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Purpose: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision., Procedures: To this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[ 18 F]fluoro-D-glucose injection and underwent routine clinical ( ∼ 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon's signed rank test and the SUVs were statistically compared using a paired t-test., Results: Twenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra., Conclusion: This study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations., (© 2024. The Author(s).)

Purpose: Estrogen receptors (ER) are implicated in psychiatric disorders. We assessed if ER availability in the human brain could be quantified using 16α-[ 18 F]-fluoro-17β-estradiol ([ 18 F]FES) positron emission tomography (PET)., Procedures: Seven post‑menopausal women underwent a dynamic [ 18 F]FES PET scan with arterial blood sampling. A T1-weighted MRI was acquired for anatomical information. After one week, four subjects received a selective ER degrader (SERD), four hours before the PET scan. Pharmacokinetic analysis was performed using a metabolite-corrected plasma curve as the input function. The optimal kinetic model was selected based on the Akaike information criterion and standard error of estimated parameters. Accuracy of Logan graphical analysis and standardized uptake value (SUV) was determined via correlational analyses., Results: The reversible two-tissue compartment model (2T4k) model with fixed K 1 /k 2 was preferred. The total volume of distribution (V T ) could be more reliably estimated than the binding potential (BP ND ). A high correlation of V T with Logan graphical analysis was observed, but only a moderate correlation with SUV. SERD administration resulted in a reduced V T in the pituitary gland, but not in other regions., Conclusions: The optimal quantification method for [ 18 F]FES was the 2T4k with fixed K 1 /k 2 or Logan graphical analysis, but specific binding was only observed in the pituitary gland., (© 2024. Crown.)

Introduction: P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease, and with drug-resistance, for example in treatment-resistant depression. The most widely used approach to measure P-gp function in vivo is (R)-[ 11 C]verapamil PET. (R)-[ 11 C]verapamil is, however, an avid P-gp substrate, which complicates the use of this tracer to measure an increase in P-gp function as its baseline uptake is already very low. [ 18 F]MC225 was developed to measure both increases and decreases in P-gp function., Aim: The aim of this study was (1) to identify the pharmacokinetic model that best describes [ 18 F]MC225 kinetics in the human brain and (2) to determine test-retest variability., Methods: Five (2 male, 3 female) of fourteen healthy subjects (8 male, 6 female, age 67 ± 5 years) were scanned twice (injected dose 201 ± 47 MBq) with a minimum interval of 2 weeks between scans. Each scanning session consisted of a 60-min dynamic [ 18 F]MC225 scan with continuous arterial sampling. Whole brain grey matter data were fitted to a single tissue compartment model, and to reversible and irreversible two tissue-compartment models to obtain various outcome parameters (in particular the volume of distribution (V T ), K i , and the rate constants K 1 and k 2 ). In addition, a reversible two-tissue compartment model with fixed k 3 /k 4 was included. The preferred model was selected based on the weighted Akaike Information Criterion (AIC) score. Test-retest variability (TRTV) was determined to assess reproducibility., Results: Sixty minutes post-injection, the parent fraction was 63.8 ± 4.0%. The reversible two tissue compartment model corrected for plasma metabolites with an estimated blood volume (V B ) showed the highest AIC weight score of 34.3 ± 17.6%. The TRVT of the V T for [ 18 F]MC225 PET scans was 28.3 ± 20.4% for the whole brain grey matter region using this preferred model., Conclusion: [ 18 F]MC225 V T , derived using a reversible two-tissue compartment model, is the preferred parameter to describe P-gp function in the human BBB. This outcome parameter has an average test-retest variability of 28%., Trial Registration: EudraCT 2020-001564-28 . Registered 25 May 2020., (© 2023. The Author(s).)

