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Purpose: The performance of detectors is key for a PET scanner to achieve high spatial resolution and high sensitivity. This work aims to develop flood histogram generating algorithms to reduce the edge effect and improve the crystal identification of a PET detector consisting of two optically coupled pixelated scintillator detectors., Methods: The PET detector consists of two optically coupled detectors, each consisting of a 23×23 LYSO crystal array with a crystal size of 1.0×1.0×20 mm 3 read out by an 8×8 SiPM array with a pixel size of 3.0×3.0 mm 2 . The SiPM array is read out with a resistor network circuit to obtain four position encoding energy signals. A novel center of gravity (COG) positioning algorithm using six signals from the two detectors was proposed and compared to the traditional COG algorithms using either four or eight signals from the detectors. The raised-to-the-power (RTP) method was applied to the three COG algorithms for the PET detector. Different powers of the RTP from 1.0 to 2.5 were evaluated., Results: The proposed COG algorithm significantly improves the crystal identification at the junction of the two detectors as compared to the COG algorithm using four signals of each detector, and improves the crystal identification at the center of the two detectors as compared to the COG algorithm using eight signals from both detectors. The RTP method significantly improves the overall flood histogram qualities of the two COG algorithms using either eight or six signals from the two detectors, and the two COG algorithm provide similar flood histogram quality when a power of 1.5 is used., Conclusion: The novel positioning algorithms reduce the edge effect and improve the flood histogram quality for a PET detector consisting of two optically coupled detectors, each consisting of a pixelated scintillator crystal array and a SiPM array with highly multiplexed four signal readout. The positioning algorithms can be used in a PET scanner to improve the spatial resolution and sensitivity., (© 2024 American Association of Physicists in Medicine.)

Objective: Pathological amyloid-β (Aβ) accumulation and hyperphosphorylated tau proteins have been described in resected temporal lobe specimens of epilepsy patients. We aimed to determine cerebrospinal fluid (CSF) Aβ1-42 and p181-tau levels and cerebral Aβ deposits on positron emission tomography (Aβ PET) and correlate these findings with cognitive performance in adults with drug-resistant temporal lobe epilepsy (TLE)., Methods: In this cross-sectional study, we enrolled individuals with drug-resistant TLE who were 25-55 years old. Each participant underwent 18 F-flutemetamol PET, determination of CSF Aβ1-42, p181-tau, and total tau, and a comprehensive neuropsychological assessment. We evaluated normalized standard uptake value ratios (SUVRs) for different brain regions on Aβ PET., Results: Thirty patients (mean age = 41.9 ± SD 8.1 years, 57% men) were included. The median disease duration was 9.5 (interquartile range = 4-24) years. Twenty-six patients (87%) had a clinically significant cognitive impairment on neuropsychological evaluation, 18 (69%) of the amnesic type. On Aβ PET, high uptake was observed in both mesial temporal regions (ipsilateral: SUVR z-score = .90, 95% confidence interval [CI] = .60-1.20; contralateral: SUVR z-score = .92, 95% CI = .57-1.27; p < .001), which was higher when compared to SUVR z-scores in all the remaining regions (p < .001) and in the ipsilateral anterior cingulate (SUVR z-score = .27, 95% CI = .04-.49, p = .020). No significant deposition was observed in other regions. Seven patients (23%) had low Aβ1-42 levels, and two (7%) had elevated p181-tau levels in CSF. Higher p181-tau levels correlated with poorer verbal fluency (R = -.427, p = .044)., Significance: Our findings reveal a considerable Aβ deposition in mesial temporal regions and ipsilateral anterior cingulate among adults with drug-resistant TLE. Additionally, abnormal CSF Aβ1-42 levels were observed in a significant proportion of patients, and p181-tau levels were associated with verbal fluency. These results suggest that markers of neuronal damage can be observed in adults with TLE, warranting further investigation., (© 2024 International League Against Epilepsy.)

Introduction: Occult nodal disease (OND) during clinically-N0 salvage total laryngectomy (TL) can be detected with the Neck-Imaging-Reporting-and-Data-Systems (NI-RADS). However, some patients will still have OND revealed on final pathology., Methods: A retrospective study on all patients who had OND during salvage TL with elective neck dissection (END) between 2009 and 2021 was performed. Repeat CT and PET scan interpretation was performed to evaluate their preoperative imaging for suspicious features., Results: Among 81 salvage TL patients undergoing END, 12 (16%) had OND and a total of 26 occult nodes were identified. On pathology, the average node length [SD] was 0.6 cm [0.3]. On CT, 31% (8 of 26) had rounded morphology. On PET, most had SUV max below blood pool. One patient scored NI-RADS 2; the rest scored 1., Conclusions: On re-review of preoperative imaging, occult nodes were subtle and challenging to identify. Despite no clear impact on survival, performing an END may provide prognostic information., (© 2024 Wiley Periodicals LLC.)

The dopamine hypothesis of schizophrenia posits that elevated striatal dopamine functioning underlies the development of psychotic symptoms. Chronic exposure to social stressors increases psychosis risk, possibly by upregulating striatal dopamine functioning. Here we systematically review single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies that examined the relationship between chronic social stress exposure and in vivo striatal dopamine functioning in humans. We searched the scientific databases PubMed and PsycINFO from inception to August 2023. The quality of the included studies was evaluated with the ten-item Observational Study Quality Evaluation (PROSPERO: CRD42022308883). Twenty-eight studies were included, which measured different aspects of striatal dopamine functioning including dopamine synthesis capacity (DSC), vesicular monoamine transporter type 2 binding, dopamine release following a pharmacological or behavioral challenge, D 2/3 receptor binding, and dopamine transporter binding. We observed preliminary evidence of an association between childhood trauma and increased striatal DSC and dopamine release. However, exposure to low socioeconomic status, stressful life events, or other social stressors was not consistently associated with altered striatal dopamine functioning. The quality of available studies was generally low. In conclusion, there is insufficient evidence that chronic social stressors upregulate striatal dopamine functioning in humans. We propose avenues for future research, in particular to improve the measurement of chronic social stressors and the methodological quality of study designs., Competing Interests: Competing interests: Jan Booij is a consultant at GE Healthcare and received research grants from GE Healthcare (all payments to the institution). The other authors report no potential conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: The present study investigated various image reconstruction protocols for amyloid PET using phantom test criteria published by the Japanese Society of Nuclear Medicine (JSNM) and compared them with the composite standardized uptake value ratio (cSUVR) in clinical imaging., Methods: Hoffman 3D phantoms and cylindrical phantoms were collected for 30 min according to the JSNM guidelines. Images were created under various reconstruction protocols by three physical evaluation items in the guidelines and were assessed: gray matter/white matter contrast (%contrast), uniformity (SDuROImean), and image noise [coefficient of variation (CV)]. We compared the cSUVR of images reconstructed under 15 protocols using 18F-flutemetamol and 18F-florbetapir in 15 cases each and the guidelines for physical evaluation of reconstruction parameters., Results: No significant differences were observed in cSUVR between reconstruction protocols that satisfied the guidelines' criteria for %contrast and CV and those that did not; however, the visual impression of images differed. SDuROImean, which evaluated uniformity, met the criteria in all data., Conclusion: Reconstruction protocols should be selected appropriately using guidelines and other information, as cSUVR remains largely the same even if the visual impression of the images differs between different reconstruction protocols. When the relationship between %contrast and CV is expressed in terms of several reconstruction protocols, the graph shows a curved shape, and the optimal protocols for both %contrast and CV are near its center. Since cSUVR is similar to optimal parameters, even under parameters outside this range, multiple parameters need to be considered when selecting image reconstruction protocols for amyloid PET., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess artificial intelligence (AI) ability to evaluate intraprostatic prostate cancer (PCa) on prostate-specific membrane antigen positron emission tomography (PSMA PET) scans prior to active treatment (radiotherapy or prostatectomy)., Materials and Methods: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO identifier: CRD42023438706). A search was performed on Medline, Embase, Web of Science, and Engineering Village with the following terms: 'artificial intelligence', 'prostate cancer', and 'PSMA PET'. All articles published up to February 2024 were considered. Studies were included if patients underwent PSMA PET scan to evaluate intraprostatic lesions prior to active treatment. The two authors independently evaluated titles, abstracts, and full text. The Prediction model Risk Of Bias Assessment Tool (PROBAST) was used., Results: Our search yield 948 articles, of which 14 were eligible for inclusion. Eight studies met the primary endpoint of differentiating high-grade PCa. Differentiating between International Society of Urological Pathology (ISUP) Grade Group (GG) ≥3 PCa had an accuracy between 0.671 to 0.992, sensitivity of 0.91, specificity of 0.35. Differentiating ISUP GG ≥4 PCa had an accuracy between 0.83 and 0.88, sensitivity was 0.89, specificity was 0.87. AI could identify non-PSMA-avid lesions with an accuracy of 0.87, specificity of 0.85, and specificity of 0.89. Three studies demonstrated ability of AI to detect extraprostatic extensions with an area under curve between 0.70 and 0.77. Lastly, AI can automate segmentation of intraprostatic lesion and measurement of gross tumour volume., Conclusion: Although the current state of AI differentiating high-grade PCa is promising, it remains experimental and not ready for routine clinical application. Benefits of using AI to assess intraprostatic lesions on PSMA PET scans include: local staging, identifying otherwise radiologically occult lesions, standardisation and expedite reporting of PSMA PET scans. Larger, prospective, multicentre studies are needed., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Cardiac positron emission tomography (PET) can visualize and quantify the molecular and physiological pathways of cardiac function. However, cardiac and respiratory motion can introduce blurring that reduces PET image quality and quantitative accuracy. Dual cardiac- and respiratory-gated PET reconstruction can mitigate motion artifacts but increases noise as only a subset of data are used for each time frame of the cardiac cycle., Aim: The objective of this study is to create a zero-shot image denoising framework using a conditional generative adversarial networks (cGANs) for improving image quality and quantitative accuracy in non-gated and dual-gated cardiac PET images., Methods: Our study included retrospective list-mode data from 40 patients who underwent an 18 F-fluorodeoxyglucose ( 18 F-FDG) cardiac PET study. We initially trained and evaluated a 3D cGAN-known as Pix2Pix-on simulated non-gated low-count PET data paired with corresponding full-count target data, and then deployed the model on an unseen test set acquired on the same PET/CT system including both non-gated and dual-gated PET data., Results: Quantitative analysis demonstrated that the 3D Pix2Pix network architecture achieved significantly (p value<0.05) enhanced image quality and accuracy in both non-gated and gated cardiac PET images. At 5%, 10%, and 15% preserved count statistics, the model increased peak signal-to-noise ratio (PSNR) by 33.7%, 21.2%, and 15.5%, structural similarity index (SSIM) by 7.1%, 3.3%, and 2.2%, and reduced mean absolute error (MAE) by 61.4%, 54.3%, and 49.7%, respectively. When tested on dual-gated PET data, the model consistently reduced noise, irrespective of cardiac/respiratory motion phases, while maintaining image resolution and accuracy. Significant improvements were observed across all gates, including a 34.7% increase in PSNR, a 7.8% improvement in SSIM, and a 60.3% reduction in MAE., Conclusion: The findings of this study indicate that dual-gated cardiac PET images, which often have post-reconstruction artifacts potentially affecting diagnostic performance, can be effectively improved using a generative pre-trained denoising network., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

