[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats

Abstract

PurposeNeuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [18F]DPA-714, it was compared directly to [11C]PK11195 in experimental cerebral ischaemia in rats.MethodsUnder anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [11C]PK11195 and/or [18F]DPA-714 under anaesthesia.ResultsUptake of [11C]PK11195 vs [18F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [11C]PK11195 or with [18F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [11C]PK11195 and [18F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [11C]PK11195 vs [18F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for [18F]DPA-714.ConclusionsIn a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [18F]DPA-714 displayed a higher signal-to-noise ratio than [11C]PK11195. Our results suggest that, with the longer half-life of [18F] which facilitates distribution of the tracer across PET centre, [18F]DPA-714 is a good alternative for TSPO imaging.

PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714

“…The low level expression of TSPO in normal brain tissues provides a decent contrast to outstand the inflammatory area. Therefore, [ 18 F]DPA-714 has been used for PET imaging of neuroinflammation in different models [9, 17, 21]. However, to the best of our knowledge, no application of this particular tracer in TBI model has been reported.…”

“…In vivo PET imaging using [ 11 C]PK11195 showed increased binding in TBI rats at day 10 after surgery [12]. However, the imaging contrast is not ideal, which may be due to the short physical half-life of 11 C and thus inadequate clearance of the tracer as well as the relatively high nonspecific binding of [ 11 C]PK11195 [21]. …”

Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe×PS1Δe9 transgenic mouse model of Alzheimer's disease

“…, ; Boutin et al . ). The correction method combined the geometric transfer matrix method and the regions of interest (ROI)‐opt method.…”

Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[18F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([18F]VUIIS1008) in Glioma

“…The purpose of the present study was to explore the in vivo imaging characteristics of the new ligand quantitatively in healthy mice and a rat model of glioma. Quantitative imaging data obtained in a preclinical glioma model using [ 18 F]VUIIS1008 were compared to an analogous study using a structurally similar pyrazolopyrimidine, [ 18 F]DPA-714, which has been advanced as a PET agent for neuroinflammation [19] and oncology [6, 16, 20]. …”