Testosterone and oestrogens play significant roles in female physiology, extending beyond reproductive functions to influence brain health, mood regulation, and behaviour. Testosterone low-dose therapy is increasingly considered for alleviating sexual dysfunction symptoms in postmenopausal women, and has been recently investigated as therapy for depressive symptoms, though the mechanisms and safety of this approach are not entirely clear. Specifically, the effects of testosterone use on brain oestrogen synthase (aromatase), which maintains the balance between androgens and oestrogens, remain unexplored. This study investigated the effects of short-term, low-dose testosterone administration on brain oestrogen synthase availability and associated mood and behavioural changes in healthy women. Healthy women were exposed to 1 week of low-dose testosterone (10 mg/day). Binding of oestrogen synthase was examined by [11C]cetrozole positron emission tomography before and during testosterone exposure. Psychometric assessment of depression, anxiety, and aggression was performed at the same time. Peripheral testosterone levels were significantly increased (up to 33-fold) upon treatment, which had no significant effect on brain oestrogen synthase binding in the thalamus, as supported by Bayesian analyses, nor in the hypothalamus and amygdala. Psychometric measures of depression, anxiety, and aggression also remained unchanged by testosterone treatment. These findings suggest that short-term, clinically relevant testosterone administration has no major effects on the brain oestrogen synthase availability in healthy women, which may reassure patients with hypoactive sexual desire disorder considering this treatment. Larger, long-term studies are needed to confirm these results and explore effects in patients with clinical need for testosterone treatment.

Using [18F]RO948 as a tau PET ligand, we assessed tau deposition in a cohort of memory clinic patients and cognitively unimpaired controls. Regional tau binding was then compared to levels of plasma p -Tau217, p -Tau181, p -Tau231 biomarkers. Thirty-seven patients from the Memory Clinic at Karolinska University Hospital Huddinge were evaluated: 27 patients with biomarker confirmed AD (CSF A+) at clinical stage of MCI ( n  = 14) or dementia ( n  = 13). Thirteen cases qualified for an early onset disease (EOAD) and fourteen for late onset (LOAD), and 10 cognitively normal (CN) participants. On the same day, participants underwent [ 18 F]RO948 tau PET imaging, magnetic resonance imaging (MRI), and blood sampling for plasma biomarker analysis using the NuLISAseq (Alamarbio) CNS panel. EOAD and LOAD patients, whether MCI or dementia, showed significantly higher [18F]RO948 uptake in the entorhinal cortex, hippocampus and amygdala compared to the CN participants (Figure A-C). Only the EOAD dementia patients displayed significantly higher uptake in the parietal cortex compared to CN participants but also compared to the other AD subgroups ( p  = 0.04) (Figure 1E-F). Voxel-wise analyses showed a significantly higher [18F]RO948 uptake confined in medial temporal lobe areas in the patients with EOAD MCI or LOAD MCI compared to the CN. The LOAD dementia patients showed involvement primarily of the temporal neocortex while the EOAD dementia a broader involvement of even parietal and frontal cortices (Figure 1G). p -Tau217, p -Tau231, and p -Tau181 plasma levels were elevated in both MCI and dementia patients, compared to controls (data not shown, all p  < 0.05). In the dementia patients (EOAD and LOAD), plasma p -Tau217 exhibited a stronger correlation with [18F]RO948 uptake across multiple brain regions compared to p -Tau231 and p -Tau181 where less broad areas were involved. In the MCI patients (EOAD and LOAD) p -Tau217 correlated with uptake in the amygdala (Figure 2). [ 18 F]RO948 PET can capture tau deposition at early stages of AD, particularly in medial temporal regions when plasma p -Tau217 levels similarly elevated. As the disease progresses to the clinical dementia stage, tau accumulation extends into cortical regions, with distinct regional deposition patterns observed between EOAD and LOAD.