This research presents the development of positron emission tomography (PET) radiotracers for detecting Mycobacterium tuberculosis (MTB) for the diagnosis and monitoring of tuberculosis. Two phage display-derived peptides with proven selective binding to MTB were identified for development into PET radiopharmaceuticals: H8 (linear peptide) and PH1 (cyclic peptide). We sought to functionalize H8/PH1 with NODASA, a bifunctional chelator that allows complexation of PET-compatible radiometals such as gallium-68. Herein, we report on the chelator functionalization, optimized radiosynthesis, and assessment of the radiopharmaceutical properties of [ 68 Ga]Ga-NODASA-H8 and [ 68 Ga]Ga-NODASA-PH1. Robust radiolabeling was achieved using the established routine method, indicating consistent production of a radiochemically pure product (RCP ≥ 99.6%). For respective [ 68 Ga]Ga-NODASA-H8 and [ 68 Ga]Ga-NODASA-PH1, relatively high levels of decay-corrected radiochemical yield (91.2% ± 2.3%, 86.7% ± 4.0%) and apparent molar activity (A m , 3.9 ± 0.8 and 34.0 ± 5.3 GBq/μmol) were reliably achieved within 42 min, suitable for imaging purposes. Notably, [ 68 Ga]Ga-NODASA-PH1 remained stable in blood plasma for up to 2 h, while [ 68 Ga]Ga-NODASA-H8 degraded within 30 min. For both 68 Ga peptides, minimal whole-blood cell binding and plasma protein binding were observed, indicating a favorable pharmaceutical behavior. [ 68 Ga]Ga-NODASA-PH1 is a promising candidate for further in vitro/in vivo evaluation as a tuberculosis-specific infection imaging agent., (© 2024 The Author(s). Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)

In patients with drug-resistant epilepsy, difficulties in identifying the epileptogenic zone are well known to correlate with poorer clinical outcomes post-surgery. The integration of PET and MRI in the presurgical assessment of pediatric patients likely improves diagnostic precision by confirming or widening treatment targets. PET and MRI together offer superior insights compared to either modality alone. For instance, PET highlights abnormal glucose metabolism, while MRI precisely localizes structural anomalies, providing a comprehensive understanding of the epileptogenic zone. Furthermore, both methodologies, whether utilized through simultaneous PET/MRI scanning or the co-registration of separately acquired PET and MRI data, present unique advantages, having complementary roles in lesional and non-lesional cases. Simultaneous FDG-PET/MRI provides precise co-registration of functional (PET) and structural (MR) imaging in a convenient one-stop-shop approach, which minimizes sedation time and reduces radiation exposure in children. Commercially available fusion software that allows retrospective co-registration of separately acquired PET and MRI images is a commonly used alternative. This review provides an overview and illustrative cases that highlight the role of combining 18F-FDG-PET and MRI imaging and shares the authors' decade-long experience utilizing simultaneous PET/MRI in the presurgical evaluation of pediatric epilepsy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) stand as pivotal diagnostic tools for brain disorders, offering the potential for mutually enriching disease diagnostic perspectives. However, the costs associated with PET scans and the inherent radioactivity have limited the widespread application of PET. Furthermore, it is noteworthy to highlight the promising potential of high-field and ultra-high-field neuroimaging in cognitive neuroscience research and clinical practice. With the enhancement of MRI resolution, a related question arises: can high-resolution MRI improve the quality of PET images?, Purpose: This study aims to enhance the quality of synthesized PET images by leveraging the superior resolution capabilities provided by high-field and ultra-high-field MRI., Methods: From a statistical perspective, the joint probability distribution is considered the most direct and fundamental approach for representing the correlation between PET and MRI. In this study, we proposed a novel model, the joint diffusion attention model, namely, the joint diffusion attention model (JDAM), which primarily focuses on learning information about the joint probability distribution. JDAM consists of two primary processes: the diffusion process and the sampling process. During the diffusion process, PET gradually transforms into a Gaussian noise distribution by adding Gaussian noise, while MRI remains fixed. The central objective of the diffusion process is to learn the gradient of the logarithm of the joint probability distribution between MRI and noise PET. The sampling process operates as a predictor-corrector. The predictor initiates a reverse diffusion process, and the corrector applies Langevin dynamics., Results: Experimental results from the publicly available Alzheimer's Disease Neuroimaging Initiative dataset highlight the effectiveness of the proposed model compared to state-of-the-art (SOTA) models such as Pix2pix and CycleGAN. Significantly, synthetic PET images guided by ultra-high-field MRI exhibit marked improvements in signal-to-noise characteristics when contrasted with those generated from high-field MRI data. These results have been endorsed by medical experts, who consider the PET images synthesized through JDAM to possess scientific merit. This endorsement is based on their symmetrical features and precise representation of regions displaying hypometabolism, a hallmark of Alzheimer's disease., Conclusions: This study establishes the feasibility of generating PET images from MRI. Synthesis of PET by JDAM significantly enhances image quality compared to SOTA models., (© 2024 American Association of Physicists in Medicine.)

Objective: This study utilized a data-driven Bayesian model to automatically identify distinct latent disease factors represented by overlapping glucose metabolism patterns from 18 F-Fluorodeoxyglucose PET ( 18 F-FDG PET) to analyze heterogeneity among patients with TLE., Methods: We employed unsupervised machine learning to estimate latent disease factors from 18 F-FDG PET scans, representing whole-brain glucose metabolism patterns in seventy patients with TLE. We estimated the extent to which multiple distinct factors were expressed within each participant and analyzed their relevance to epilepsy burden, including seizure onset, duration, and frequency. Additionally, we established a predictive model for clinical prognosis and decision-making., Results: We identified three latent disease factors: hypometabolism in the unilateral temporal lobe and hippocampus (factor 1), hypometabolism in bilateral prefrontal lobes (factor 2), and hypometabolism in bilateral temporal lobes (factor 3), variably co-expressed within each patient. Factor 3 demonstrated the strongest negative correlation with the age of onset and duration (r =  - 0.33, - 0.38 respectively, P < 0.05). The supervised classifier, trained on latent disease factors for predicting patient-specific antiepileptic drug (AED) responses, achieved an area under the curve (AUC) of 0.655. For post-surgical seizure outcomes, the AUC was 0.857, and for clinical decision-making, it was 0.965., Conclusions: Decomposing 18 F-FDG PET-based phenotypic heterogeneity facilitates individual-level predictions relevant to disease monitoring and personalized therapeutic strategies., (© 2024. Fondazione Società Italiana di Neurologia.)

