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Background: Correct classification of estrogen receptor (ER) status is essential for prognosis and treatment planning in patients with breast cancer (BC). Therefore, it is recommended to sample tumor tissue from an accessible metastasis. However, ER expression can show intra- and intertumoral heterogeneity. 16α-[18F]fluoroestradiol ([18F]FES) Positron Emission Tomography/Computed Tomography (PET/CT) allows noninvasive whole-body (WB) identification of ER distribution and is usually performed as a single static image 60 min after radiotracer injection. Using dynamic whole-body (D-WB) PET imaging, we examine [18F]FES kinetics and explore whether Patlak parametric images ( K i ) are quantitative and improve lesion visibility. Results: This prospective study included eight patients with metastatic ER-positive BC scanned using a D-WB PET acquisition protocol. The kinetics of [18F]FES were best characterized by the irreversible two-tissue compartment model in tumor lesions and in the majority of organ tissues. K i values from Patlak parametric images correlated with K i values from the full kinetic analysis, r2 = 0.77, and with the semiquantitative mean standardized uptake value (SUVmean), r2 = 0.91. Furthermore, parametric K i images had the highest target-to-background ratio (TBR) in 162/164 metastatic lesions and the highest contrast-to-noise ratio (CNR) in 99/164 lesions compared to conventional SUV images. TBR was 2.45 (95% confidence interval (CI): 2.25–2.68) and CNR 1.17 (95% CI: 1.08–1.26) times higher in K i images compared to SUV images. These quantitative differences were seen as reduced background activity in the K i images. Conclusion: [18F]FES uptake is best described by an irreversible two-tissue compartment model. D-WB [18F]FES PET/CT scans can be used for direct reconstruction of parametric K i images, with superior lesion visibility and K i values comparable to K i values found from full kinetic analyses. This may aid correct ER classification and treatment decisions. Trial registration ClinicalTrials.gov: NCT04150731, https://clinicaltrials.gov/study/NCT04150731 [ABSTRACT FROM AUTHOR]

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = −0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = −0.52, P = 0.0104) and a measure of non-motor symptoms (rs = −0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia. [ABSTRACT FROM AUTHOR]

Background: Routine prostate-specific membrane antigen (PSMA) positron emission tomography (PET) performed for primary staging or restaging of prostate cancer patients is usually done as a single static image acquisition 60 min after tracer administration. In this study, we employ dynamic whole-body (D-WB) PET imaging to compare the pharmacokinetics of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in various tissues and lesions, and to assess whether Patlak parametric images are quantitative and improve lesion detection and image readability. Methods: Twenty male patients with prostate cancer were examined using a D-WB PSMA PET protocol. Ten patients were scanned with [68Ga]Ga-PSMA-11 and ten with [18F]PSMA-1007. Kinetic analyses were made using time-activity curves (TACs) extracted from organs (liver, spleen, bone, and muscle) and lesions. For each patient, three images were produced: SUV + Patlak parametric images (Ki and DV). All images were reviewed visually to compare lesion detection, image readability was quantified using target-to-background ratios (TBR), and Ki and DV values were compared. Results: The two PSMA tracers exhibited markedly different pharmacokinetics in organs: reversible for [68Ga]Ga-PSMA-11 and irreversible for [18F]PSMA-1007. For both tracers, lesions kinetics were best described by an irreversible model. All parametric images were of good visual quality using both radiotracers. In general, Ki images were characterized by reduced vascular signal and increased lesion TBR compared with SUV images. No additional malignant lesions were identified on the parametric images. Conclusion: D-WB PET/CT is feasible for both PSMA tracers allowing for direct reconstruction of parametric Ki images. The use of multiparametric PSMA images increased TBR but did not lead to the detection of more lesions. For quantitative whole-body Ki imaging, [18F]PSMA-1007 should be preferred over [68Ga]Ga-PSMA-11 due to its irreversible kinetics in organs and lesions. [ABSTRACT FROM AUTHOR]

