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We report on the development of the first-ever inorganic radiation-hard moisture-insensitive large volume spectroscopic semiconductor-based scintillator with less than 2 ns decay time and light yields as high as 8000 ph/MeV. Despite extensive research into scintillator materials, the quest for an ideal scintillator combining ultrafast decay times (akin to BaF2 and Yb-doped scintillators such as Lu2O3:Yb), high light yields (exceeding 2000 photons per MeV), spectroscopic capabilities, and exceptional radiation hardness remain unfulfilled. In this study, we demonstrate and report for the first time the viability of large-volume (up to 20 mm thickness) gallium oxide (β-Ga2O3) semiconductor-based scintillators for applications requiring these properties. These β-Ga2O3 scintillators were grown using the fast turnaround (∼2 days) crucible-free optical float zone (FZ) technique. The high light yield and ultrafast decay time of these high-purity n-type semiconductors with free carrier concentration of 6 × 1017 cm−3 are attributed to native defects, specifically oxygen vacancies (VO) and gallium–oxygen vacancy pairs (VGa–VO), generated during optimized FZ growth. The ultrafast decay, along with high light yield, enables excellent timing resolution and high count rate detection for applications like time-of-flight positron emission tomography, physics experiments, and nuclear safety. The radiation hardness of these devices has been documented in a separate publication. [ABSTRACT FROM AUTHOR]

Radiation treatment plays a mainstream role in the management of head and necksquamous cell carcinomas (HNSCCs). Adverse effects from radiation therapy include osteoradionecrosis of the jaw, and rarely, pathologic fracture. Immune checkpoint inhibitors (ICI) such as pembrolizumab are of growing relevance to the management of metastatic and recurrent HNSCCs. Adverse impacts on bone secondary to medications such as pembrolizumab and nivolumab have been sporadically documented in the literature. The objective of this manuscript is to raise awareness of possible increase in risk for adverse jaw outcomes in patients with HNSCCs exposed to both radiation treatment to the jaws and ICI therapy. This manuscript documents adverse jaw outcomes including osteonecrosis and pathologic fracture of the mandible in two patients receiving pembrolizumab for management of HNSCC who had received prior radiation treatment. A potential link between immunotherapy and adverse jaw outcomes is consistent with the growing understanding of osteoimmunology, investigating the closely interrelated processes in bone remodeling and immune system function, in health and disease. It is important to ascertain if pembrolizumab poses an incremental risk for such outcomes, beyond the risk from prior radiation, for patients managed with radiation treatment and ICI therapy for HNSCC. The general dental practitioner may encoun-tersuch patients either in the context of facilitating dental clearance prior to initiation of chemotherapy, or rarely, with poorly explained jaw symptoms and must be alert to the possibility of occurrence of such adverse jaw events to facilitate timely diagnosis and optimal patient management. [ABSTRACT FROM AUTHOR]

Cd2+ cation doped CsPbCl3 single crystals were synthesized, and their luminescent properties were investigated under excitation with synchrotron radiation quanta with energy greater than Eg and at a sample temperature of 12 K. Pure single crystals exhibit a narrow band of exciton emission at 416.7 nm. Doping the single crystals leads to a high-energy shift of the excitonic luminescence, the appearance of new luminescent bands, the broadening of the luminescent bands, an increase in the decay time constants, and a significant enhancement of the luminescence intensity. The observed changes in luminescent parameters upon doping are discussed in terms of the crystal structure ordering, a decrease in the number of defects responsible for capturing charge carriers at the stage of electronic excitation thermalization, and a decrease in defects that quench excitonic luminescence. Doped single crystals with decay times of the order of 0.4 ns and intensities that significantly exceed the intensity of pure single crystals can be promising scintillation materials for positron emission tomography in the time-of-flight mode. [ABSTRACT FROM AUTHOR]

Objective. Penalty parameters in penalized likelihood positron emission tomography (PET) reconstruction are typically determined empirically. The cross-validation log-likelihood (CVLL) method has been introduced to optimize these parameters by maximizing a CVLL function, which assesses the likelihood of reconstructed images using one subset of a list-mode dataset based on another subset. This study aims to validate the efficacy of the CVLL method in whole-body imaging for cancer patients using a conventional clinical PET scanner. Approach. Fifteen lung cancer patients were injected with 243.7 ± 23.8 MBq of [18F]FDG and underwent a 22 min PET scan on a Biograph mCT PET/CT scanner, starting at 60 ± 5 min post-injection. The PET list-mode data were partitioned by subsampling without replacement, with 20 minutes of data for image reconstruction using an in-house ordered subset expectation maximization algorithm and the remaining 2 minutes of data for cross-validation. Two penalty parameters, penalty strength β and Fair penalty function parameter δ, were subjected to optimization. Whole-body images were reconstructed, and CVLL values were computed across various penalty parameter combinations. The optimal image corresponding to the maximum CVLL value was selected by a grid search for each patient. Main results. The δ value required to maximize the CVLL value was notably small (⩽10−6 in this study). The influences of voxel size and scan duration on image optimization were investigated. A correlation analysis revealed a significant inverse relationship between optimal β and scan count level, with a correlation coefficient of −0.68 (p -value = 3.5 × 10−5). The optimal images selected by the CVLL method were compared with those chosen by two radiologists based on their diagnostic preferences. Differences were observed in the selection of optimal images. Significance. This study demonstrates the feasibility of incorporating the CVLL method into routine imaging protocols, potentially allowing for a wide range of combinations of injected radioactivity amounts and scan durations in modern PET imaging. [ABSTRACT FROM AUTHOR]

Background: Cardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR). Results: Twenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p < 0.001). A systematic underestimation (bias) was found for PET (RegVol: 15O-water − 11 ± 13 mL, p = 0.002, 11C-acetate − 28 ± 16 mL, p < 0.001 and RegF: 15O-water − 4 ± 6%, p = 0.01, 11C-acetate − 10 ± 7%, p < 0.001). PET measurements in patients were compared to healthy volunteers (n = 18). Mean RegVol and RegF was significantly lower in healthy volunteers compared to patients for both tracers. The accuracy of diagnosing moderately elevated regurgitant volume (> 30mL) was 95% for 15O-water and 92% for 11C-acetate. Conclusions: LV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers. [ABSTRACT FROM AUTHOR]

