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 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 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 Quantification of [18F]florbetapir: A test–retest tracer kinetic modelling study

2018 ◽  
Vol 39 (11) ◽  
pp. 2172-2180 ◽  
Author(s):  
Sandeep SV Golla ◽  
Sander CJ Verfaillie ◽  
Ronald Boellaard ◽  
Sofie M Adriaanse ◽  
Marissa D Zwan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Volume Ratio ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Retest Reliability ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
Test Retest Reliability

Accumulation of amyloid beta can be visualized using [18F]florbetapir positron emission tomography. The aim of this study was to identify the optimal model for quantifying [18F]florbetapir uptake and to assess test–retest reliability of corresponding outcome measures. Eight Alzheimer’s disease patients (age: 67 ± 6 years, Mini-Mental State Examination (MMSE): 23 ± 3) and eight controls (age: 63 ± 4 years, MMSE: 30 ± 0) were included. Ninety-minute dynamic positron emission tomography scans, together with arterial blood sampling, were acquired immediately following a bolus injection of 294 ± 32 MBq [18F]florbetapir. Several plasma input models and the simplified reference tissue model (SRTM) were evaluated. The Akaike information criterion was used to identify the preferred kinetic model. Compared to controls, Alzheimer’s disease patients had lower MMSE scores and evidence for cortical Aβ pathology. A reversible two-tissue compartment model with fitted blood volume fraction (2T4k_VB) was the preferred model for describing [18F]florbetapir kinetics. SRTM-derived non-displaceable binding potential (BPND) correlated well (r2 = 0.83, slope = 0.86) with plasma input-derived distribution volume ratio. Test–retest reliability for plasma input-derived distribution volume ratio, SRTM-derived BPND and SUVr(50–70) were r = 0.88, r = 0.91 and r = 0.86, respectively. In vivo kinetics of [18F]florbetapir could best be described by a reversible two-tissue compartmental model and [18F]florbetapir BPND can be reliably estimated using an SRTM.

scholarly journals In Vivo Measurement of Density and Affinity of the Monoamine Vesicular Transporter in a Unilateral 6-Hydroxydopamine Rat Model of PD

2007 ◽  
Vol 27 (7) ◽  
pp. 1407-1415 ◽  
Author(s):  
Vesna Sossi ◽  
James E Holden ◽  
Geoffrey J Topping ◽  
Marie-Laure Camborde ◽  
Rich A Kornelsen ◽  
...  
Keyword(s):  
Rat Model ◽  
Specific Activity ◽  
Indirect Measurement ◽  
Binding Potential ◽  
Scatchard Analysis ◽  
In Vivo Measurement ◽  
Quantitative Pet ◽  
Significant Difference ◽  
6 Hydroxydopamine

This is the first in vivo determination of the vesicular monoamine transporter (VMAT2) density ( Bmax) and ligand–transporter affinity ( Kdapp) in six unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats using micro-positron emission tomography (PET) imaging with [11C]-(+)-α-dihydrotetrabenazine (DTBZ). A multiple ligand concentration transporter assay (MLCTA) was used to determine a Bmax value of 178 ± 32 pmol/mL and a Kdapp of 47.7 ± 9.3 pmol/mL for the non-lesioned side and 30.52 ± 5.84 and 43.4 ± 15.52 pmol/mL for the lesioned side, respectively. While Bmax was significantly different between the two sides, no significant difference was observed for the Kdapp. In addition to demonstrating the feasibility of in vivo Scatchard analysis in rats, these data confirm the expectation that a 6-OHDA lesion does not affect the affinity; a much simpler binding potential (BP) measure can thus be used as a marker of lesion severity (LS) in this rat model of Parkinson's disease. A transporter occupancy curve demonstrated negligible transporter occupancy (∼1%) at a specific activity (SA) of 1100 nCi/pmol (assuming an injected dose of 100 μCi/100 g), while 10% occupancy was estimated at 100 nCi/pmol. An indirect measurement indicated that the degree of occupancy as a function of SA is independent of LS. Finally, BP measurement reproducibility was assessed and found to be 11% ± 7% for the healthy and 8% ± 12% for the lesioned side. Quantitative PET results can thus be obtained even for severely lesioned animals with the striatum on one side not clearly visible provided accurate image analysis methods are used.

scholarly journals The Use of Alternative Forms of Graphical Analysis to Balance Bias and Precision in PET Images

2010 ◽  
Vol 31 (2) ◽  
pp. 535-546 ◽  
Author(s):  
Jean Logan ◽  
David Alexoff ◽  
Joanna S Fowler
Keyword(s):  
Volume Ratio ◽  
Image Data ◽  
Compartment Model ◽  
Graphical Analysis ◽  
Distribution Volume ◽  
Good Precision ◽  
Reference Tissue ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
Uptake Data

