| Title |
Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats
|
|---|---|
| Published in |
Molecular Imaging and Biology, August 2016
|
| DOI | 10.1007/s11307-016-0984-3 |
| Pubmed ID | |
| Authors |
Sujata Sridharan, Francois-Xavier Lepelletier, William Trigg, Samuel Banister, Tristan Reekie, Michael Kassiou, Alexander Gerhard, Rainer Hinz, Hervé Boutin |
| Abstract |
Over the past 20 years, neuroinflammation (NI) has increasingly been recognised as having an important role in many neurodegenerative diseases, including Alzheimer's disease. As such, being able to image NI non-invasively in patients is critical to monitor pathological processes and potential therapies targeting neuroinflammation. The translocator protein (TSPO) has proven a reliable NI biomarker for positron emission tomography (PET) imaging. However, if TSPO imaging in acute conditions such as stroke provides strong and reliable signals, TSPO imaging in neurodegenerative diseases has proven more challenging. Here, we report results comparing the recently developed TSPO tracers [(18)F]GE-180 and [(18)F]DPA-714 with (R)-[(11)C]PK11195 in a rodent model of subtle focal inflammation. Adult male Wistar rats were stereotactically injected with 1 μg lipopolysaccharide in the right striatum. Three days later, animals underwent a 60-min PET scan with (R)-[(11)C]PK11195 and [(18)F]GE-180 (n = 6) or [(18)F]DPA-714 (n = 6). Ten animals were scanned with either [(18)F]GE-180 (n = 5) or [(18)F]DPA-714 (n = 5) only. Kinetic analysis of PET data was performed using the simplified reference tissue model (SRTM) with a contralateral reference region or a novel data-driven input to estimate binding potential BPND. Autoradiography and immunohistochemistry were performed to confirm in vivo results. At 40-60 min post-injection, [(18)F]GE-180 dual-scanned animals showed a significantly increased core/contralateral uptake ratio vs. the same animals scanned with (R)-[(11)C]PK11195 (3.41 ± 1.09 vs. 2.43 ± 0.39, p = 0.03); [(18)]DPA-714 did not (2.80 ± 0.69 vs. 2.26 ± 0.41). Kinetic modelling with a contralateral reference region identified significantly higher binding potential (BPND) in the core of the LPS injection site with [(18)F]GE-180 but not with [(18)F]DPA-714 vs. (R)-[(11)C]PK11195. A cerebellar reference region and novel data-driven input to the SRTM were unable to distinguish differences in tracer BPND. Second-generation TSPO-PET tracers are able to accurately detect mild-level NI. In this model, [(18)F]GE-180 shows a higher core/contralateral ratio and BPND when compared to (R)-[(11)C]PK11195, while [(18)F]DPA-714 did not. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 84 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 84 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 23 | 27% |
| Student > Ph. D. Student | 17 | 20% |
| Student > Master | 12 | 14% |
| Professor > Associate Professor | 4 | 5% |
| Student > Bachelor | 3 | 4% |
| Other | 13 | 15% |
| Unknown | 12 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 16 | 19% |
| Neuroscience | 14 | 17% |
| Chemistry | 9 | 11% |
| Agricultural and Biological Sciences | 6 | 7% |
| Computer Science | 3 | 4% |
| Other | 20 | 24% |
| Unknown | 16 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 January 2017.
All research outputs
#3,561,046
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Outputs from Molecular Imaging and Biology
#53
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Outputs of similar age
#62,794
of 381,036 outputs
Outputs of similar age from Molecular Imaging and Biology
#1
of 19 outputs
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