Purpose: Histone deacetylase 6 (HDAC6) has emerged as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease. Noninvasive imaging of HDAC6 in the brain by positron emission tomography (PET) would accelerate research into its roles in these diseases. We recently discovered an 18 F-labeled derivative of the selective HDAC6 inhibitor SW-100 ([ 18 F]FSW-100) as a potential candidate for brain HDAC6 radioligand. As a mandatory step prior to clinical translation, we performed preclinical validation of [ 18 F]FSW-100., Methods: Process validation of [ 18 F]FSW-100 radiosynthesis for clinical use and assessment of preclinical toxicity and radiation dosimetry estimated from mouse distribution data were performed. In vitro selectivity of FSW-100 for 28 common receptors in the brain and HDAC isoforms was characterized. [ 18 F]FSW-100 PET imaging was performed in non-human primates in a conscious state to estimate the feasibility of HDAC6 imaging in humans., Results: Three consecutive validation runs of the automated radiosynthesis gave [ 18 F]FSW-100 injections with radiochemical yields of 12%, and the injections conformed to specified quality control criteria for batch release. No acute toxicity was observed for non-radiolabeled FSW-100 or radioactivity decayed [ 18 F]FSW-100 injection, and the former was negative in the Ames test. The whole-body effective dose estimated from biodistribution in mice was within the range of that of previously reported 18 F-radioligands in humans. In vitro selectivity against common receptors and other HDAC isoforms was confirmed. [ 18 F]FSW-100 demonstrated good penetration in monkey brain, and in vivo blocking studies suggested that the uptake was specific., Conclusion: These results support the clinical utility of [ 18 F]FSW-100 for in vivo imaging of HDAC6 in the brain., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Primary pediatric lung tumors are uncommon and have many overlapping clinical and imaging features. In contrast to adult lung tumors, these rare pediatric neoplasms have a relatively broad histologic spectrum. Informed by a single-institution 13-year retrospective record review, we present an overview of the most common primary pediatric lung neoplasms, with a focus on the role of positron emission tomography (PET), specifically 18 F-fluorodeoxyglucose (FDG) PET and 68 Ga-DOTATATE PET, in the management of primary pediatric lung tumors. In addition to characteristic conventional radiographic and cross-sectional imaging findings, knowledge of patient age, underlying cancer predisposition syndromes, and PET imaging features may help narrow the differential. While metastases from other primary malignancies remain the most commonly encountered pediatric lung malignancy, the examples presented in this pictorial essay highlight many of the important conventional radiologic and PET imaging features of primary pediatric lung malignancies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: A solid-state PET/CT system uses bismuth germanium oxide (BGO) scintillating crystals coupled to silicon photomultipliers over an extended 32 cm axial field-of-view (FOV) to provide high spatial resolution and very high sensitivity. Performance characteristics were determined for this digital-BGO system, including NEMA and EARL standards., Methods: Spatial resolution, scatter fraction (SF), noise equivalent count rate (NECR), sensitivity, count rate accuracy, and image quality (IQ) were evaluated for the digital-BGO system as per NEMA NU 2-2018, at 2 sites of first clinical install. System energy resolution was measured. Bayesian penalized-likelihood reconstruction (BPL) was used for IQ. EARL Standards 2 studies were reconstructed by BPL combined with a contrast-enhancing deep learning algorithm. An Esser PET phantom was evaluated. Three patient examples were obtained with low-dose radiotracer activity: 2 MBq/kg of [ 18 F]FDG ([ 18 F]-2-fluoro-2-deoxy-D-glucose), 2.3 MBq/kg [ 68 Ga]Ga-DOTA-TATE ([dodecane tetra-acetic acid,Tyr 3 ]-octreotate), and 14.5 MBq/kg [ 82 Rb]RbCl ([ 82 Rb]-rubidium-chloride). Total scan times were ≤ 8 min., Results: NEMA sensitivity was 47.6 cps/kBq at the axial center. Spatial resolution at 1 cm from the center axis was ≤4.5 mm (filtered back projection) and ≤3.8 mm (ordered subset expectation maximization). SF was 35.6%, count rate accuracy was 2.16%, and peak NECR was 485.2 kcps at 16.9 kBq/mL. Contrast for IQ was 61.1 to 90.7% (smallest to largest sphere) with background variations from 7.6 to 2.1%, and a "lung" error of 4.7%. The average detector energy resolution was 9.67%. Image quality for patient scans was good. EARL Standards 2 criteria were robustly met and Esser phantom features ≥4.8 mm were resolved at 2 min per bed position., Conclusion: A solid-state 32 cm axial FOV digital-BGO PET/CT system provides good spatial and energy resolution, high count rates, and superior NEMA sensitivity in its class, enabling fast clinical acquisitions with low-dose radiotracer activity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study explored the feasibility of reducing the scan time of Patlak parametric imaging on the uEXPLORER., Methods: A total of 65 patients (27 females and 38 males, age 56.1 ± 10.4) were recruited in this study. 18F fluorodeoxyglucose was injected, and its dose was adjusted by body weight (4.07 MBq/kg). Total-body dynamic scanning was performed on the uEXPLORER total-body Positron emission tomography/computed tomography (CT) scanner with a total scan time of 60 min from the injection. The image derived input function (IDIF) was obtained from the aortic arch. The voxelwise Patlak analysis was applied to generate the K i images designated as G IDIF with different acquisition times (20-60, 30-60, 40-60, and 44-60 min). The population-based input function (PBIF) was constructed from the mean value of the IDIF from the population, and K i images designated as G PBIF were generated using the PBIF. Nonlocalmeans (NLM) denoising was applied to the generated images to get two extra groups of (NLM-designated) images: G IDIF+NLM and G PBIF+NLM . Two radiologists evaluated the overall image quality, noise, and lesion detectability of the K i images from different groups. The 20-60 min scans in G IDIF were selected as the gold standard for each patient. We determined that image quality is at sufficient level if all the lesions can be recognized and meet the clinical criteria. K i values in muscle and lesion were compared across different groups to evaluate the quantitative accuracy., Results: The overall image quality, image noise, and lesion conspicuity were significantly better in long time series than short time series in all four groups (all p < 0.001). The K i images in the G IDIF and G PBIF groups generated from 30-min scans showed diagnostic value equivalent to the 40-min scans of G IDIF . While the image quality of the 16-min scans was poor, all lesions could still be detected. No significant difference was found between K i values estimated with G IDIF and G PBIF in muscle and lesion regions (all p > 0.5). After applying the NLM filter, the coefficient of variation could be reduced on the order of (1%, 15%, 19%, and 37%) and (110%, 125%, 94%, and 69%) with four acquisition time schemes for lesion and muscle. The reduction percentage did not have a substantial difference in IDIF and PBIF group. The K i images in the G IDIF+NLM and G PBIF+NLM groups generated from the 20-min acquisitions showed acceptable quality. All lesions could be found on the NLM processed images of the 16-min scans. No significant difference was found between K i values produced with G IDIF+NLM and G PBIF+NLM in muscle and lesion regions(all p > 0.7)., Conclusions: The K i images generated by the PBIF-based Patlak model using a 20-min dynamic scan with the NLM filter achieved a similar diagnostic efficiency to images with G IDIF from 40-min dynamic data, and there is no significant difference between K i images generated using IDIF or PBIF (p > 0.5)., (© 2022 American Association of Physicists in Medicine.)

Positron emission tomography (PET) is a powerful tool in medicine and drug development, allowing for non-invasive imaging and quantitation of biological processes in live organisms. Targets are often probed with small molecules, but antibody-based PET is expanding because of many benefits, including ease of design of new antibodies toward targets, as well as the very strong affinities that can be expected. Application of antibodies to PET imaging of targets in the central nervous system (CNS) is a particularly nascent field, but one with tremendous potential. In this review, we discuss the growth of PET in imaging of CNS targets, present the promises and progress in antibody-based CNS PET, explore challenges faced by the field, and discuss questions that this promising approach will need to answer moving forward for imaging and perhaps even radiotherapy., (© 2023 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)

Functional imaging is playing an increasingly important role in pediatric radiology. Hybrid imaging techniques utilizing PET/CT (positron emission tomography/computed tomography), PET/MRI (positron emission tomography/magnetic resonance imaging), or SPECT/CT (single photon emission computed tomography/computed tomography) are now available in nearly every clinical practice. There are an increasing number of indications for the use of functional imaging, including oncologic and infectious indications, and it is essential to select and design the hybrid imaging protocol in order to optimize both the functional and anatomic components of the examination. Optimizing the protocol includes strategies for dose reduction, judicious use of contrast media and diagnostic quality imaging as appropriate, and for the greatest reduction in exposure to ionizing radiation, utilizing PET/MRI, whenever available. This review will provide an overview of hybrid imaging protocol considerations with a focus on oncologic and infectious indications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We wished to document the prevalence and quantitative effects of compromised 82 Rb PET data acquisitions on myocardial flow reserve (MFR)., Methods and Results: Data were analyzed retrospectively for 246 rest and regadenoson-stress studies of 123 patients evaluated for known or suspected CAD. An automated injector delivered pre-determined activities of 82 Rb. Automated quality assurance algorithms identified technical problems for 7% (9/123) of patients. Stress data exhibited 2 instances of scanner saturation, 1 blood peak detection, 1 blood peak width, 1 gradual patient motion, and 2 abrupt patient motion problems. Rest data showed 1 instance of blood peak width and 2 abrupt patient motion problems. MFR was lower for patients with technical problems flagged by the quality assurance algorithms than those without technical problems (1.5 ± 0.5 versus 2.1 ± 0.7, P = 0.01), even though rest and stress ejection fraction, asynchrony and relative myocardial perfusion measures were similar for these two groups (P > 0.05), suggesting that MFR accuracy was adversely affected by technical errors., Conclusion: It is important to verify integrity of 82 Rb data to ensure MFR computation quality., (© 2021. American Society of Nuclear Cardiology.)

