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

ABSTRACT: 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_V_B) was the preferred model for describing [¹⁸F]florbetapir kinetics. SRTM-derived non-displaceable binding potential (BP_ND) 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 BP_ND 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 BP_ND can be reliably estimated using an SRTM.

SUBMITTER: Golla SS

PROVIDER: S-EPMC6826855 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Golla Sandeep Sv SS Verfaillie Sander Cj SC Boellaard Ronald R Adriaanse Sofie M SM Zwan Marissa D MD Schuit Robert C RC Timmers Tessa T Groot Colin C Schober Patrick P Scheltens Philip P van der Flier Wiesje M WM Windhorst Albert D AD van Berckel Bart Nm BN Lammertsma Adriaan A AA

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20180613 11

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 ...[more]

PMID: 29897009

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Project description:ObjectivesQuantification of myocardial blood flow (MBF) and stress/rest flow reserve is used increasingly to diagnose multi-vessel coronary artery disease and micro-vascular disease with PET imaging. However, variability in the measurements may limit physician confidence to direct revascularization therapies based on specific threshold values. This study evaluated the effects of rubidium-82 (82Rb) tracer injection profile using a constant-activity-rate (CA) vs a constant-flow-rate (CF) infusion to improve test-retest repeatability of MBF measurements.Method22 participants underwent single-session 82Rb dynamic PET imaging during rest and dipyridamole stress using one of 2 test-retest infusion protocols: CA-CA (n = 12) or CA-CF (n = 10). MBF was quantified using a single-tissue-compartment model (1TCM) and a simplified retention model (SRM). Non-parametric test-retest repeatability coefficients (RPCnp) were compared between groups. Myocardium-to-blood contrast and signal-to-noise ratios of the late uptake images (2 to 6 minutes) were also compared to evaluate standard myocardial perfusion image (MPI) quality.ResultsMBF values in the CA-CA group were more repeatable (smaller RPCnp) than the CA-CF group using the 1TCM at rest alone, rest and stress combined, and stress/rest reserve (21% vs 36%, 16% vs 19%, and 20% vs 27%, P < 0.05, respectively), and using the SRM at Rest and Stress alone, Rest and Stress combined, and stress/rest reserve (21% vs 38%, 15% vs 25%, 22% vs 38%, and 23% vs 49%, P < 0.05, respectively). In terms of image quality, myocardium-to-blood contrast and signal-to-noise ratios were not significantly different between groups.ConclusionsConstant-activity-rate 'square-wave' infusion of 82Rb produces more repeatable tracer injection profiles and decreases the test-retest variability of MBF measurements, when compared to a constant-flow-rate 'bolus' administration of 82Rb, especially with SRM, and without compromising standard MPI quality.

Project description:ObjectivesThis study aimed to explore the potential of full dynamic PET kinetic analysis in assessing amyloid binding and perfusion in the cardiac region using 18F-Florbetapir PET, establishing a quantitative approach in the clinical assessment of cardiac amyloidosis disease.Materials & methodsThe distribution volume ratios (DVRs) and the relative transport rate constant (R1), were estimated by a pseudo-simplified reference tissue model (pSRTM2) and pseudo-Logan plot (pLogan plot) with kidney reference for the region of interest-based and voxel-wise-based analyses. The parametric images generated using the pSRTM2 and linear regression with spatially constrained (LRSC) algorithm were then evaluated. Semi-quantitative analyses include standardized uptake value ratios at the early phase (SUVREP, 0.5-5 min) and late phase (SUVRLP, 50-60 min) were also calculated.ResultsTen participants [7 healthy controls (HC) and 3 cardiac amyloidosis (CA) subjects] underwent a 60-min dynamic 18F-Florbetapir PET scan. The DVRs estimated from pSRTM2 and Logan plot were significantly increased (HC vs CA; DVRpSRTM2: 0.95 ± 0.11 vs 2.77 ± 0.42, t'(2.13) = 7.39, P = 0.015; DVRLogan: 0.80 ± 0.12 vs 2.90 ± 0.55, t'(2.08) = 6.56, P = 0.020), and R1 were remarkably decreased in CA groups, as compared to HCs (HC vs CA; 1.08 ± 0.37 vs 0.56 ± 0.10, t'(7.63) = 3.38, P = 0.010). The SUVREP and SUVRLP were highly correlated to R1 (r = 0.97, P < 0.001) and DVR(r = 0.99, P < 0.001), respectively. The DVRs in the total myocardium region increased slightly as the size of FWHM increased and became stable at a Gaussian filter ≥6 mm. The secular equilibrium of SUVR was reached at around 50-min p.i. time.ConclusionThe DVR and R1 estimated from cardiac dynamic 18F-Florbetapir PET using pSRTM with kidney pseudo-reference tissue are suggested to quantify cardiac amyloid deposition and relative perfusion, respectively, in amyloidosis patients and healthy controls. We recommend a dual-phase scan: 0.5-5 min and 50-60 min p.i. as the appropriate time window for clinically assessing cardiac amyloidosis and perfusion measurements using 18F-Florbetapir PET.

