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Abstract: Aim of this work was the implementation of a generalized in-loop synthesis for 11C-carboxylations and subsequent 11C-acylations on the TRACERlab FxC Pro platform. The set-up was tested using [carbonyl- 11C]WAY-100635 and, for the first time, [11C]-(+)-PHNO. Its general applicability could be demonstrated and both [carbonyl-11C]WAY-100635 and [11C]-(+)-PHNO were prepared with high reliability and satisfying outcome. [Copyright &y& Elsevier]

The melanin-concentrating hormone (MCH) system is a new target for the treatment of human disorders. Since the knowledge of the MCH system's involvement in a variety of pathologies (obesity, diabetes, and deregulation of metabolic feedback mechanism) is based on in vitro or preclinical studies, a suitable positron emission tomography (PET) tracer needs to be developed. We herein present the preparation and first preclinical evaluation of [18F]FE@SNAP - a new PET tracer for MCH receptor-1 (MCHR1). The synthesis was performed using a microfluidic device. Preclinical evaluation included binding affinity, plasma stability, plasma free fraction, stability against the cytochrome P- 450 (CYP450) system using liver microsomes, stability against carboxylesterase, and methods to assess the penetration of the blood-brain barrier (BBB) such as logD analysis and immobilized artificial membrane (IAM)chromatography. Levels at 374 ± 202 MBq [18F]FE@SNAP were obtained after purification. The obtained Kd value of [18F]FE@SNAP was 2.9 nM. [18F]FE@SNAP evinced high stability against carboxylesterase, CYP450 enzymes, and in human plasma. LogD (3.83) and IAM chromatography results (Pm=0.51) were in the same range as for known BBB-penetrating compounds. The synthesis of [18F]FE@SNAP was reliable and successful. Due to high binding affinity and stability, [18F]FE@SNAP is a promising tracer for MCHR1. [ABSTRACT FROM AUTHOR]

Objectives: To compare fused gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI (diffusion-weighted imaging) for the assessment of abdominal neuroendocrine tumours (NETs). Methods: Eighteen patients with suspected or histologically proven NETs of the abdomen were enrolled in this retrospective study. All patients underwent Ga-68-DOTANOC PET/CT for a primary search, staging, or restaging, and received an additional MRI, including dynamic gadoxetate-enhanced T1-weighted sequences and DWI (b-values 50, 300 and 600). Co-registered gadoxetate-enhanced PET/MRI and PET/DWI were separately analysed for NET lesions by a nuclear medicine physician and a radiologist in consensus. Sensitivity and specificity were calculated on a per-region, per-organ and per-patient basis. Results: Eighty-seven out of 684 anatomical regions, and 23 out of 270 organs, were NET-positive in 14 out of 18 patients. Region-based sensitivities and specificities were 97.7 % and 99.7 % for gadoxetate-enhanced PET/MRI and 98.9 % and 99.7 % for PET/DWI. Organ-based sensitivities and specificities were 91.3 % and 99.6 % for gadoxetate-enhanced PET/MRI and 95.7 % and 99.6 % for PET/DWI. Finally, patient-based sensitivities and specificities were 100 % and 100 % for gadoxetate-enhanced PET/MRI and 100 % and 75 % for PET/DWI. Sensitivities and specificities of the two methods did not differ significantly. Conclusions: Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI are equally useful for the assessment of abdominal NETs. Key Points: • Positron emission tomography and magnetic resonance imaging can both assess neuroendocrine tumours. • Fusion of PET/MR imaging provides helpful information. • Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI assess neuroendocrine tumours equally well. • PET/DWI is inherently simpler than gadoxetate-enhanced PET/MRI. • Only benign hepatic lesions pose a potential diagnostic dilemma for PET/DWI. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Image-derived input functions (IDIFs) represent a promising non-invasive alternative to arterial blood sampling for quantification in positron emission tomography (PET) studies. However, routine applications in patients and longitudinal designs are largely missing despite widespread attempts in healthy subjects. The aim of this study was to apply a previously validated approach to a clinical sample of patients with major depressive disorder (MDD) before and after electroconvulsive therapy (ECT). Methods: Eleven scans from 5 patients with venous blood sampling were obtained with the radioligand [carbonyl-11C]WAY-100635 at baseline, before and after 11.0±1.2 ECT sessions. IDIFs were defined by two different image reconstruction algorithms 1) OSEM with subsequent partial volume correction (OSEM+PVC) and 2) reconstruction based modelling of the point spread function (TrueX). Serotonin-1A receptor (5-HT1A) binding potentials (BPP, BPND) were quantified with a two-tissue compartment (2TCM) and reference region model (MRTM2). Results: Compared to MRTM2, good agreement in 5-HT1A BPND was found when using input functions from OSEM+PVC (R2 =0.82) but not TrueX (R2 =0.57, p<0.001), which is further reflected by lower IDIF peaks for TrueX (p<0.001). Following ECT, decreased 5-HT1A BPND and BPP were found with the 2TCM using OSEM+PVC (23%–35%), except for one patient showing only subtle changes. In contrast, MRTM2 and IDIFs from TrueX gave unstable results for this patient, most probably due to a 2.4-fold underestimation of non-specific binding. Conclusions: Using image-derived and venous input functions defined by OSEM with subsequent PVC we confirm previously reported decreases in 5-HT1A binding in MDD patients after ECT. In contrast to reference region modeling, quantification with image-derived input functions showed consistent results in a clinical setting due to accurate modeling of non-specific binding with OSEM+PVC. [Copyright &y& Elsevier]

Objectives: To determine, in patients with melanoma, the dependence of PET sensitivity on pulmonary metastasis size, and to determine patients who require further evaluation for definite staging.Methods: Of 183 melanoma patients who underwent (18)F-fluorodeoxyglucose PET/computed tomography (CT) for staging or follow-up between January 2008 and June 2011, 38 patients (18 women and 20 men; mean age 62.0 ± 14.7 years) with one or more pulmonary metastases visible on CT were included in the retrospective study. Each pulmonary metastasis was rated as positive or negative on PET, and lesion size (maximum transverse diameter) was assessed on CT. PET sensitivity was calculated according to the lesions' size, in 2-mm steps.Results: A total of 181 pulmonary metastases were analysed. PET sensitivity was 7.9 % for lesions of 4-5 mm; 33.3 % for lesions of 6-7 mm; 56.8 % for lesions of 8-9 mm; 63.6 % for lesions of 10-11 mm; 100 % for lesions of 12-14 mm; and 100 % for lesions of at least 15 mm. The differences in sensitivity between the size groups were significant (P < 0.001) CONCLUSIONS: With current state-of-the-art PET/CT technology, additional tests are necessary for definitive staging of melanoma patients who have one or more PET-negative lung nodules less than 12 mm in diameter on expiratory CT.Key Points: • PET cannot rule out malignancy in pulmonary nodules less than 12 mm on expiratory CT. • Melanoma patients with PET-negative pulmonary nodules less than 12 mm require additional tests. • Knowledge of these factors can help interpretation of PET and PET/CT findings. [ABSTRACT FROM AUTHOR]

Abstract: Recent mathematical models suggest restored serotonergic burst-firing to underlie the antidepressant effect of selective serotonin reuptake inhibitors (SSRI), resulting from down-regulated serotonin transporters (SERT) in terminal regions. This mechanism possibly depends on the interregional balance between SERTs in the raphe nuclei and in terminal regions before treatment. To evaluate these hypotheses on a systems level in humans in vivo, we investigated SERT availability and occupancy longitudinally in patients with major depressive disorder using positron emission tomography (PET) and the radioligand [11C]DASB. Measurements were performed before and after a single oral dose, as well as after three weeks (mean 24.73±3.3days) of continuous oral treatment with either escitalopram (10mg/day) or citalopram (20mg/day). Data were analyzed using voxel-wise linear regression and ANOVA to evaluate SERT binding, occupancy and binding ratios (SERT binding of the entire brain compared to SERT binding in the dorsal and median raphe nuclei) in relation to treatment outcome. Regression analysis revealed that treatment response was predicted by pre-treatment SERT binding ratios, i.e., SERT binding in key regions of depression including bilateral habenula, amygdala–hippocampus complex and subgenual cingulate cortex in relation to SERT binding in the median but not dorsal raphe nucleus (p <0.05 FDR-corrected). Similar results were observed in the direct comparison of responders and non-responders. Our data provide a first proof-of-concept for recent modeling studies and further underlie the importance of the habenula and subgenual cingulate cortex in the etiology of and recovery from major depression. These findings may indicate a promising molecular predictor of treatment response and stimulate new treatment approaches based on regional differences in SERT binding. [Copyright &y& Elsevier]

