Journal article Open Access

[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke.

Boutin, Hervé; Murray, Katie; Pradillo, Jesus; Maroy, Renaud; Smigova, Alison; Gerhard, Alexander; Jones, Paul A; Trigg, William


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    <subfield code="u">Faculty of Life Sciences, University of Manchester, Manchester, UK; Present address: Universidad Complutense/Politecnica de Madrid, Madrid, Spain</subfield>
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    <subfield code="u">Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK</subfield>
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    <subfield code="u">Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK and Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK</subfield>
    <subfield code="a">Boutin, Hervé</subfield>
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    <subfield code="a">[18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke.</subfield>
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    <subfield code="a">Imaging of Neuroinflammation in Neurodegenerative Diseases</subfield>
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    <subfield code="a">Creative Commons Attribution 4.0 International</subfield>
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    <subfield code="a">&lt;p&gt;PURPOSE: Neuroinflammation plays a critical role in various neuropathological conditions, and hence there is renewed interest in the translocator protein (TSPO) as a biomarker of microglial activation and macrophage infiltration in the brain. This is reflected in the large amount of research conducted seeking to replace the prototypical PET radiotracer 11C-R-PK11195 with a TSPO ligand with higher performance. Here we report the in vivo preclinical investigation of the novel TSPO tracer 18F-GE-180 in a rat model of stroke.&lt;/p&gt;

&lt;p&gt;METHODS: Focal cerebral ischaemia was induced in Wistar rats by 60-min occlusion of the middle cerebral artery (MCAO). Brain damage was assessed 24 h after MCAO by T2 MRI. Rats were scanned with 11C-R-PK11195 and 18F-GE-180 5 or 6 days after MCAO. Specificity of binding was confirmed by injection of unlabelled R-PK11195 or GE-180 20 min after injection of 18F-GE-180. In vivo data were confirmed by ex vivo immunohistochemistry for microglial (CD11b) and astrocytic biomarkers (GFAP).&lt;/p&gt;

&lt;p&gt;RESULTS: 18F-GE-180 uptake was 24 % higher in the core of the ischaemic lesion and 18 % lower in the contralateral healthy tissue than that of 11C-R-PK11195 uptake (1.5&amp;thinsp;&amp;plusmn;&amp;thinsp;0.2-fold higher signal to noise ratio). We confirmed this finding using the simplified reference tissue model (BPND&amp;thinsp;=&amp;thinsp;3.5&amp;thinsp;&amp;plusmn;&amp;thinsp;0.4 and 2.4&amp;thinsp;&amp;plusmn;&amp;thinsp;0.5 for 18F-GE-180 and 11C-R-PK11195, respectively, with R 1 = 1). Injection of unlabelled R-PK11195 or GE-180 20 min after injection of 18F-GE-180 significantly displaced 18F-GE-180 (69&amp;thinsp;&amp;plusmn;&amp;thinsp;5 % and 63&amp;thinsp;&amp;plusmn;&amp;thinsp;4 %, respectively). Specificity of the binding was also confirmed by in vitro autoradiography, and the location and presence of activated microglia and infiltrated macrophages were confirmed by immunohistochemistry.&lt;/p&gt;

&lt;p&gt;CONCLUSION: The in vivo binding characteristics of 18F-GE-180 demonstrate a better signal to noise ratio than 11C-R-PK11195 due to both a better signal in the lesion and lower nonspecific binding in healthy tissue. These results provide evidence that 18F-GE-180 is a strong candidate to replace 11C-R-PK11195.&lt;/p&gt;</subfield>
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