Background: As clinical use of myocardial blood flow (MBF) increases, dynamic series are becoming part of the typical workflow. The methods and parameters used to reconstruct these series require investigation to ensure accurate quantification., Methods: Fifty-nine rest/stress dynamic 82 Rb PET studies, acquired on a Biograph mCT, from a combination of normal volunteers and low-likelihood patients were reconstructed with and without time of flight (TOF) for varying iterations and processed to obtain relative perfusion and MBF polar maps. Regional values from mean polar maps were fit to a linear mixed-effect model to quantify convergence and select the optimal number of iterations., Results: TOF reconstructions converged faster and yielded more uniform relative perfusion polar maps. However, the stress MBF distribution for TOF reconstructions was more heterogeneous, with a higher-intensity septal wall. This phenomenon requires further investigation, with right ventricle blood pool spillover possibly having an effect. Optimal reconstructions were defined as 5-iteration non-TOF (24-subset) reconstructions and 3-iteration TOF (21-subset) reconstructions., Conclusion: Optimal cardiac reconstructions were identified for non-TOF and TOF reconstructions of dynamic series. TOF reconstruction presents as the more accurate method, given the more uniform relative perfusion distribution., (© 2021. American Society of Nuclear Cardiology.)

Purpose of Review: Adrenal imaging forms an important role in the workup of adrenal masses. The purpose of this review is to briefly review the traditional role of imaging in adrenal diseases and highlight the most recent research and new applications aimed to improve diagnostic accuracy., Recent Findings: The current review will focus on new applications of computed tomography (CT), MRI and PET/CT imaging, addressing the implications of artificial intelligence and radiomics in progressing diagnostic accuracy., Summary: The new applications of adrenal imaging are improving diagnostic accuracy and expanding the role of imaging, particularly with novel PET radiotracers and the use of artificial intelligence., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The positron emission tomography (PET) insert for a magnetic resonance imaging (MRI) system that implements the radiofrequency (RF) built-in body coil of the MRI system as a transmitter is designed to be RF-transparent, as the coil resides outside the RF-shielded PET ring. This approach reduces the design complexities (e.g., large PET ring diameter) related to implementing a transmit coil inside the PET ring. However, achieving the required field transmission into the imaging region of interest (ROI) becomes challenging because of the RF shield of the PET insert. In this study, a modularly RF-shielded PET insert is used to investigate the RF transparency considering two electrical configurations of the RF shield, namely the electrical floating and ground configurations. The purpose is to find the differences, advantages and disadvantages of these two configurations., Methods: Eight copper-shielded PET detector modules (intermodular gap: 3 mm) were oriented cylindrically with an inner diameter of 234 mm. Each PET module included four-layer Lutetium-yttrium oxyorthosilicate scintillation crystal blocks and front-end readout electronics. RF-shielded twisted-pair cables were used to connect the front-end electronics with the power sources and PET data acquisition systems located outside the MRI room. In the ground configuration, both the detector and cable shields were connected to the RF ground of the MRI system. In the floating configuration, only the RF shields of the PET modules were isolated from the RF ground. Experiments were conducted using two cylindrical homogeneous phantoms in a 3 T clinical MRI system, in which the built-in body RF coil (a cylindrical volume coil of diameter 700 mm and length 540 mm) was implemented as a transceiver., Results: For both PET configurations, the RF and MR imaging performances were lower than those for the MRI-only case, and the MRI system provided specific absorption ratio (SAR) values that were almost double. The RF homogeneity and field strength, and the signal-to-noise ratio (SNR) of the MR images were mostly higher for the floating PET configuration than they were for the ground PET configuration. However, for a shorter axial field-of-view (FOV) of 125 mm, both configurations offered almost the same performance with high RF homogeneities (e.g., 76 ± 10%). Moreover, for both PET configurations, 56 ± 6% larger RF pulse amplitudes were required for MR imaging purposes. The increased power is mostly absorbed in the conductive shields in the form of shielding RF eddy currents; as a result, the SAR values only in the phantoms were estimated to be close to the MRI-only values., Conclusions: The floating PET configuration showed higher RF transparency under all experimental setups. For a relatively short axial FOV of 125 mm, the ground configuration also performed well which indicated that an RF-penetrable PET insert with the conventional design (e.g., the ground configuration) might also become possible. However, some design modifications (e.g., a wider intermodular gap and using the RF receiver coil inside the PET insert) should improve the RF performance to the level of the MRI-only case., (© 2022 American Association of Physicists in Medicine.)

Positron Emission Tomography (PET) has emerged as a powerful imaging technique in molecular medicine, enabling the non-invasive visualisation and quantification of biological processes at the molecular level. Antibody-based PET imaging has recently gained prominence, offering specific targeting capabilities for various diseases. This scientific article delves into the intricate chemistry underlying antibody conjugation strategies for PET, providing a comprehensive understanding of the key principles and advancements in this rapidly evolving field. The article begins with a detailed exploration of various antibody conjugation methodologies, encompassing both covalent and non-covalent approaches. The chemical intricacies of bioconjugation reactions, such as amine and thiol chemistry, click chemistry, and bioorthogonal chemistry, are thoroughly discussed in the context of antibody modification. Additionally, the article critically analyses recent advancements in radiolabeling strategies for PET, including using radionuclides with favourable decay characteristics. This discussion covers both traditional radioisotopes and emerging alternatives, demonstrating their potential to raise the effectiveness of PET imaging agents based on antibodies. Ultimately, this article aims to contribute to the ongoing efforts to advance the field toward more effective diagnostic tools for personalized medicine., 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Visual and visual processing deficits are implicated in freezing, falling, and cognitive impairments in Parkinson's disease (PD). In particular, contrast sensitivity deficits are common and may be related to cognitive impairment in PD. While dopaminergic deficits play a role in PD-related visual dysfunction, brain cholinergic systems also modulate many aspects of visual processing. The aim of this study was to explore regional cerebral cholinergic terminal density correlates of contrast sensitivity in PD. Ninety-one PD subjects underwent contrast sensitivity testing, motor testing, cognitive testing, and brain MRI and [ 18 F]-fluoroethoxybenzovesamicol [ 18 F]-FEOBV PET imaging. Whole brain false discovery error-corrected (p < 0.05) correlations revealed significant associations between VAChT deficits in pericentral, limbic, and visual processing regions and contrast sensitivity performance, independent of disease duration and dopaminergic medication doses. These results suggest that brain cholinergic deficits correlate with contrast sensitivity deficits in PD. Additionally, decreased Rabin contrast sensitivity scores were associated with lower total scores in the Parkinson's Disease Cognitive Rating Scale. These findings suggest that diminished cognitive performance correlated with contrast sensitivity partly reflects underlying vulnerabilities of brain cholinergic systems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prabesh Kanel reports financial support was provided by National Institutes of Health. Nicolaas Bohnen reports a relationship with National Institutes of Health that includes: funding grants. Roger Albin reports a relationship with Parkinson's Disease Foundation that includes: funding grants. No other relationships to declare If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Tumor-specific molecular probe-based imaging strategies have shown great potential for tumor diagnosis. However, the sensitivity and contrast of imaging may interfere with the complex labeling process and degradation of tumor-specific imaging probes. We sought to adapt a pretargeting strategy and an in vivo bioorthogonal reaction to improve hyaluronan (HA)-based tumor multimodal imaging diagnosis., Methods: Transcyclooctene-labeled HA (HA-TCO) and tetrazine-labeled NODA (NODA-Tz) were synthesized and purified. Probes Gd-NODA-Tz and [ 18 F]AlF-NODA-Tz for magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging were prepared. The bioorthogonal reaction of HA-TCO with NODA-Tz and the stability of the products were confirmed and analyzed. CD44 + A549 tumor-bearing mice were injected with HA-TCO via the tail vein, followed by Gd-NODA-Tz or [ 18 F]AlF-NODA-Tz administration half an hour later, and subsequently imaged by MR or PET. The images were analyzed and tumor uptake was quantified., Results: HA-TCO efficiently bound to CD44-overexpressing A549 cells and selectively reacted with the Tz-imaging group. In vivo MR and PET images were obtained after probe injection and subsequent bioorthogonal labeling. The images showed a tumor mass with a high target background ratio (TBR) and clear boundaries., Conclusion: In situ labeling of pretargeted HA-TCO enabled MRI and PET imaging of tumor tissues in mice with high sensitivity and improved TBR., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Dopamine transporter imaging is routinely used in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) diagnosis. While [ 11 C]CFT PET is prevalent in Asia with a large APS database, Europe relies on [ 123 I]FP-CIT SPECT with limited APS data. Our aim was to develop a deep learning-based method to convert [ 11 C]CFT PET images to [ 123 I]FP-CIT SPECT images, facilitating multicenter studies and overcoming data scarcity to promote Artificial Intelligence (AI) advancements., Methods: A CycleGAN was trained on [ 11 C]CFT PET (n = 602, 72%PD) and [ 123 I]FP-CIT SPECT (n = 1152, 85%PD) images from PD and non-parkinsonian control (NC) subjects. The model generated synthetic SPECT images from a real PET test set (n = 67, 75%PD). Synthetic images were quantitatively and visually evaluated., Results: Fréchet Inception Distance indicated higher similarity between synthetic and real SPECT than between synthetic SPECT and real PET. A deep learning classification model trained on synthetic SPECT achieved sensitivity of 97.2% and specificity of 90.0% on real SPECT images. Striatal specific binding ratios of synthetic SPECT were not significantly different from real SPECT. The striatal left-right differences and putamen binding ratio were significantly different only in the PD cohort. Real PET and real SPECT had higher contrast-to-noise ratio compared to synthetic SPECT. Visual grading analysis scores showed no significant differences between real and synthetic SPECT, although reduced diagnostic performance on synthetic images was observed., Conclusion: CycleGAN generated synthetic SPECT images visually indistinguishable from real ones and retained disease-specific information, demonstrating the feasibility of translating [ 11 C]CFT PET to [ 123 I]FP-CIT SPECT. This cross-modality synthesis could enhance further AI classification accuracy, supporting the diagnosis of PD and APS., Competing Interests: Declarations. Ethics approval and consent to participate: Study protocols were approved by the ethics committee of Huashan Hospital, and voluntary informed consent was obtained from each subject or their caregivers after an explanation of the procedures, according to the Declaration of Helsinki. Consent for publication: Each subject or their caregivers offered written consent for publication and no personal information was presented in the current paper. Competing interests: MB received speaker honoraria from GE healthcare, Roche and LMI and is an advisor of LMI. BS, RF and AS are full-time employees of Siemens Medical Solutions USA, Inc. KS receives research grants from Novartis and Siemens Healthineers, and sponsorships from Novartis, Siemens Healthineers, Hermes Medical Solution, DosiSoft, Varian, THQ Medical Products, QDose, PMOD, Boston Scientific, SIRTEX, MIM Software, and the ICPO Foundation. KS and AR are editors of the European Journal of Nuclear Medicine and Molecular Imaging., (© 2024. The Author(s).)