Introduction: Biology-guided radiotherapy (BgRT) is a novel radiation delivery approach utilizing fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) imaging performed in real-time to track and direct RT. Our institution recently acquired the RefleXion X1 BgRT system and sought to assess the feasibility of targeting metastatic sites in various organs, including the liver. However, in order for BgRT to function appropriate, adequate contrast in FDG activity between the tumor and the background tissue, referred to as the normalized SUV (NSUV), is necessary for optimal functioning of BgRT. Methods: We reviewed the charts of 50 lung adenocarcinoma patients with liver metastases. The following variables were collected: SUVmax and SUVmean for each liver metastasis, SUVmean and SUVmax at 5 and 10 mm radially from the lesion, and NSUV at 5 mm and 10 mm (SUVmax of the liver metastasis divided by SUV mean at 5 mm at 10 mm respectively). Results: 82 measurable liver metastases were included in the final analysis. The average SUVbackground of liver was 2.26 (95% confidence interval [CI] 2.17–2.35); average SUVmean for liver metastases was 5.31 (95% CI 4.87–5.75), and average SUVmax of liver metastases was 9.19 (95% CI 7.59–10.78). The average SUVmean at 5 mm and 10 mm radially from each lesion were 3.08 (95% CI 3.00-2.16) and 2.60 (95% CI 2.52–2.68), respectively. The mean NSUV at 5 mm and 10 mm were 3.13 (95% CI 2.53–3.73) and 3.69 (95% CI 3.00-4.41) respectively. Furthermore, 90% of lesions had NSUV greater than 1.45 at 5 mm and greater than 1.77 at 10 mm. Conclusions: This is the first study to comprehensively characterize FDG contrast between the liver tumor and background, referred to as NSUV. Due to the high background SUV normally found in the liver, this work will be valuable for guiding optimization of BgRT for treating liver metastases in the future using the RefleXion® X1 and potentially other similar BgRT platforms. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Radiolabeling is critical in complex chemical reactions involving positron emission tomography (PET) radiotracer production. The process is now automated within a synthesis module to enhance efficiency and reduce radiation exposure. The key to this automation is the use of radiation detectors to monitor radioactivity transfer and ensure the progression of reactions. However, the high cost of these detectors has motivated the need for a more affordable alternative.This study aimed to develop a compact and cost‐efficient detector using scintillating fibers and silicon photomultipliers (SiPMs) to track radioactivity throughout PET radiotracer production.Monte Carlo simulations were performed with the Geant4‐based M‐TAG software for four detector geometries (single fiber, single fiber with bolus, 16‐fiber bundle, and spiral) to optimize the detector construction for better detection efficiency. The simulations scored the energy deposited into the scintillating fibers per simulated particle, which was used to estimate the expected voltage pulse height from the SiPM considering the total light collection efficiency. Based on the simulation results, two detector configurations (16‐fiber bundle and spiral fiber) were constructed using plastic scintillating fibers, optical fibers, a 6 mm ×$\times$ 6 mm SiPM, and commonly available electronic components. The detectors were calibrated using a Fluorine‐18 (18F$^{18}{\rm F}$) source with typical activity levels used in radiotracer production. Detector performances were subsequently evaluated through linearity tests and measurement uncertainty assessments. Errors up to ±5%$\pm 5\%$ were considered acceptable for troubleshooting purposes.The calibration curves showed a linear response with changing activity for both detectors. The calibrated detectors offered real‐time activity measurements ranging from 0.10 to 49.41 GBq, with a 3‐s refresh rate. In the activity range above 0.145 GBq, the uncertainties were less than 5%$5\%$ for both the 16‐fiber and spiral configurations. The spiral detector recorded a signal with a half‐life of 105.88±0.40$105.88 \pm 0.40$ min, closely aligning with the reference half‐life of 18F$^{18}{\rm F}$.Cost‐efficient plastic scintillation fiber detectors were developed to facilitate the troubleshooting of automated synthesis of PET radiotracers. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Positron emission tomography (PET) response criteria in solid tumours (PERCIST 1.0) is a systematic assessment of therapy response with fluorine 18 fluorodeoxyglucose ([18F]FDG) PET. The ordered subset expectation maximization (OSEM) and block sequential regularized expectation maximization (BSREM) reconstruction algorithms are both commonly used. The impact of using OSEM or BSREM on PERCIST 1.0 is not fully determined. This study aimed to compare treatment response evaluation between the reconstructions OSEM and BSREM according to PERCIST 1.0.The highest peak standardized uptake value corrected for lean body mass (SULpeak) in a lesion were measured in PET‐CT scans from 90 patients with metastatic breast cancer or malignant melanoma, who had undergone two [18F]FDG PET with computer tomography (CT) scans for treatment evaluation purpose. SUL measurements in the reference organ were also calculated. All scans were reconstructed with OSEM and BSREM. Bland Altman plots and Spearman correlation coefficient were used for comparing measurements obtained from OSEM and BSREM images. Patients were categorized as a complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD).The mean standard deviation (SD) of SULmean in the reference organ was slightly lower for BSREM images, resulting in a slightly lower threshold. Lesion SULpeak was slightly higher for BSREM images compared with OSEM images. Only 5 out of 90 patients had different response evaluations for the different reconstructions.PERCIST 1.0 serves as a robust response evaluation criterion and is only marginally dependent on the reconstruction used. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Superior outcomes have been obtained for neoadjuvant treatment with immune checkpoint inhibitors (ICI) plus chemotherapy over neoadjuvant chemotherapy alone, especially in patients with high programmed cell death ligand 1 (PD‐L1) expression. However, it is not always possible to obtain sufficient tumor specimens for biomarker testing before surgery. In this study, we explored clinical factors that can predict high PD‐L1 expression.We retrospectively enrolled 340 lung cancer patients who received pulmonary resection between 2014 and 2023 and who had PD‐L1 expression data. Chi‐squared tests and logistic regression analyses were used to identify clinical factors associated with high PD‐L1 status.Univariable and multivariable analyses revealed that smoking, high maximum standardized uptake value (SUVmax) of 18F‐fluorodeoxyglucose positron emission computed tomography (18F‐FDG PET/CT), and high plasma fibrinogen are independent predictors of high PD‐L1 expression. A predictive score for high PD‐L1 expression (ranging from 0 to 3) was developed based on these parameters. Notably, only 5% of patients with a score of 0 exhibited high PD‐L1 expression, whereas this proportion increased to 53% for patients with a score of 3.These results showed that plasma fibrinogen, smoking history, and SUVmax are predictors of high PD‐L1 expression, providing a basis for identifying patients expected to benefit from neoadjuvant ICI treatment. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Modern PET reconstruction algorithms incorporate point‐spread‐function (PSF) correction to mitigate partial volume effect. However, PSF correction can introduce edge artifacts that lead to quantification errors. Consequently, current international guidelines advise against using PSF correction in brain PET reconstruction.We aimed to investigate PSF‐induced quantification errors in recent digital PET systems and identify conditions that mitigate them. This study utilized brain PET imaging with alginate‐based realistic phantoms, simulating lesion‐to‐background activity ratios of 10:1 and 2:1, with eleven reconstruction parameter sets.Phantoms were prepared using a commercial anthropomorphic head phantom and two homemade inserts. Each insert contained a homogeneous 18F‐FDG alginate background with hot spheres of varying diameter (3, 4, 6, 8, 10, 12, and 15 mm). PET imaging was conducted on a digital PET‐CT system Biograph Vision 600 (Siemens), with a 10 min scan duration. Imaging was performed with and without PSF correction, with 2, 4, 6, 12, 18, or 24 iterations in reconstruction, and with or without additional Gaussian postfiltering. We assessed the recovery coefficient (RC), contrast recovery coefficient (CRC), variability, and CRC‐to‐variability ratios for each sphere size and reconstruction parameter set.PSF‐corrected images of the 10:1 spheres exhibited a nonmonotonic CRC‐to‐sphere diameter relationship due to edge artifacts overshoot in the 10 mm‐diameter sphere. In contrast, PSF images of the 2:1 spheres showed a monotonically increasing relationship. Non‐PSF images of both phantoms showed an expected monotonically increasing CRC‐to‐sphere diameter relationship but with lower CRC values compared to PSF images. The nonmonotonic relationship observed with 10:1 spheres was mitigated by applying a 3‐mm FWHM Gaussian postfiltering. For both phantoms, reconstructions with 6 iterations, PSF correction, and additional 3‐mm FWHM Gaussian postfiltering demonstrated the highest CRC‐to‐variability ratios.Our findings indicate that Gaussian postfiltering suppresses PSF artifacts. This parameter set corrected the nonmonotonic CRC‐to‐sphere diameter relationship and improved the CRC‐to‐variability ratio compared to non‐PSF reconstructions. Therefore, to enhance lesion detectability without compromising quantification accuracy, PSF correction coupled with Gaussian postfiltering should be used in brain PET. [ABSTRACT FROM AUTHOR]