Abstract: Introduction: Our aim was the optimization of radiochemical parameters for the microfluidic preparation of [18F]altanserin. The four main parameters evaluated were (1) precursor concentration, (2) reaction temperature, (3) bolus flow rate through the microreactor and (4) bolus volume. Methods: For the determination of optimal reaction conditions within a flow-through microreactor synthesizer, 5–400 μL of precursor and dried [18F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (180–220°C) with defined bolus flow rates of 10–60 μL/min. Radiochemical incorporation yields (RCIYs) were examined using a thin layer chromatography (TLC) set-up and radio- high-performance liquid chromatography (HPLC). Results: Optimum reaction parameters for the microfluidic set-up were determined as following: 220°C, 5–10 μL/min pump rate per reactant (10–20 μL/min reaction overall flow rate) and 2mg/mL precursor concentration in the reaction mixture. Applying these optimized conditions, RCIYs of 53.7±7.9 were observed for scaled-up preparations. A positive “bolus effect” was observed: applying higher reaction volume resulted in increased RCIYs. Conclusion: This study proved that the reaction bolus volume is an essential parameter influencing the RCIY of [18F]altanserin. A possible explanation is the inhomogeneous distribution within the reaction volume probably caused by diffusion at the bolus interface. This important finding should be considered an important variable for the evaluation of all novel radiotracers labeled using a flow-through reactor device. [Copyright &y& Elsevier]

Abstract: Changes in the expression of the melanin concentrating hormone receptor 1 (MCHR1) are involved in a variety of pathologies, especially obesity and anxiety disorders. To monitor these pathologies in-vivo positron emission tomography (PET) is a suitable method. After the successful radiosynthesis of [11C]SNAP-7941—the first PET-Tracer for the MCHR1, we aimed to synthesize its [18F]fluoroethylated analogue: [18F]FE@SNAP. Therefore, microfluidic and vessel-based approaches were tested. [18F]fluoroethylation was conducted via various [18F]fluoroalkylated synthons and direct [18F]fluorination. Only the direct [18F]fluorination of a tosylated precursor using a flow-through microreactor was successful, affording [18F]FE@SNAP in 44.3±2.6%. [Copyright &y& Elsevier]

Abstract: Image-derived input functions (IDIFs) represent a promising technique for a simpler and less invasive quantification of PET studies as compared to arterial cannulation. However, a number of limitations complicate the routine use of IDIFs in clinical research protocols and the full substitution of manual arterial samples by venous ones has hardly been evaluated. This study aims for a direct validation of IDIFs and venous data for the quantification of serotonin-1A receptor binding (5-HT1A) with [carbonyl-11C]WAY-100635 before and after hormone treatment. Methods: Fifteen PET measurements with arterial and venous blood sampling were obtained from 10 healthy women, 8 scans before and 7 after eight weeks of hormone replacement therapy. Image-derived input functions were derived automatically from cerebral blood vessels, corrected for partial volume effects and combined with venous manual samples from 10min onward (IDIF+VIF). Corrections for plasma/whole-blood ratio and metabolites were done separately with arterial and venous samples. 5-HT1A receptor quantification was achieved with arterial input functions (AIF) and IDIF+VIF using a two-tissue compartment model. Results: Comparison between arterial and venous manual blood samples yielded excellent reproducibility. Variability (VAR) was less than 10% for whole-blood activity (p>0.4) and below 2% for plasma to whole-blood ratios (p>0.4). Variability was slightly higher for parent fractions (VARmax=24% at 5min, p<0.05 and VAR<13% after 20min, p>0.1) but still within previously reported values. IDIFs after partial volume correction had peak values comparable to AIFs (mean difference Δ=−7.6±16.9kBq/ml, p>0.1), whereas AIFs exhibited a delay (Δ=4±6.4s, p<0.05) and higher peak width (Δ=15.9±5.2s, p<0.001). Linear regression analysis showed strong agreement for 5-HT1A binding as obtained with AIF and IDIF+VIF at baseline (R2 =0.95), after treatment (R2 =0.93) and when pooling all scans (R2 =0.93), with slopes and intercepts in the range of 0.97 to 1.07 and −0.05 to 0.16, respectively. In addition to the region of interest analysis, the approach yielded virtually identical results for voxel-wise quantification as compared to the AIF. Conclusions: Despite the fast metabolism of the radioligand, manual arterial blood samples can be substituted by venous ones for parent fractions and plasma to whole-blood ratios. Moreover, the combination of image-derived and venous input functions provides a reliable quantification of 5-HT1A receptors. This holds true for 5-HT1A binding estimates before and after treatment for both regions of interest-based and voxel-wise modeling. Taken together, the approach provides less invasive receptor quantification by full independence of arterial cannulation. This offers great potential for the routine use in clinical research protocols and encourages further investigation for other radioligands with different kinetic characteristics. [Copyright &y& Elsevier]

Objectives: To determine the value of intravenous contrast medium in (68)Ga-DOTA-Phe(1)-Tyr(3)-octreotide - (68)Ga-DOTATOC - PET/CT for the detection of abdominal neuroendocrine tumours (NET). Methods: In fifty-five patients with known or suspected NETs of the abdomen PET/CT was performed on a 64-row multi-detector hybrid system. For PET, 150 MBq of (68)Ga-DOTATOC were injected intravenously. Full-dose unenhanced, and arterial- and venous-phase contrast-enhanced CT images were obtained. Unenhanced and contrast-enhanced PET/CT images were evaluated separately for the presence of NETs on a per-region basis, by two separate teams with different experience levels. Results: On unenhanced PET/CT, sensitivity and specificity ranged from 89.3% (junior team) to 92% (senior team), and 99.1% (junior team) to 99.2% (senior team), respectively. On contrast-enhanced PET/CT, sensitivity and specificity ranged from 92.3% (junior team) to 98.5% (senior team), and 99.4% (junior team) to 99.5% (senior team), respectively. These increases in sensitivity and specificity, due to the use of contrast-enhanced images, were statistically significant ( P < 0.05). Conclusions: Intravenous contrast medium only moderately, aleit significantly, improves the sensitivity of (68)Ga-DOTATOC PET/CT for the detection of abdominal NETs, and hardly affects specificity. Thus, while contrast enhancement is justified to achieve maximum sensitivity, unenhanced images may be sufficient for routine PET/CT in NET patients. Key Points: • Contrast media moderately improve the sensitivity of (68)Ga-DOTATOC PET/CT for neuroendocrine tumours. • Contrast media hardly affect the specificity of (68)Ga-DOTATOC PET/CT for neuroendocrine tumours. • Unenhanced PET/CT is sufficient for routine imaging of patients with neuroendocrine tumours. [ABSTRACT FROM AUTHOR]

Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT1A), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT1A binding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5-HT1A binding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5-HT1A inhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT1A binding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT1A binding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network. [ABSTRACT FROM AUTHOR]

Objective: Correct diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial to treat patients. The purpose of this study was to evaluate the diagnostic and prognostic value of [18F]F-DOPA PET/CT in patients with MTC., Methods: We reviewed MTC patients who underwent [18F]F-DOPA PET/CT from June 2008 to November 2023. Clinical characteristics, follow-up data, and the following [18F]F-DOPA PET/CT parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and SUVmean of multiple organs. The diagnostic value of PET/CT for the detection of tumor lesions was calculated. Serum basal calcitonin (bCt) and stimulated calcitonin (sCt) were determined. Receiver operating characteristics, Kaplan-Meier, and Cox regression analyses were performed., Results: In total, 109 patients (50 women, 59 men; average age, 55 ± 14 years) were included in the analysis. The patient-related sensitivity, specificity, and accuracy of [18F]F-DOPA PET/CT were 95%, 93%, and 94%, respectively. The lesion-related sensitivity, specificity, and accuracy were 65%, 99%, and 72%, respectively. The optimal cutoff values of bCt, sCt, and CEA to obtain positive [18F]F-DOPA PET/CT results were 64 pg/mL, 1808 pg/mL, and 4 µg/L, respectively. Patients with negative [18F]F-DOPA PET/CT had longer overall survival than patients with positive [18F]F-DOPA PET/CT results (P = 0.017). Significant positive correlations were found between bCt, sCt, and CEA with SUVmax, SUVmean, and MTV of [18F]F-DOPA PET/CT (P < 0.001). [18F]F-DOPA PET/CT results and MTV may be useful for the evaluation of the prognosis of patients with recurrent MTC, while age and MTV were independent prognostic factors in patients with primary MTC. For all patients, SUVmean of the left kidney, liver, aorta, and pancreas might be used to independently predict OS., Conclusion: [18F]F-DOPA PET/CT had great value for diagnosis and prognostic assessment in patients with MTC. The DOPA PET/CT parameter SUVmean and MTV showed significant association with OS.