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, including canagliflozin, reduce the risk of cardiovascular and kidney outcomes in patients with and without type 2 diabetes, albeit with a large interindividual variation. The underlying mechanisms for this variation in response might be attributed to differences in SGLT2 occupancy, resulting from individual variation in plasma and tissue drug exposure and receptor availability. We performed a feasibility study for the use of [ 18 F]canagliflozin positron emission tomography (PET) imaging to determine the association between clinical canagliflozin doses and SGLT2 occupancy in patients with type 2 diabetes. We obtained two 90-minute dynamic PET scans with diagnostic intravenous [ 18 F]canagliflozin administration and a full kinetic analysis in 7 patients with type 2 diabetes. Patients received 50, 100, or 300 mg oral canagliflozin (n = 2:4:1) 2.5 hours before the second scan. Canagliflozin pharmacokinetics and urinary glucose excretion were measured. The apparent SGLT2 occupancy was derived from the difference between the apparent volume of distribution of [ 18 F]canagliflozin in the baseline and post-drug PET scans. Individual canagliflozin area under the curve from oral dosing until 24-hours (AUC P0-24h ) varied largely (range 1,715-25,747 μg/L*hour, mean 10,580 μg/L*hour) and increased dose dependently with mean values of 4,543, 6,525, and 20,012 μg/L*hour for 50, 100, and 300 mg, respectively (P = 0.046). SGLT2 occupancy ranged between 65% and 87%, but did not correlate with canagliflozin dose, plasma exposure, or urinary glucose excretion. We report the feasibility of [ 18 F]canagliflozin PET imaging to determine canagliflozin kidney disposition and SGLT2 occupancy. This suggests the potential of [ 18 F]canagliflozin as a tool to visualize and quantify clinically SGLT2 tissue binding., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling prevents its widespread clinical application. Several methods have been developed to avoid arterial sampling, in particular reference region methods. Unfortunately, for some tracers or diseases, no suitable reference region can be defined. For these cases, other potentially non-invasive approaches have been proposed: (1) a population based input function (PBIF), (2) an image derived input function (IDIF), or (3) simultaneous estimation of the input function (SIME). This systematic review aims to assess the correspondence of these non-invasive methods with the gold standard. Studies comparing non-invasive pharmacokinetic modelling methods with the current gold standard methods using an input function derived from arterial blood samples were retrieved from PubMed/MEDLINE (until December 2021). Correlation measurements were extracted from the studies. The search yielded 30 studies that correlated outcome parameters (V T , DVR, or BP ND for reversible tracers; K i or CMR glu for irreversible tracers) from a potentially non-invasive method with those obtained from modelling using an arterial input function. Some studies provided similar results for PBIF, IDIF, and SIME-based methods as for modelling with an arterial input function (R 2  = 0.59-1.00, R 2  = 0.71-1.00, R 2  = 0.56-0.96, respectively), if the non-invasive input curve was calibrated with arterial blood samples. Even when the non-invasive input curve was calibrated with venous blood samples or when no calibration was applied, moderate to good correlations were reported, especially for the IDIF and SIME (R 2  = 0.71-1.00 and R 2  = 0.36-0.96, respectively). Overall, this systematic review illustrates that non-invasive methods to generate an input function are still in their infancy. Yet, IDIF and SIME performed well, not only with arterial blood calibration, but also with venous or no blood calibration, especially for some tracers without plasma metabolites, which would potentially make these methods better suited for clinical application. However, these methods should still be properly validated for each individual tracer and application before implementation., (© 2023. The Author(s).)

Multiple sclerosis (MS) is an inflammatory demyelinating disease. Current treatments are focussed on immune suppression to modulate pathogenic activity that causes myelin damage. New treatment strategies are needed to prevent demyelination and promote remyelination. Development of such myelin repair therapies require a sensitive and specific biomarker for efficacy evaluation. Recently, it has been shown that quantification of myelin density is possible using [ 11 C]MeDAS PET. This method, however, requires arterial blood sampling to generate an arterial input function (AIF). As the invasive nature of arterial sampling will reduce clinical applicability, the purpose of this study was to assess whether an image-derived input function (IDIF) can be used as an alternative way to facilitate its routine clinical use. Six healthy controls and 11 MS patients underwent MRI and [ 11 C]MeDAS PET with arterial blood sampling. The application of both population-based whole blood-to-plasma conversion and metabolite corrections were assessed for the AIF. Next, summed images of the early time frames (0-70 s) and the frame with the highest blood-brain contrast were used to generate IDIFs. IDIFs were created using either the hottest 2, 4, 6 or 12 voxels, or an isocontour of the hottest 10% voxels of the carotid artery. This was followed by blood-to-plasma conversion and metabolite correction of the IDIF. The application of a population-based metabolite correction of the AIF resulted in high correlations of tracer binding (K i ) within subjects, but variable bias across subjects. All IDIFs had a sharper and higher peak in the blood curves than the AIF, most likely due to dispersion during blood sampling. All IDIF methods resulted in similar high correlations within subjects (r = 0.95-0.98), but highly variable bias across subjects (mean slope=0.90-1.09). Therefore, both the use of population based blood-plasma and metabolite corrections and the generation of the image-derived whole-blood curve resulted in substantial bias in [ 11 C]MeDAS PET quantification, due to high inter-subject variability. Consequently, when unbiased quantification of [ 11 C]MeDAS PET data is required, individual AIF needs to be used., (Copyright © 2022. Published by Elsevier Inc.)

