[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats
Creators
- 1. Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom and Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom
- 2. Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom
- 3. Service Hospitalier Fre´de´ ric Joliot – Commissariat a` l’Energie Atomique, Orsay, France
- 4. Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom and Brain Injury Research Group, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom
- 5. Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom
- 6. North Western Medical Physics, Christie Hospital, Manchester, United Kingdom
- 7. School of Chemistry, University of Sydney, Sydney, Australia
- 8. School of Chemistry, University of Sydney, Sydney, Australia; Discipline of Medical Radiation Sciences, University of Sydney, Sydney, Australia and Brain and Mind Research Institute, University of Sydney, Sydney, Australia
Description
Purpose: Neuroinflammation 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.
Methods: Under 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.
Results: Uptake of [11C]PK11195 vs [18F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.8460.67 vs 2.2860.34 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 (3.3561.21 vs 4.6662.50 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.
Conclusions: In 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-tonoise 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.
Files
Boutin_PlosOne_2013_P10b.pdf
Files
(759.4 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:7f9f24dfacd8365d9e34a399403bf665
|
759.4 kB | Preview Download |