Background: The most important part of the follow-up of differentiated thyroid carcinoma (DTC) is the measurement of serum thyroglobulin (Tg). An increase of Tg levels indicates likely tumor recurrence. According to the guidelines of the European Society of Medical Oncology (ESMO), the follow-up should consist of serum Tg assays and a neck ultrasound, while the American Thyroid Association (ATA) recommends serum Tg assays, neck ultrasounds, and a diagnostic radioiodine whole-body scan (WBS) if non-stimulated Tg is greater than 10 ng/mL or if Tg is rising. This study questions the necessity of a diagnostic WBS in patients with low stimulated Tg levels during the initial follow-up., Design: This study is a retrospective data analysis., Methods: The data of 185 patients, who were in regular treatment and aftercare between 2015 and 2018 at the Department of Nuclear Medicine in Vienna, as well as the data of 185 patients who were treated in Tbilisi between 2015 and 2019, were analyzed., Results: There was a highly significant relationship between low stimulated Tg levels (<0.5 ng/mL) and the outcome of the diagnostic WBS at the first follow-up (χ 2 = 14.7, P < 0.001). In total, 31 out of 370 patients (8.4%) had positive findings in the diagnostic WBS. Seventy-five of 370 patients (19.74%) had stimulated Tg levels >0.5 ng/mL., Conclusion: Our data suggest that the first follow-up, 4-12 months after the initial therapy of DTC, including the measurement of basal and stimulated Tg levels and Tg antibody levels, does not mandate a diagnostic WBS on all patients., Significance Statement: In this study, we examined the still commonly used routine diagnostic radioiodine whole-body scan in the first follow-up of patients with differentiated thyroid carcinoma. We questioned the necessity of the scan in patients with low stimulated thyroglobulin levels. Therefore, we combined retrospective data from the University Hospital in Vienna and in Tbilisi to analyze 370 patients. We were able to demostrate a highly significant relationship between low stimulated thyroglobulin levels (<0.5 ng/mL) and the outcome of the diagnostic scan at the first follow-up (χ = 14.7, P < 0.001).

Iatrogenic subclinical hyperthyroidism is induced intentionally in patients with differentiated thyroid cancer to reduce the risk of tumor recurrence. This retrospective study aimed to investigate the effect of thyroid-stimulating hormone (TSH) suppressive therapy on bone mineral density in men and women. Two cohorts of endocrine cancer patients were compared. In cohort A, 42 patients with long-lasting suppressed serum TSH were assessed. Cohort B consisted of 41 euthyroid patients. Bone density was measured in the L1-L4 lumbar vertebrae of all patients using PET/CT scans performed for cancer staging. In 17 patients of cohort A who received a second PET/CT scan, bone density was measured again to provide longitudinal analysis. A non-significant difference in age (p = .572) and equal distribution of sex (p = .916) was determined when comparing both cohorts. A significant difference (p = .011) with a moderate effect (η 2  = .08; 20.4%) was observed regarding higher bone mineral density (BMD^HU) in cohort B with normal TSH levels (M 160.63 ± 54.7 HU) versus cohort A under TSH suppression therapy (M 127.9 ± 59.5 HU) for a mean duration of 4.45 ± 2.64 years. Furthermore, no significant change in BMD^HU (p = .786) was found in those patients who received a second PET/CT scan after a mean observation time of 2.3 ± 1.2 years. In conclusion, long-lasting TSH suppression therapy caused a statistically significant decrease in BMD^HU while short-lasting therapy didn't. Therefore, we can assume a higher likelihood of osteoporosis in those patients under prolonged TSH suppression., (© 2023. The Author(s).)

The nervous and circulatory system interconnects the various organs of the human body, building hierarchically organized subsystems, enabling fine-tuned, metabolically expensive brain-body and inter-organ crosstalk to appropriately adapt to internal and external demands. A deviation or failure in the function of a single organ or subsystem could trigger unforeseen biases or dysfunctions of the entire network, leading to maladaptive physiological or psychological responses. Therefore, quantifying these networks in healthy individuals and patients may help further our understanding of complex disorders involving body-brain crosstalk. Here we present a generalized framework to automatically estimate metabolic inter-organ connectivity utilizing whole-body functional positron emission tomography (fPET). The developed framework was applied to 16 healthy subjects (mean age ± SD, 25 ± 6 years; 13 female) that underwent one dynamic 18 F-FDG PET/CT scan. Multiple procedures of organ segmentation (manual, automatic, circular volumes) and connectivity estimation (polynomial fitting, spatiotemporal filtering, covariance matrices) were compared to provide an optimized thorough overview of the workflow. The proposed approach was able to estimate the metabolic connectivity patterns within brain regions and organs as well as their interactions. Automated organ delineation, but not simplified circular volumes, showed high agreement with manual delineation. Polynomial fitting yielded similar connectivity as spatiotemporal filtering at the individual subject level. Furthermore, connectivity measures and group-level covariance matrices did not match. The strongest brain-body connectivity was observed for the liver and kidneys. The proposed framework offers novel opportunities towards analyzing metabolic function from a systemic, hierarchical perspective in a multitude of physiological pathological states., Competing Interests: Declaration of Competing Interest M. Hacker received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers. R. Lanzenberger received travel grants and/or conference speaker honoraria from Bruker BioSpin within the last three years and investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. Ivo Rausch received a research grant from Siemens Healthineers not related to this study. All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Dynamic positron emission tomography (PET) and the application of kinetic models can provide important quantitative information based on its temporal information. This however requires arterial blood sampling, which can be challenging to acquire. Nowadays, state-of-the-art PET/CT systems offer fully automated, whole-body (WB) kinetic modelling protocols using image-derived input functions (IDIF) to replace arterial blood sampling. Here, we compared the validity of an automatic WB kinetic model protocol to the reference standard arterial input function (AIF) for both clinical and research settings. Methods: Sixteen healthy participants underwent dynamic WB [ 18 F]FDG scans using a continuous bed motion PET/CT system with simultaneous arterial blood sampling. Multiple processing pipelines that included automatic and manually generated IDIFs derived from the aorta and left ventricle, with and without motion correction were compared to the AIF. Subsequently generated quantitative images of glucose metabolism were compared to evaluate performance of the different input functions. Results: We observed moderate to high correlations between IDIFs and the AIF regarding area under the curve (r = 0.49-0.89) as well as for the cerebral metabolic rate of glucose (CMRGlu) (r = 0.68-0.95). Manual placing of IDIFs and motion correction further improved their similarity to the AIF. Discussion: In general, the automatic vendor protocol is a feasible approach for the quantification of CMRGlu for both, clinical and research settings where expertise or time is not available. However, we advise on a rigorous inspection of the placement of the volume of interest, the resulting IDIF, and the quantitative values to ensure valid interpretations. In protocols requiring longer scan times or where cohorts are prone to involuntary movement, manual IDIF definition with additional motion correction is recommended, as this has greater accuracy and reliability., Competing Interests: RL received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. MH received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers. IR received a research grant from Siemens Healthineers not related to this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor CC declared a past co-authorship with the authors TB and IR., (Copyright © 2023 Reed, Godbersen, Vraka, Rausch, Ponce de León, Popper, Geist, Nics, Komorowski, Karanikas, Beyer, Traub-Weidinger, Hahn, Langsteger, Hacker and Lanzenberger.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background/aim: Positron emission tomography/computed tomography (PET/CT) plays an important role in cancer localization in ectopic Cushing's syndrome (ECS). However, the choice of the optimal tracer for investigation of this disease is still unclear. We aimed to evaluate the diagnostic feasibility of [ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG), [ 18 F]fluoro-L-dihydroxyphenylalanine ([ 18 F] FDOPA), and [ 68 Ga]-DOTA-1-Nal3-octreotide ([ 68 Ga]-DOTANOC) in ECS., Patients and Methods: All PET/CT scans of patients admitted to our department for suspected ECS between 2010 and 2020 were retrospectively analysed., Results: Collectively, 30 PET/CT examinations, 11 with [ 18 F]FDOPA, 11 with [ 18 F]FDG and 8 with [ 68 Ga]GaDOTANOC were conducted for 18 patients eligible for analysis. [ 18 F]FDG detected the tumour in 3/6 of the cases, [ 18 F]FDOPA in 3/4, and [ 68 Ga]GaDOTANOC in 3/3. [ 18 F]FDOPA was the only tracer without false positive results., Conclusion: [ 68 Ga]GaDOTANOC and [ 18 F]FDOPA showed superior results compared to [ 18 F]FDG, although the sensitivity of the tracers might be influenced by the aetiology of the tumour underlying the ECS., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To assess in healthy volunteers the whole-body distribution and dosimetry of [ 11 C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier., Procedures: Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [ 11 C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module., Results: The majority of the administered dose of [ 11 C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [ 11 C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively., Conclusions: [ 11 C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [ 11 C]metoclopramide was comparable to other 11 C-labeled PET tracers.