Objective: To study information needs after receiving abnormal amyloid-PET results, and how individual characteristics moderate effects of different communication strategies on information recall., Methods: In an online video-vignette experiment, seven vignettes each depicted a consultation of a physician sharing abnormal amyloid-PET results with a patient with Mild Cognitive Impairment(MCI), using different communication strategies. Healthy individuals (N = 1017; age 64 ± 8, 808(79 %) female), instructed to imagine themselves as the video-patient, viewed a randomly-assigned vignette and completed questionnaires to assess information needs and test moderation effects of gender, age, care-partner experience, health literacy, and coping., Results: Sixty-three percent of participants (645/1017) would have liked to receive more information, e.g., on prognosis, additional information sources, lifestyle advice, and/or treatment. Emotional support benefited information recall in women, but not men. Emotional support and visually presenting the PET-scan were less beneficial for individuals with a stronger avoidant coping style, compared to most other strategies., Conclusion: Most people wanted more information on varying topics, and gender and coping style influenced how communication strategies impacted information recall. PRACTICE IMPLICATIONS The importance of personalized information provision was emphasized, both in terms of what information is provided and how physicians share information, by paying attention to individuals' needs and characteristics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Research programs of Wiesje van der Flier (WF) have been funded by ZonMW, NWO, EU-JPND, EU-IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, Eisai, Combinostics. WF holds the Pasman chair. WF has been an invited speaker at Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), NovoNordisk, Springer Healthcare, European Brain Council. All funding is paid to her institution. WF is consultant to Oxford Health Policy Forum CIC, Roche, Biogen MA Inc, and Eisai. WF is member of steering cie of NovoNordisk evoke/evoke+ . All funding is paid to her institution. WF participated in advisory boards of Biogen MA Inc, Roche, and Eli Lilly. WF is member of the steering committee of PAVE and Think Brain Health. WF was associate editor of Alzheimer, Research & Therapy in 2020/2021. WF is associate editor at Brain. Leonie Visser (LNCV) has been invited speaker for the Schwabe Group, and her research has been funded by ZonMW, Health Holland, Eisai, the Amsterdam Public Health research institute, and Alzheimer Nederland. All fees and funding are paid to her institution. JvdS wrote a book for a layman's audience about the personal impact of dominantly inherited AD, for which she received grants or contracts from Aegon Nederland and Alzheimer Nederland and royalties from Uitgeverij Prometheus. She is a member of the advisory board for the National Dementia Strategy of the Dutch Ministry of Health, Welfare and Sport. All other 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rubidium-82 ( 82 Rb) is a radioactive isotope widely used for cardiac PET imaging. Despite numerous benefits of 82 Rb, there are several factors that limits its image quality and quantitative accuracy. First, the short half-life of 82 Rb results in noisy dynamic frames. Low signal-to-noise ratio would result in inaccurate and biased image quantification. Noisy dynamic frames also lead to highly noisy parametric images. The noise levels also vary substantially in different dynamic frames due to radiotracer decay and short half-life. Existing denoising methods are not applicable for this task due to the lack of paired training inputs/labels and inability to generalize across varying noise levels. Second, 82 Rb emits high-energy positrons. Compared with other tracers such as 18 F, 82 Rb travels a longer distance before annihilation, which negatively affect image spatial resolution. Here, the goal of this study is to propose a self-supervised method for simultaneous (1) noise-aware dynamic image denoising and (2) positron range correction for 82 Rb cardiac PET imaging. Tested on a series of PET scans from a cohort of normal volunteers, the proposed method produced images with superior visual quality. To demonstrate the improvement in image quantification, we compared image-derived input functions (IDIFs) with arterial input functions (AIFs) from continuous arterial blood samples. The IDIF derived from the proposed method led to lower AUC differences, decreasing from 11.09% to 7.58% on average, compared to the original dynamic frames. The proposed method also improved the quantification of myocardium blood flow (MBF), as validated against 15 O-water scans, with mean MBF differences decreased from 0.43 to 0.09, compared to the original dynamic frames. We also conducted a generalizability experiment on 37 patient scans obtained from a different country using a different scanner. The presented method enhanced defect contrast and resulted in lower regional MBF in areas with perfusion defects. Lastly, comparison with other related methods is included to show the effectiveness of the proposed method., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chi Liu reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Febrile Infection-Related Epilepsy Syndrome (FIRES) is an infrequent yet severe form of epilepsy that rapidly evolves into status epilepticus following a febrile episode. Prompt diagnosis coupled with effective treatment strategies is critical for improving patient outcomes. Herein, we describe the case of an 11-year-old male with FIRES who was successfully treated with tocilizumab, resulting in no further seizures or residual disability. The patient initially did not respond to antiseizure medications and first-line immunomodulatory therapy. Characteristic EEG patterns and elevated interleukin 6 levels in the cerebrospinal fluid contributed to an early presumptive diagnosis of FIRES. Tocilizumab was administered on day 10 after the seizure onset, leading to seizure cessation within 24 h, with no subsequent episodes. Serial cranial MRI imaging studies demonstrated transient abnormalities that resolved over time. Notably, on day 9, the patient exhibited bilateral frontal lobe hypermetabolism on FDG-PET, with EEG showing global slow waves predominantly in the bilateral frontal regions. As seizure control was achieved and encephalopathy symptoms improved, a follow-up EEG on day 25 revealed persistent slow waves in the bilateral frontal regions, with FDG-PET hypermetabolism present only in the left frontal lobe. By day 88, both EEG and FDG-PET had returned to normal. These findings suggest tocilizumab may play a role in the management of FIRES, though further studies are required to substantiate its therapeutic efficacy. Additionally, early bilateral frontal FDG-PET hypermetabolism and EEG slow-wave activity, may serve as an early biomarker in FIRES patients. However, more research is necessary to establish its validity., 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective . Position-sensitive silicon photomultipliers (PS-SiPMs) are promising photodetectors for ultra-high spatial resolution small-animal positron emission tomography (PET) scanners. This paper evaluated the performance of the latest generation of linearly-graded SiPMs (LG-SiPMs), a type of PS-SiPM, for ultra-high spatial resolution PET applications using LYSO arrays from two vendors. Approach . Two dual-ended readout detectors were developed by coupling LG-SiPMs to both ends of the two LYSO arrays. Each LG-SiPM has an active area of 9.8 × 9.8 mm 2 . Both LYSO arrays consist of 20 × 20 arrays of 0.44 × 0.44 × 20 mm 3 polished LYSOs with a pitch of 0.5 mm. The performance of the two detectors was compared in terms of flood histogram, energy resolution, timing resolution, and depth-of-interaction (DOI) resolutions. Main results . Flood histograms showed clear identification of all LYSO elements except for some edge crystals due to the larger size of the LYSO arrays compared to the active area of the LG-SiPMs and the misalignment between LG-SiPMs and LYSO arrays in the assembled detectors. At a bias voltage of 37.0 V, the detectors utilizing the Tianle LYSO array and EBO LYSO array provided energy resolutions of 17.5 ± 2.2 and 18.6 ± 2.0%, timing resolutions of 0.75 ± 0.03 and 0.78 ± 0.03 ns, and DOI resolutions of 2.16 ± 0.15 and 2.31 ± 0.12 mm, respectively. Significance . The results presented in this paper demonstrate that the new generation LG-SiPMs are promising photodetectors for ultra-high spatial resolution small-animal PET scanner applications., (© 2025 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The presence of aggregated Tau in the brain is a dominant pathological hallmark of Tauopathies, particularly in Alzheimer's disease (AD). Therefore, developing ligands that can specifically and sensitively bind to Tau aggregates is essential for diagnosing and monitoring therapeutic interventions. In this study, we further investigated the structural optimization of the diarylamine skeleton, which exhibited promising binding characteristics and biological properties. We supplementarily explored the effects of the number and position of nitrogen atoms, types of heteroatoms and aromatic moieties, and radioactive positions on affinity for Tau. Through a structure-activity relationship (SAR) analysis based on 125 I-labeled diarylamine derivatives, [ 125 I]A6 was identified as a lead compound due to its desirable binding properties and ability to penetrate the brain, making it suitable for conversion into a 18 F-labeled PET tracer. Satisfactorily, [ 18 F]FA1 fulfilled critical requirements as a Tau radiotracer, demonstrating high specificity and selectivity for Tau, a clean off-target profile against Aβ plaques and monoamine oxidase B (MAO-B), and favorable in vivo brain kinetics, as confirmed by dynamic PET studies in rodents and non-human primates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mengchao Cui has patent pending to Beijing Normal University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The quest for a cancer-specific positron emission tomography (PET) tracer has been ongoing for decades. Current evidence shows that targeting amino acid metabolism dysregulation is a valid alternative cancer detection method and can complement the conventional approach, which relies on targeting increased glucose metabolism. The rate of amino acid metabolism in all major organs is mostly equally low and does not change in any physiological dynamics. The amino acid metabolism rate only spikes in malignant tissues. PET imaging targeting LAT1 (L-type amino acid transporter 1) demonstrated accurate cancer imaging of various cancer types with nearly negligible background uptake. LAT1 is a pan-cancer biomarker of amino acid metabolism dysregulation. The upregulated LAT1 expression in cancer cells depicts their dynamic behavior and aggressiveness. This review discussed PET radiotracers developed as a LAT1-specific agent and how this new class of cancer-specific radiopharmaceuticals could deliver PET images with clinical properties we yearn for, such as high specificity toward various malignancies, robust non-cancer exclusion (mainly inflammatory reactions), accurate malignant lesion delineation, representative therapeutic monitoring, and long-term prognostication., Competing Interests: Competing Interests: The authors are former (A.A., H.H., K.E.) and current (Y.T.) educational staff at the academic institution where the [¹⁸F]FAMT is developed. The remaining authors (H.A.H., A.H.S.K.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The funder (Universitas Padjadjaran) had no role in the study's design, data collection, analysis, interpretation, manuscript writing, or decision to publish the results., (© The author(s).)