Background: Colonic metastasis from lung cancer is very rare and is typically associated with poor prognosis. Herein, we report the case of a patient who achieved intermediate-term survival using a multimodal treatment approach, including chemotherapy, immunotherapy, radiotherapy, and surgical resection for obstructive colonic metastasis from primary lung adenocarcinoma. Case presentation: A woman in her 50s presented with anemia and a positive fecal occult blood test. Computed tomography revealed a tumor in the right upper lobe of the lung with mediastinal lymphadenopathy and wall thickening in the transverse colon. Colonoscopy revealed a stricture involving 50% of the colonic lumen. Biopsy revealed a poorly differentiated adenocarcinoma positive for CK-7 and TTF-1, very focally positive for napsin A, and negative for CK-20 and CDX-2. Furthermore, positron emission tomography/CT (PET/CT) showed a high maximum standardized uptake value (SUVmax) of 8.2 in the iliac bone. Based on these findings, the patient was diagnosed with primary lung adenocarcinoma with simultaneous metastasis to the transverse colon and iliac bone (cT4N3M1c, cStage IVB). After receiving first-line chemotherapy with atezolizumab, pemetrexed, and carboplatin, the tumors shrank after 4 courses. Subsequently, the patient received maintenance therapy with atezolizumab and pemetrexed. However, the tumor enlarged after 10 courses. Second-line chemotherapy with docetaxel and ramucirumab (3 courses) failed to achieve tumor reduction. Colonoscopy revealed an impassable colonic tumor. Nineteen months after diagnosis, surgery was planned for imminent intestinal obstruction. We determined that the colonic tumor was resectable, because laparoscopic exploration revealed no other metastases. The tumor was resected by partial colectomy with ileocolonic anastomosis. The postoperative course was uneventful. Pathological examination revealed a resection margin that was negative for malignancy, and the histological type was consistent with metastatic lung adenocarcinoma. The patient then received nab-paclitaxel therapy; however, she developed symptoms of superior vena cava syndrome after 3 courses. The patient received palliative irradiation (30 Gy/10 fr) followed by nivolumab. She soon developed a solitary brain metastasis, and stereotactic irradiation was planned. After 3 courses of nivolumab, the metastasis was reduced significantly, and stereotactic brain irradiation was canceled. The lung tumor and mediastinal lymphadenopathy gradually shrank, and the patient survived for 13 months after surgery without disease progression. Conclusions: In this case, surgical resection of colonic metastasis from primary lung adenocarcinoma may have contributed to the short-term prognosis as a bridge-to-next available multimodal treatment. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is a heterogeneous disease comprising various molecular subtypes, including Luminal A, Luminal B, human epidermal growth factor receptor-2 (HER2) positive, and triple negative types, each with distinct biological characteristics and behaviors. Triple negative breast cancer (TNBC) remains a particularly challenging subtype worldwide. Our study aims to evaluate whether Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) parameters, clinical pathological features, and biochemical indicators serve as prognostic risk factors for TNBC. Additionally, we explore correlations between biochemical indicators and 18F-FDG PET/CT parameters. Methods: We conducted a retrospective analysis of 95 TNBC patients who underwent preoperative 18F-FDG PET/CT examinations at Tianjin Medical University Cancer Institute and Hospital from 2013 to 2018. Collected data included 18F-FDG PET/CT parameters, clinical and pathological features, and biochemical indicators. We used Kaplan-Meier survival analysis and multivariate Cox regression analysis to evaluate associations between 18F-FDG PET/CT parameters/biochemical indicators and disease free survival (DFS)/overall survival (OS). The log-rank test determined significant differences in survival curves, and the Spearman correlation coefficient analyzed correlations between quantitative variables. Visualization and analysis were performed using R packages. Results: Among 95 TNBC patients, mean standardized uptake value (SUVmean) was significantly correlated with DFS. Fasting blood glucose (FBG), a-L-fucosylase (AFU) and Creatine kinase (CK) were independent predictors of DFS, while Precursor albumin (PALB) and CK were independent predictors of OS. FBG showed correlations with SUVpeak and SUVmean, and CK was correlated with peak standardized uptake value (SUVpeak). Our results indicated that 18F-FDG PET/CT parameters and biochemical indicators may constitute a new prognostic model for TNBC patients post-surgery. Discussion: We found that SUVmean, FBG, AFU and CK are predictive factors for DFS in TNBC patients post-surgery, while PALB and CK are predictive factors for OS, which prompts us to pay more attention to these indicators in clinical practice. Also 18F-FDG PET/CT parameters and biochemical indicators have potential utility in constituting a new prognostic model for TNBC patients postsurgery. [ABSTRACT FROM AUTHOR]

Background: Appropriate staging of lung cancer is of paramount importance, as it customizes treatment and predicts prognosis. Both Fludeoxyglucose-18 (FDG) positron emission tomography (PET) combined with contrast computed tomography (CT) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are two widely used diagnostic modalities in the field of staging & diagnosis of lung malignancies, the former depends on image analysis while the later enables real-time sampling of lymph nodes under sonographic guidance. Objective: To compare the diagnostic and staging accuracy of convex probe EBUS-TBNA versus FDG – PET/CT as two modalities in diagnosis & mediastinal staging of lung cancer patients. Methods: This prospective, observational (daignostic accuracy) research was performed on 40 cases with lung malignancies. All cases were examined via FDG-PET/CT followed by convex probe EBUS-TBNA for diagnosis & staging of concurrent mediastinal lymphadenopathy (MLN). Results: The diagnostic yield of EBUS-TBNA reached 92.5% (37/40) compared to 70% (28/40) for FDG-PET/CT. There was poor agreement between EBUS-TBNA & FDG-PET/CT regarding (MLN) staging (k = 0.043), in 16/40 patients (40%), EBUS MLN staging matched that of FDG-PET/CT, while in 24/40(60%) there were discrepancies between the two diagnostic modalities; 18/40(45%) were up-staged after EBUS while 6/40(15%) were down staged after EBUS. In addition, EBUS-TBNA confirmed occult mediastinal nodal involvement in 9/10 FDG-PET/CT negative scans (N0). The overall diagnostic accuracy of EBUS-TBNA was significantly greater than FDG-PET/CT in staging of lung cancer (97.37% & 70% respectively, p < 0.001). Conclusion: EBUS-TBNA is a minimally invasive procedure that we currently recommend as a first choice for MLN staging. Trial registration: ClinicalTrials.gov, NCT06479798. Registered 26 June 2024—Retrospectively registered, https://clinicaltrials.gov/study/NCT06479798. [ABSTRACT FROM AUTHOR]