Purpose: Contemporary PET/CT scanners can use 70-min dynamic whole-body (D-WB) PET to generate more quantitative information about FDG uptake than just the SUV by generating parametric images of FDG metabolic rate (MRFDG). The analysis requires the late (50–70 min) D-WB tissue data combined with the full (0–70 min) arterial input function (AIF). Our aim was to assess whether the use of a scaled population-based input function (sPBIF) obviates the need for the early D-WB PET acquisition and allows for a clinically feasible 20-min D-WB PET examination. Methods: A PBIF was calculated based on AIFs from 20 patients that were D-WB PET scanned for 120 min with simultaneous arterial blood sampling. MRFDG imaging using PBIF requires that the area under the curve (AUC) of the sPBIF is equal to the AUC of the individual patient's input function because sPBIF AUC bias translates into MRFDG bias. Special patient characteristics could affect the shape of their AIF. Thus, we validated the use of PBIF in 171 patients that were divided into 12 subgroups according to the following characteristics: diabetes, cardiac ejection fraction, blood pressure, weight, eGFR and age. For each patient, the PBIF was scaled to the aorta image-derived input function (IDIF) to calculate a sPBIF, and the AUC bias was calculated. Results: We found excellent agreement between the AIF and IDIF at all times. For the clinical validation, the use of sPBIF led to an acceptable AUC bias of 1–5% in most subgroups except for patients with diabetes or patients with low eGFR, where the biases were marginally higher at 7%. Multiparametric MRFDG images based on a short 20-min D-WB PET and sPBIF were visually indistinguishable from images produced by the full 70-min D-WB PET and individual IDIF. Conclusions: A short 20-min D-WB PET examination using PBIF can be used for multiparametric imaging without compromising the image quality or precision of MRFDG. The D-WB PET examination may therefore be used in clinical routine for a wide range of patients, potentially allowing for more precise quantification in e.g. treatment response imaging. [ABSTRACT FROM AUTHOR]

Modeling physiological processes using tracer kinetic methods requires knowledge of the time course of the tracer concentration in blood supplying the organ. For liver studies, however, inaccessibility of the portal vein makes direct measurement of the hepatic dual-input function impossible in humans. We want to develop a method to predict the portal venous time-activity curve from measurements of an arterial time-activity curve. An impulse-response function based on a continuous distribution of washout constants is developed and validated for the gut. Experiments with simultaneous blood sampling in aorta and portal vein were made in 13 anesthetized pigs following inhalation of intravascular [[.sup.15]0]CO or injections of diffusible 3-0[[.sup. 11]C]methylglucose (MG). The parameters of the impulse-response function have a physiological interpretation in terms of the distribution of washout constants and are mathematically equivalent to the mean transit time ([bar]T) and standard deviation of transit times. The results include estimates of mean transit times from the aorta to the portal vein in pigs: [bar]T = 0.35 [+ or -] 0.05 min for CO and 1.7 [+ or -] 0.1 min for MG. The prediction of the portal venous time-activity curve benefits from constraining the regression fits by parameters estimated independently. This is strong evidence for the physiological relevance of the impulse-response function, which includes asymptotically, and thereby justifies kinetically, a useful and simple power law. Similarity between our parameter estimates in pigs and parameter estimates in normal humans suggests that the proposed model can be adapted for use in humans. modeling; mean transit time; portal vein; spleen; power-law kinetics

Background: This study examines the clinical feasibility and impact of implementing a fully automated whole-body PET protocol with data-driven respiratory gating in patients with a broad range of oncological and non-oncological pathologies 592 FDG PET/CT patients were prospectively included. 200 patients with lesions in the torso were selected for further analysis, and ungated (UG), belt gated (BG) and data-driven gating (DDG) images were reconstructed. All images were reconstructed using the same data and without prolonged acquisition time for gated images. Images were quantitatively analysed for lesion uptake and metabolic volume, complemented by a qualitative analysis of visual lesion detection. In addition, the impact of gating on treatment response evaluation was evaluated in 23 patients with malignant lymphoma. Results: Placement of the belt needed for BG was associated with problems in 27% of the BG scans, whereas no issues were reported using DDG imaging. For lesion quantification, DDG and BG images had significantly greater SUV values and smaller volumes than UG. The physicians reported notable image blurring in 44% of the UG images that was problematic for clinical evaluation in 4.5% of cases. Conclusion: Respiratory motion compensation using DDG is readily integrated into clinical routine and produce images with more accurate and significantly greater SUV values and smaller metabolic volumes. In our broad cohort of patients, the physicians overwhelmingly preferred gated over ungated images, with a slight preference for DDG images. However, even in patients with malignant disease in the torso, no additional diagnostic information was obtained by the gated images that could not be derived from the ungated images. [ABSTRACT FROM AUTHOR]

