scholarly journals [18F]VUIIS1009B Features a Superior Imaging Performance to [18F]DPA-714 in TSPO Density Characterization for Neuroinflammatory PET Imaging

2020 ◽  
Author(s):  
Chen Huang ◽  
Fan Ding ◽  
Yong Hao ◽  
Zhoumi Hu ◽  
Cheng Wang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Rat Model ◽  
Density Measurement ◽  
Volume Ratio ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Binding Potential ◽  
Great Promise ◽  
Parametric Images

Abstract Purpose: Translocator protein (TSPO), an outer mitochondrial membrane protein, is regarded as a key biomarker for neuroinflammation in a variety of neurodegenerative diseases. In this study, we aim to evaluate two highly specific TSPO radiotracers [18F]VUIIS1009A and [18F]VUIIS1009B in a mild cerebral ischemic rat model, and to compare their in vivo performance to the well-established TSPO probe [18F]DPA-714 for neuroinflammation imaging. With multiple graphic analytical methods tested and macro parameters determined, we propose to find a suitable and best quantification method to profile neuroinflammation and measure TSPO density with the three TSPO radiotracers.Methods: Cerebral ischemia rat model was created and imaged using [18F]VUIIS1009A, [18F]VUIIS1009B and [18F]DPA-714. Displacement studies using non-radioactive analogs were performed to evaluate the binding specificities of [18F]VUIIS1009A and [18F]VUIIS1009B individually. Imaging analysis using arterial plasma input functions (AIFs) was employed to generate Logan plots and parametric images of total distribution volume (VT) for each radiotracer. Reference Logan model using contralateral brain as a reference region was introduced to generate parametric images for binding potential (BPND). Results: When compared to [18F]DPA-714, [18F]VUIIS1009B demonstrated higher binding potential (BPND) and distribution volume ratio (DVR). Parameter images of BPND and VT also indicate [18F]VUIIS1009B has a superior imaging profile with higher BPND and DVR when compared with other two radiotracers in TSPO imaging. Correlation analysis between BPND for [18F]VUIIS1009B and [18F]DPA-714 also indicates [18F]VUIIS1009B is more sensitive than [18F]DPA-714 in TSPO density measurement.Conclusions: This study demonstrates the superiority of [18F]VUIIS1009B to [18F]VUIIS1009A and [18F]DPA-714 in the neuroinflammation imaging. It also demonstrates that [18F]VUIIS1009B PET imaging coupled with parameter mapping (VT and BPND) and graphic analysis using Logan analysis and reference Logan analysis holds great promise for neuroinflammation characterization and TSPO density measurement.

scholarly journals 18F-VUIIS1009B Features a Superior Imaging Performance to 18F-DPA-714 in TSPO Density Characterization for Neuroinflammatory PET Imaging

2020 ◽  
Author(s):  
Chen Huang ◽  
Fan Ding ◽  
Zhoumi Hu ◽  
Mengxin Wang ◽  
Wenxian Peng ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Rat Model ◽  
Density Measurement ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Binding Potential ◽  
Great Promise ◽  
Parametric Images

Abstract Purpose Translocator protein (TSPO), an out-mitochondrial membrane protein, is regarded as a key biomarker for neuroinflammation in a variety of neurodegenerative diseases. In this study, we aim to evaluate two highly specific TSPO radiotracers 18F-VUIIS1009A and 18F-VUIIS1009B in a mild cerebral ischemic rat model, and to compare their in vivo performance to the well-established TSPO probe 18F-DPA-714 for neuroinflammation imaging. With multiple graphic analytical methods tested and macro parameters determined, we propose to find a suitable and best quantification method to profile neuroinflammation and measure TSPO density with the three TSPO radiotracers. Methods Cerebral ischemia rat model was created and imaged using 18F-VUIIS1009A, 18F-VUIIS1009B and 18F-DPA-714. Displacement studies using cold analogs were performed to evaluate the binding specificities of 18F-VUIIS1009A and 18F-VUIIS1009B individually. Imaging analysis using arterial plasma input functions (AIFs) was employed to generate Logan plots and parametric images of total distribution volume (VT) for each radiotracer. Reference Logan model using healthy brain as a reference region was introduced to generate parametric images for binding potential (BPND). Results When compared to 18F-DPA-714, 18F-VUIIS1009B demonstrated higher in vitro binding specificity, binding potential (BPND) and distribution volume ratio (DVR). Parameter images of BPND and VT also indicate 18F-VUIIS1009B has a superior imaging profile when compared with other two radiotracers in TSPO imaging. Correlation analysis between BPND for 18F-VUIIS1009B and 18F-DPA-714 also indicates 18F-VUIIS1009B is more sensitive than 18F-DPA-714 in TSPO density measurement. Conclusions This study demonstrates the superiority of 18F-VUIIS1009B to 18F-VUIIS1009A and 18F-DPA-714 in the neuroinflammation imaging. It also demonstrates that 18F-VUIIS1009B PET imaging coupled with parameter mapping (VT and BPND) and graphic analysis holds great promise for neuroinflammation characterization and TSPO density measurement.

