Highlights► Risk factors for stroke include atherosclerosis, obesity, diabetes and hypertension. ► Stroke risk factors are associated with peripheral inflammation. ► Corpulent rats and atherogenic mice show increased inflammation in the brain. ► Pilot data show that patients at risk of stroke may also develop brain inflammation. ► Chronic peripheral inflammation can drive inflammatory changes in the brain.

N-(llC) methyl, N-(methyl-1 propyl), (chloro-2 phenylj-1 isoquinoleine carboxamide-3 (PK 11195) o r ( l l C ) MPCI was synthetized in a short time (45 min) and high s p e c i f i c a c t i v i t y (769 Ci/mmol) for the positron emission tomography of peripheral benzodiazepine receptors in heart, kidney and brain. The precursor used was the N-desmethyl MPCI (PCI). The radioactive reagent was the ( l k ) methyl iodide obtained from nuclear reaction 14N ( p , a ) 11C vit: 11CO2 and 11CH30H. The chemical p u r i t y of the end-product was checked, a f t e r HPLC p u r i f ication, by chemical ionisation mass spectrometry i n the para1 l e l synthesis of cold MPCI. The methylation, reversed phase HPLC p u r i f i c a t i o n , evaporation times were 10, 6 min respectively so t h a t s t e r i l e and i s o t o n i c i n j e c t a b l e solution o f ( l k ) MPCI ready f o r use may be obtained, i n l e s s t h a n 45 min a f t e r the end of nuclear bombardment.

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.

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