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[18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain.

Tiwari AK, Ji B, Yui J, Fujinaga M, Yamasaki T, Xie L, Luo R, Shimoda Y, Kumata K, Zhang Y, Hatori A, Maeda J, Higuchi M, Wang F, Zhang MR - Theranostics (2015)

Bottom Line: PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 ± 0.12, compared to non-injured striatum.In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [(18)F]FEBMP.These findings suggest that [(18)F]FEBMP is a promising new tool for visualization of neuroinflammation.

View Article: PubMed Central - PubMed

Affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan ; 2. Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.

ABSTRACT
We evaluated the efficacy of 2-[5-(4-[(18)F]fluoroethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methyl-N-phenylacetamide] ([(18)F]FEBMP) for positron emission tomography (PET) imaging of translocator protein (18 kDa, TSPO). Dissection was used to determine the distribution of [(18)F]FEBMP in mice, while small-animal PET and metabolite analysis were used for a rat model of focal cerebral ischemia. [(18)F]FEBMP showed high radioactivity uptake in mouse peripheral organs enriched with TSPO, and relatively high initial brain uptake (2.67 ± 0.12% ID/g). PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 ± 0.12, compared to non-injured striatum. Displacement with specific TSPO ligands lowered the accumulation levels in infarcts to those on the contralateral side. This suggests that the increased accumulation reflected TPSO-specific binding of [(18)F]FEBMP in vivo. Using a simplified reference tissue model, the binding potential on the infarcted area was 2.72 ± 0.27. Metabolite analysis in brain tissues showed that 83.2 ± 7.4% and 76.4 ± 2.1% of radioactivity was from intact [(18)F]FEBMP at 30 and 60 min, respectively, and that this ratio was higher than in plasma (8.6 ± 1.9% and 3.9 ± 1.1%, respectively). In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [(18)F]FEBMP. These findings suggest that [(18)F]FEBMP is a promising new tool for visualization of neuroinflammation.

No MeSH data available.


Related in: MedlinePlus

Displacement with unlabelled TSPO ligands for [18F]FEBMP uptake. A-C: Representative coronal PET summation images (A; 0-20 min, B; 30-90 min) of [18F]FEBMP and the time-activity curve (C; mean ± SEM, n = 3) in an ischemic rat model that received additional treatment with unlabelled MBMP at 20 min after [18F]FEBMP bolus injection. D-F: Representative coronal PET summation images (D; 0-20 min, E; 30-90 min) of [18F]FEBMP and the time-activity curve (F; mean ± SEM, n = 3) in a rat model of ischemia. The rat received additional treatment with unlabelled PK11195 at 20 min after [18F]FEBMP bolus injection. Ipsilateral and contralateral indicate ipsilateral and contralateral sides of the ischemic brain in the striatum.
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Figure 3: Displacement with unlabelled TSPO ligands for [18F]FEBMP uptake. A-C: Representative coronal PET summation images (A; 0-20 min, B; 30-90 min) of [18F]FEBMP and the time-activity curve (C; mean ± SEM, n = 3) in an ischemic rat model that received additional treatment with unlabelled MBMP at 20 min after [18F]FEBMP bolus injection. D-F: Representative coronal PET summation images (D; 0-20 min, E; 30-90 min) of [18F]FEBMP and the time-activity curve (F; mean ± SEM, n = 3) in a rat model of ischemia. The rat received additional treatment with unlabelled PK11195 at 20 min after [18F]FEBMP bolus injection. Ipsilateral and contralateral indicate ipsilateral and contralateral sides of the ischemic brain in the striatum.

Mentions: PET images with [18F]FEBMP and time-activity curves (TACs) showed higher accumulation of radioactivity in the ipsilateral striatum of the rat model of transient focal ischemia compared to radioactivity that accumulated in the corresponding contralateral area. The maximum ipsilateral-to-contralateral ratio was 3.20 ± 0.12 at 60 min post-injection (Fig. 2). Treatment with unlabelled MBMP or PK11195 led to an overt decrease in radioactivity on the ipsilateral side of the brain. Moreover, after 30 min of treatment, levels appeared to be similar to those contralateral to the infarct (Fig. 3). Using SRTM, with the contralateral side of the brain as reference tissue, the BPND value for [18F]FEBMP on the ipsilateral side of the brain was 2.72 ± 0.27.


[18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain.