scholarly journals Parametric methods for [18F]flortaucipir PET

2018 ◽  
Vol 40 (2) ◽  
pp. 365-373 ◽  
Author(s):  
Sandeep SV Golla ◽  
Emma E Wolters ◽  
Tessa Timmers ◽  
Rik Ossenkoppele ◽  
Chris WJ van der Weijden ◽  
...  
Keyword(s):  
Specific Binding ◽  
Volume Ratio ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Distribution Volume ◽  
Binding Potential ◽  
Parametric Images ◽  
Distribution Volume Ratio ◽  
Pet Scans

[18F]Flortaucipir is a PET tau tracer used to visualize tau binding in Alzheimer’s disease (AD) in vivo. The present study evaluated the performance of several methods to obtain parametric images of [18F]flortaucipir. One hundred and thirty minutes dynamic PET scans were performed in 10 AD patients and 10 controls. Parametric images were generated using different linearization and basis function approaches. Regional binding potential (BPND) and volume of distribution (VT) values obtained from the parametric images were compared with corresponding values derived using the reversible two-tissue compartment model (2T4k_VB). Performance of SUVr parametric images was assessed by comparing values with distribution volume ratio (DVR) and SRTM-derived BPND estimates obtained using non-linear regression (NLR). Spectral analysis (SA) ( r2 = 0.92; slope = 0.99) derived VT correlated well with NLR-derived VT. RPM ( r2 = 0.95; slope = 0.98) derived BPND correlated well with NLR-derived DVR. Although SUVr80–100 min correlated well with NLR-derived DVR ( r2 = 0.91; slope = 1.09), bias in SUVr appeared to depend on uptake time and underlying level of specific binding. In conclusion, RPM and SA provide parametric images comparable to the NLR estimates. Individual SUVr values are biased compared with DVR and this bias requires further study in a larger dataset in order to understand its consequences.

scholarly journals Insights into smouldering MS brain pathology with multimodal diffusion tensor and PET imaging

2020 ◽  
Author(s):  
Svetlana Bezukladova ◽  
Jouni Tuisku ◽  
Markus Matilainen ◽  
Anna Vuorimaa ◽  
Marjo Nylund ◽  
...  
Keyword(s):  
White Matter ◽  
Pet Imaging ◽  
Microglial Activation ◽  
Diffusion Tensor ◽  
Volume Ratio ◽  
Translocator Protein ◽  
Control Group ◽  
In Vivo Evaluation ◽  
Conventional Mri

Objective: To evaluate in vivo the co-occurrence of microglial activation and microstructural white matter damage in multiple sclerosis (MS) brain, and to examine their association with clinical disability. Methods: 18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [11C](R)-PK11195. TSPO-binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images. Diffusion tensor imaging (DTI) and conventional MRI were performed at the same time. Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated within the whole normal appearing white matter (NAWM) and segmented NAWM regions appearing normal in conventional MRI. 55 MS patients and 15 healthy controls were examined. Results: Microstructural damage was observed in the NAWM of MS brain. DTI parameters of MS patients were significantly altered in the NAWM, when compared to an age- and sex-matched healthy control group: mean FA was decreased, and MD, AD and RD were increased. These structural abnormalities correlated with increased TSPO binding in the whole NAWM and in the temporal NAWM (p<0.05 for all correlations; p<0.01 for RD in the temporal NAWM). Both compromised WM integrity and increased microglial activation in the NAWM correlated significantly with higher clinical disability measured with expanded disability status scale (EDSS). Conclusions: Widespread structural disruption in the NAWM is linked to neuroinflammation, and both phenomena associate with clinical disability. Multimodal PET and DTI imaging allows in vivo evaluation of widespread MS pathology not visible using conventional MRI.

scholarly journals Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging

2020 ◽  
Vol 7 (3) ◽  
pp. e691 ◽  
Author(s):  
Svetlana Bezukladova ◽  
Jouni Tuisku ◽  
Markus Matilainen ◽  
Anna Vuorimaa ◽  
Marjo Nylund ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Microglial Activation ◽  
Diffusion Tensor ◽  
Volume Ratio ◽  
Translocator Protein ◽  
In Vivo Evaluation ◽  
Conventional Mri ◽  
Disability Status ◽  
Distribution Volume Ratio