The aim of this study was to compare regional brain tau extent across the disease spectrum in early- and late-onset Alzheimer’s disease using the second-generation tau PET tracer [18F]RO948, and to investigate the relationship between PET-derived patterns, plasma p-tau217, brain atrophy, and cognition. We examined 57 participants: 39 patients from the Cognitive Assessment Unit at Karolinska University Hospital (Stockholm/Sweden)—diagnosed as MCI Aβ– (n = 10), MCI Aβ + (n = 16; 8 EO and 6 LO), and AD (n = 13; 5 EOAD and 8 LOAD)—and 18 cognitively normal controls. All participants underwent [18F]RO948 tau-PET, structural MRI, cognitive testing, and plasma p-tau217 analysis. Both EO and LO MCI (Aß +) showed higher [18F]RO948 binding in amygdala, entorhinal cortex, hippocampus (p < 0.001) and extending to inferior temporal regions (p < 0.01) compared to controls, with some MCI-EO cases already showing advanced neocortical tau burden. At the AD stage, EOAD patients showed greater neocortical tau extent in temporo-parietal and frontal cortices than LOAD. P‑tau217 positively correlated with [18F]RO948 in amygdala, entorhinal cortex, hippocampus (rho = 0.81) followed by temporal (rho = 0.71), and parietal cortices (rho = 0.56, all p < 0.001). The Tau‑PET/p-tau217 association was different between EOAD and LOAD with greater differences in parietal cortices. Tau‑PET also showed stronger region‑specific associations with cognitive impairment than p‑tau217, especially in EOAD. [18F]RO948-PET captured interindividual heterogeneity in tau accumulation that was not reflected by plasma p-tau217. This dissociation was particularly evident in neocortical regions, where LOAD showed elevated plasma p-tau217 levels despite low tau PET binding. These findings highlight the value of tau-PET as a sensitive biomarker for detecting early disease heterogeneity, assessing disease severity, and improving patient stratification for disease-modifying treatments.

INTRODUCTION:Endometriosis, affecting up to 10% of women, is a chronic estrogen dependent disorder where ectopic endometrial-like tissue causes pelvic pain and infertility. Endometriosis is challenging to diagnose due to symptom overlap and limited imaging accuracy, often requiring surgical visualization. Positron emission tomography (PET) potentially offers a non-invasive, molecular-based approach for highly specific diagnosis and monitoring of endometriosis. Aromatase, typically low in normal endometrial tissue, is elevated in endometriotic lesions, while neutrophils, which are scarce in normal tissue, are increased in these lesions. Fibrosis, resulting from activated platelet-derived growth factor receptor β (PDGFR-β)-expressing myofibroblasts, has been observed in endometriosis lesions. In this study, three PET tracers; [11C]cetrozole ([11C]CET), [11C]GW457427 ([11C]NES), and [68Ga]Ga-ATH001, targeting aromatase, neutrophil elastase (NE), and PDGFR-β, respectively, were tested in endometriosis patient biopsies through autoradiography (ARG) combined with histological examinations. A pilot PET/Magnetic resonance imaging (PET/MR) study was performed in endometriosis patients with [11C]NES. METHODS:Ten biopsies from patients with endometriosis were collected. Frozen tissue was sectioned at 20 μm for ARG and 4 μm for immunohistochemistry (IHC). Total binding and non-specific binding, with quantification using ImageJ (fmol/mm3) was determined. Specific binding was calculated as total minus non-specific binding and expressed as a percentage. Sections were stained with Hematoxylin and Eosin (H/E) and Cytokeratin7 (CK7) for morphology, Sirius Red (SIR) for fibrosis, antibodies against PDGFR-β and NE. Neutrophil extracellular traps (NETs) were identified by combined staining for NE and Histone H3. Three endometriosis patients were scanned with [11C]NES by PET/MR. RESULTS:All three tracers showed high in vitro binding to endometriotic tissue in ARG. [11C]NES and [68Ga]Ga-ATH001 had high degree of specific binding to elastase and PDGFR-β, respectively, whereas no specific binding could be shown for [11C]CET. ARG results were validated by IHC: CK7 confirmed epithelial lesions, NE and Histone H3 verified neutrophils and NETs, and PDGFR-β/SIR indicated fibrosis. However, in vivo, no [11C]NES uptake was detected on the PET/MR scans of the three endometriosis patients. CONCLUSION:In ARG on endometriotic tissue samples, [68Ga]Ga-ATH001 and [11C]NES showed specific binding to their respective targets. However, tracer delivery potentially forms a challenge in visualizing fibrotic endometriosis lesions in vivo, as seen by [11C]NES PET/MR in patients.