Objective: We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). Methods: This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. Results: There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. Conclusion: ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients. [ABSTRACT FROM AUTHOR]

Background: A range of imaging modalities have reported Alzheimer's disease-related abnormalities in individuals experiencing subjective cognitive decline (SCD). However, there has been no consistent local abnormality identified across multiple neuroimaging modalities for SCD. Objective: We aimed to investigate the convergent local alterations in amyloid-β (Aβ) deposition, glucose metabolism, and resting-state functional MRI (RS-fMRI) metrics in SCD. Methods: Fifty SCD patients (66.4±5.7 years old, 19 men [38%]) and 15 normal controls (NC) (66.3±4.4 years old, 5 men [33.3%]) were scanned with both [18F]-florbetapir PET and [18F]-fluorodeoxyglucose PET, as well as simultaneous RS-fMRI from February 2018 to November 2018. Voxel-wise metrics were retrospectively analyzed, including Aβ deposition, glucose metabolism, amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality(DC). Results: The SCD group showed increased Aβ deposition and glucose metabolism (p < 0.05, corrected), as well as decreased ALFF, ReHo, and DC (p < 0.05, uncorrected) in the left dorsal precuneus (dPCu). Furthermore, the dPCu illustrated negative resting-state functional connectivity with the default mode network. Regarding global Aβ deposition positivity, the Aβ deposition in the left dPCu showed a gradient change, i.e., Aβ positive SCD > Aβ negative SCD > Aβ negative NC. Additionally, both Aβ positive SCD and Aβ negative SCD showed increased glucose metabolism and decreased RS-fMRI metrics in the dPCu. Conclusions: The dorsal precuneus, an area implicated in early AD, shows convergent neuroimaging alterations in SCD, and might be more related to other cognitive functions (e.g., unfocused attention) than episodic memory. [ABSTRACT FROM AUTHOR]

The role of torso computed tomography (CT) in evaluating body composition has been unexplored. This study assessed the potential of low-dose torso CT from positron emission tomography (PET)/CT for analyzing body composition and its relation to muscle strength. We retrospectively recruited 384 healthy Korean adults (231 men, 153 women) who underwent torso 18F-FDG PET/CT, bioelectrical impedance analysis (BIA), and muscle strength tests (handgrip strength [HGS] and knee extension strength [KES]). CT images were segmented into three compartments: torso volumetric, abdominal volumetric, and abdominal areal. Muscle amounts from each compartment were indexed to height (m2). BIA and HGS served as reference standards, with correlation coefficients (r) calculated. Torso muscle volumetric index (TorsoMVI) had the strongest correlations with BIA-derived values (r = 0.80 for men; r = 0.73 for women), surpassing those from the abdominal compartments. TorsoMVI was also correlated significantly with HGS (r = 0.39, p < 0.01) and differentiated between normal and possible sarcopenia in men (n = 225, 5960 ± 785 cm3/m2 vs. n = 6, 5210 ± 487 cm3/m2, p = 0.02). In women, KES correlated more strongly with muscle parameters than HGS. Despite gender-specific variations, torso CT-derived parameters show promise for evaluating body composition and sarcopenia. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMaterials and methodsResultsConclusionTo investigate the value and applicability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomics in differentiating primary lung cancer (PLC) from solitary lung metastasis (SLM) in patients with colorectal cancer (CRC).This retrospective study included 103 patients with CRC and solitary pulmonary nodules (SPNs). The least absolute shrinkage and selection operator (LASSO) was used to screen for optimal radiomics features and establish a PET/CT radiomics model. PET/CT Visual and complex models (combining radiomics with PET/CT visual features) were developed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to determine the predictive value and diagnostic efficiency of the models.The AUC of the PET/CT radiomics model for differentiating PLC from SLM was 0.872 (95% CI: 0.806–0.939), which was not different from that of the visual (0.829 [95% CI: 0.749–0.908; p = .352]). However, the AUC of the complex model (0.936 [95% CI:0.892–0.981]) was significantly higher than that of the PET/CT radiomics (p = .005) and visual model (p = .001). The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of PET/CT radiomics for differentiating PLC from SLM were 0.720, 0.887, 0.806, 0.857, and 0.770, respectively.PET/CT radiomics can effectively distinguish PLC and SLM in patients with CRC and SPNs and guide the implementation of personalized treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD. Positron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25). Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r ≥ 0.904, p ≤ 0.005) and attention (r ≥ 0.809, p ≤ 0.028). The modest sample size is the primary limitation. Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights. • Functional (fMRI) and molecular (PET) imaging performed in the same individuals with bipolar disorder (BD) and major depressive disorder (MDD). • Findings provide evidence of relationships between prefrontal mGlu5 and brain function during emotional processing that is unique to BD. • We propose a mechanism by which deficient prefrontal mGlu5 in BD contributes to alterations in clinically relevant brain function. • Understanding the role of mGlu5 in BD pathology could aid in the development of targeted, mechanistically informed treatments. [ABSTRACT FROM AUTHOR]

Medical therapy for aortic stenosis (AS) remains an elusive goal. This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (−5.27; 95% CI: −55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (−18.83; 95% CI: −32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108–163 vs 102 mm3; 95% CI: 75–129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (−1,325.6; 95% CI: −2,285.9 to −365.4; P = 0.008) and 10-mg groups (−1,582.2; 95% CI: −2,610.8 to −553.5; P = 0.0038) compared with the placebo group. This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883) [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor (CAR) T-cell therapy has attracted considerable attention since its recent endorsement by the Food and Drug Administration, as it has emerged as a promising immunotherapeutic modality within the landscape of oncology. This study explores the prognostic utility of [18F] Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in lymphoma patients undergoing CAR T-cell therapy. Through meta-analysis, pooled hazard ratio (HR) values were calculated for specific PET metrics in this context. Methods: PubMed, Scopus, and Ovid databases were explored to search for relevant topics. Dataset retrieval from inception until March 12, 2024, was carried out. The primary endpoints were impact of specific PET metrics on overall survival (OS) and progression-free survival (PFS) before and after treatment. Data from the studies were extracted for a meta-analysis using Stata 17.0. Results: Out of 27 studies identified for systematic review, 15 met the criteria for meta-analysis. Baseline OS analysis showed that total metabolic tumor volume (TMTV) had the highest HR of 2.66 (95% CI: 1.52-4.66), followed by Total-body total lesion glycolysis (TTLG) at 2.45 (95% CI: 0.98-6.08), and maximum standardized uptake values (SUVmax) at 1.30 (95% CI: 0.77-2.19). TMTV and TTLG were statistically significant (p < 0.0001), whereas SUVmax was not (p = 0.33). For PFS, TMTV again showed the highest HR at 2.65 (95% CI: 1.63-4.30), with TTLG at 2.35 (95% CI: 1.40-3.93), and SUVmax at 1.48 (95% CI: 1.08-2.04), all statistically significant (p ≤ 0.01). The DSUVmax was a significant predictor for PFS with an HR of 2.05 (95% CI: 1.13-3.69, p = 0.015). Conclusion: [18F]FDG PET parameters are valuable prognostic tools for predicting outcome of lymphoma patients undergoing CAR T-cell therapy. [ABSTRACT FROM AUTHOR]

