title: [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.
abstract: OBJECTIVE
  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. [(18)F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [(18)F]DPA-714, it was compared directly to [(11)C]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 [(11)C]PK11195 and/or [(18)F]DPA-714 under anaesthesia.
  
  
  RESULTS
  Uptake of [(11)C]PK11195 vs [(18)F]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 [(11)C]PK11195 or with [(18)F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [(11)C]PK11195 and [(18)F]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 [(11)C]PK11195 vs [(18)F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3-1.9, 95%CI) fold by linear regression) for [(18)F]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 [(18)F]DPA-714 displayed a higher signal-to-noise ratio than [(11)C]PK11195. Our results suggest that, with the longer half-life of [(18)F] which facilitates distribution of the tracer across PET centre, [(18)F]DPA-714 is a good alternative for TSPO imaging.
authors: Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom. herve.boutin@manchester.ac.uk
authors: Hervé
authors: H
authors: Boutin
authors: Christian
authors: C
authors: Prenant
authors: Renaud
authors: R
authors: Maroy
authors: James
authors: J
authors: Galea
authors: Andrew D
authors: AD
authors: Greenhalgh
authors: Alison
authors: A
authors: Smigova
authors: Christopher
authors: C
authors: Cawthorne
authors: Peter
authors: P
authors: Julyan
authors: Shane M
authors: SM
authors: Wilkinson
authors: Samuel D
authors: SD
authors: Banister
authors: Gavin
authors: G
authors: Brown
authors: Karl
authors: K
authors: Herholz
authors: Michael
authors: M
authors: Kassiou
authors: Nancy J
authors: NJ
authors: Rothwell
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000175:diagnosis* / Q000000981:diagnostic imaging; D039481:CD11b Antigen / Q000378:metabolism; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007546:Isoquinolines; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles; D011743:Pyrimidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio
chemical_list: D039481:CD11b Antigen; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D005904:Glial Fibrillary Acidic Protein; D007546:Isoquinolines; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; C037850:PK 11195