Objective: The pancreatic uptake of [ 11 C]methionine ([ 11 C]MET) is associated with beta-cell function and insulin secretion, but [ 11 C]MET uptake and its relationship with exocrine pancreatic performance are less well studied. The postprandial release of cholecystokinin (CCK) depends on gastric emptying velocity and triggers exocrine pancreas secretion. Therefore, we assumed that high postprandial CCK concentrations stimulate the uptake of [ 11 C]MET in the residual pancreas following pancreaticoduodenectomy., Methods: Nineteen tumor-free patients after pancreaticoduodenectomy (median age: 64; 25/75 quantile: 56-67 years); ten males, nine females and ten healthy controls (median age: 24; 25/75 quantile: 23.8-26 years) were given a mixed meal. Plasma CCK, insulin and glucose concentrations were measured before and at 10, 20, 30, 60, 90, 150 and 180 min after ingestion. Simultaneously, 800 MBq of [ 11 C]MET were administered and the activity [maximum tissue standardized uptake values (SUVmax)] over the pancreas was measured using PET-CT at 15, 30 and 60 min after injection., Results: Integrated CCK (AUC 30 ) correlated with SUVmax (AUC 60 , R 2  = 0.45, p value = 0.0013). Multivariate analysis revealed postprandial insulin (AUC 60 ) and CCK concentrations and young age as significant independent predictors of [ 11 C] methionine uptake., Conclusion: The association between CCK concentrations and pancreatic [ 11 C]MET uptake might indicate a causal relationship. Further research should assess whether [ 11 C]MET uptake could serve as a less invasive tool to assess exocrine pancreas activity.

Purpose: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI., Methods: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [ 18 F]FDG, [ 68 Ga]Ga-DOTANOC, or [ 18 F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated., Results: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients., Conclusions: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.

Background: The objective of this study was to characterize tumor activity and mineralization status in newly-detected multiple myeloma (MM) bone lesions using 2- 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG)-PET/CT and 18 F-sodium fluoride ( 18 F-NaF)-PET/CT before and after antitumor treatment., Materials and Methods: In this retrospective study, seven patients with histologically-verified MM were included (four women, three men; median age=57 years, standard deviation=11.23 years). PET/CT was performed with 18 F-FDG and with 18 F-NaF, both at baseline and after treatment. All patients had positive scans. Volumes of interest (VOIs) were drawn over all 18 F-FDG-PET/CT-positive bone lesions, as well as the corresponding regions in 18 F-NaF-PET/CT. For characterization of bone lesions, semi-quantitative standard uptake value (SUV) parameters were measured., Results: 18 F-FDG-PET/CT in the seven patients detected 39 metabolically active lesions that were correlated with the corresponding sites in 18 F-fluoride-PET/CT. Overall, the lesions showed a response to therapy, with a significant decrease in SUV max on PET/CT using 18 F-FDG (p<0.001) and with 18 F-NaF (p<0.001). In four patients with a second follow-up scan (at a median of 17 months after baseline scan), there was no significant change in lesion uptake., Conclusion: Based on our data, antitumor therapy in MM reduces not only tumor activity, but also the mineralization status of bone lesions. A second follow-up scan in a subset of the cohort yielded no change in mineralization status., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate [ 11 C]acetate PET-surrogate parameter of fatty acid synthase activity-as suitable tool for diagnosis and monitoring of liver steatosis., Methods: In this retrospective study, data were obtained from 83 prostatic carcinoma patients from 1/2008 to 1/2014. Mean HU was calculated from unenhanced CT of all patients from liver with liver HU less than 40 as threshold for liver steatosis. SUV max of the liver and of the blood pool in thoracic aorta (as background for calculation of a liver/background ratio [SUV l/b ]) was measured. t test was used with a P < 0.05 considered as statistically significant difference and ROC analysis was used for calculating specificity and sensitivity., Results: 19/83 patients (20%) had diagnosis of hepatic steatosis according to CT. Uptake of [ 11 C]acetate was significantly higher in patients with hepatic steatosis as compared to control group (SUV max 7.96 ± 2.0 vs. 5.48 ± 2.3 [P < 0.001]). There was also a significant correlation between both SUV max (r = - 0.52, P < 0.001) and SUV l/b (r = - 0.59, P < 0.001) with the density (HU) of the liver. In ROC analysis for detection of liver steatosis SUV max (threshold: 5.86) had a sensitivity of 94% and specificity of 69% with an AUC of 0.81. Increasing body mass index is correlated with the severity of steatosis., Conclusion: We showed for the first time that hepatic steatosis associates with increased [ 11 C]acetate uptake. Also, severity of steatosis correlates with [ 11 C]acetate uptake. [ 11 C]acetate uptake PET seems promising for the assessment of liver steatosis.

Purpose: Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [ 18 F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection., Methods: A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse., Results: Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02)., Conclusion: This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

Rationale and Objectives: This study aimed to determine the diagnostic utility of standardized uptake values (SUV) and apparent diffusion coefficients (ADC) for assessment of focal and diffuse bone marrow involvement in patients with malignant lymphoma., Materials and Methods: Sixty treatment-naive patients (28 males; mean age 51.2 ± 16.7 years) with histologically proven lymphoma, who underwent fludeoxyglucose ( 18 F) positron emission tomography-computed tomography ([F18]-FDG-PET/CT) and whole-body diffusion-weighted imaging (WB-DWI) within 7 days, and also routine bone marrow biopsy, were included in this institutional review board-approved, retrospective study. The maximum SUV (SUVmax) on [F18]-FDG-PET/CT, and the mean ADC (ADCmean, ×10 -3 mm 2 /s) on whole-body-DWI, were extracted from focal lesions, or, in their absence, from the thoracic (Th8) and lumbar vertebral bodies (L4), the sacral bone (S1), and the iliac crest. Lesion-to-liver-ratios (SUVmax-ratio) were calculated. Pearson correlation coefficients were used to assess the correlation between SUVmax-ratios and ADCmean values., Results: Bone marrow involvement was observed in 16 of 60 patients (8 of 16 with diffuse infiltration). The SUVmax-ratio cutoff value was 95.25% for focal and 70.2% for diffuse bone marrow involvement (sensitivity/specificity of 87.5%/86.4% and 100%/43.2%, respectively). The ADCmean cutoff value was 0.498 for focal and 0.401 for diffuse bone marrow involvement (sensitivity/specificity of 100%/90.9% and 87.5%/56.8%, respectively). No significant correlations were found between SUVmax-ratios and ADCmean values in the different groups., Conclusion: With the liver as reference tissue, quantitative [F18]-FDG-PET/CT may be useful to differentiate bone marrow involvement from normal bone marrow in patients with lymphoma, even though the specificity for diffuse marrow involvement is rather low. Quantitative DWI can be used only to distinguish focal bone marrow lesions from normal bone marrow., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The current study aimed to determine the optimum diagnostic imaging technique out of magnetic resonance imaging (MRI), 18 F-fludeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT, otherwise known as PET/CT) and [ 18 F]FDG-PET/MRI (otherwise known as PET/MRI) for the pelvic lymph node staging (N-staging) of untreated cervical carcinoma (CC). A total of 27 patients were included in the present study. All patients had undergone pre-treatment with PET/CT and MRI ≤45 days prior to undergoing a lymphadenectomy. The results from PET (separated from PET/CT), MRI and the statistically combined results of (virtual) PET/MRI were compared to those from histological analyses (the gold standard). A per-patient-based analysis of the detection of pelvic lymph node metastases indicated that PET/MRI had a sensitivity of 64%. The specificity of PET/CT and MRI were 69 and 62%, respectively. The positive predictive value (PPV) was 69 and 64% for PET/CT and MRI, respectively. The negative predictive value (NPV) was 64 and 62% for PET/CT and MRI, respectively. The sensitivity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 64% for both. The specificity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 77 and 62%, respectively. The PPV was 75% for PET-guided PET/MRI and 64% for MRI-guided PET/MRI, and the NPV was 67 and 62%, respectively. PET/CT and the virtual PET/MRI exhibited the same low sensitivity (64%). PET/MRI exhibited slightly better results than PET/CT regarding specificity (77 vs. 69%, respectively), PPV (75 vs. 69%, respectively) and NPV (67 vs. 64%, respectively). The results of the present study suggested that PET/CT and MRI are not optimal diagnostic modalities, and that PET/MRI does not necessarily lead to better results than PET/CT, in the pelvic N-staging of CC.