The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin-1 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary-albumin-to-creatinine-ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66 years, median UACR 297 mg/g) after 4 weeks treatment with 80 mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC) = -0.64, P = 0.046, median change UACR: -40.1%, 95% confidence interval (CI): -22.9 to -77.4%, mean telmisartan area under the curve (AUC) = 2927.1 ng·hour/mL, 95% CI: 723.0 to 6501.6 ng·hour/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin-1 RO in five patients with T2D (mean age 60 years, median UACR 72 mg/g) in a separate positron emission tomography imaging study with [ 11 C]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC = 0.976, P = 0.024). A meaningful RO could be calculated in three patients receiving 120 mg oral telmisartan, and although high exposure seems related to higher RO, with AUC 0-last of 31, 840, and 274 ng·hour/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (P = 0.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [ 11 C]MeDAS as a PET tracer for myelin imaging in humans., Methods: Six healthy controls and 11 MS patients underwent MRI and dynamic [ 11 C]MeDAS PET scanning with arterial sampling. Lesion detection and classification were performed on MRI. [ 11 C]MeDAS time-activity curves of brain regions and MS lesions were fitted with various compartment models for the identification of the best model to describe [ 11 C]MeDAS kinetics. Several simplified methods were compared to the optimal compartment model., Results: Visual analysis of the fits of [ 11 C]MeDAS time-activity curves showed no preference for irreversible (2T3k) or reversible (2T4k) two-tissue compartment model. Both volume of distribution and binding potential estimates showed a high degree of variability. As this was not the case for 2T3k-derived net influx rate (K i ), the 2T3k model was selected as the model of choice. Simplified methods, such as SUV and MLAIR2 correlated well with 2T3k-derived K i , but SUV showed subject-dependent bias when compared to 2T3k. Both the 2T3k model and the simplified methods were able to differentiate not only between gray and white matter, but also between lesions with different myelin densities., Conclusion: [ 11 C]MeDAS PET can be used for quantification of myelin density in MS patients and is able to distinguish differences in myelin density within MS lesions. The 2T3k model is the optimal compartment model and MLAIR2 is the best simplified method for quantification., Trial Registration: NL7262. Registered 18 September 2018., (© 2022. The Author(s).)

Adenosine A 2A and dopamine D 2 receptors in the basal ganglia form heterotetrameric structures that are involved in the regulation of motor activity and neuropsychiatric functions. The present study examines the A 2A receptor-mediated modulation of D 2 receptor binding in vivo using positron emission tomography (PET) with the D 2 antagonist tracer [ 11 C]raclopride. Healthy male Wistar rats ( n = 8) were scanned (60 min dynamic scan) with [ 11 C]raclopride at baseline and 7 days later following an acute administration of the A 2A agonist CGS21680 (1 mg/kg), using a MicroPET Focus-220 camera. Nondisplaceable binding potential (BP ND ) values were calculated using a simplified reference tissue model (SRTM), with cerebellum as the reference tissue. SRTM analysis did not show any significant changes in [ 11 C]raclopride BP ND ( p = 0.102) in striatum after CGS21680 administration compared to the baseline. As CGS21680 strongly affects hemodynamics, we also used arterial blood sampling and a metabolite-corrected plasma input function for compartment modeling using the reversible two-tissue compartment model (2TCM) to obtain the BP ND from the k 3 / k 4 ratio and from the striatum/cerebellum volume of distribution ratio (DVR) in a second group of animals. These rats underwent dynamic [ 11 C]raclopride scans after pretreatment with a vehicle ( n = 5), a single dose of CGS21680 (1 mg/kg, n = 5), or a single dose of the A 2A antagonist KW6002 (1 mg/kg, n = 5). The parent fraction in plasma was significantly higher in the CGS21680-treated group ( p = 0.0001) compared to the vehicle-treated group. GCS21680 administration significantly reduced the striatal k 3 / k 4 ratio ( p < 0.01), but k 3 and k 4 estimates may be less reliable. The BP ND (DVR-1) decreased from 1.963 ± 0.27 in the vehicle-treated group to 1.53 ± 0.55 ( p = 0.080) or 1.961 ± 0.11 ( p = 0.993) after the administration of CGS21680 or KW6002, respectively. Our study suggests that the A 2A agonist CGS21680, but not the antagonist KW6002, may reduce the D 2 receptor availability in the striatum.