ObjectiveTo evaluate in vivo the co-occurrence of microglial activation and microstructural white matter (WM) damage in the MS brain and to examine their association with clinical disability.Methods18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [11C](R)-PK11195. TSPO binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images. Diffusion tensor imaging (DTI) and conventional MRI (cMRI) were performed at the same time. Mean fractional anisotropy (FA) and mean (MD), axial, and radial (RD) diffusivities were calculated within the whole normal-appearing WM (NAWM) and segmented NAWM regions appearing normal in cMRI. Fifty-five patients with MS and 15 healthy controls (HCs) were examined.ResultsMicrostructural damage was observed in the NAWM of the MS brain. DTI parameters of patients with MS were significantly altered in the NAWM compared with an age- and sex-matched HC group: mean FA was decreased, and MD and RD were increased. These structural abnormalities correlated with increased TSPO binding in the whole NAWM and in the temporal NAWM (p < 0.05 for all correlations; p < 0.01 for RD in the temporal NAWM). Both compromised WM integrity and increased microglial activation in the NAWM correlated significantly with higher clinical disability measured with the Expanded Disability Status Scale score.ConclusionsWidespread structural disruption in the NAWM is linked to neuroinflammation, and both phenomena associate with clinical disability. Multimodal PET and DTI allow in vivo evaluation of widespread MS pathology not visible using cMRI.

scholarly journals Quantitative Analysis for Estimating Binding Potential of the Brain Serotonin Transporter with [11C]McN5652

2002 ◽  
Vol 22 (4) ◽  
pp. 490-501 ◽  
Author(s):  
Yoko Ikoma ◽  
Tetsuya Suhara ◽  
Hinako Toyama ◽  
Tetsuya Ichimiya ◽  
Akihiro Takano ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Arterial Input Function ◽  
Volume Ratio ◽  
Least Square Method ◽  
Distribution Volume ◽  
Least Square ◽  
Binding Potential ◽  
Nonspecific Binding ◽  
Distribution Volume Ratio

[11C](+)McN5652 is a selective serotonin reuptake inhibitor with subnanomolar potency for the serotonin transporter, and is currently being used for positron emission tomography studies. However, quantification of the regional [11C](+)McN5652 binding potential in vivo is a controversial issue because of its complex characteristics. The authors examined the regional differences in nonspecific binding and proposed simple methods for estimating the binding potential of [11C](+)McN5652. The regional difference in nonspecific binding was evaluated by the activity ratio of the thalamus compared with the cerebellum for inactive-isomer [11C](−)McN5652 and [11C](+)McN5652 saturation studies. The distribution volume of the thalamus was approximately 1.16 times larger than that of the cerebellum. The thalamus-to-cerebellum distribution volume ratio was estimated by nonlinear least square and graphical methods, with and without arterial input function. The graphical method with k2′ without blood sampling was practical and most applicable for estimation of the distribution volume ratio because this method is more stable than the nonlinear least square method in the simulation study. Binding potential estimated with the distribution volume ratio of [11C](+)McN5652 and the correction with distribution volume ratio of [11C](−)McN5652 represent the most reliable parameters for the assessment of serotonin transporter binding.

scholarly journals In-vivo Measurement of LDOPA Uptake, Dopamine Reserve and Turnover in the Rat Brain Using [18F]FDOPA PET

2012 ◽  
Vol 33 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Matthew D Walker ◽  
Katherine Dinelle ◽  
Rick Kornelsen ◽  
Siobhan McCormick ◽  
Chenoa Mah ◽  
...  
Keyword(s):  
Volume Ratio ◽  
Distribution Volume ◽  
Binding Potential ◽  
In Vivo Measurement ◽  
Longitudinal Measurements ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
6 Hydroxydopamine ◽  
Effective Distribution