Background: Few data exist regarding the prognostic value of L-[S-methyl-11C]methionine (MET) PET for treatment-naïve gliomas., Methods: A total of 160 glioma patients (89 men, 71 women; mean age: 45, range 18-84 y) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by analysis of receiver operating characteristics. Additionally, isocitrate dehydrogenase 1-R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan-Meier estimates and the Cox proportional hazards model., Results: Significantly shorter mean survival times (7.2 vs 8.6 y; P = 0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cutoff, independent of histopathology (P < 0.01; mean survival: 10.2 ± 0.8 y vs 5.5 ± 0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naïve glioma patients without (P = 0.031) and with IDH1-R132H characterization of gliomas (P = 0.024; odds ratio 1.57)., Conclusion: This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naïve glioma patients., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Aim: We evaluated the clinical usefulness of 6-[ 18 F]fluoro-3,4-dihydroxy-L-phenylalanine( 18 F-FDOPA)-positron-emission tomography (PET)/computed tomography (CT) in insulinoma detection with contrast enhancement, early acquisition time, and no carbidopa premedication., Patients and Methods: Twenty-six patients diagnosed with hyperinsulinemic hypoglycemia underwent an 18 F-FDOPA PET/CT examination. Patients without carbidopa premedication and contrast-enhanced CT were included. Imaging findings were compared to the overall final diagnosis (histological findings)., Results: In 10 of 26 patients (eight women, two men; mean age=53 years; age range=30-94 years), a detected lesion was confirmed histologically as an insulinoma. 18 F-FDOPA PET detected the tumor in five out of ten patients. Contrast-enhanced CT also detected the tumor in five out of ten. Overall, 18 F-FDOPA PET/CT, with contrast enhancement and without carbidopa premedication, was able to detect the insulinoma in seven out of ten patients (70%)., Conclusion: Based on our data, 18 F-DOPA PET/CT, with contrast enhancement and without carbidopa premedication, as a 'one-stop' diagnostic modality is a viable option for insulinoma detection., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The aim of this study was to assess the diagnostic performance of simultaneous whole-body Ga-DOTANOC PET/MRI compared with Ga-DOTANOC PET/CT for detection of distant metastatic disease in patients with well-differentiated neuroendocrine tumors (NETs)., Methods: Patients with histologically proven, well-differentiated NET (G1 or G2) were included in this prospective, institutional review board-approved study. Patients underwent Ga-DOTANOC PET/CT and subsequent Ga-DOTANOC PET/MRI after a single tracer injection on the same day for staging or restaging purposes. Images were evaluated for the presence of NET lesions by 2 rater teams, each consisting of a nuclear medicine physician and a radiologist, in an observer-blinded fashion. Overall agreement, accuracy, sensitivity, and specificity, relative to a composite reference standard (consensus review including follow-up data), were calculated., Results: Between July 2014 and June 2016, 28 patients were enrolled. Overall agreement and accuracy between the 2 rater teams were 91.7% (95% confidence interval [CI], 87.5%-95.9%) and 97% (95% CI, 94.4%-99.6%) for PET/MRI and 92.3% (95% CI, 88.3%-96.3%) and 94.6% (95% CI, 91.2%-98.1%) for PET/CT, respectively (P = 1.00).Overall, PET/MRI reached 89.8% sensitivity (95% CI, 77.8%-96.6%) and 100% specificity (95% CI, 97%-100%); PET/CT showed 81.6% sensitivity (95% CI, 68%-91.2%) and 100% specificity (95% CI, 97%-100%) for the detection of metastatic disease in NETs., Conclusions: Whole-body Ga-DOTANOC PET/MRI appears to be comparable to Ga-DOTANOC PET/CT for lesion detection in patients with well-differentiated NETs.

18 F-FDG is the most widely validated PET tracer for the evaluation of atherosclerotic inflammation. Recently, 18 F-NaF has also been considered a potential novel biomarker of osteogenesis in atherosclerosis. We aimed to analyze the association between inflammation and osteogenesis at different stages of atherosclerosis, as well as the interrelationship between these 2 processes during disease progression. Methods: Thirty-four myeloma patients underwent 18 F-NaF and 18 F-FDG PET/CT examinations. Lesions were divided into 3 groups (noncalcified, mildly calcified, and severely calcified lesions) on the basis of calcium density as measured in Hounsfield units by CT. Tissue-to-background ratios were determined from PET for both tracers. The association between inflammation and osteogenesis during atherosclerosis progression was evaluated in 19 patients who had at least 2 examinations with both tracers. Results: There were significant correlations between the maximum tissue-to-background ratios of the 2 tracers (Spearman r = 0.5 [ P < 0.01]; Pearson r = 0.4 [ P < 0.01]) in the 221 lesions at baseline. The highest uptake of both tracers was observed in noncalcified lesions, but without any correlation between the tracers (Pearson r = 0.06; P = 0.76). Compared with noncalcified plaques, mildly calcified plaques showed concordant significantly lower accumulation, with good correlation between the tracers (Pearson r = 0.7; P < 0.01). In addition, enhanced osteogenesis-derived 18 F-NaF uptake and regressive inflammation-derived 18 F-FDG uptake were observed in severely calcified lesions (Pearson r = 0.4; P < 0.01). During follow-up, increased calcium density and increased mean 18 F-NaF uptake were observed, whereas mean 18 F-FDG uptake decreased. Most noncalcified (86%) and mildly calcified (81%) lesions and 47% of severely calcified lesions had concordant development of both vascular inflammation and osteogenesis. Conclusion: The combination of 18 F-NaF PET imaging and 18 F-FDG PET imaging promotes an understanding of the mechanism of plaque progression, thereby providing new insights into plaque stabilization., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

OBJECTIVE The objective of this study was to investigate whether fluorine-18 fluorodeoxyglucose PET ( 18 F-FDG PET) can help to predict seizure outcome after hemispherotomy and therefore may be useful in decision making and patient selection. METHODS Children and adolescents less than 18 years of age who underwent 18 F-FDG PET studies during presurgical evaluation prior to hemispherotomy and had follow-up data of at least 12 months after surgery were included. Seizure outcome was classified according to the recommendations of the International League Against Epilepsy. PET data were reevaluated by two specialists in nuclear medicine blinded to clinical data and to MRI. MRI studies were also reinterpreted visually by an experienced neuroradiologist blinded to clinical data and PET findings. RESULTS Thirty-five patients (17 girls) with a median age of 5 years (range 0.4-17.8 years) were evaluable. Of the 35 patients, 91.4% were seizure free after surgery, including 100% of those with unilateral 18 F-FDG-PET hypometabolism compared with only 75% of those with bilateral hypometabolism. With respect to MRI, seizure freedom after surgery was observed in 96.4% of the patients with unilateral lesions compared with only 71.4% in those with bilateral MRI lesions. The best seizure outcomes were noted in patients with unilateral findings in both PET and MRI (100% seizure freedom) whereas only 50% of those with bilateral findings in both imaging techniques were seizure free. Furthermore, 100% of the patients with unilateral PET hypometabolism and bilateral MRI findings were also seizure free, but only 87.5% of those with bilateral PET hypometabolism and unilateral MRI findings. CONCLUSIONS According to these results, candidate selection for hemispherotomy can be optimized by the use of 18 F-FDG PET as part of a multimodal presurgical evaluation program, especially in patients with inconsistent (bilateral) MRI findings.