Positronium is abundantly produced within the molecular voids of a patient's body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Amyloid β (Aβ), a major biomarker of Alzheimer's disease, leads to tau accumulation, neurodegeneration and cognitive decline. Modelling the trajectory of Aβ accumulation in cognitively unimpaired (CU) individuals is crucial, as treatments targeting Aβ are anticipated. The evolution of Aβ levels was investigated to determine whether it could lead to classification into different groups by studying longitudinal Aβ changes in older CU individuals, and differences between the groups were compared.A total of 297 CU participants were included from the Alzheimer's Disease Neuroimaging Initiative database, and these participants underwent apolipoprotein E (APOE) genotyping, neuropsychological testing, brain magnetic resonance imaging, and an average of 3.03 follow‐up 18F‐florbetapir positron emission tomography scans. Distinct Aβ trajectory patterns were classified using latent class growth analysis, and longitudinal cognitive performances across these patterns were assessed with a linear mixed effects model.The optimal model consisted of three classes, with a high entropy value of 0.947. The classes were designated as follows: class 1, non‐accumulation group (n  = 197); class 2, late accumulation group (n  = 70); and class 3, early accumulation group (n  = 30). The late accumulation and early accumulation groups had more APOE ε4 carriers than the non‐accumulation group. The longitudinal analysis of cognitive performance revealed that the early accumulation group showed the steepest decline (modified Preclinical Alzheimer's Cognitive Composite with digit symbol substitution [mPACCdigit], p < 0.001; modified Preclinical Alzheimer's Cognitive Composite with trails B [mPACCtrailsB], p < 0.001) and the late accumulation group showed a steeper decline (mPACCdigit, p = 0.014; mPACCtrailsB, p = 0.007) compared to the non‐accumulation group.Our study showed the heterogeneity of Aβ accumulation trajectories in CU older individuals. The prognoses for cognitive decline differ according to the Aβ trajectory patterns. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with radioiodine refractory (RAI-R) thyroid carcinoma (TC) have a significantly worse prognosis than patients with radiosensitive TC. These refractory malignancies are often dedifferentiated, hindering the effectiveness of iodine-based imaging. Additionally, the role of metabolic imaging using [18F]FDG PET/CT is also limited in these cases, making adequate staging of RAI-R TC challenging. Recent case series have shown promising results regarding the role of the prostate-specific membrane antigen (PSMA) in TC. In this study we explored the value of [18F]AlF-PSMA-11 PET/CT in RAI-R TC. Methods: In this phase II study, lesions detected on [18F]AlF-PSMA-11 PET were compared to findings from [18F]FDG PET/CT. Additionally, the serologic soluble prostate-specific membrane antigen (sPSMA) was measured using ELISA. PSMA-expression on tumor tissue in any available resection specimens was analysed with an immunostainer. Results: Eight patients were included, with a total of 39 identified lesions based on PET imaging. [18F]AlF-PSMA-11 PET identified 30 of 39 lesions, and [18F]FDG PET identified 33 lesions, leading to a detection rate of 76.9% and 84.6%, respectively. Interestingly, while nine lesions were solely visualized on [18F]FDG, six were uniquely seen on [18F]AlF-PSMA-11 PET. While sPSMA was immeasurable in all female patients, no correlation was found between sPSMA in male patients and disease-related factors. In five out of eight patients immunohistology showed PSMA expression on the primary tumor. Conclusions: Although not all lesions could be visualized, [18F]PSMA-11 PET identified multiple lesions imperceptible on [18F]FDG PET. These results display the potential additional diagnostic role of PSMA-targeted imaging in patients with RAI-R TC. Trial registration number No. EudraCT 2021-000456-19. [ABSTRACT FROM AUTHOR]

A study published in EJNMMI Research examines the use of 11C-Choline PET/CT imaging for prognostic evaluation in recurrent glioma, a type of brain tumor. The study finds that this imaging technology provides valuable information about tumor characteristics, aids in personalized treatment planning, and improves overall prognosis. The research analyzes 38 patients with recurrent glioma and demonstrates the significant prognostic value of 11C-Choline PET/CT imaging in assessing glioma outcomes. The study serves as a reliable reference for prognosis evaluations in clinical settings. The study also highlights the benefits of 11C-Choline PET/CT in understanding the metabolic activity of glioma cells, which can inform clinical decision-making and treatment planning. However, the study acknowledges limitations such as a small sample size and the need for larger trials to validate the findings. [Extracted from the article]

Background: Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer's disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer's Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods: Non-demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6- or 12-month intervals. Linear mixed-effect models were employed to examine the interaction between plasma NfL and various variables of interest, such as Aβ (evaluated using Florbetapir positron emission tomography), hypertension, DM, impaired kidney function, or obesity. Results: Over a mean follow-up period of 62.5 months, participants with a mean age of 72.1 years (n = 720, 48.8% female) at baseline were observed. Higher plasma NfL levels at baseline were associated with steeper increases in ADAS-Cog scores and WMH volumes, and steeper decreases in hippocampal volumes over time (all p-values < 0.001). Notably, Aβ at baseline significantly enhanced the association between plasma NfL and longitudinal changes in ADAS-Cog scores (p-value 0.005) and hippocampal volumes (p-value 0.004). Regarding ADAS-Cog score and WMH volume, the impact of Aβ was more prominent in cognitively unimpaired than in mild cognitive impairment. Hypertension significantly heightened the association between plasma NfL and longitudinal changes in ADAS-Cog scores, hippocampal volumes, and WMH volumes (all p-values < 0.001). DM influenced the association between plasma NfL and changes in ADAS-Cog scores (p-value < 0.001) without affecting hippocampal and WMH volumes. Impaired kidney function did not significantly alter the association between plasma NfL and longitudinal changes in any outcome variables. Obesity heightened the association between plasma NfL and changes in hippocampal volumes only (p-value 0.026). Conclusion: This study suggests that the prognostic capacity of plasma NfL may be amplified in individuals with Aβ or hypertension. This finding emphasizes the importance of considering these factors in the NfL-based prognostic model for neurodegeneration in non-demented older adults. [ABSTRACT FROM AUTHOR]

This single-arm multi-institutional prospective study aimed to evaluate the 10-year outcomes of sublobar resection for small-sized ground-glass opacity-dominant lung cancer. Among 73 patients prospectively enrolled from 13 institutions between November 2006 and April 2012, 53 ground-glass opacity-dominant lung cancer patients underwent sublobar resection with wedge resection as the first choice. The inclusion criteria were maximum tumor size of 8–20 mm; ≥ 80% ground-glass opacity ratio on high-resolution computed tomography; lower 18F-fluorodeoxyglucose accumulation than the mediastinum; intraoperative pathological diagnosis of adenocarcinoma in situ; and no cancer cells on intraoperative cut margins. The primary endpoint was a 10-year disease-specific survival. The 53 eligible patients had a mean tumor size of 14 ± 3.4 mm and a mean ground-glass opacity ratio of 95.9 ± 7.2%. Wedge resection and segmentectomy were performed in 39 and 14 patients, respectively. The final pathological diagnoses were adenocarcinoma in situ in 47 patients (88.7%) and adenocarcinoma with mixed subtype in 6 patients (11.3%). The 10-year disease-specific survival and overall survival were 100% and 96.2%, respectively, during a median follow-up period of 120 months (range, 37–162 months). Ground-glass opacity-dominant small lung cancer is cured by sublobar resection when patients are strictly selected by the inclusion criteria of this study. [ABSTRACT FROM AUTHOR]

