Purpose
Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation ...tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer
18
FPI-2620 as a potential substitute for
18
Ffluorodeoxyglucose (
18
FFDG).
Methods
Twenty-six subjects were referred with suspected tauopathies or overlapping parkinsonian syndromes (Alzheimer’s disease, progressive supranuclear palsy, corticobasal syndrome, multi-system atrophy, Parkinson’s disease, multi-system atrophy, Parkinson's disease, frontotemporal dementia) and received a dynamic
18
FPI-2620 tau-PET (0–60 min p.i.) and static
18
FFDG-PET (30–50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R
1
) of
18
FPI-2620-PET were correlated with corresponding quantification of
18
FFDG-PET (global mean/cerebellar normalization). Reduced tracer uptake in cortical target regions was also interpreted visually using 3-dimensional stereotactic surface projections by three more and three less experienced readers. Spearman rank correlation coefficients were calculated between early-phase
18
FPI-2620 tau-PET and
18
FFDG-PET images for all cortical regions and frequencies of disagreement between images were compared for both more and less experienced readers.
Results
Highest agreement with
18
FFDG-PET quantification was reached for
18
FPI-2620-PET acquisition from 0.5 to 2.5 min p.i. for global mean (lowest
R
= 0.69) and cerebellar scaling (lowest
R
= 0.63). Correlation coefficients (summed 0.5–2.5 min SUVr & R
1
) displayed strong agreement in all cortical target regions for global mean (R
SUVr
0.76,
R
R1
= 0.77) and cerebellar normalization (R
SUVr
0.68,
R
R1
= 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and
18
FFDG-PET. There were no relevant differences between more and less experienced readers.
Conclusion
Early-phase imaging of
18
FPI-2620 can serve as a surrogate biomarker for neuronal injury. Dynamic imaging or a dual time-point protocol for tau-PET imaging could supersede additional
18
FFDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.
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Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
18F-FIBT, 2-(p-Methylaminophenyl)-7-(2-18Ffluoroethoxy)imidazo-2,1-bbenzothiazole, is a new selective PET tracer under clinical investigation to specifically image β-amyloid depositions (Aβ) in ...humans in-vivo that binds to Aβ with excellent affinity (Kd 0.7 ± 0.2) and high selectivity over tau and α-synuclein aggregates (Ki > 1000 nM). We aimed to characterize 18F-FIBT in a series of patients with different clinical-pathophysiological phenotypes and to compare its binding characteristics to the reference compound PiB. Six patients (mild late-onset and moderate early-onset AD dementia, mild cognitive impairment due to AD, intermediate likelihood, mild behavioral variant of frontotemporal dementia, subjective memory impairment without evidence of neurodegeneration, and mild dementia due to Posterior Cortical Atrophy) underwent PET imaging with 18F-FIBT on PET/MR. With the guidance of MRI, PET images were corrected for partial volume effect, time-activity curves (TACs) of regions of interest (ROIs) were extracted, and non-displaceable binding potentials (BPnd), standardized uptake value ratios (SUVR), and distribution volume ratio (DVR) were compared. Specific binding was detected in the cases with evidence of the AD pathophysiological process visualized in images of BPnd, DVR and SUVR, consistently with patterns of different tracers in previous studies. SUVR showed the highest correlation with clinical severity. The previous preclinical characterization and the results of this case series suggest the clinical usefulness of FIBT as a selective and highly affine next-generation 18F-labeled tracer for amyloid-imaging with excellent pharmacokinetics in the diagnosis of neurodegenerative diseases. The results compare well to the gold standard PiB and hence support further investigation in larger human samples.
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Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
In head and neck cancers (HNCs), fibroblast activation protein (FAP) is expressed by cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Preliminary evidence suggests ...that detection and staging is feasible with positron emission tomography (PET/CT) imaging using
68
Ga-radiolabeled inhibitors of FAP (
68
GaGa-FAPI-46) in HNCs. This study aims to compare
68
GaGa-FAPI-46 PET/CT and
18
F-fluorodeoxy-
d
-glucose (
18
FF-FDG) PET/CT with a focus on improved target volume definition and radiotherapy planning in patients with HNC referred for chemoradiation.