OBJECTIVE:Type 1 diabetes (T1D) is an autoimmune disease, but knowledge of immune cell infiltration in the human pancreas is limited due to the risks associated with pancreatic biopsies. This study aimed to evaluate the feasibility of imaging innate immune cells in vivo using positron emission tomography (PET). METHODS:We used PET tracers targeting M1 macrophages ([68Ga]-DOTATATE) and neutrophil elastase ([11C]-NES) to assess pancreatic immune cell infiltration in individuals with new-onset T1D (n = 4), long-standing T1D (n = 6), and healthy controls (n = 6). RESULTS:Both tracers enabled visualisation and quantification of pancreatic uptake. Uptake of both [68Ga]-DOTATATE and [11C]-NES was not increased in new-onset T1D compared to healthy controls but was elevated in individuals with long-standing T1D. DISCUSSION:PET imaging of innate immune cells in the pancreas is feasible. While no increased macrophage or neutrophil activity was observed in new-onset T1D, increased tracer uptake in long-standing T1D may reflect late-stage inflammatory processes and fibrosis.

Although the diagnosis of Alzheimer´s disease (AD) dominates in the tertiary memory clinic setting, there are also patients which show no sign for presence of amyloid in brain when assessed for CSF biomarkers after lumbar puncture (LP) or amyloid PET. Since these amyloid negative (A-) patients can clinically mimic symptomatic AD patients, it is important to obtain further insight into the in vivo pathology of these patients. This study therefore aimed to perform tau PET imaging with the tracer [18F]RO948 and measure plasma biomarkers in patients clinically diagnosed as primary age-related tauopathy (PART) and limbic dominant TDP-43 age-related encephalopathy (LATE) at the clinic for cognitive disorders at Karolinska University Hospital. Four patients diagnosed with PART (mean age 76 years) and four with LATE (mean age 79 years) were included in the study. Clinical characteristics and biomarkers are reported in Table 1. The ATN classification for PART patients was A-T+N+ and for LATE patients A-T-N+. On the same day, all participants underwent [18F]RO948 tau PET and MRI scans, and blood sampling for plasma biomarker analysis using the NuLISAseq (Alamarbio) CNS panel. The obtained data was compared with 27 amyloid positive MCI and AD patients from Karolinska as well as 10 cognitive healthy controls. Low uptake of [18F]RO948 was observed in PART and LATE brains compared to MCI A+ as shown in Figure 1, including also Radar plots of different brain regions. Box plot data (Figure 2) showed low [18F]RO948 regional uptake except for a higher uptake ( p  <0.05) in the putamen in PART and LATE compared to controls. Higher plasma levels of ptau217, ptau181, ptau231 were observed in PART patients ( p  <0.05) but not in LATE compared to cognitively healthy controls. Plasma ptau217 levels were however higher in LOAD ( p  <0.05) compared to PART. Higher plasma Aß42 values were observed both in LATE and PART compared to LOAD. PART and LATE patients exhibit Tau PET uptake similar to that of controls, except in the putamen. Additionally, PART patients show elevated plasma levels of p -tau 217, p -tau 181, and p -tau 231, whereas LATE patients do not.

