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).
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 labeled DPA-714 to C-11 labeled 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.
[18F]DPA-714 may be suitable for following development of muscular inflammation (Wu et al., 2014).
[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).
Published analysis methods
Chauveau et al. (2009) analyzed [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 analyzed mouse studies (Gargiulo et al., 2016). 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). 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 analyzed separately, with own control groups. SRTM or Logan plot with reference input can be used for computing parametric BPND images.
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Created at: 2009-02-27
Updated at: 2018-10-06
Written by: Vesa Oikonen