Methods
A total of 15 patients with HNCs received both
68
GaGa-FAPI-46 PET/CT and
18
FF-FDG PET/CT with a thermoplastic mask, in addition to initial tumor staging by conventional imaging with contrast-enhanced CT and/or MRI. Mean intervals between FAPI/FDG and FAPI/conventional imaging were 4 ± 20 and 17 ± 18 days, respectively. Location and number of suspicious lesions revealed by the different procedures were recorded. Subsequently, expert-generated gross tumor volumes (GTVs) based on conventional imaging were compared to those based on
18
FF-FDG and
68
GaGa-FAPI-46 PET/CT to measure the impact on subsequent radiation planning.
Results
All patients had focal FAPI uptake above background in tumor lesions. Compared to FDG, tumor uptake (median SUVmax 10.2 vs. 7.3,
p
= 0.008) and tumor-to-background ratios were significantly higher with FAPI than with FDG (SUVmean liver: 9.3 vs. 3.2,
p
< 0.001; SUVmean bloodpool: 6.9 vs. 4.0,
p
< 0.001). A total of 49 lesions were recorded. Of these, 40 (82%) were FDG
+
and 41 (84%) were FAP
+
. There were 5 (10%) FAP
+
/FDG
−
lesions and 4 (8%) FAP
−
/FDG
+
lesions. Volumetrically, a significant difference was found between the GTVs (median 57.9 ml in the FAPI-GTV, 42.5 ml in the FDG-GTV, compared to 39.2 ml in the conventional-GTV). Disease stage identified by FAPI PET/CT was mostly concordant with FDG PET/CT. Compared to conventional imaging, five patients (33%) were upstaged following imaging with FAPI and FDG PET/CT.
Conclusion
We demonstrate that
68
GaGa-FAPI-46 -PET/CT is useful for detecting tumor lesions in patients with HNCs. There is now a need for prospective randomized studies to confirm the role of
68
GaGa-FAPI-46 PET/CT in relation to
18
FF-FDG PET/CT in HNCs and to evaluate its impact on clinical outcome.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
A main advantage of PET is that it provides quantitative measures of the radiotracer concentration, but its accuracy is confounded by several factors, including attenuation, subject motion, and ...limited spatial resolution. Using the information from one simultaneously acquired morphological MR sequence with embedded navigators, we propose an efficient method called MR-assisted PET data optimization (MaPET) to perform attenuation correction (AC), motion correction, and anatomy-aided reconstruction.
For attenuation correction, voxel-wise linear attenuation coefficient maps were generated using an SPM8-based approach method on the MR volume. The embedded navigators were used to derive head motion estimates for event-based PET motion correction. The anatomy provided by the MR volume was incorporated into the PET image reconstruction using a kernel-based method. Region-based analyses were carried out to assess the quality of images generated through various stages of PET data optimization.
The optimized PET images reconstructed with MaPET was superior in image quality compared to images reconstructed using only attenuation correction, with high SNR and low coefficient of variation (5.08 and 0.229 in a composite cortical region compared to 3.12 and 0.570). The optimized images were also shown using the Cohen's d metric to achieve a greater effect size in distinguishing cortical regions with hypometabolism from regions of preserved metabolism in each individual for different diagnosis groups.
We have shown the spatiotemporally correlated data acquired using a single MR sequence can be used for PET attenuation, motion and partial volume effects corrections and the MaPET method may enable more accurate assessment of pathological changes in dementia and other brain disorders.
Functional connectivity of blood oxygenation level dependent signal fluctuations (BOLD-FC) is decreased in Alzheimer’s disease (AD), and suggested to reflect reduced coherence in neural population ...activity; however, as both neuronal and vascular-hemodynamic processes underlie BOLD signals, impaired perfusion might also contribute to reduced BOLD-FC; 42 AD patients and 27 controls underwent simultaneous PET/MR imaging. Resting-state functional MRI assessed BOLD co-activity to quantify BOLD-FC, pulsed arterial spin labeling (pASL) assessed cerebral blood flow (CBF) as proxy for vascular hemodynamics, and 18F-fluorodeoxyglucose PET assessed glucose metabolism (GluMet) to index neuronal activity. Patients’ BOLD-FC, CBF, and GluMet were reduced within the same precuneal parietal regions. BOLD-FC was positively associated with mean CBF, specifically in patients and controlled for GluMet levels, suggesting that BOLD-FC reductions correlate with pASL-derived hypoperfusion in AD, independently from 18F-fluorodeoxyglucose PET-derived hypometabolism. Data indicate that impaired vascular hemodynamic processes contribute to reduced BOLD connectivity in AD.