Abstract Background Neutrophil granulocytes are important parts of the defence against bacterial infections. Their action is a two-edged sword, the mediators killing the intruding bacteria are at the same time causing tissue damage. Neutrophil activation is part of the dysregulated immune response to infection defining sepsis and neutrophil elastase is one of the powerful proteases causing both effects and damage. Inhibition of neutrophil elastase has been tried in sepsis and ARDS, so far with inconclusive results. Methods We used positron emission tomography (PET) combined with computed tomography (CT) and the selective and specific neutrophil elastase inhibitor PET-tracer [11C]GW457427 ([11C]NES), in an intensive care unit porcine Escherichia coli sepsis model with the primary aim to visualise the biodistribution of neutrophil elastase in the initial acute phase of the septic reaction. Repeated PET–CT investigations were performed before and after induction of sepsis. Results At baseline [11C]NES uptake was found in the bone marrow, spleen and liver. The uptake in the bone marrow was markedly increased two hours into the sepsis, whereas in spleen and liver the uptake was not as markedly changed compared to baseline. At 4 h after the sepsis induction [11C]NES in the bone marrow decreased while the uptake increased in the spleen, liver and lungs. Conclusion The neutrophil elastase PET-tracer [11C]NES is a novel and unique instrument to study the acute innate neutrophil immune response in sepsis and associated vital organ failure. We here present images and quantitative data of the neutrophil elastase distribution the first hours of acute experimental sepsis. Surprisingly, a pronounced increase of neutrophil elastase was found in the bone marrow 2 h into the sepsis reaction followed at 4 h by increase in the liver, spleen and lungs and a concomitant reduction of the tracer uptake in bone marrow.

Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [11C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA). However, the availability of [11C]metomidate is limited to centers with an on-site cyclotron. Here, we report an early-phase human study with the 18F-labeled analog, para-chloro-2-[18F]fluoroethyletomidate ([18F]CETO). Methods: We conducted a phase I/IIa, single-center, open-label, microdosing study. The primary objective was to evaluate the safety of up to 2 administrations of [18F]CETO in 6 patients with PA (3 unilateral disease, 3 bilateral disease) and 5 healthy volunteers. Safety evaluation included assessment of adrenal function after the first [18F]CETO administration. The biodistribution of [18F]CETO was assessed in a 90-min dynamic PET acquisition. In patients with PA, the effect of pretreatment with oral dexamethasone on [18F]CETO uptake by normal adrenal tissue and APAs was also assessed. Results: Eleven participants were recruited to the trial, including 6 patients and 5 healthy volunteers. No subjects experienced serious adverse events or reactions, and all participants had normal adrenal function after [18F]CETO administration. [18F]CETO demonstrated high selectivity for the adrenal glands with low uptake in other tissues. Visualization of APAs was enhanced after dexamethasone pretreatment, which suppressed [18F]CETO uptake by normal adrenal tissue. Conclusion: [18F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this study. [18F]CETO demonstrates selective high affinity for adrenal tissue, particularly APAs. Distinction between APAs and normal adrenal tissue is enhanced by dexamethasone pretreatment to suppress [18F]CETO uptake by normal glands. This positions [18F]CETO as a promising imaging tool for evaluation in the context of PA.

