[18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.

<h4>Purpose</h4>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...

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Autores principales: Hervé Boutin, Christian Prenant, Renaud Maroy, James Galea, Andrew D Greenhalgh, Alison Smigova, Christopher Cawthorne, Peter Julyan, Shane M Wilkinson, Samuel D Banister, Gavin Brown, Karl Herholz, Michael Kassiou, Nancy J Rothwell
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spelling oai:doaj.org-article:aa87008173174959b566bbd213706a642021-11-18T07:57:37Z[18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.1932-620310.1371/journal.pone.0056441https://doaj.org/article/aa87008173174959b566bbd213706a642013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23418569/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Hervé BoutinChristian PrenantRenaud MaroyJames GaleaAndrew D GreenhalghAlison SmigovaChristopher CawthornePeter JulyanShane M WilkinsonSamuel D BanisterGavin BrownKarl HerholzMichael KassiouNancy J RothwellPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56441 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hervé Boutin
Christian Prenant
Renaud Maroy
James Galea
Andrew D Greenhalgh
Alison Smigova
Christopher Cawthorne
Peter Julyan
Shane M Wilkinson
Samuel D Banister
Gavin Brown
Karl Herholz
Michael Kassiou
Nancy J Rothwell
[18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.
description <h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
format article
author Hervé Boutin
Christian Prenant
Renaud Maroy
James Galea
Andrew D Greenhalgh
Alison Smigova
Christopher Cawthorne
Peter Julyan
Shane M Wilkinson
Samuel D Banister
Gavin Brown
Karl Herholz
Michael Kassiou
Nancy J Rothwell
author_facet Hervé Boutin
Christian Prenant
Renaud Maroy
James Galea
Andrew D Greenhalgh
Alison Smigova
Christopher Cawthorne
Peter Julyan
Shane M Wilkinson
Samuel D Banister
Gavin Brown
Karl Herholz
Michael Kassiou
Nancy J Rothwell
author_sort Hervé Boutin
title [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.
title_short [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.
title_full [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.
title_fullStr [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.
title_full_unstemmed [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.
title_sort [18f]dpa-714: direct comparison with [11c]pk11195 in a model of cerebral ischemia in rats.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/aa87008173174959b566bbd213706a64
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