Background: Dynamic whole-body (D-WB) FDG PET/CT is a recently developed technique that allows direct reconstruction of multiparametric images of metabolic rate of FDG uptake (MRFDG) and "free" FDG (DVFDG). Multiparametric images have a markedly different appearance than the conventional SUV images obtained by static PET imaging, and normal values of MRFDG and DVFDG in frequently used reference tissues and organs are lacking. The aim of this study was therefore to: (1) provide an overview of normal MRFDG and DVFDG values and range of variation in organs and tissues; (2) analyse organ time-activity curves (TACs); (3) validate the accuracy of directly reconstructed MRFDG tissue values versus manually calculated Ki (and MRFDG) values; and (4) explore correlations between demographics, blood glucose levels and MRFDG values. D-WB data from 126 prospectively recruited patients (100 without diabetes and 26 with diabetes) were retrospectively analysed. Participants were scanned using a 70-min multiparametric PET acquisition protocol on a Siemens Biograph Vision 600 PET/CT scanner. 13 regions (bone, brain grey and white matter, colon, heart, kidney, liver, lung, skeletal muscle of the back and thigh, pancreas, spleen, and stomach) as well as representative pathological findings were manually delineated, and values of static PET (SUV), D-WB PET (Ki, MRFDG and DVFDG) and individual TACs were extracted. Multiparametric values were compared with manual TAC-based calculations of Ki and MRFDG, and correlations with blood glucose, age, weight, BMI, and injected tracer dose were explored. Results: Tissue and organ MRFDG values showed little variation, comparable to corresponding SUV variation. All regional TACs were in line with previously published FDG kinetics, and the multiparametric metrics correlated well with manual TAC-based calculations (r2 = 0.97, p < 0.0001). No correlations were observed between glucose levels and MRFDG in tissues known not to be substrate driven, while tissues with substrate driven glucose uptake had significantly correlated glucose levels and MRFDG values. Conclusion: The multiparametric D-WB PET scan protocol provides normal MRFDG values with little inter-subject variation and in agreement with manual TAC-based calculations and literature values. The technique therefore facilitates both accurate clinical reports and simpler acquisition of quantitative estimates of whole-body tissue glucose metabolism. [ABSTRACT FROM AUTHOR]

The positron emission tomography (PET) tracer [18F]GE-179 binds to the phencyclidine (PCP) site in the open N -methyl-D-aspartate receptor ion channel (NMDAR-IC). To demonstrate that PET can visualise increased [18F]GE-179 uptake by active NMDAR-ICs and that this can be blocked by the PCP antagonist S-ketamine, 15 rats had an electrode unilaterally implanted in their ventral hippocampus. Seven rats had no stimulation, five received pulsed 400 µA supra-threshold 60 Hz stimulation alone, and three received intravenous S-ketamine injection prior to stimulation. Six other rats were not implanted. Each rat had a 90 min [18F]GE-179 PET scan. Stimulated rats had simultaneous depth-EEG recordings of induced seizure activity. [18F]GE-179 uptake (volume of distribution, VT) was compared between hemispheres and between groups. Electrical stimulation induced a significant increase in [18F]GE-179 uptake at the electrode site compared to the contralateral hippocampus (mean 22% increase in VT, p = 0.0014) and to non-stimulated comparator groups. Rats injected with S-ketamine prior to stimulation maintained non-stimulated levels of [18F]GE-179 uptake during stimulation. In conclusion, PET visualisation of focal [18F]GE-179 uptake during electrically activated NMDAR-ICs and the demonstration of specificity for PCP sites by blockade with S-ketamine support the in vivo utility of [18F]GE-179 PET as a use-dependent marker of NMDAR-IC activation. [ABSTRACT FROM AUTHOR]