Fever of unknown origin (FUO) was originally characterised in 1961 by Petersdorf and Beeson as a disease condition of temperature exceeding 38.3 °C on at least three occasions over a period of at least three weeks, with no diagnosis made despite one week of inpatient investigation. However, since underlying diseases are often reported for classical FUO, these presentations may not be considered to be of "unknown origin". Rather, the aetiology of prolonged fever may resolve, or not resolve. The definition of fever with unresolved cause (true FUO) is difficult, as it is a moving target, given the constant advancement of imaging and biomarker analysis. Therefore, the prevalence of fever with unresolved cause (FUO) is unknown.In this review, we report such a case of prolonged fever, which initially has presented as classical FUO, and discuss current literature. Furthermore, we will give an outlook, how a prospective study on FUO will allow to solve outstanding issues like the utility of different diagnostic investigations, and the types and prevalence of various underlying diseases., Competing Interests: Compliance with ethical guidelines Conflict of interest M. Unger, G. Karanikas, A. Kerschbaumer, S. Winkler, and D. Aletaha declare that they have no competing interests. Ethical standards The FEBRIX study has been approved by the local ethics committee (EK No.: 1206/2015) and was registered in the German Clinical Trials Register (DRKS-ID: DRKS00009591). All patients participating in the FEBRIX study, e. g. the patient mentioned in the case report, gave informed consent.

Aim: To evaluate (18)F-fluorodihydroxyphenylalanine-positron emission tomography/ contrast-enhanced computed tomography ((18)F-DOPA PET/CT) for the detection of paragangliomas (PARA) without any patient selection, such as genetic predisposition for the development of these tumors, history of metastatic PARA or hormonal status., Patients and Methods: In this retrospective study, 28 consecutive patients (15 women, 13 men; mean age=46.4 years; age range=19-73 years), who were referred to our PET/CT center for the detection of clinically suspected PARA, were included. Final diagnosis was confirmed by histological reports of surgically proven lesions and/or clinical follow-up (including laboratory results and/or PET/CT follow-up)., Results: On a per-lesion basis (45 lesions) analysis, there was a sensitivity of 64.3% for CT, 73.8% for PET, 100% for PET/CT and a positive predictive value (PPV) of 93.1% for CT, 96.9% for PET and 100% for PET/CT. On a per-patient basis analysis, the sensitivity, specificity and accuracy for CT was 86.7%, 84.6% and 85.7%, respectively, and, for PET 80%, 100% and 89.3%, respectively, and, for PET/CT 100%., Conclusion: Based on our data, (18)F-DOPA PET/CT is a "one-stop diagnostic modality" for the assessment of patients with suspected PARA., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To evaluate the diagnostic accuracy of (11)C-acetate positron-emission tomography (PET) in the detection of bone metastasis in patients with prostate cancer with biochemical recurrence., Patients and Methods: Ninety patients (100%) with rising prostate-specific antigen (PSA) levels (>0.2 ng/ml) after radical prostatectomy, who had both (11)C-acetate PET and bone scan performed and who had clinical follow-up/imaging follow-up for bone metastasis, considered a gold standard, were included. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for (11)C-acetate PET were calculated on a per-patient basis., Results: (11)C-Acetate PET and (99m)Tc-dicarboxypropane-diphosphonate findings were concordant in 84 (93.3%) patients [35 (38.9%) true-positive, 49 (54.4%) true-negative]. Discordant findings were observed in six patients (6.7%). (11)C-Acetate PET presented two (2.2%) false-positive and four (4.4%) false-negative findings. The sensitivity, specificity, PPV, and NPV for (11)C-acetate PET were 89.7%, 96.1%, 94.6%, and 92.2%, respectively. The median PSA of patients with multiple skeletal metastases (median=23.64 ng/ml, range=3.16-551.1 ng/ml) differed significantly (p=0.018) from that of patients with focal metastases (median=6.7 ng/ml, range=0.31-12.8 ng/ml)., Conclusion: (11)C-Acetate PET is a useful tool for patients with prostate cancer with biochemical recurrence, as it can depict multiple sites of recurrence and in particularly shows a high diagnostic value equivalent to that of bone scan for the detection of bone metastases., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: High levels of fatty acid synthase have shown to correlate with the aggressiveness of prostate cancer. As [(11) C]acetate exhibits a close correlation with the level of fatty acid synthase, we aimed to assess whether the SUV in [(11) C]acetate PET serves as a suitable prognostic marker in patients with recurrent prostate cancer., Materials and Methods: In 123 consecutive patients, examined between 2010 and 2014, the maximum standardized uptake value (SUVmax) of local recurrences as well as lymph node and bone metastases was measured. Choosing the spleen as a standard for relatively high physiological uptake, a ratio of tumor to spleen uptake (SUVts) was calculated for standardizing the uptake, too. The corresponding initial Gleason scores (GS) and serum-PSA levels around the time of the performed PET/CT for each patient were retrospectively collected and PSA doubling together with PSA velocity were determined. For further analysis patients were divided with regard to their initial Gleason score (≤3 + 4 and ≥ 4 + 3). The median of PSA velocity was calculated to separate patients with a high and low PSA velocity and Mann-Whitney U or Student's t-test were used, testing for significant differences. For correlation Spearmen-Rho test was used., Results: PET was positive for recurrence in 82/123 patients. PSA was significantly higher in PET-positive than in negative patients (5.9 vs. 3.2 ng/ml; P = 0.006). Initial Gleason score did not differ in PET negative and positive patients (P = 0.3), whereas PSA velocity was markedly higher in PET positive patients (0.4 vs. 0.1 ng/ml/month; P = 0.01). Median SUVmax of PET positive patients was 5.23 (mean 5.78; range 0.9-16.8) and meadian SUVts was 0.78 (mean 0.84, range 0.14-2.50). SUVts was significantly higher in patients with high PSA velocity (SUVts 0.76 vs. 0.92; P = 0.009), whereas SUVmax failed statistical significance (5.4 vs. 6.3 ng/ml/month; P = 0.08). Patients with a high SUVmax proved to have a significantly higher median Gleason score compared to low uptake 8.0 vs. 7.0; P = 0.004). Vice versa both SUVmax (GS 6: 5.0; GS 7: 5.6; GS 8: 5.7; GS 9: 6.5; r = 0.30, P = 0.008) and SUVts (GS 6: 0.63; GS 7: 0.68; GS 8: 0.85; GS 9: 0.89; r = 0.30, P = 0.006) significantly correlated with Gleason score. Patients with a Gleason score ≤ 3 + 4 had a significantly lower SUVmax (4.8 vs. 5.7; P = 0.02) and SUVts (0.67 vs. 0.85; P = 0.02) as compared to a Gleason score ≥ 4 + 3., Conclusion: [(11) C]acetate uptake demonstrated to correlate with initial Gleason score. Furthermore, patients with a high PSA velocity proved to have higher [(11) C]acetate uptake in tumor lesions., (© 2015 Wiley Periodicals, Inc.)