Abstract: Understanding tau pathology progression across the Alzheimer′s disease (AD) continuum is critical for diagnosis and stratification. This study examined how age of onset and disease stage influence regional tau deposition using [18F]RO948-PET, and its relationship with plasma biomarkers, cognition, and cortical atrophy. In total, 57 participants underwent tau-PET, MRI, blood sampling, and neuropsychological testing: 39 patients with MCI (Aβ−/Aβ+) or AD, and 18 cognitively normal controls. The MCI Aβ+ and AD groups were further divided into early-onset (EOAD, <65y) and late-onset (LOAD, >65y) subgroups. MCI Aβ+ patients showed early tau accumulation in medial-temporal regions, extending to inferior-temporal cortex. MCI-EOAD exhibited more advanced neocortical tau binding, while MCI-LOAD showed intermediate lateral temporal involvement. In AD, EOAD patients had higher parietal tau burden than LOAD. Plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NFL) were elevated in MCI Aβ+ and AD. Plasma p-tau217 showed strong correlations with tau-PET in medial and inferior temporal regions, with weaker correlations in neocortical areas. EOAD showed non-linear tau-PET/p-tau217 associations, contrasting with LOAD ′s linear pattern. Tau-PET was negatively correlated with global cognition and executive function, while p-tau217 better reflected early episodic memory decline. Both tau measures correlated with cortical thinning, especially in the entorhinal cortex. These findings highlight [18F]RO948-PET′s sensitivity in detecting early tau pathology and superiority in capturing individual differences in tau burden, particularly in advanced stages where plasma biomarkers plateaued. Tau-PET demonstrated superior resolution of disease progression and individual variability, reinforcing its value as a prognostic biomarker and a critical tool for patient stratification in clinical trials. ### Competing Interest Statement MZF, MB, KC, OA, AW,JE,GA,IP,KT,WT,AB, NA, and NB have nothing to declare. AN has served as consultant for AG Lundbeck AB, Hoffmann La Roche, AVVA Pharmaceuticals , given lectures for Hoffman La Roche and Astra Zeneca and served on the advisory board for Dementia Platform UK. KB has served as a consultant and at advisory boards for Abbvie, AC Immune, ALZpath, AriBio, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merck Sharp & Dohme, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, ScandiBio Therapeutics AB, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, LabCorp, Lilly, Novo Nordisk, Oy Medix Biochemica AB, Roche, and WebMD, is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, and is a shareholder of CERimmune Therapeutics (outside submitted work). ### Funding Statement AN was supported by grants from the Swedish Research Council (2017-02965,2017-06087, 2020-01990, 2023-02649), the Swedish Foundation for Strategic Research (SSF; RB13-0192), the Swedish Brain Foundation (Häjrnfonden), the Center for Innovative Medicine (CIMED) at Region Stockholm - Karolinska institutet, the Swedish Alzheimer Foundation (Alzheimerfonden), Fondation pour la Recherche sur Alzheimer, Paris, France, the Region Stockholm-Karolinska Institutet regional agreement on medical training and clinical research (ALF), private bequests, the Family Kaudert donation, Rainwater foundation, US. MZF was supported by grants from the the Swedish Dementia Foundation (Demensfonden), and Karolinska Institute Research grants. KB is supported by the Swedish Research Council (#2017-00915 and #2022-00732), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721, #AF-968270, and #AF-994551), Hjärnfonden, Sweden (#FO2017-0243 and #ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the Alzheimer′s Association 2021 Zenith Award (ZEN-21-848495), the Alzheimer′s Association 2022-2025 Grant (SG-23-1038904 QC), La Fondation Recherche Alzheimer (FRA), Paris, France, the Kirsten and Freddy Johansen Foundation, Copenhagen, Denmark, and Familjen Rönströms Stiftelse, Stockholm, Sweden. HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union′s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer ′s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the Bluefield Project, Cure Alzheimer′s Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Familjen Rönströms Stiftelse, Stiftelsen for Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union′s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme - Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003).NB was funded by King Gustav V:s and Queen Victorias Foundation, and ALF-Projects Region Stockholm. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Swedish Ethical Review Authority gave ethical approval for this work. All participants provided written informed consent in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author upon reasonable request. Due to participant privacy and ethical restrictions, individual-level imaging and clinical data cannot be made publicly available.