Introduction : Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction and a diverse range of nonmotor symptoms. Functional relationships between the dopaminergic and histaminergic systems suggest that dual-action pharmaceuticals like AG-0029 (D 2 /D 3 agonist/H 3 antagonist) could ameliorate both the motor and cognitive symptoms of PD. The current study aimed to demonstrate the interaction of AG-0029 with its intended targets in the mammalian brain using positron emission tomography (PET). Methods : Healthy male Wistar rats were scanned with a small-animal PET camera, using either the dopamine D 2 /D 3 receptor ligand [ 11 C]raclopride or the histamine H 3 receptor ligand [ 11 C]GSK-189254, before and after treatment with an intravenous, acute, single dose of AG-0029. Dynamic [ 11 C]raclopride PET data (60 min duration) were analyzed using the simplified reference tissue model 2 (SRTM2) with cerebellum as reference tissue and the nondisplaceable binding potential as the outcome parameter. Data from dynamic [ 11 C]GSK-189254 scans (60 min duration) with arterial blood sampling were analyzed using Logan graphical analysis with the volume of distribution ( V T ) as the outcome parameter. Receptor occupancy was estimated using a Lassen plot. Results : Dopamine D 2/3 receptor occupancies in the striatum were 22.6 ± 18.0 and 84.0 ± 3.5% (mean ± SD) after administration of 0.1 and 1 mg/kg AG-0029, respectively. In several brain regions, the V T values of [ 11 C]GSK-189254 were significantly reduced after pretreatment of rats with 1 or 10 mg/kg AG-0029. The H 3 receptor occupancies were 11.9 ± 8.5 and 40.3 ± 11.3% for the 1 and 10 mg/kg doses of AG-0029, respectively. Conclusions : Target engagement of AG-0029 as an agonist at dopamine D 2 /D 3 receptors and an antagonist at histamine H 3 receptors could be demonstrated in the rat brain with [ 11 C]raclopride and [ 11 C]GSK-189254 PET, respectively. The measured occupancy values reflect the previously reported high (subnanomolar) affinity of AG-0029 to D 2 /D 3 and moderate (submicromolar) affinity to H 3 receptors.

The Blood-Brain Barrier P-glycoprotein (P-gp) function can be altered in several neurodegenerative diseases and due to the administration of different drugs which may cause alterations in drug concentrations and consequently lead to a reduced effectiveness or increased side-effects. The novel PET radiotracer [ 18 F]MC225 is a weak P-gp substrate that may show higher sensitivity to detect small changes in P-gp function than previously developed radiotracers. This study explores the sensitivity of [ 18 F]MC225 to measure the dose-dependent effect of P-gp inhibitor tariquidar. Twenty-three rats were intravenously injected with different doses of tariquidar ranging from 0.75 to 12 mg/kg, 30-min before the dynamic [ 18 F]MC225-PET acquisition with arterial sampling. Tissue and blood data were fitted to a 1-Tissue-Compartment-Model to obtain influx constant K 1 and distribution volume V T , which allow the estimation of P-gp function. ANOVA and post-hoc analyses of K 1 values showed significant differences between controls and groups with tariquidar doses >3 mg/kg; while applying V T the analyses showed significant differences between controls and groups with tariquidar doses >6 mg/kg. Dose-response curves were fitted using different models. The four-parameter logistic sigmoidal curve provided the best fit for K 1 and V T data. Half-maximal inhibitory doses (ID 50 ) were 2.23 mg/kg (95%CI: 1.669-2.783) and 2.93 mg/kg (95%CI: 1.135-3.651), calculated with K 1 or V T values respectively. According to the dose-response fit, differences in [ 18 F]MC225-K 1 values could be detected at tariquidar doses ranging from 1.37 to 3.25 mg/kg. Our findings showed that small changes in the P-gp function, caused by low doses of tariquidar, could be detected by [ 18 F]MC225-K 1 values, which confirms the high sensitivity of the radiotracer. The results suggest that [ 18 F]MC225 may allow the quantification of moderate P-gp impairments, which may allow the detection of P-gp dysfunctions at the early stages of a disease and potential transporter-mediated drug-drug interactions., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The histamine H 3 receptor has been considered as a target for the treatment of various central nervous system diseases. Positron emission tomography (PET) studies with the radiolabeled potent and selective histamine H 3 receptor antagonist [ 11 C]GSK-189254 in rodents could be used to examine the mechanisms of action of novel therapeutic drugs or to assess changes of regional H 3 receptor density in animal models of neurodegenerative disease. [ 11 C]GSK-189254 was intravenously administered to healthy Wistar rats ( n = 10), and a 60 min dynamic PET scan was carried out. Arterial blood samples were obtained during the scan to generate a metabolite-corrected plasma input function. PET data were analyzed using a one-tissue compartment model (1T2k), irreversible (2T3k) or reversible two-tissue compartment models (2T4k), graphical analysis (Logan and Patlak), reference tissue models (SRTM and SRTM2), and standard uptake values (SUVs). The Akaike information criterion and the standard error of the estimated parameters were used to select the most optimal quantification method. This study demonstrated that the 2T4k model with a fixed blood volume fraction and Logan graphical analysis can best describe the kinetics of [ 11 C]GSK-189254 in the rat brain. SUV 40-60 and the reference tissue-based measurements DVR(2T4k), BP ND (SRTM), and SUV ratio could also be used as a simplified method to estimate H 3 receptor availability in case blood sampling is not feasible.