Mesothelioma is a malignant tumor associated primarily with asbestos exposure, characterized by an aggressive nature and poor prognosis. Accurate diagnosis, staging, and monitoring of therapeutic response are crucial for effective patient management. Along with a computed tomography (CT) scan, fluorodeoxyglucose labeled with fluorine-18 ([ 18 F]FDG) positron emission tomography (PET) is commonly used in mesothelioma evaluation. However, it has some limitations, including lower sensitivity after pleurodesis and poor accuracy for involved lymph node evaluation. Thus, there is the need to explore other agents. The aim of the present review is to analyze the current literature on the use of alternative radiopharmaceuticals for PET imaging in patients with mesothelioma. A comprehensive search of scientific databases (PubMed, Scopus, and Web of Science) for studies published in the last decade was performed by using the following keywords: "mesothelioma" AND "PET" AND "PET/CT" "radiopharmaceuticals", "[ 18 F]FDG alternatives". Articles focused solely on [ 18 F]FDG, non-English publications or preclinical studies, reviews, meeting abstracts, letters to the editors, and editorials were excluded. A qualitative assessment was made by using the Critical Appraisal Skills Programme (CASP) checklist for diagnostic test studies, when applicable. In total, 14 papers were selected; in seven articles more than five patients were enrolled, while the other seven were only clinical cases (enrolling up to two subjects). [ 18 F]/gallium-68 ([ 68 Ga])-labeled fibroblast activation protein inhibitor (FAPI) compounds, [ 18 F]Fluorothymidine ([ 18 F]FLT), methionine labeled with carbon-11 ([ 11 C]MET), and fluoromisonidazole labeled with fluorine-18 ([ 18 F]FMISO) PET/CT were the alternative agents used most often. In 12 articles, [ 18 F]FDG PET/CT was used as a comparator imaging modality. Detection rate of [ 18 F]FDG was similar to the other radiopharmaceuticals ([ 68 Ga]/[18F]-labeled FAPI compounds, [ 18 F]FLT, [ 18 F]FMISO, [ 11 C]MET, and [ 68 Ga]-Pentaxifor), although radiolabeled FAPI seems to exhibit a higher diagnostic performance. [ 18 F]FDG is still a valuable agent in patients with mesothelioma. However, radiolabeled FAPI appears to be promising and its theranostic properties should therefore be further assessed., Competing Interests: Declarations. Funding: Not applicable. Conflict of Interest: The authors (P.G., C.C., A.C., C.M.D.C., M.P., S.M., M.O., P.A.Z., and L.E.) declare no conflicts of interest. Availability of Data and Material: Not applicable. Informed Consent: Not applicable. Ethical Approval:: Institutional review board approval was not required, because the paper is a review. Consent to Participate: Not applicable. Consent to Publication: Not applicable. Author Contributions: Priscilla Guglielmo (data acquisition, analysis, or interpretation; intellectual content development or critical review; and final version approval), Cinzia Crivellaro (data acquisition, analysis, or interpretation; intellectual content development or critical review; and final version approval), Angelo Castello (data acquisition, analysis, or interpretation; intellectual content development or critical review; and final version approval), Carminia Maria Della Corte (data acquisition, analysis, or interpretation; intellectual content development or critical review; and final version approval), Maria Pagano (data acquisition, analysis, or interpretation; intellectual content development or critical review; and final version approval), Silvia Marchesi (data acquisition, analysis, or interpretation; intellectual content development or critical review; and final version approval), Mario Occhipinti (intellectual content development, or critical review; final version approval; and integrity), Paolo Andrea Zucali (intellectual content development, or critical review; final version approval; and integrity), Laura Evangelista (conception or design; data acquisition, analysis, or interpretation; intellectual content development or critical review; final version approval; and integrity)., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

As the incidence of Alzheimer's disease (AD) continues to rise, the need for an effective PET radiotracer to facilitate early diagnosis has become more pressing than ever before in modern medicine. Phosphodiesterase (PDE) is closely related to cognitive impairment and neuroinflammatory processes in AD. Current research progress shows that specific PDE4D inhibitors radioligands can bind specifically to the PDE4D enzyme in the brain, thereby showing pathology-related signal enhancement in AD animal models, indicating the potential of these ligands as effective radiotracers. At the same time, we need to pay attention to the important role computer aided drug design (CADD) plays in advancing AD drug design and PET imaging. Future research will verify the potential of these ligands in clinical applications through computer simulation techniques, providing patients with timely intervention and treatment, which is of great significance., 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., (Copyright © 2024. Published by Elsevier Ltd.)