Aim: The American thyroid association (ATA) recommends that additional imaging procedures supplement cervical ultrasonography (US) in any patient with a basal calcitonin value above 150 pg/ml in the follow-up of medullary thyroid carcinoma (MTC). The aim of the present study was to reaffirm or challenge this cut-off for 18-Fluorine-Fluorodihydroxyphenylalanine positron emission tomography (18F-DOPA PET) and conventional imaging ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI))., Materials and Methods: Thirty-nine patients (18 females, 21 males), mean age 62 years, range from 35 to 86, followed-up for MTC were included in the present retrospective study. In our patients 64 18F-DOPA scans, 28 neck US, 28 CT and 8 MRI were performed. For all cases basal calcitonin values were available. Sensitivity and specificity of 18F-DOPA PET and conventional imaging (US, CT, MRI) related to calcitonin values were calculated., Results: According to the calcitonin cut-off of 150 pg/ml, we found the following sensitivities and specificities: 79% and 80% for 18F-DOPA PET, 75% and 92% for US, 80% and 25% for CT, 50% and 75% for MRI. Taking the level of detectable calcitonin, we calculated the following sensitivities: 52% for 18F-DOPA PET, 46% for US, 79% for CT and 38% for MRI., Conclusion: We cannot confirm the calcitonin cut-off proposed by the ATA for the detection of MTC recurrences and contemporaneously we cannot state that 18F-DOPA PET has a very high sensitivity. For the neck region 18F-DOPA PET and US showed similar results. 18F-DOPA PET/CT seems to be the best imaging modality for whole-body tumor detection. Bone metastases are best detected by MRI., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Context: (99m)Tc-Methoxy-isobutyl-isonitrile (MIBI) scintigraphy is a standard preoperative localization imaging modality in patients with primary hyperparathyroidism (pHPT). Its accuracy in localizing a hyperactive parathyroid gland after previous cervical surgery is limited. Recently, (11)C-methionine has been introduced as a promising radiotracer for pHPT imaging. Yet, few data exist for this technique in patients with persisting or recurrent pHPT before reoperation., Objectives: We aimed to investigate the ability of (11)C-methionine positron emission tomography (PET)/computed tomography (CT) to localize a parathyroid disorder after cervical surgery and negative postsurgical (99m)Tc-MIBI single-photon emission CT (SPECT)/CT., Design, Setting, and Participants: Fifteen patients (6 males, 9 females; age range, 36-85 years) with pHPT and negative (99m)Tc-MIBI SPECT/CT who had undergone earlier neck surgery because of pHPT and/or thyroid disorder were recruited. Twelve of the 15 patients had thyroidectomy for goiter or differentiated thyroid carcinoma. Ten patients had previous parathyroid surgery for pHPT, and 2 patients had a history of parathyroid carcinoma. Thirteen of 15 patients showed elevated levels of intact PTH at the time of PET/CT imaging, whereas all patients had elevated serum calcium values., Main Outcome Measurements: Pathological results of contrast-enhanced (11)C-methionine PET/CT and surgical results were evaluated., Results: In 6 of 15 patients (11)C-methionine PET/CT showed a hypermetabolic focus in the upper mediastinum in 2 patients, in the thoracic outlet in 1 patient, and in the cervical region in 3 patients. In 9 of the 15 patients, no hyperactive parathyroid gland could be visualized. Reoperation was performed in 5 of 6 patients without surgical complications. One patient refused surgery. In 2 of the 5 patients, a transsternal procedure was performed. Correlating with the (11)C-methionine PET/CT results, a single parathyroid adenoma was found in 4 patients and parathyroid carcinoma metastasis in 1 patient., Conclusion: (11)C-Methionine PET/CT is a useful complementary imaging technique to localize parathyroid adenoma or carcinoma in (99m)Tc-MIBI SPECT/CT-negative patients.

Purpose: This phase I study was performed to evaluate coagulation alterations during extracorporeal circulation (ECC) induced whole body hyperthermia (WBHT) in 12 patients with advanced soft tissue sarcomas., Methods: To distinguish between effects of normothermic ECC and ECC-WBHT, blood samples were drawn at different time points: at baseline, after 30 min on normothermic ECC, at the end of the heating period, and 24 h and 7 days thereafter. Standard coagulation tests, coagulation factors, thrombelastography,platelets and reticulated platelets, liver enzymes, and scintigraphic platelet imaging were performed., Results: Normothermic ECC resulted in coagulation alterations most likely due to systemic anticoagulation. Induction of hyperthermia caused thrombocytopenia, increased fibrin degradation products,prolonged clotting times, alteration in coagulation factors, and increased liver enzymes. The majority of these effects was most pronounced 24 h after ECC-WBHT. In addition, late liver sequestration of platelets was demonstrated in scintigraphic imaging at that time point., Conclusions: Temporal correlation between hemostatic alterations and elevation in liver enzymes leads to the assumption that liver impairment might play a crucial role in coagulation disturbances observed during ECC-WBHT and thereafter, thus strongly supported by liver sequestration of platelets.Therefore a close monitoring of hepatic derived coagulation alterations in patients undergoing extracorporeal whole body hypothermia is warranted.

(11)C-acetate PET is used in the assessment of various cardiologic and oncologic diseases. This article describes the physiologic uptake of (11)C-acetate and presents the common benign findings in different anatomic parts of the body. Salivary glands, tonsils, thyroid, meningeal tuberculoma, meningiomas, and macroadenomas of pituitary gland are sites of mild to moderate tracer uptake in the head and neck region. Parenchymal diseases of the lung and reactive and/or inflammatory mediastinal lymphadenopathies cause benign (11)C-acetate uptake in the thorax. Liver, spleen, pancreas, and rectum show an increased uptake. Urinary tract and prostate gland show faint tracer uptake., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To describe the (18)F-fluorodihydro-xyphenylalanine ((18)F-DOPA), positron emission tomography (PET) and magnetic resonance imaging (MRI) appearance of pheochromocytomas, with a focus on the presence or absence of typical MRI features., Materials and Methods: Eleven patients with histologically-verified pheochromocytoma [sporadic (n=9), multiple endocrine neoplasia (MEN) 2A syndrome (n=2)] were enrolled retrospectively. All patients underwent an MRI examination of the upper abdomen. Nine out of 11 patients underwent (18)F-DOPA PET/CT, and the remaining two patients underwent independent PET and computed tomography (CT) examinations. (18)F-DOPA-PET/CT examinations were considered positive when an increased tracer accumulation in the adrenal region, as shown on CT images, was observed. When an adrenal mass was detected on MRI, the T1 and T2 signal intensity and contrast enhancement pattern were recorded. Based on MR characteristics, the lesions were divided into typical and atypical., Results: Ten out of 11 patients had one lesion, while one patient had two lesions. All pheochromocytomas were detected by both PET/CT and MRI. On (18)F-DOPA scans, all lesions showed an increased tracer accumulation, with a mean maximum standardized uptake value (SUVmax) of 13.7±5.75. Eight out of 12 pheochromocytomas exhibited typical MRI features, with intermediate signal intensity on T1-weighted images in-phase, absence of signal drop on T1-weighted images out-of-phase, high signal intensity on T2-weighted images, and clear contrast enhancement in the arterial phase. The remaining four lesions exhibited atypical MRI features, namely absence of one of the listed criteria., Conclusion: In the assessment of pheochromocytoma, the combination of (18)F-DOPA PET with MRI is superior to MRI-alone. (18)F-DOPA PET/MRI may yield a higher diagnostic confidence for the detection of pheochromocytoma than (18)F-DOPA PET/CT.

Aim of this work was the implementation of a generalized in-loop synthesis for (11)C-carboxylations and subsequent (11)C-acylations on the TRACERlab FxC Pro platform. The set-up was tested using [carbonyl-(11)C]WAY-100635 and, for the first time, [(11)C]-(+)-PHNO. Its general applicability could be demonstrated and both [carbonyl-(11)C]WAY-100635 and [(11)C]-(+)-PHNO were prepared with high reliability and satisfying outcome., (© 2013 The Authors. Published by Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to determine the diagnostic value of the serum tumor marker beta-2 microglobulin (β2M) as well as positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) in confirming or eliminating the diagnosis of non-Hodgkin lymphoma (NHL)., Patients and Methods: Retrospective analysis of 180 patients with NHL referred for a PET scan was performed. Patients' data regarding demographic information, clinical history, and diagnostic procedures were collected. The sensitivity, specificity, and positive/negative predictive value of serum β2M levels and FDG-PET, compared to a compound gold standard consisting of imaging modalities (computed tomography, magnetic resonance tomography, ultrasound) and/or biopsy, were assessed and compared., Results: β2M had a sensitivity and specificity of 49% and 52% for all types and settings, respectively, as well as a low positive predictive value (66%) and a very low negative predictive value (36%). The overall sensitivity and specificity of FDG-PET for all types of NHL in all settings was 87% and 92%, respectively., Conclusion: Due to its low sensitivity and specificity, β2M cannot be used in the clinical routine as a diagnostic marker for the diagnosis of NHL. On the other hand, in accordance with previous studies, we found that FDG-PET is an excellent tool for the diagnosis of NHL.