Graphical analysis (GA) is an efficient method for estimating total tissue distribution volume ( VT) from positron emission tomography (PET) uptake data. The original GA produces a negative bias in VT in the presence of noise. Estimates of VT using other GA forms have less bias but less precision. Here, we show how the bias terms are related between the GA methods and how using an instrumental variable (IV) can also reduce bias. Results are based on simulations of a two-compartment model with VT's ranging from 10.5 to 64 mL/cm3 and from PET image data with the tracer [11C]DASB ([11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl) benzonitrile). Four estimates of VT (or distribution volume ratio (DVR) using a reference tissue) can be easily computed from different formulations of GA including the IV. As noise affects the estimates from all four differently, they generally do not provide the same estimates. By taking the median value of the four estimates, we can decrease the bias and reduce the effect of large values contributing to noisy images. The variance of the four estimates can serve as a guide to the reliability of the median estimate. This may provide a general method for the generation of parametric images with little bias and good precision.

scholarly journals First D1-like receptor PET imaging of the rat and primate kidney: implications for human disease monitoring

2014 ◽  
Vol 307 (1) ◽  
pp. F116-F121 ◽  
Author(s):  
Michael L. Granda ◽  
Frederick A. Schroeder ◽  
Ronald H. J. Borra ◽  
Nathan Schauer ◽  
Ehimen Aisaborhale ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Binding Potential ◽  
Sprague Dawley ◽  
Papio Anubis ◽  
Dopamine System ◽  
In Vivo Measurement ◽  
Saturable Binding ◽  
Positron Emission ◽  
Renal Dopamine

The intrarenal dopamine system is important for signaling and natriuresis, and significant dysfunction is associated with hypertension and kidney disease in ex vivo studies. Dopamine receptors also modulate and are modulated by the renin-angiotensin-aldosterone system. Here, we show the first in vivo measurement of D1-like receptors in the renal cortex of Sprague-Dawley rat and Papio anubis baboon using [11C]NNC 112, a positron emission tomography radioligand for D1-like receptors. In addition, we show a D1-like binding potential response to angiotensin II blockade in rats using losartan. Demonstration of self-saturable binding in the rat as well as specific and saturable binding in Papio anubis validate the use of [11C]NNC 112 in the first in vivo measurement of renal dopamine D1-like receptors. Furthermore, [11C]NNC 112 is a radioligand tool already validated for use in probing human central nervous system (CNS) D1-like receptors. Our work demonstrates specific and saturable non-CNS binding in higher animals and the ability to quantify physiological response to drug treatment and provides a clear path to extend use of [11C]NNC 112 to study renal dopamine in humans.

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 Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948

2019 ◽  
Vol 47 (2) ◽  
pp. 342-354 ◽  
Author(s):  
Ruben Smith ◽  
Michael Schöll ◽  
Antoine Leuzy ◽  
Jonas Jögi ◽  
Tomas Ohlsson ◽  
...  
Keyword(s):  
Medial Temporal Lobe ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Volume Ratio ◽  
Brain Regions ◽  
Positron Emission ◽  
Binding Time ◽  
Distribution Volume Ratio ◽  
Target Binding

Abstract Purpose [18F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer’s disease (AD). However, “off-target” binding interferes with the quantification of [18F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [18F]flortaucipir with the novel tau tracer [18F]RO948 head-to-head in vivo. Methods We included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent [18F]flortaucipir (80–100 min) and [18F]RO948 (70–90) PET scans within approximately 1 month. Four study participants underwent 0–100-min dynamic scanning. Standardized uptake value ratios (SUVRs) were created using an inferior cerebellar reference region. Results Neocortical tracer retention was highly comparable using both SUVR and distribution volume ratio-1 values obtained from dynamic scans. However, [18F]RO948 retention was significantly higher in the entorhinal cortex and lower in the basal ganglia, thalamus, and choroid plexus compared with [18F]flortaucipir. Increased off-target binding was observed with age for both tracers. Several cases exhibited strong [18F]RO948 retention in the skull/meninges. This extra-cerebral signal, however, did not affect diagnostic accuracy and remained relatively unchanged when re-examining a subsample after 1 year. Kinetic modeling showed an increase in [18F]flortaucipir SUVR over the scanning interval, compared with a plateau for [18F]RO948. Conclusion [18F]RO948 and [18F]flortaucipir bound comparably in neocortical regions, but [18F]RO948 showed higher retention in the medial temporal lobe and lower intracerebral “off-target” binding. Time-dependent bias of SUVR estimates may prove less of a factor with [18F]RO948, compared with previous tau ligands.

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