The non-specificity of 18 F-FDG, coupled with high false-positive rates in pancreatitis, underscores an unmet clinical need for using specific positron emission tomography (PET) radiopharmaceuticals in noninvasive pancreatic cancer detection. ST14, a trypsin-like protease and a member of the type II transmembrane serine protease family, is overexpressed in various solid malignancies, including pancreatic cancer. This study aimed to develop a 68 Ga-labeled PET radiopharmaceutical targeting ST14 for pancreatic cancer detection. A precursor ST14-06 was designed, and molecular docking was employed to preliminarily predict the binding mode. ST14-06 emerged as the preferred precursor with experimental inhibition assays confirming its high affinity for ST14 (IC 50  = 1.06 ± 0.08 nM). 68 Ga-ST14-06 was successfully synthesized with high radiochemical purity (RCP, >95 %) and molar activity (25-30 GBq/μmol) and was stable in saline and serum. In vitro studies demonstrated specific binding of the tracer to ST14-positive AsPC-1 cells compared to the blocking group (11.45 ± 0.12 % vs. 2.48 ± 0.34 %, P < 0.01). PET/CT imaging in AsPC-1 tumor-bearing mice confirmed ST14-specific uptake, which was reduced by co-administration of an excess blocking agent. Biodistribution studies revealed higher distribution in AsPC-1 tumors (0.99 ± 0.08 %ID/g) than in PANC-1 tumors (0.32 ± 0.02 %ID/g) and the blocking group (0.32 ± 0.04 %ID/g) at 1 h post-injection. Immunohistochemistry results showed that ST14 was highly positive in AsPC-1 tumors, but was negative in PANC-1 tumors. These preliminary findings suggest that 68 Ga-ST14-06 has potential as a first-generation PET radiopharmaceutical for ST14-specific imaging, offering a promising tool for pancreatic cancer detection., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The role of radiotherapy in the treatment of lymphoma is rapidly evolving. The development of modern systemic therapies and the adoption of FDG-PET-scanning as metabolic prognosticators are leading to a process of refinement of the treatment regimens. In this scenario, radiotherapy utilization is decreasing in several settings, including lower risk patients, to prevent the risk of long-term complications. Over the last decade, the most relevant changes in the treatment landscape are evident for advanced stage Hodgkin lymphoma and diffuse large B cell lymphoma. The main purpose of this paper is to review radiotherapy indications in these settings, to highlight pros and cons of a PET-guided strategy for radiotherapy recommendations, and to introduce future perspectives on the combination of radiotherapy and modern systemic therapies in both frontline and relapsed setting of advanced stage Hodgkin and diffuse large B cell lymphomas., Competing Interests: Conflict of interest Both authors declare that they do not have any conflict of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate neuroinflammation in Parkinson's disease (PD) with [ 11 C]PBR28 positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers, and the relationship to dopaminergic functioning measured with 6-[ 18 F]-fluoro-L-dopa ([ 18 F]FDOPA) PET., Methods: The clinical cohort consisted of 20 subjects with PD and 51 healthy controls (HC). All HC and 15 PD participants underwent [ 11 C]PBR28 High Resolution Research Tomograph (HRRT) PET for the quantitative assessment of cerebral binding to the translocator protein (TSPO), a neuroinflammation marker. CSF samples were available from 17 subjects with PD and 21 HC and were examined for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), neurogranin (NG), alpha-synuclein (aSyn) and oligo-alpha-synuclein. All subjects with PD underwent [ 18 F]FDOPA HRRT PET., Results: While the subjects with PD and HC did not differ in the total volume of distribution (V T ) of [ 11 C]PBR28 in any studied brain regions, higher levels of neuroinflammation and neurodegeneration CSF biomarkers sTREM2 and NG, respectively were associated with more severe motor symptoms evaluated by The Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) (r = 0.52, p = 0.041 and r = 0.59, p = 0.016 respectively). Additionally, in the PD group increased [ 11 C]PBR28 V T in the basal ganglia and substantia nigra (SN) was related to higher levels of neuroinflammation biomarker YKL-40 (p < 0.01)., Conclusion: Associations between CSF biomarkers, motor disability and [ 11 C]PBR28 V T in the striatum and SN may support a role for neuroinflammation in PD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Haidar Al-Abdulrasul reports financial support was provided by Finnish Parkinson Foundation. Riikka Ajalin reports financial support was provided by Finnish Parkinson Foundation. Anna Bruck reports financial support was provided by Finnish Parkinson Foundation. Haidar Al-Abdulrasul reports financial support was provided by Helsinki University research funds. Anna Bruck reports financial support was provided by Finnish State Research Funding (VTR). Henrik Zetterberg reports a relationship with Swedish Research Council (2018 02532) that includes: funding grants. Henrik Zetterberg reports a relationship with The European Research Council (681 712) that includes: funding grants. Henrik Zetterberg reports a relationship with Swedish State Support for Clinical Research (ALFGBG 720931) that includes: funding grants. Henrik Zetterberg reports a relationship with the Alzheimer Drug Discovery Foundation (ADDF), USA (201 809 2016862) that includes: funding grants. Henrik Zetterberg reports a relationship with The AD Strategic Fund and the Alzheimer's Association (ADSF 21 831376C, ADSF 21 831381 C and ADSF 21 831377 C) that includes: funding grants. Henrik Zetterberg reports a relationship with the Olav Thon Foundation that includes: funding grants. Henrik Zetterberg reports a relationship with The Erling-Persson Family Foundation that includes: funding grants. Henrik Zetterberg reports a relationship with Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (FO2019 0228) that includes: funding grants. Henrik Zetterberg reports a relationship with The European Union's Horizon 2020 research and innovation programme under the Marie Sktodowska Curie grant agreement No 860197 (MIRIADE) that includes: funding grants. Henrik Zetterberg reports a relationship with European Union Joint Program for Neurodegenerative Disorders (JPND2021 00694) that includes: funding grants. Henrik Zetterberg reports a relationship with the UK Dementia Research Institute at UCL that includes: funding grants. Kaj Blennow reports a relationship with Swedish Research Council (2017 00915) that includes: funding grants. Kaj Blennow reports a relationship with the Alzheimer Drug Discovery Foundation (ADDF), USA (RDAPB 201809 2016615) that includes: funding grants. Kaj Blennow reports a relationship with the Swedish Alzheimer Foundation (AF 742 881) that includes: funding grants. Kaj Blennow reports a relationship with Hjärnfonden, Sweden (FO2017 0243) that includes: funding grants. Kaj Blennow reports a relationship with the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (ALFGBG 715986) that includes: funding grants. Kaj Blennow reports a relationship with European Union Joint Program for Neurodegenerative Disorders (JPND2019 466 236) that includes: funding grants. Kaj Blennow reports a relationship with The Alzheimer's Association 2021 Zenith Award (ZEN 21 848495). that includes: funding grants. Laura Ekblad reports a relationship with Emil Aaltonen Foundation that includes: funding grants. Juha Rinne reports a relationship with Academy of Finland research grants (310 962) that includes: funding grants. Juha Rinne reports a relationship with the Sigrid Juselius Foundation that includes: funding grants. Juha Rinne reports a relationship with Finnish State Research Funding (VTR) that includes: funding grants. Henrik Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). Kaj Blennow has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). Juha Rinne serves as a consultant neurologist for Clincal Research Services Turku (CRST) and as a member of data monitoring board (Lundbeck) and global expert panel (Novo Nordisk). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Multiple sclerosis (MS) is divided into Relapsing-Remitting (RRMS) and Progressive (PMS) phenotypes, both associated with spinal cord (SC) damage. MS-related disability and SC atrophy are not yet fully understood and can differ across phenotypes. A combined approach using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) could provide a broader understanding of myelin changes in the cervical SC (CSC) in different MS phenotypes and the associations with disability., Objectives: To evaluate CSC myelin content using a PET-MRI with [ 11 C]PIB and its association with disability in PMS and RRMS compared to healthy volunteers (HV)., Methods: [ 11 C]PIB PET images and T1-MRI of 49 patients with MS and 19 HV were evaluated at C1-C2, C3, and C4 vertebrae levels. [ 11 C]PIB uptake and volume were compared between groups., Results: [ 11 C]PIB uptake was significantly lower at C1-C4, C1-C2, and C3 segments when comparing PMS to RRMS and HV. [ 11 C]PIB uptake inversely correlated with overall disability in all CSC segments in all patients with MS, and in the RRMS phenotype separately., Conclusions: Our findings suggest an association between [ 11 C]PIB CSC uptake and overall disability score measured by EDSS. MRI and PET can be used as complementary methods for studying MS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniele de Paula Faria reports financial support was provided by Sao Paulo University Faculty of Medicine. Daniele de Paula Faria reports a relationship with State of Sao Paulo Research Foundation that includes: funding grants. Daniele de Paula Faria reports a relationship with National Council for Scientific and Technological Development that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The cynomolgus monkey has emerged as a predominant nonhuman primate model in neuroscience research. A comprehensive grasp of the growth and development patterns in the cynomolgus monkey brain is crucial for the judicious utilization of this species in neuroscience investigations. This project involved the collection of brain [ 18 F]FDG PET-MRI data from 228 healthy cynomolgus monkeys spanning the age range of 0.5-29.5 years to construct an age-specific multimodal image brain template toolset tailored to cynomolgus monkeys. Their brain volume and glucose metabolism were quantitatively analyzed by utilizing an individualized spatial segmentation algorithm. Our findings encapsulated the growth and development trends, sex differences, and asymmetrical variations in brain volume and glucose metabolism in cynomolgus monkeys, and analyzed the correlation between the brain volume and glucose metabolism. This endeavor enhances our capacity to