Project description:There is evidence that subtle breakdown of the blood-brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n=201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a "sham" DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and K(Trans) estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low-permeability states, which has the potential to provide valuable information regarding BBB integrity in a range of diseases. However, absolute values of the resulting tracer kinetic parameters should be interpreted with extreme caution, and the size and influence of signal drift should be measured where possible.

Project description:BackgroundCardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements. 124I-evuzamitide is a novel pan-amyloid radiotracer binding to amyloid deposits from multiple amyloidogenic proteins. Its ability to quantify cardiac amyloid has not yet been investigated.ObjectivesThe objectives of this pilot study were to quantify myocardial 124I-evuzamitide uptake and to compare its diagnostic value to 18F-florbetapir in participants with amyloid CMP and control subjects.MethodsThis study included 46 participants: 12 with light-chain (AL) CMP, 12 with wild-type transthyretin (ATTRwt) CMP, 2 with hereditary amyloidosis, and 20 control subjects. All amyloidosis participants underwent positron emission tomography/computed tomography with 124I-evuzamitide and 18F-florbetapir. Control subjects underwent 124I-evuzamitide (n = 10) or 18F-florbetapir (n = 8) positron emission tomography/computed tomography. Left ventricular percent injected dose (LV% ID) was measured as mean activity concentration × myocardial volume/injected activity. High LV %ID was defined using Youden's index.ResultsIn CMP participants, median age was 74 years and 92% were men. 124I-evuzamitide LV %ID differed across groups: median AL-CMP 1.48 (IQR: 1.12-1.89), ATTRwt-CMP 2.12 (IQR: 1.66-2.47), and control subjects 0.00 (IQR: 0.00-0.01; overall P < 0.001). High LV %ID perfectly discriminated CMP from control subjects. Discrimination performance was similar for 18F-florbetapir LV %ID. Notably, for ATTRwt-CMP, LV %ID was higher with 124I-evuzamitide than 18F-florbetapir (P = 0.002). 124I-evuzamitide LV %ID was correlated with interventricular septum thickness (Spearman's ρ = 0.78) and LV global longitudinal strain (ρ = 0.54) from echocardiography, and with LV mass index (ρ = 0.82) and extracellular volume (ρ = 0.51) from cardiac magnetic resonance.Conclusions124I-evuzamitide demonstrates uptake by cardiac amyloid and accurately discriminates amyloid CMP from control subjects. In AL-CMP, discrimination performance is similar to 18F-florbetapir. In ATTRwt-CMP, performance may be better with 124I-evuzamitide. Moderate-to-strong correlations of 124I-evuzamitide uptake with cardiac structural and functional metrics suggest valid amyloid quantification. Hence, 124I-evuzamitide is a promising novel radiotracer to detect and quantify cardiac amyloid.