Acquired angioedema with low C1‐inhibitor (AAE‐C1‐INH) is a rare disorder characterized by an acquired deficiency in the C1 esterase inhibitor (C1‐INH). This case report describes a 79‐year‐old patient presenting to the emergency department for painless swelling of his scrotum, penile shaft, and left lower and upper extremities with lab values consistent with acquired angioedema without identifiable lymphoreticular or rheumatic disorder on history, exam, or total body PET scan. Proper diagnosis of AAE‐C1‐INH is essential to prevent life‐threatening airway compromise, ensure proper therapy, and exclude lymphoreticular disorders as the etiology of AAE‐C1‐INH. [ABSTRACT FROM AUTHOR]

The objective of this work is to showcase the ortho-positronium lifetime as a probe for soft-tissue characterization. We employed positron annihilation lifetime spectroscopy to experimentally measure the three components of the positron annihilation lifetime—para-positronium (p-Ps), positron, and ortho-positronium (o-Ps)—for three types of porcine, non-fixated soft tissues ex vivo: adipose, hepatic, and muscle. Then, we benchmarked our measurements with X-ray phase-contrast imaging, which is the current state-of-the-art for soft-tissue analysis. We found that the o-Ps lifetime in adipose tissues (2.54 ± 0.12 ns) was approximately 20% longer than in hepatic (2.04 ± 0.09 ns) and muscle (2.03 ± 0.12 ns) tissues. In addition, the separation between the measurements for adipose tissue and the other tissues was better from o-Ps lifetime measurement than from X-ray phase-contrast imaging. This experimental study proved that the o-Ps lifetime is a viable non-invasive probe for characterizing and classifying the different soft tissues. Specifically, o-Ps lifetime as a soft-tissue characterization probe had a strong sensitivity to the lipid content that can be potentially implemented in commercial positron emission tomography scanners that feature list-mode data acquisition. [ABSTRACT FROM AUTHOR]

Low body mass index is closely related to a high risk of Alzheimer's disease (AD) and related biomarkers including amyloid-β (Aβ) deposition. However, the association between sarcopenia and Aβ-confirmed AD remains controversial. Therefore, we investigated the relationship between sarcopenia and the AD continuum. We explored sarcopenia's association with clinical implications of participants on the AD continuum. We prospectively enrolled 142 participants on the AD continuum (19 with preclinical AD, 96 with mild cognitive impairment due to AD, and 28 with AD dementia) and 58 Aβ-negative cognitively unimpaired participants. Sarcopenia, assessed using dual-energy X-ray absorptiometry and hand grip measurements, was considered a predictor. AD continuum, defined by Aβ deposition on positron emission tomography served as an outcome. Clinical severity in participants on the AD continuum assessed using hippocampal volume, Mini-Mental State Examination (MMSE), Seoul Verbal Learning Test (SVLT), and Clinical Dementia Rating Scale Sum of Boxes Scores (CDR-SOB) were also considered an outcome. Sarcopenia (odds ratio = 4.99, p = 0.004) was associated independently with the AD continuum after controlling for potential confounders. Moreover, sarcopenia was associated with poor downstream imaging markers (decreased hippocampal volume, β = − 0.206, p = 0.020) and clinical outcomes (low MMSE, β = − 1.364, p = 0.025; low SVLT, β = − 1.077, p = 0.025; and high CDR-SOB scores, β = 0.783, p = 0.022) in participants on the AD continuum. Sarcopenia was associated with the AD continuum and poor clinical outcome in individuals with AD continuum. Therefore, our results provide evidence for future studies to confirm whether proper management of sarcopenia can effective strategies are required for sarcopenia management to prevent the AD continuum and its clinical implications. [ABSTRACT FROM AUTHOR]

Background: Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). Materials and methods: Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI–avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann–Whitney U test, and McNemar's test was used to assess the diagnostic accuracy between the two techniques. Results: In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG. Conclusions: [18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC. Trial registration: Clinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1. [ABSTRACT FROM AUTHOR]

Background: A novel positron emission tomography (PET) imaging tracer, [18F] SynVesT-1, targeting synaptic vesicle glycoprotein 2 (SV2A), has been developed to meet clinical demand. Utilizing the Trasis AllinOne-36 (AIO) module, we've automated synthesis to Good Manufacturing Practice (GMP) standards, ensuring sterile, pyrogen-free production. The fully GMP-compliant robust synthesis of [18F] SynVesT-1 boosting reliability and introducing a significant degree of simplicity and its comprehensive validation for routine human use. Results: [18F] SynVesT-1 was synthesized by small modifications to the original [18F] SynVesT-1 synthesis protocol to better fit AIO module using an in-house designed cassette and sequence. With a relatively small precursor load of 5 mg, [18F] SynVesT-1 was obtained with consistently high radiochemical yields (RCY) of 20.6 ± 1.2% (the decay-corrected RCY, n = 3) at end of synthesis. Each of the final formulated batches demonstrated radiochemical purity (RCP) and enantiomeric purity surpassing 99%. The entire synthesis process was completed within a timeframe of 80 min (75 ± 3.1 min, n = 3), saves 11 min compared to reported GMP automated synthesis procedures. The in-human PET imaging of total body PET/CT and time-of-flight (TOF) PET/MR showed that [18F] SynVesT-1 is an excellent tracer for SV2A. It is advantageous for decentralized promotion and application in multi-center studies. Conclusion: The use of AIO synthesizer maintains high production yields and increases reliability, reduces production time and allows rapid training of production staff. Besides, the as-prepared [18F] SynVesT-1 displays excellent in vivo binding properties in humans and holds great potential for the imaging and quantification of synaptic density in vivo. [ABSTRACT FROM AUTHOR]

This review addresses the disease diagnosis from brain, eye, and lung scan images based on non-invasive imaging technologies using the Internet of Medical Things (IoMT) and Artificial Intelligence (AI) systems, a topic that has been neglected in the recent literature. Combining imaging modalities with IoMT and AI is expected to enhance both medical diagnoses and personalized treatment plans. We searched various scientific databases for details on IoMT and AI in medical imaging technologies from 2019 to 2023, focusing on different imaging modalities. We investigated the performance of AI-based algorithms in imaging modalities such as X-ray, Computed Tomography, Magnetic Resonance Imaging, Positron Emission Tomography, and Optical Coherence Tomography using the following metrics: accuracy, precision, recall, sensitivity, specificity, and F-1 score, and then analyzed their balanced performance in six issues: enhancement of medical image quality, improvement of clinical diagnoses, support for clinical decision-making, consideration of input data, time efficiency, and data management. Advanced understanding of the IoMT and AI applications in medical imaging technologies would help identify unexplored opportunities and provide directions for future research to enhance the clinical applicability. [ABSTRACT FROM AUTHOR]