Purpose: The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation., Methods: A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging., Results: Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage., Conclusion: Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice., (© 2021. The Author(s).)

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecular imaging community can expect from these new PET/CT scanners is the delivery of more comprehensive information to the clinicians for advancing diagnosis, therapy evaluation and clinical research., (© 2021. The Author(s).)

Background: Positron emission tomography (PET) with 16α-[ 18 F]-fluoro-17β-estradiol ([ 18 F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [ 18 F]-FES uptake. We evaluated whether [ 18 F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard., Methods: Patients with metastatic breast cancer ( n = 23) were included if they had undergone a [ 18 F]-FES-PET, liver metastasis biopsy, CT-scan, and [ 18 F]-FDG-PET. [ 18 F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined., Results: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER- metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive., Conclusion: In the majority of liver metastases, ER status can be determined with [ 18 F]-FES-PET if background correction and separate thresholds are applied.

The aim of this study is to investigate the influence of sex, age, fat mass, fasting blood glucose level (FBGL), and estimated glomerular filtration rate (eGFR) on blood pool activity in patients with large vessel vasculitis (LVV). Blood pool activity was measured in the superior caval vein using mean, maximum, and peak standardized uptake values corrected for body weight (SUVs) and lean body mass (SULs) in 41 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans of LVV patients. Sex influence on the blood pool activity was assessed with t-tests, while linear correlation analyses were used for age, fat mass, FBGL, and eGFR. Significantly higher SUVs were found in women compared with men, whereas SULs were similar between sexes. In addition, higher fat mass was associated with increased SUVs (r = 0.56 to 0.65; all p < 0.001) in the blood pool, but no correlations were found between SULs and fat mass (r = -0.25 to -0.15; all p > 0.05). Lower eGFR was associated with a higher FDG blood pool activity for all uptake values. In FDG-PET/CT studies with LVV patients, we recommend using SUL over SUV, while caution is advised in interpreting SUV and SUL measures when patients have impaired kidney function.

Quantification of amyloid load with positron emission tomography can be useful to assess Alzheimer's Disease in-vivo. However, quantification can be affected by the image processing methodology applied. This study's goal was to address how amyloid quantification is influenced by different semi-automatic image processing pipelines. Images were analysed in their Native Space and Standard Space; non-rigid spatial transformation methods based on maximum a posteriori approaches and tissue probability maps (TPM) for regularisation were explored. Furthermore, grey matter tissue segmentations were defined before and after spatial normalisation, and also using a population-based template. Five quantification metrics were analysed: two intensity-based, two volumetric-based, and one multi-parametric feature. Intensity-related metrics were not substantially affected by spatial normalisation and did not significantly depend on the grey matter segmentation method, with an impact similar to that expected from test-retest studies (≤10%). Yet, volumetric and multi-parametric features were sensitive to the image processing methodology, with an overall variability up to 45%. Therefore, the analysis should be carried out in Native Space avoiding non-rigid spatial transformations. For analyses in Standard Space, spatial normalisation regularised by TPM is preferred. Volumetric-based measurements should be done in Native Space, while intensity-based metrics are more robust against differences in image processing pipelines., Competing Interests: The authors have declared that no competing interests exist.