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Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Radiohalogenated agents are often the first line of pursuit in the development of new radiopharmaceuticals-whether antibodies, peptides, or small molecules-because of their ease of synthesis, lack of ...substantial steric perturbation of the original affinity agent (in some cases, providing enhanced affinity), and capacity to be transformed into therapeutics (in some cases, with a mere switch of an isotope). They often provide proof of a principle before optimization for pharmacokinetics or generation of radiometallated agents, when the latter are necessary. In particular,
F has been well integrated into normal clinical work flow in the form of
F-FDG for oncologic imaging, with reliable daily production and distribution to sites for immediate use, without the need for on-site preparation. Here we discuss radiohalogenated versions of imaging and therapeutic agents targeting the prostate-specific membrane antigen (PSMA); these were among the first such agents to be synthesized and used clinically. PSMA is highly expressed on prostate cancer epithelial cells and is currently being extensively investigated around the world as a target for imaging and therapy of prostate cancer. Additionally, the presence of PSMA on nonprostate tumor neovasculature has opened the possibility of PSMA-targeted molecules as generalizable cancer imaging and therapy agents. We focus on
F-labeled agents for PET, as they begin to redefine-along with the corresponding
Ga-labeled agents discussed elsewhere in this supplement to The Journal of Nuclear Medicine-the management of prostate cancer across a variety of clinical contexts.
Integrated PET/MRI systems open exciting possibilities for clinical and research applications. However, compared with PET/CT, PET/MRI is a complex technique resulting in new problems and challenges, ...especially regarding workflow, scan protocols, and data analysis. This complexity applies in particular to examinations in oncology with partial- or whole-body coverage extending over several bed positions. Unlike diagnostic PET/CT, for which the clinical CT protocols can largely be copied from stand-alone CT, the design of a diagnostic MRI protocol for partial- or whole-body coverage is more complex and has to be adapted to the special requirements of PET/MRI to be both time-efficient and comprehensive. Here, we describe basic considerations concerning workflow, imaging protocols, and image analysis for whole-body PET/MRI in oncology, based on our experience with the first integrated PET/MRI scanner. The aim is to fully and optimally make use of the combined PET/MRI measurements in oncology, including identifying and reducing image artifacts as well as optimizing workflow beyond the mere fusion of 2 image datasets.
Background
Subjective cognitive decline (SCD) may occur very early in the course of Parkinson’s disease (PD) before the onset of objective cognitive decline. Data on neural correlates and ...determinants of SCD in PD are rare.
Objective
The aim of the present study was to identify neural correlates as well as sociodemographic, clinical, and neuropsychological predictors of SCD in patients with PD.
Methods
We retrospectively analyzed 30 patients with PD without cognitive impairment (23% female, 66.90 ± 7.20 years, UPDRS-III: 19.83 ± 9.29), of which
n
= 12 patients were classified as having no SCD (control group, PD-CG) and
n
= 18 as having SCD (PD-SCD). Neuropsychological testing and 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) were conducted. SCD was assessed using a questionnaire covering multiple cognitive domains.
Results
SCD subscores differed significantly between PD-CG and PD-SCD and correlated significantly with other scales measuring related concepts. FDG-PET whole-brain voxel-wise regression analysis revealed hypometabolism in middle frontal, middle temporal, and occipital areas, and the angular gyrus as neural correlates of SCD in PD. Next to this hypometabolism, depressive symptoms were an independent significant determinant of SCD in a stepwise regression analysis (adjusted
R
2
= 50.3%).
Conclusion
This study strengthens the hypothesis of SCD being an early manifestation of future cognitive decline in PD and, more generally, early pathological changes in PD. The early identification of the vulnerability for future cognitive decline constitutes the basis for successful prevention and delay of this non-motor symptom.
Full text
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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