Key points There is evidence that aerobic exercise improves brain health. Benefits may be modulated by acute physiological responses to exercise, but this has not been well characterized in older or cognitively impaired adults. The randomized controlled trial ‘AEROBIC’ (NCT04299308) enrolled 60 older adults who were cognitively healthy (n = 30) or cognitively impaired (n = 30) to characterize the acute brain responses to moderate [45–55% heart rate reserve (HRR)] and higher (65–75% HRR) intensity acute exercise. Each participant received two fluorodeoxyglucose positron emission tomography (FDG‐PET) scans, one at rest and one following acute exercise. Change in cerebral glucose metabolism from rest to exercise was the primary outcome. Blood biomarker responses were also characterized as secondary outcomes. Whole grey matter FDG‐PET standardized uptake value ratio (SUVR) differed between exercise (1.045 ± 0.082) and rest (0.985 ± 0.077) across subjects [Diff = −0.060, t(58) = 13.8, P < 0.001] regardless of diagnosis. Exercise increased lactate area under the curve (AUC) [F(1,56) = 161.99, P < 0.001] more in the higher intensity group [mean difference (MD) = 97.0 ± 50.8] than the moderate intensity group (MD = 40.3 ± 27.5; t = −5.252, P < 0.001). Change in lactate AUC and FDG‐PET SUVR correlated significantly (R2 = 0.179, P < 0.001). Acute exercise decreased whole grey matter cerebral glucose metabolism. This effect tracked with the systemic lactate response, suggesting that lactate may serve as a key brain fuel during exercise. Direct measurements of brain lactate metabolism in response to exercise are warranted. Acute exercise is associated with a drop in global brain glucose metabolism in both cognitively healthy older adults and those with Alzheimer's disease. Blood lactate levels increase following acute exercise. Change in brain metabolism tracks with blood lactate, suggesting it may be an important brain fuel. Acute exercise stimulates changes in brain‐derived neurotrophic factor and other blood biomarkers. [ABSTRACT FROM AUTHOR]

Solitary primary extraosseous plasmacytoma is a rare disease in the gastrointestinal tract, recently classified as an "exceptional" tumor of the colon site. The real incidence (one case/population/year) is unknown but reasonably less than 1/10,000,000 cases/year with very few descriptions in the literature. The rare cases described in the literature are often diagnosed after surgery for perforation and with predominant localization of the left colon. The main endoscopic presentation mimics colon carcinoma with ulcerated mass and obstructing lumen. In this paper, we report a rare case of isolated mass mimicking a submucosal lesion of the ascending colon diagnosed in an older female patient by colonoscopy. The patient was almost asymptomatic; she reported only a history of hematochezia without anemia. This mass was successfully treated by surgery and followed by hematological investigations, including bone marrow biopsy, specific laboratory tests, and CT/PET scan, which confirmed primary isolated plasmacytoma of the colon. [ABSTRACT FROM AUTHOR]

Introduction: The Next Move in Movement Disorders (NEMO) study is an initiative aimed at advancing our understanding and the classification of hyperkinetic movement disorders, including tremor, myoclonus, dystonia, and myoclonusdystonia. The study has two main objectives: (a) to develop a computer-aided tool for precise and consistent classification of these movement disorder phenotypes, and (b) to deepen our understanding of brain pathophysiology through advanced neuroimaging techniques. This protocol review details the neuroimaging data acquisition and preprocessing procedures employed by the NEMO team to achieve these goals. Methods and analysis: To meet the study's objectives, NEMO utilizes multiple imaging techniques, including T1-weighted structural MRI, resting-state fMRI, motor task fMRI, and 18F-FDG PET scans. We will outline our efforts over the past 4 years to enhance the quality of our collected data, and address challenges such as head movements during image acquisition, choosing acquisition parameters and constructing data preprocessing pipelines. This study is the first to employ these neuroimaging modalities in a standardized approach contributing to more uniformity in the analyses of future studies comparing these patient groups. The data collected will contribute to the development of a machine learningbased classification tool and improve our understanding of disorder-specific neurobiological factors. Ethics and dissemination: Ethical approval has been obtained from the relevant local ethics committee. The NEMO study is designed to pioneer the application of machine learning of movement disorders. We expect to publish articles in multiple related fields of research and patients will be informed of important results via patient associations and press releases. [ABSTRACT FROM AUTHOR]

First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014–2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72–1.09) and OS (HR = 0.93; 95% CI, 0.73–1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, −0.4%−34.1% and OS = 12.1%; 95% CI, −5.4–29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL. Methods: Relevant observational studies pertaining to the purpose of the metaanalysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between study heterogeneity. Results: Fifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival(hazard ratio[HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I² = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I² = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all <0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05). Conclusion: A high MTV at baseline is associated with a poor survival of NHL patients after CAR-T. [ABSTRACT FROM AUTHOR]

This systematic review aimed to evaluate the potential of deep learning algorithms for converting low-dose Positron Emission Tomography (PET) images to full-dose PET images in different body regions. A total of 55 articles published between 2017 and 2023 by searching PubMed, Web of Science, Scopus and IEEE databases were included in this review, which utilized various deep learning models, such as generative adversarial networks and UNET, to synthesize high-quality PET images. The studies involved different datasets, image preprocessing techniques, input data types, and loss functions. The evaluation of the generated PET images was conducted using both quantitative and qualitative methods, including physician evaluations and various denoising techniques. The findings of this review suggest that deep learning algorithms have promising potential in generating high-quality PET images from low-dose PET images, which can be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Challenging differential diagnosis Background: Pheochromocytoma, a rare catecholamine-secreting tumor, often presents with paroxysmal or sustained hypertension, tachycardia, headache, and diaphoresis. Timely diagnosis is essential to prevent adverse complications. Less common presentations include pheochromocytoma crisis, with severe neurological and cardiac complications. Case Report: We report a unique case of a 25-year-old woman who initially presented with pheochromocytoma-induced hypertensive encephalopathy and acute coronary syndrome. Echocardiography revealed takotsubo-like cardiomyopathy, and magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Initial treatment focused on controlling her blood pressure and supporting cardiac function. Due to her recovering from immediate crisis and absence of further symptoms, the patient refused further follow-up. However, she eventually experienced another episode of hypertensive crisis 2 years later. Subsequent investigations with 24-h urine tests revealed elevated vanillylmandelic acid levels (7.93 mg/24 h), normetanephrine (2638.72 µg/24 h), and nor-metanephrine to creatinine ratio (3546.67) and normal urine metanephrine levels (195.92 µg/24 h) and metanephrine to creatinine ratio (263.33). Contrast-enhanced computed tomography of the abdomen revealed a 4.3 x 3.1 x 4-cm mass in the right adrenal gland. A DOTATATE positron emission tomography scan revealed a 3.9 x 4.3 x 2.7-cm localized right adrenal pheochromocytoma. Biochemical testing and adrenal imaging revealed a previously undiagnosed pheochromocytoma. Following targeted medical therapy and right adrenalectomy, the patient achieved complete resolution of her hypertension and associated symptoms. Conclusions: Our case is a unique simultaneous presentation of posterior reversible encephalopathy syndrome and takotsubo- like cardiomyopathy, highlighting the importance to consider pheochromocytoma in acute neurological and cardiac presentations, even in the absence of typical symptoms. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion We evaluated the treatment outcomes and failure patterns in cT3N0 breast cancer patients classified for rigorous pretreatment evaluation and treated with neoadjuvant chemotherapy (NAC) and curative surgery.We reviewed the records of 87 cT3N0 breast cancer patients who received NAC and curative surgery between 2000 and 2015. The clinical high‐risk group was defined as having two or more risk factors: age < 40, histologic grade 3, lymphovascular invasion, hormone receptor negativity, and Ki‐67 labeling index >20%.Of the patients, 84 (96.6%) and 79 (90.8%) were initially evaluated using magnetic resonance imaging and positron emission tomography/computed tomography. Most patients received anthracycline based NAC regimen (n = 69, 79.3%) and modified radical mastectomy (n = 61, 70.1%). During a 91.5‐month median follow‐up, ten patients experienced distant metastasis (DM) only, two had isolated local recurrence, one had local recurrence and DM, and another had local recurrence, regional recurrence, and DM. The 5‐year rates of locoregional recurrence, DM, any recurrence (AR), and overall survival (OS) were 1.2%, 11.6%, 11.6%, and 90.8%, respectively. The risk group was an independent prognostic factor of recurrence, and the high‐risk group had worse rates of DM (19.2% vs. 0%, P = 0.009), AR (19.2% vs. 0%, P = 0.016) and OS (82.8% vs. 100%, P = 0.001).Patients with cT3N0 breast cancer classified for rigorous pretreatment evaluation and treated with NAC and radical surgery had favourable oncological outcomes. A clinical risk group based on clinical and immunohistochemical risk factors was an excellent predictor of survival and recurrence. [ABSTRACT FROM AUTHOR]