Rationale Monoamine triple reuptake inhibitors (TRIs) inhibit central dopamine, norepinephrine, and serotonin transporters, restoring functional monoamine neurotransmission. Objectives This clinical trial evaluated the safety, tolerability, and pharmacokinetics in healthy volunteers after single-ascending-doses (SAD) of the novel monoamine TRI CSTI-500. In addition, we estimated the peak and duration of striatal serotonin transporter (SERT) and dopamine transporter (DAT) occupancies, by using positron emission tomography (PET). Methods Part A was a double-blinded, randomized, placebo-controlled, sequential SAD study with seven sequential dose panels (0.5-150 mg) where subjects in each panel received either a single oral dose of CSTI-500 ( n= 6) or placebo ( n= 2). Part B was an open-label, single-dose PET study to assess the peak and duration of SERT ( n= 4) and DAT ( n= 5) striatal occupancies, using the radioligands [ 11 C]MADAM and [ 11 C]PE2I, respectively. Results The maximum tolerable acute single-dose of CSTI-500 was determined as 100 mg. No serious adverse events occurred. The median maximum CSTI-500 concentrations were attained at 1-2 hours post-dose (h pd); the estimated plasma elimination half-life was 44-50 h pd. Subsequent to a single-dose of 100 mg CSTI-500, mean striatal SERT occupancy was 72% and 62% at 4-6 and 24 h pd, respectively. Mean striatal DAT occupancy was 36% and 31% at 4-9 and 24 h pd, respectively. Conclusions CSTI-500 is a potent monoamine TRI with substantial striatal SERT and moderate DAT occupancies in healthy subjects. Together with promising safety-tolerability and pharmacokinetics profiles, the continued clinical development of CSTI-500 is strongly supported.

Testosterone and estrogens play significant roles in female physiology, extending beyond reproductive functions to influence brain health, mood regulation, and behavior. Testosterone low-dosage therapy is increasingly considered for alleviating sexual dysfunction symptoms in women, and has been recently proposed as therapy for depressive symptoms, though the mechanisms and safety of this approach are not entirely clear. Specifically, the effects of testosterone use on brain estrogen synthase (aromatase), which maintains the balance between androgens and estrogens, remain unexplored. This study investigated the effects of short-term, low-dose testosterone administration on brain estrogen synthase availability and associated mood and behavioral changes in healthy premenopausal women. Healthy women (aged 22–33) were exposed to one week of low-dose testosterone (10 mg/day). Availability of estrogen synthase was examined by [11C]cetrozole positron emission tomography before and after testosterone exposure. Psychometric assessments of depression, anxiety, and aggression were administered at the same times. Peripheral testosterone levels were significantly increased (up to 33-fold) by the treatment, which had no significant effect on brain estrogen synthase availability. Psychometric measures of depression, anxiety, and aggression also remained unchanged post-treatment. These findings suggest that short-term, clinically relevant testosterone administration does not impact the brain androgen-estrogen conversion in healthy premenopausal women, which may reassure patients with hypoactive sexual desire disorder considering this treatment modality. Larger, long-term studies are needed to confirm these results and explore effects in patients with diverse symptoms and treated with testosterone.

Abstract Background [11C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer’s rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[18F]fluoroethyl-etomidate, [18F]CETO, a fluorine-18 (T1/2=109.8 min) analogue, as a potential new adrenocortical PET tracer. The aim of this study was to assess radiation dosimetry of [18F]CETO. Results [18F]CETO showed a high uptake in adrenal glands, still increasing at 5 h post injection. Adrenal glands (absorbed dose coefficients 0.100 ± 0.032 mGy/MBq in males and 0.124 ± 0.013 mGy/MBq in females) received the highest absorbed dose. The effective dose coefficient was 20 µSv/MBq. Conclusions [18F]CETO has a favourable biodistribution in humans for adrenal imaging. The effective dose for a typical clinical PET examination with 200 MBq [18F]CETO is 4 mSv. Trial registration ClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, URL: https://clinicaltrials.gov/ct2/show/NCT05361083.

Abstract Background In preclinical studies, the positron emission tomography (PET) imaging with [11C]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [11C]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding. Results Twelve healthy subjects underwent 90-min baseline [11C]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [11C]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [11C]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue. Conclusions [11C]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.