SUV ratios have been used to analyse mouse studies (Gargiulo et al., 2016; Hosomi et al., 2019). Pottier et al (2014) quantified [18F]DPA-714 uptake as simple %ID/cc values at 45-60 min p.i. in a rat model of rheumatoid arthritis.

In cynomolgus monkeys VT was calculated using Logan plot and one-tissue compartmental model, and both methods provided similar results (Lavisse et al., 2015a).

For human studies it is necessary to do genotyping for high, mixed, and low affinity binders (HAB, MAB, and LAB, respectively), and LABs (about 11% of population) should be excluded from PET studies with [18F]DPA-714. Human brain data have been quantified using reversible 2-tissue compartmental model, Logan plot, and simplified reference tissue model using cerebellar grey matter as reference tissue (Golla et al., 2015 and 2016; Lavisse et al., 2015b; Van Weehaeghe et al., 2020). SRTM2 and Logan plot with reference input can provide accurate BPND images (Golla et al., 2016).

Suggested analysis method for Turku

Calculation of VT using Logan plot or reversible two-tissue compartmental model is recommended, if arterial input can be measured. If arterial input is not available, SUV can be used, or SUV ratio and simplified reference tissue model, if reference tissue is not affected by the studied disease or medication.

In human studies the different binding groups must be analysed separately, with own control groups. SRTM or Logan plot with reference input can be used for computing parametric BPND images.

See also:


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Updated at: 2023-01-01
Created at: 2009-02-27
Written by: Vesa Oikonen