Skull base metastases, including those from small‐cell lung carcinoma (SCLC), can present with various syndromes depending on the site of involvement, such as orbital syndrome, parasellar syndrome, middle fossa syndrome, jugular foramen syndrome, and occipital condyle syndrome (OCS). One such example is OCS, which consists of unilateral occipital headache accompanied with ipsilateral hypoglossal palsy. This case report describes a 51‐year‐old man initially diagnosed with OCS, which led to the discovery of systemic bone metastases from SCLC. Magnetic resonance imaging showed lesions in the occipital condyle and hypoglossal canal, while positron emission tomography‐computed tomography identified a lung mass and widespread metastases. SCLC is highly aggressive and metastatic, with the bone being a common site of spread. In this case, the OCS preceded the diagnosis of the underlying malignancy. Prompt diagnosis and treatment are crucial, as patients with OCS often have advanced disease. This case highlights the importance of considering SCLC as a potential etiology for OCS, given the propensity for bone metastases. Early recognition and evaluation of OCS is essential to initiate appropriate management. [ABSTRACT FROM AUTHOR]

Objective. This work proposes, for the first time, an image-based end-to-end self-normalization framework for positron emission tomography (PET) using conditional generative adversarial networks (cGANs). Approach. We evaluated different approaches by exploring each of the following three methodologies. First, we used images that were either unnormalized or corrected for geometric factors, which encompass all time-invariant factors, as input data types. Second, we set the input tensor shape as either a single axial slice (2D) or three contiguous axial slices (2.5D). Third, we chose either Pix2Pix or polarized self-attention (PSA) Pix2Pix, which we developed for this work, as a deep learning network. The targets for all approaches were the axial slices of images normalized using the direct normalization method. We performed Monte Carlo simulations of ten voxelized phantoms with the SimSET simulation tool and produced 26,000 pairs of axial image slices for training and testing. Main results. The results showed that 2.5D PSA Pix2Pix trained with geometric-factors-corrected input images achieved the best performance among all the methods we tested. All approaches improved general image quality figures of merit peak signal to noise ratio (PSNR) and structural similarity index (SSIM) from ∼15 % to ∼55 %, and 2.5D PSA Pix2Pix showed the highest PSNR (28.074) and SSIM (0.921). Lesion detectability, measured with region of interest (ROI) PSNR, SSIM, normalized contrast recovery coefficient, and contrast-to-noise ratio, was generally improved for all approaches, and 2.5D PSA Pix2Pix trained with geometric-factors-corrected input images achieved the highest ROI PSNR (28.920) and SSIM (0.973). Significance. This study demonstrates the potential of an image-based end-to-end self-normalization framework using cGANs for improving PET image quality and lesion detectability without the need for separate normalization scans. [ABSTRACT FROM AUTHOR]

A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 μm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET. [ABSTRACT FROM AUTHOR]

A study published in Translational Neurodegeneration introduces a new blood-based biomarker, the plasma p-tau181 assay, which accurately reflects tau pathology in Alzheimer's disease (AD). Unlike current assays, this new biomarker is not affected by amyloid accumulation and shows higher specificity for tau pathology. It has the potential to detect and stage AD tau pathologies in the brain, offering a more accessible and functional alternative to PET scans. The assay may also help predict therapeutic response to current treatments and identify suitable patients for anti-amyloid therapies. However, more research with larger sample sizes is needed to confirm these findings. [Extracted from the article]

Background: Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake. Methods: Seven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method. Results: Compared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls. Conclusions: In this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis. [ABSTRACT FROM AUTHOR]

Background: The orexin receptor (OXR) plays a role in drug addiction and is aberrantly expressed in colorectal tumors. Subtype-selective OXR PET ligands suitable for in vivo use have not yet been reported. This work reports the development of 18F-labeled OXR PET ligand candidates derived from the OXR antagonist suvorexant and the OX1R-selective antagonist JH112. Results: Computational analysis predicted that fluorine substitution (1e) and introduction of the fluorobenzothiazole scaffold (1f) would be suitable for maintaining high OX1R affinity. After multi-step synthesis of 1a–1f, in vitro OXR binding studies confirmed the molecular dynamics calculations and revealed single-digit nanomolar OX1R affinities for 1a–f, ranging from 0.69 to 2.5 nM. The benzothiazole 1f showed high OX1R affinity (Ki = 0.69 nM), along with 77-fold subtype selectivity over OX2R. Cu-mediated 18F-fluorination of boroxine precursors allowed for a shortened reaction time of 5 min to provide the non-selective OXR ligand [18F]1c and its selective OX1R congener [18F]1f in activity yields of 14% and 22%, respectively, within a total synthesis time of 52–76 min. [18F]1c and [18F]1f were stable in plasma and serum in vitro, with logD7.4 of 2.28 ([18F]1c) and 2.37 ([18F]1f), and high plasma protein binding of 66% and 77%, respectively. Dynamic PET imaging in rats showed similar brain uptake of [18F]1c (0.17%ID/g) and [18F]1f (0.15%ID/g). However, preinjection of suvorexant did not significantly block [18F]1c or [18F]1f uptake in the rat brain. Pretreatment with cyclosporine A to study the role of P-glycoprotein (P-gp) in limiting brain accumulation moderately increased brain uptake of [18F]1c and [18F]1f. Accordingly, in vitro experiments demonstrated that the P-gp inhibitor zosuquidar only moderately inhibited polarized, basal to apical transport of 1c (p < 0.05) and had no effect on the transport of 1f, indicating that P-gp does not play a relevant role in brain accumulation of [18F]1c and [18F]1f in vivo. Conclusions: The in vitro and in vivo results of [18F]1c and [18F]1f provide a solid basis for further development of suitable OXR PET ligands for brain imaging. [ABSTRACT FROM AUTHOR]