Purpose: [ 18 F]Fluoroethoxybenzovesamicol ([ 18 F]FEOBV) is a radioligand for the vesicular acetylcholine transporter (VAChT), a marker of the cholinergic system. We evaluated the quantification of [ 18 F]FEOBV in rats in control conditions and after partial saturation of VAChT using plasma and reference tissue input models and test-retest reliability., Procedure: Ninety-minute dynamic [ 18 F]FEOBV PET scans with arterial blood sampling were performed in control rats and rats pretreated with 10 μg/kg FEOBV. Kinetic analyses were performed using one- (1TCM) and two-tissue compartmental models (2TCM), Logan and Patlak graphical analyses with metabolite-corrected plasma input, reference tissue Patlak with cerebellum as reference tissue, standard uptake value (SUV) and SUV ratio (SUVR) using 60- or 90-min acquisition. To assess test-retest reliability, two dynamic [ 18 F]FEOBV scans were performed 1 week apart., Results: The 1TCM did not fit the data. Time-activity curves were more reliably estimated by the irreversible than the reversible 2TCM for 60 and 90 min as the influx rate K i showed a lower coefficient of variation (COV, 14-24 %) than the volume of distribution V T (16-108 %). Patlak graphical analysis showed a good fit to the data for both acquisition times with a COV (12-27 %) comparable to the irreversible 2TCM. For 60 min, Logan analysis performed comparably to both irreversible models (COV 14-32 %) but showed lower sensitivity to VAChT saturation. Partial saturation of VAChT did not affect model selection when using plasma input. However, poor correlations were found between irreversible 2TCM and SUV and SUVR in partially saturated VAChT states. Test-retest reliability and intraclass correlation for SUV were good., Conclusion: [ 18 F]FEOBV is best modeled using the irreversible 2TCM or Patlak graphical analysis. SUV should only be used if blood sampling is not possible.

The interaction of dopaminergic and cholinergic neurotransmission in, e.g., Parkinson's disease has been well established. Here, D 2 receptor antagonists were used to assess changes in [ 18 F]-FEOBV binding to the vesicular acetylcholine transporter (VAChT) in rodents using positron emission tomography (PET). After pretreatment with either 10 mg/kg haloperidol, 1 mg/kg raclopride, or vehicle, 90 min dynamic PET scans were performed with arterial blood sampling. The net influx rate ( K i ) was obtained from Patlak graphical analysis, using a metabolite-corrected plasma input function and dynamic PET data. [ 18 F]-FEOBV concentration in whole-blood or plasma and the metabolite-corrected plasma input function were not significantly changed by the pretreatments (adjusted p > 0.07, Cohen's d 0.28-1.89) while the area-under-the-curve (AUC) of the parent fraction of [ 18 F]-FEOBV was significantly higher after haloperidol treatment (adjusted p = 0.022, Cohen's d = 2.51) than in controls. Compared to controls, the AUC of [ 18 F]-FEOBV, normalized for injected dose and body weight, was nonsignificantly increased in the striatum after haloperidol (adjusted p = 0.4, Cohen's d = 1.77) and raclopride (adjusted p = 0.052, Cohen's d = 1.49) treatment, respectively. No changes in the AUC of [ 18 F]-FEOBV were found in the cerebellum (Cohen's d 0.63-0.74). Raclopride treatment nonsignificantly increased K i in the striatum 1.3-fold compared to control rats (adjusted p = 0.1, Cohen's d = 1.1) while it reduced K i in the cerebellum by 28% (adjusted p = 0.0004, Cohen's d = 2.2) compared to control rats. Pretreatment with haloperidol led to a nonsignificant reduction in K i in the striatum (10%, adjusted p = 1, Cohen's d = 0.44) and a 40-50% lower K i than controls in all other brain regions (adjusted p < 0.0005, Cohen's d = 3.3-4.7). The changes in K i induced by the selective D 2 receptor antagonist raclopride can in part be quantified using [ 18 F]-FEOBV PET imaging. Haloperidol, a nonselective D 2 /σ receptor antagonist, either paradoxically decreased cholinergic activity or blocked off-target [ 18 F]-FEOBV binding to σ receptors. Hence, further studies evaluating the binding of [ 18 F]-FEOBV to σ receptors using selective σ receptor ligands are necessary.

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [ 15 O]H 2 O positron emission tomography-computed tomography (PET-CT). During a single hemodialysis session, three [ 15 O]H 2 O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, -4.1 ml/100 g per minute; 95% confidence interval, -7.3 to -0.9 ml/100 g per minute; P =0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury., (Copyright © 2018 by the American Society of Nephrology.)