The melanin-concentrating hormone (MCH) system is a new target for the treatment of human disorders. Since the knowledge of the MCH system's involvement in a variety of pathologies (obesity, diabetes, and deregulation of metabolic feedback mechanism) is based on in vitro or preclinical studies, a suitable positron emission tomography (PET) tracer needs to be developed. We herein present the preparation and first preclinical evaluation of [(18)F]FE@SNAP - a new PET tracer for MCH receptor-1 (MCHR1). The synthesis was performed using a microfluidic device. Preclinical evaluation included binding affinity, plasma stability, plasma free fraction, stability against the cytochrome P-450 (CYP450) system using liver microsomes, stability against carboxyl-esterase, and methods to assess the penetration of the blood-brain barrier (BBB) such as logD analysis and immobilized artificial membrane (IAM) chromatography. Levels at 374 ± 202 MBq [(18)F]FE@SNAP were obtained after purification. The obtained K d value of [(18)F]FE@SNAP was 2.9 nM. [(18)F]FE@SNAP evinced high stability against carboxylesterase, CYP450 enzymes, and in human plasma. LogD (3.83) and IAM chromatography results (Pm=0.51) were in the same range as for known BBB-penetrating compounds. The synthesis of [(18)F]FE@SNAP was reliable and successful. Due to high binding affinity and stability, [(18)F]FE@SNAP is a promising tracer for MCHR1.

Changes in the expression of the melanin concentrating hormone receptor 1 (MCHR1) are involved in a variety of pathologies, especially obesity and anxiety disorders. To monitor these pathologies in-vivo positron emission tomography (PET) is a suitable method. After the successful radiosynthesis of [(11)C]SNAP-7941-the first PET-Tracer for the MCHR1, we aimed to synthesize its [(18)F]fluoroethylated analogue: [(18)F]FE@SNAP. Therefore, microfluidic and vessel-based approaches were tested. [(18)F]fluoroethylation was conducted via various [(18)F]fluoroalkylated synthons and direct [(18)F]fluorination. Only the direct [(18)F]fluorination of a tosylated precursor using a flow-through microreactor was successful, affording [(18)F]FE@SNAP in 44.3 ± 2.6%., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer (18)F-fluoroazomycin-arabinoside ((18)FAZA )., Material and Methods: Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm(3) (+/- 67, SD). Dynamic and static (18)FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/- concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk., Results: Five patients had visually identifiable tumours on (18)FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five (18)FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten (18)FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/-12, SD)., Conclusion: PET imaging with (18)FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of (18)FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance.

The number of functional subsets of CD4+ T lymphocytes distinguished by their cytokine production has been extended in the last decade. The in vitro generation of a T cell subset characterized by IL-6 production has resurrected the question of cytokine co-expression patterns in T cells. In order to delineate these cells as a specific functional subpopulation in vivo, we profiled the cytokine production pattern of human peripheral blood CD4+ T lymphocytes across established subsets. We provide evidence for a new T cell subset Th6, with an IL-6 signature. Freshly isolated PBMC were analyzed using intracellular cytokine detection (IDC). Cytokine co-expression patterns of up to three cytokines, as well as their correlation with selected transcription factors, were determined in CD4+ T lymphocytes. Co-expression of two of these signature cytokines used for the definition of functional subsets, e.g. IL-4, IFN-gamma, IL-17 and IL-6 were observed, but nearly excluded the production of a third (or fourth) signature cytokine. In this respect, Th1 (key cytokine IFN-gamma), Th2 (IL-4), Th6 (IL-6) and Th17 (IL-17) subsets can be defined, along with overlaps of any two of them. In contrast, TNF-alpha and IL-2 are not signature cytokines, but their absence or expression in single cells introduces further divisions across established subsets. Our study supports the concept of a further functional T cell Th6 subset, and contributes to the reference cytokine profiles of healthy individuals relevant to further studies in a variety of disease states.

The aim of the study was to evaluate the possible changes in CD4+ and CD8+ T-cell cytokine production patterns in Hashimoto's thyroiditis (HT) with elevated calcitonin (CT). Fourteen consecutive patients with verified HT were included in the present study. Patients were divided into two groups. Group I: 7 HT patients with elevated CT levels (>10 pg/ml); Group II: 7 HT patients with CT levels <10 pg/ml). All patients underwent intracellular cytokine detection in CD4+ and CD8+ T-cells of peripheral blood mononuclear cells (PBMC) by flow cytometry. Patients with elevated CT levels (group I) had significantly higher percentages of CD8+ cells producing IFN-gamma compared to healthy donors. A detailed analysis of cytokine production patterns revealed that this was accompanied by an increased frequency of single IFN-gamma positive cells, i.e., cells not expressing most of the other cytokines tested. Similarly, patients in group I also showed higher percentages of CD8+ TNF-alpha positive cells than healthy donors. In this case, cells co-expressing TNF-alpha and IFN-gamma were found at significantly higher frequencies. No increase in Th1 type cytokines, such as IFN-gamma or TNF-alpha, was detectable in CD4+ T-cells. In contrast, CD4+ T-cells from group I patients showed significantly higher percentages of cells producing Th2 cytokines, such as IL-4 or IL-13. The lack of increased Th1 cytokine production accompanied by an increased Th2 cytokine production seems to be a special feature of HT patients with elevated CT levels that may reflect a pathogenetic mechanism for tumor initiation.

Purpose: 11beta-Hydroxylase is a key enzyme in the biosynthesis of adrenocortical steroid hormones and is a suitable target for the imaging of the adrenal cortex. [(11)C]Metomidate (MTO), [(11)C]etomidate (ETO) and desethyl-[(18)F]fluoroethyl-etomidate (FETO) are potent inhibitors of this enzyme and are used for PET imaging of adrenocortical pathologies. The aims of this study were (1) to evaluate and compare the metabolic stability of MTO, ETO and FETO against esterases and (2) to investigate the metabolic pattern of FETO in vivo., Methods: In vitro assays were performed using different concentrations of MTO, ETO and FETO with constant concentrations of carboxylesterase. Human in vivo studies were performed with human blood samples drawn from the cubital vein. After sample clean-up, the serum was analysed by HPLC methods., Results: In vitro assays showed Michaelis-Menten constants of 115.1 mumol for FETO, 162.0 mumol for MTO and 168.6 mumol for ETO. Limiting velocities were 1.54 mumol/min (FETO), 1.47 mumol/min (MTO) and 1.35 mumol/min (ETO). This implies insignificantly decreased esterase stability of FETO compared with MTO and ETO. In vivo investigations showed a rapid metabolisation of FETO within the first 10 min (2 min: 91.41%+/-6.44%, n=6; 10 min: 23.78%+/-5.54%, n=4) followed by a smooth decrease in FETO from 20 to 90 min (20 min: 11.23%+/-3.79% n=4; 90 min: 3.68%+/-3.65%, n=4). Recovery rate was 61.43%+/-3.19% (n=12)., Conclusion: In vitro experiments demonstrated that FETO stability against esterases is comparable to that of ETO and MTO. The metabolic profile showed that FETO kinetics in humans are fast.

Purpose: Functional imaging of the adrenal cortex by means of PET may play an important clinical role. Recently, we presented the synthesis and first evaluation of a novel 11beta-hydroxylase inhibitor, [(18)F]FETO, in rats displaying high tracer accumulation in the adrenals. In this study, we aimed to investigate for the first time the potency of [(18)F]FETO as a PET tracer for the adrenal cortex in humans., Methods: An average preparation yielded 1-2 GBq of [(18)F]FETO ready to use. Ten healthy volunteers aged 24-57 years (five male and five female) were included in the study. After i.v. administration of 365 MBq [(18)F]FETO (246-391 MBq), dynamic images were acquired in 2D standard mode in 14 frames over 45 min. Afterwards, whole-body scanning was performed. In addition to visual interpretation, semi-quantitative analysis using standardised uptake values (SUVs) was conducted., Results: [(18)F]FETO distribution was similar in all scanned volunteers. Visually, pronounced accumulation of [(18)F]FETO was found in the adrenals, whereas moderate uptake was observed-at least in some of the subjects-for liver, renal calices, gallbladder, stomach walls and pancreas. Kidney and bowels showed only faint uptake. Median SUVs for the right and left adrenal glands were 15.6 (10.0-28.6) and 15.7 (10.3-35.9), respectively. The reference tissue (liver) displayed a median SUV of 2.5 (2.2-4.6)., Conclusion: [(18)F]FETO is a valuable tracer for adrenocortical PET imaging, combining the longer half-life of( 18)F with a high 11beta-hydroxylase selectivity. In accordance with our findings in rats, FETO PET revealed very high accumulation in the adrenal glands in healthy volunteers.