Longitudinal measurements of dopamine (DA) uptake and turnover in transgenic rodents may be critical when developing disease-modifying therapies for Parkinson's disease (PD). We demonstrate methodology for such measurements using [18F]fluoro-3,4-dihydroxyphenyl- L-alanine ([18F]FDOPA) positron emission tomography (PET). The method was applied to 6-hydroxydopamine lesioned rats, providing the first PET-derived estimates of DA turnover for this species. Control ( n = 4) and unilaterally lesioned ( n = 11) rats were imaged multiple times. Kinetic modeling was performed using extended Patlak, incorporating a kloss term for metabolite washout, and modified Logan methods. Dopaminergic terminal loss was measured via [11C]-(+)-dihydrotetrabenazine (DTBZ) PET. Clear striatal [18F]FDOPA uptake was observed. In the lesioned striatum the effective DA turnover increased, shown by a reduced effective distribution volume ratio ( EDVR) for [18F]FDOPA. Effective distribution volume ratio correlated ( r > 0.9) with the [11C]DTBZ binding potential ( BPND). The uptake and trapping rate ( kref) decreased after lesioning, but relatively less so than [11C]DTBZ BPND. For normal controls, striatal estimates were kref = 0.037 ± 0.005 per minute, EDVR = 1.07 ± 0.22 and kloss = 0.024 ± 0.003 per minute (30 minutes turnover half-time), with repeatability (coefficient of variation) ≤11%. [18F]fluoro-3,4-dihydroxyphenyl- L-alanine PET enables measurements of DA turnover in the rat, which is useful for developing novel therapies for PD.

scholarly journals Natalizumab treatment reduces microglial activation in the white matter of the MS brain

2019 ◽  
Vol 6 (4) ◽  
pp. e574 ◽  
Author(s):  
Marcus Sucksdorff ◽  
Jouni Tuisku ◽  
Markus Matilainen ◽  
Anna Vuorimaa ◽  
Sarah Smith ◽  
...  
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Pet Imaging ◽  
Microglial Activation ◽  
Volume Ratio ◽  
Translocator Protein ◽  
Cns Inflammation ◽  
Normal Appearing White Matter ◽  
Natalizumab Treatment

ObjectiveTo evaluate whether natalizumab treatment reduces microglial activation in MS.MethodsWe measured microglial activation using the 18-kDa translocator protein (TSPO)-binding radioligand [11C]PK11195 and PET imaging in 10 patients with MS before and after 1 year treatment with natalizumab. Microglial activation was evaluated as the distribution volume ratio (DVR) of the specifically bound radioligand in brain white and gray matter regions of interest. MRI and disability measurements were performed for comparison. Evaluation was performed identically with 11 age- and sex-matched patients with MS who had no MS therapy.ResultsNatalizumab treatment reduced microglial activation in the normal-appearing white matter (NAWM; baseline DVR vs DVR after 1 year of treatment 1.25 vs 1.22, p = 0.014, Wilcoxon) and at the rim of chronic lesions (baseline DVR vs DVR after 1 year of treatment 1.24 vs 1.18, p = 0.014). In patients with MS with no treatment, there was an increase in microglial activation at the rim of chronic lesions (1.23 vs 1.27, p = 0.045). No alteration was observed in microglial activation in gray matter areas. In the untreated patient group, higher microglial activation at baseline was associated with more rapid disability progression during an average of 4 years of follow-up.ConclusionsTSPO-PET imaging can be used as a tool to assess longitudinal changes in microglial activation in the NAWM and in the perilesional areas in the MS brain in vivo. Natalizumab treatment reduces the diffuse compartmentalized CNS inflammation related to brain resident innate immune cells.

scholarly journals Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

2011 ◽  
Vol 31 (8) ◽  
pp. 1807-1816 ◽  
Author(s):  
Pablo M Rusjan ◽  
Alan A Wilson ◽  
Peter M Bloomfield ◽  
Irina Vitcu ◽  
Jeffrey H Meyer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Specific Binding ◽  
Compartment Model ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Specific Distribution ◽  
Positron Emission

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

scholarly journals In vivo (R)-[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Thalia F van der Doef ◽  
Lot D de Witte ◽  
Arjen L Sutterland ◽  
Ellen Jobse ◽  
Maqsood Yaqub ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Translocator Protein ◽  
Recent Onset

scholarly journals Evaluation of the PBR/TSPO Radioligand [18F]DPA-714 in a Rat Model of Focal Cerebral Ischemia

2009 ◽  
Vol 30 (1) ◽  
pp. 230-241 ◽  
Author(s):  
Abraham Martín ◽  
Raphaël Boisgard ◽  
Benoit Thézé ◽  
Nadja Van Camp ◽  
Bertrand Kuhnast ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Pet Imaging ◽  
Time Course ◽  
Focal Cerebral Ischemia ◽  
Quantitative Information ◽  
Translocator Protein ◽  
Experimental Stroke ◽  
Tspo Expression

Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [18F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. In vivo PET imaging showed significant increase in DPA ( N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. In vitro autoradiography confirmed these in vivo results. In vivo and in vitro [18F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [18F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.

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