Tiwari AK, Ji B, Yui J, Fujinaga M, Yamasaki T, Xie L, Luo R, Shimoda Y, Kumata K, Zhang Y, Hatori A, Maeda J, Higuchi M, Wang F, Zhang MR - Theranostics (2015)

Displacement with unlabelled TSPO ligands for [18F]FEBMP uptake. A-C: Representative coronal PET summation images (A; 0-20 min, B; 30-90 min) of [18F]FEBMP and the time-activity curve (C; mean ± SEM, n = 3) in an ischemic rat model that received additional treatment with unlabelled MBMP at 20 min after [18F]FEBMP bolus injection. D-F: Representative coronal PET summation images (D; 0-20 min, E; 30-90 min) of [18F]FEBMP and the time-activity curve (F; mean ± SEM, n = 3) in a rat model of ischemia. The rat received additional treatment with unlabelled PK11195 at 20 min after [18F]FEBMP bolus injection. Ipsilateral and contralateral indicate ipsilateral and contralateral sides of the ischemic brain in the striatum.
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Related In: Results  -  Collection

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Figure 3: Displacement with unlabelled TSPO ligands for [18F]FEBMP uptake. A-C: Representative coronal PET summation images (A; 0-20 min, B; 30-90 min) of [18F]FEBMP and the time-activity curve (C; mean ± SEM, n = 3) in an ischemic rat model that received additional treatment with unlabelled MBMP at 20 min after [18F]FEBMP bolus injection. D-F: Representative coronal PET summation images (D; 0-20 min, E; 30-90 min) of [18F]FEBMP and the time-activity curve (F; mean ± SEM, n = 3) in a rat model of ischemia. The rat received additional treatment with unlabelled PK11195 at 20 min after [18F]FEBMP bolus injection. Ipsilateral and contralateral indicate ipsilateral and contralateral sides of the ischemic brain in the striatum.
Mentions: PET images with [18F]FEBMP and time-activity curves (TACs) showed higher accumulation of radioactivity in the ipsilateral striatum of the rat model of transient focal ischemia compared to radioactivity that accumulated in the corresponding contralateral area. The maximum ipsilateral-to-contralateral ratio was 3.20 ± 0.12 at 60 min post-injection (Fig. 2). Treatment with unlabelled MBMP or PK11195 led to an overt decrease in radioactivity on the ipsilateral side of the brain. Moreover, after 30 min of treatment, levels appeared to be similar to those contralateral to the infarct (Fig. 3). Using SRTM, with the contralateral side of the brain as reference tissue, the BPND value for [18F]FEBMP on the ipsilateral side of the brain was 2.72 ± 0.27.

Bottom Line: PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 ± 0.12, compared to non-injured striatum.In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [(18)F]FEBMP.These findings suggest that [(18)F]FEBMP is a promising new tool for visualization of neuroinflammation.

View Article: PubMed Central - PubMed

Affiliation: 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan ; 2. Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.

ABSTRACT
We evaluated the efficacy of 2-[5-(4-[(18)F]fluoroethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methyl-N-phenylacetamide] ([(18)F]FEBMP) for positron emission tomography (PET) imaging of translocator protein (18 kDa, TSPO). Dissection was used to determine the distribution of [(18)F]FEBMP in mice, while small-animal PET and metabolite analysis were used for a rat model of focal cerebral ischemia. [(18)F]FEBMP showed high radioactivity uptake in mouse peripheral organs enriched with TSPO, and relatively high initial brain uptake (2.67 ± 0.12% ID/g). PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 ± 0.12, compared to non-injured striatum. Displacement with specific TSPO ligands lowered the accumulation levels in infarcts to those on the contralateral side. This suggests that the increased accumulation reflected TPSO-specific binding of [(18)F]FEBMP in vivo. Using a simplified reference tissue model, the binding potential on the infarcted area was 2.72 ± 0.27. Metabolite analysis in brain tissues showed that 83.2 ± 7.4% and 76.4 ± 2.1% of radioactivity was from intact [(18)F]FEBMP at 30 and 60 min, respectively, and that this ratio was higher than in plasma (8.6 ± 1.9% and 3.9 ± 1.1%, respectively). In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [(18)F]FEBMP. These findings suggest that [(18)F]FEBMP is a promising new tool for visualization of neuroinflammation.

No MeSH data available.


Related in: MedlinePlus