Project description:PurposeBeta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [18F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [18F]PF-06684511 estimated in non-human primates was relatively high. This study was therefore designed to evaluate the whole-body distribution, dosimetry, quantification, and test-retest reliability of imaging brain BACE1 with [18F]PF-06684511 in healthy volunteers.MethodsFive subjects were studied for the dosimetry study. Whole-body PET was performed for 366 min with 4 PET-CT sessions. Estimates of the absorbed radiation dose were calculated using the male adult model. Eight subjects participated in the test-retest study. Brain PET measurements were conducted for 123 min with an interval of 5 to 19 days between test and retest conditions. The total distribution volume (VT) was estimated with one-tissue (1T), two-tissue (2T), compartment model (CM), and graphical analysis. Test-retest variability (TRV) and intraclass correlation coefficient (ICC) of VT were calculated as reliability measures.ResultsIn the dosimetry study, the highest uptake was found in the liver (25.2 ± 2.3 %ID at 0.5 h) and the largest dose was observed in the pancreas (92.9 ± 52.2 μSv/MBq). The calculated ED was 24.7 ± 0.8 μSv/MBq. In the test-retest study, 2TCM described the time-activity curves well. VT (2TCM) was the highest in the anterior cingulate cortex (6.28 ± 1.09 and 6.85 ± 0.81) and the lowest in the cerebellum (4.23 ± 0.88 and 4.20 ± 0.75). Mean TRV and ICC of VT (2TCM) were 16.5% (12.4-20.5%) and 0.496 (0.291-0.644).ConclusionThe ED of [18F]PF-06684511 was similar to other 18F radioligands, allowing repeated PET measurements. 2TCM was the most appropriate quantification method. TRV of VT was similar to other radioligands without a reference region, albeit with lower ICC. These data indicated that [18F]PF-06684511 is a suitable radioligand to measure BACE1 level in the human brain.Trial registrationEudraCT 2016-001110-19 (registered 2016-08-08).

Project description:PurposeOur aim in this study was to compare different non-invasive pharmacokinetic models and assess test-retest reproducibility of the radioligand [11C]SCH23390 for the quantification of dopamine D1-like receptor (D1R) in both wild-type (WT) mice and heterozygous (HET) Q175DN mice as Huntington's disease (HD) model.ProceduresAdult WT (n = 9) and HET (n = 14) mice underwent a 90-min [11C]SCH23390 positron emission tomography (PET) scan followed by computed tomography (CT) to evaluate the pharmacokinetic modelling in healthy and diseased conditions. Additionally, 5 WT mice and 7 HET animals received a second [11C]SCH23390 PET scan for test-retest reproducibility. Parallel assessment of the simplified reference tissue model (SRTM), the multilinear reference tissue model (MRTM) and the Logan reference tissue model (Logan Ref) using the striatum as a receptor-rich region and the cerebellum as a receptor-free (reference) region was performed to define the most suitable method for regional- and voxel-based quantification of the binding potential (BPND). Finally, standardised uptake value ratio (SUVR-1) was assessed as a potential simplified measurement.ResultsFor all models, we measured a significant decline in dopamine D1R density (e.g. SRTM = - 38.5 ± 5.0 %, p < 0.0001) in HET mice compared to WT littermates. Shortening the 90-min scan duration resulted in large underestimation of striatal BPND in both WT mice (SRTM 60 min: - 17.7 ± 2.8 %, p = 0.0078) and diseased HET (SRTM 60 min: - 13.1 ± 4.1 %, p = 0.0001). Striatal BPND measurements were very reproducible with an average test-retest variability below 5 % when using both MRTM and SRTM. Parametric BPND maps generated with SRTM were highly reliable, showing nearly perfect agreement to the regional analysis (r2 = 0.99, p < 0.0001). Finally, SRTM provided the most accurate estimate for relative tracer delivery R1 with both regional- and voxel-based analyses. SUVR-1 at different time intervals were not sufficiently reliable when compared to BPND (r2 < 0.66).ConclusionsNinety-minute acquisition and the use of SRTM for pharmacokinetic modelling is recommended. [11C]SCH23390 PET imaging demonstrates optimal characteristics for the study of dopamine D1R density in models of psychiatric and neurological disorders as exemplified in the Q175DN mouse model of HD.

Dataset Information

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

Publications

Quantification of [<sup>18</sup>F]florbetapir: A test-retest tracer kinetic modelling study.

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