leverage the cynomolgus monkey model in neuroscience research by providing a valuable resource for researchers. The age-specific brain template toolset and associated data offer a robust foundation for future investigations, facilitating a nuanced understanding of brain development in this primate species and, consequently, informing and advancing neuroscience research employing cynomolgus monkeys., 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Multimodal neuroimaging data, including magnetic resonance imaging (MRI) and positron emission tomography (PET), provides complementary information about the brain that can aid in Alzheimer's disease (AD) diagnosis. However, most existing deep learning methods still rely on patch-based extraction from neuroimaging data, which typically yields suboptimal performance due to its isolation from the subsequent network and does not effectively capture the varying scales of structural changes in the cerebrum. Moreover, these methods often simply concatenate multimodal data, ignoring the interactions between them that can highlight discriminative regions and thereby improve the diagnosis of AD. To tackle these issues, we develop a multimodal and multi-scale deep learning model that effectively leverages the interaction between the multimodal and multiscale of the neuroimaging data. First, we employ a convolutional neural network to embed each scale of the multimodal images. Second, we propose multimodal scale fusion mechanisms that utilize both multi-head self-attention and multi-head cross-attention, which capture global relations among the embedded features and weigh each modality's contribution to another, and hence enhancing feature extraction and interaction between each scale of MRI and PET images. Third, we introduce a cross-modality fusion module that includes a multi-head cross-attention to fuse MRI and PET data at different scales and promote global features from the previous attention layers. Finally, all the features from every scale are fused to discriminate between the different stages of AD. We evaluated our proposed method on the ADNI dataset, and the results show that our model achieves better performance than the state-of-the-art methods., 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To summarise existing literature examining amino acid positron emission tomography (AA-PET) for radiotherapy target volume delineation in patients with gliomas., Methods: Systematic search of MEDLINE and EMBASE databases., Results: Twenty studies met inclusion criteria. Studies comparing MRI- and AA-PET- derived target volumes consistently found these to be complementary. Across studies, AA-PET was a strong predictor of the site of subsequent relapse. In studies examining AA-PET-guided radiotherapy at standard doses, including one study using reduced margins, survival outcomes were similar to historical cohorts whose volumes were generated using MRI alone. Four prospective single-arm trials examining AA-PET-guided dose-escalated radiotherapy reported mixed results. The two trials that used both a higher biologically-effective dose and boost-volumes defined using both MRI and AA-PET reported promising outcomes., Conclusion: AA-PET is a promising complementary tool to MRI for radiotherapy target volume delineation, with potential benefits requiring further validation including margin reduction and facilitation of dose-escalation., 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Positron emission tomography (PET) is a highly sensitive, quantitative imaging technique that can track sub-nanomolar quantities of positron-emitting radionuclides throughout the body. By incorporating such radionuclides into molecules of interest, we can directly assess their pharmacokinetic and pharmacodynamic (PK/PD) characteristics in vivo without changing their physicochemical characteristics or eliciting a pharmacological response. As such, PET imaging has long been used as a tool to aid drug discovery programs from preclinical biomarker validation all the way through to clinical trials. In this perspective we discuss the use of PET radioligands in central nervous system (CNS) drug discovery and development, with a focus on recent applications in psychiatry (e.g. 5-HT 2 A, 11β-HSD1), neuro-oncology (e.g. KRAS G12C , ATM, ALK2), and neurodegeneration (e.g. amyloid beta plaques, MAPK p38), while exploring the intricacies associated with developing novel radiotracers for CNS targets. Examples highlight the preclinical and clinical uses of PET for studying biomarker function, drug candidate PK/PD, target occupancy/engagement, dosing regimen determination, clinical trial patient selection, and quantifying biomarker changes in response to treatments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Neil Vasdev reports financial support was provided by Azrieli Foundation and the Canada Research Chairs Program. Melissa Chasse reports financial support was provided by Canadian Institutes of Health Research for a Canada Graduate Scholarships. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The histone deacetylase 6 (HDAC6) is closely related to the pathogenesis of depression in epigenetic regulation. However, it remains unclear how HDAC6 expression changes in depression pathophysiology and whether it is a target for antidepressant treatment. Herein, we investigate the expression change of HDAC6 in major depressive disorder (MDD) and evaluate the efficacy of a novel HDAC6 inhibitor, PB200, using positron emission tomography (PET) imaging. PET imaging studies with an HDAC6 PET probe [ 18 F]Bavarostat allied with in vitro experiments demonstrated significantly increased HDAC6 expression in the brains of MDD mice. To investigate if pharmacological inhibition of HDAC6 can exert antidepressant effects, a series of naphthyridine-based HDAC6 inhibitors were designed and synthesized, among which PB200 demonstrated high selectivity and inhibitory activity against HDAC6, favorable metabolic stability, and excellent brain uptake. Moreover, PB200 exhibited significant antidepressant effects by restoring abnormal HDAC6 expression level and alleviating neuroinflammation. These results imply that targeting HDAC6 shows promise as a therapeutic strategy for depression, and PB200 is a potential therapeutic option for treating MDD., 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., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The serotonergic system has shown to be altered during epileptogenesis and in chronic epilepsy, making selective serotonin reuptake inhibitors interesting candidates for antiepileptogenic therapy. In this study, we aimed to evaluate disease-modifying effects of fluoxetine during experimental epileptogenesis. Status epilepticus (SE) was induced by lithium-pilocarpine, and female rats were treated either with vehicle or fluoxetine over 15 days. Animals were subjected to 18 F-FDG (7 days post-SE), 18 F-GE180 (15 days post-SE) and 18 F-flumazenil positron emission tomography (PET, 21 days post-SE). Uptake ( 18 F-FDG), volume of distribution ( 18 F-GE180) and binding potential ( 18 F-flumazenil) were calculated. In addition, hyperexcitability testing and video-EEG monitoring were performed. Fluoxetine treatment did not alter brain glucose metabolism. 18 F-GE180 PET indicated lower neuroinflammation in the hippocampus of treated animals (-22.6%, p = 0.042), but no differences were found in GABA A receptor density. Video-EEG monitoring did not reveal a treatment effect on seizure frequency. However, independently of the treatment, hippocampal FDG uptake 7 days after SE correlated with seizure frequency during the chronic phase (r = -0.58; p = 0.015). Fluoxetine treatment exerted anti-inflammatory effects in rats during epileptogenesis. However, this effect did not alter disease outcome. Importantly, FDG-PET in early epileptogenesis showed biomarker potential as higher glucose metabolism correlated to lower seizure frequency in the chronic phase., 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Imaging of type 1 metabotropic glutamate receptor (mGluR1), which is predominantly expressed in Purkinje cells, is currently possible using positron emission tomography (PET). We have previously shown that cerebellar mGluR1 availability decreases in patients with cerebellar ataxia and that the degree of ataxia is related to the magnitude of cerebellar mGluR1 availability. This study presents the longitudinal changes in cerebellar mGluR1 availability after an interval of years in patients with spinocerebellar ataxia type 6 (SCA6)., Methods: Three patients with SCA6 underwent baseline and follow-up mGluR1 PET and magnetic resonance imaging (MRI) at intervals of 2-6 years. The volume-of-interest was placed on the cerebellum. The binding potential (BP ND ) was calculated to estimate the mGluR1 availability using a simplified reference tissue model. Cerebellar volume was measured using MRI. The degree of ataxia was scored with the Scale for the Assessment and Rating of Ataxia (SARA)., Results: The cerebellar BP ND values, cerebellar volume, and SARA scores changed by 2.73-7.49 %, 0.60-1.75 %, and 0.5-3, respectively, from baseline to follow-up assessments. The rates of reduction in cerebellar mGluR1 availability were higher than those in cerebellar volume., Conclusions: This study shows that cerebellar mGluR1 availability decreases with disease progression in SCA6, and that mGluR1 imaging is likely superior to MRI in identifying small changes in the cerebellum. Therefore, mGluR1 imaging can be used as a specific biomarker for monitoring cerebellar function., 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a promising target for the diagnosis and treatment of various diseases, especially neurodegenerative disorders. Developing PET imaging probes targeting RIPK1 is beneficial for visualizing the connections between RIPK1 and diseases, as well as for related drug development. In this study, we report the design and synthesis of a series of novel RIPK1 inhibitors. Three potent inhibitors, 7i, 7k, and 8a, with good cell anti-necroptosis potency and physicochemical properties, were identified and selected for PET imaging probe development. Subsequently, three PET imaging radioligands ([ 11 C]7k, [ 18 F]7i, and [ 18 F]8a) were successfully synthesized. In mouse PET imaging studies, all three radioligands showed good brain uptake. Among them, probe [ 18 F]8a exhibited good binding specificity in both in vitro autoradiography and in vivo PET imaging studies. Additionally, [ 18 F]8a demonstrated good in vivo metabolic stability. This work highlights the potential of probe [ 18 F]8a for imaging brain RIPK1 in live animals, laying the groundwork for the future development of RIPK1 PET radioligands., 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., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)