Search

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]

INTRODUCTION: In trials of amyloid-lowering drugs for Alzheimers disease (AD), differential eligibility may contribute to under-inclusion of racial and ethnic underrepresented groups. We examined plasma amyloid beta 42/40 and positron emission tomography (PET) amyloid eligibility for the ongoing AHEAD Study preclinical AD program (NCT04468659). METHODS: Univariate logistic regression models were used to examine group differences in plasma and PET amyloid screening eligibility. RESULTS: Of 4905 participants screened at time of analysis, 1724 were plasma eligible to continue in screening: 13.3% Hispanic Black, 24.7% Hispanic White, 20.8% non-Hispanic (NH) Asian, 24.7% NH Black, and 38.9% NH White. Plasma eligibility differed across groups in models controlling for covariates (odds ratio from 1.9 to 4.0 compared to the NH White reference group, P

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]

Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([111In]-WBC SPECT, [18F]FDG PET) techniques are used in clinical practice but lack specificity for the causative microorganisms themselves. To meet this challenge, many groups have developed imaging methods that target pathogen-specific metabolism, including PET tracers integrated into the bacterial cell wall. We have previously reported the d-amino acid derived PET radiotracers d-methyl-[11C]-methionine, d-[3-11C]-alanine, and d-[3-11C]-alanine-d-alanine, which showed robust bacterial accumulation in vitro and in vivo. Given the clinical importance of radionuclide half-life, in the current study, we developed [18F]3,3,3-trifluoro-d-alanine (d-[18F]-CF3-ala), a fluorine-18 labeled tracer. We tested the hypothesis that d-[18F]-CF3-ala would be incorporated into bacterial peptidoglycan given its structural similarity to d-alanine itself. NMR analysis showed that the fluorine-19 parent amino acid d-[19F]-CF3-ala was stable in human and mouse serum. d-[19F]-CF3-ala was also a poor substrate for d-amino acid oxidase, the enzyme largely responsible for mammalian d-amino acid metabolism and a likely contributor to background signals using d-amino acid derived PET tracers. In addition, d-[19F]-CF3-ala showed robust incorporation into Escherichia coli peptidoglycan, as detected by HPLC/mass spectrometry. Based on these promising results, we developed a radiosynthesis of d-[18F]-CF3-ala via displacement of a bromo-precursor with [18F]fluoride followed by chiral stationary phase HPLC. Unexpectedly, the accumulation of d-[18F]-CF3-ala by bacteria in vitro was highest for Gram-negative pathogens in particular E. coli. In a murine model of acute bacterial infection, d-[18F]-CF3-ala could distinguish live from heat-killed E. coli, with low background signals. These results indicate the viability of [18F]-modified d-amino acids for infection imaging and indicate that improved specificity for bacterial metabolism can improve tracer performance.

BACKGROUND: The Anti-Amyloid in Asymptomatic Alzheimers Disease (A4) Study failed to show a treatment benefit with solanezumab, but the longitudinal consequences of elevated amyloid were observed in study participants with objective decline on the Preclinical Alzheimer Cognitive Composite (PACC) and subjective decline on the combined Cognitive Function Index (participant + study partner CFI), during the trial period. OBJECTIVES: We sought to expand on previous findings by comparing longitudinal patterns of participant and study partner CFI separately and their associations with the PACC stratified by baseline amyloid tertile over the course of the A4 Study. DESIGN: Cognitively unimpaired older adult participants and their study partners were independently administered the CFI at screen prior to amyloid PET disclosure and then at 3 subsequent visits (week 48, week 168, week 240) of the study. PACC collected at visits concurrent with CFI administration were also examined longitudinally. SETTING: The A4 Study was conducted at 67 sites in Australia, Canada, Japan, and the United States. PARTICIPANTS: 1,147 participants with elevated amyloid based on florbetapir PET were enrolled in the A4 Study and included in these analyses. 583 were on placebo and 564 were treated with solanezumab. MEASUREMENTS: The PACC was used to assess objective cognitive performance and the CFI was used to assess change in everyday cognitive functioning by the participant and their study partner independently. Amyloid level was characterized by Centiloid tertiles (77.2 CL). Participants were aware of their elevated amyloid status, but not their CL tertile, or specific level of amyloid. Longitudinal correlations between participant and study partner CFI and PACC were examined at all visits where assessments were available. The impact of baseline amyloid tertile on CFI and PACC associations was also examined. RESULTS: Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. Results did not differ by treatment group. The association between higher CFI and worse PACC for both for participant and study partner became progressively stronger over the course of the study. PACC had a significantly higher correlation with study partner CFI than with participant CFI by week 168. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile. CONCLUSION: Both participant and study partner report captured subtle changes in everyday cognitive functioning for participants with biomarker confirmed and disclosed preclinical AD. Moreover, study partner report was most highly aligned with cognitive decline, particularly among those with the highest amyloid load.

BackgroundHypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors.ResultsThirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV.Conclusions[18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

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]

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]

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]

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]

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]

The aim of this study was to establish and validate the precision of a novel radiomics approach that integrates 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scan data with clinical information to improve the prognostication of survival rates in patients diagnosed with stage III Non-Small Cell Lung Cancer (NSCLC) who are not candidates for surgery. We evaluated pretreatment 18F-FDG PET-CT scans from 156 individuals diagnosed with stage III inoperable NSCLC at Shandong Cancer Hospital. These individuals were divided into two groups: a training set comprising 110 patients and an internal validation set consisting of 46 patients. By employing random forest classifier and cox proportional hazards model , we identified and utilized relevant features to create predictive models and a nomogram. The effectiveness of these models was assessed through the use of the receiver operating characteristics(ROC) curves, Kaplan–Meier (KM) curves, and the application of the nomogram. Our findings showed that the combined model, which integrates both clinical and radiomic data, outperformed those based solely on clinical or radiomic features in predicting 3-year overall survival(OS). Furthermore, calibration plots revealed a high level of agreement between predicted and actual survival times. The research successfully established a predictive radiomics model that integrates 18F-FDG PET/CT imaging with clinical indicators to enhance survival predictions for patients with stage III inoperable NSCLC. [ABSTRACT FROM AUTHOR]

The objectives of this study were to investigate the variable factors associated with cognitive function and cortical atrophy and estimated variable importance of those factors in affecting cognitive function and cortical atrophy in patients with EOAD and LOAD. Patients with EOAD (n = 40), LOAD (n = 34), and healthy volunteers with normal cognition were included (n = 65). All of them performed 3T MRI, [18F]THK5351 PET (THK), [18F]flutemetamol PET (FLUTE), and detailed neuropsychological tests. To investigate factors associated with neuropsychological test results and cortical thickness in each group, we conducted multivariable linear regression models, including amyloid, tau, cerebral small vessel disease markers on MRI, and vascular risk factors. Then, we estimated variable importance in associating cognitive functions and cortical thickness, using relative importance analysis. In patients with EOAD, global THK retention was the most important contributor to the model variances for most neuropsychological tests, except for memory. However, in patients with LOAD, multiple contributors beyond tau were important in explaining variance of neuropsychological tests. In analyses with mean cortical thickness, global THK retention was the main contributor in patients with EOAD, while in LOAD patients, multiple factors contributed equally to mean cortical thickness. Therefore, EOAD and LOAD may have different pathomechanistic courses. [ABSTRACT FROM AUTHOR]

Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson's disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic "Parkinson-Disease-related-Pattern (PDRP)"-z-score in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). After 3 weeks ADLL-treatment, the RBD-SS-3 drops markedly in both patients and remains reduced for >18 months of ADLL-treatment. In patient 1 (female), the DAT-SPECT putaminal binding ratio (PBR) decreases in the 5 years pretreatment from normal (1.88) to pathological (1.22) and the patient's FDG-PET-PDRP-z-score rises from 1.72 to 3.28 (pathological). After 22 months of ADLL-treatment, the DAT-SPECT-PBR increases to 1.67 and the FDG-PET-PDRP-z-score stabilizes at 3.18. Similar results are seen in patient 2 (male): his DAT-SPECT-PBR rises from a pretreatment value of 1.42 to 1.72 (close to normal) and the FDG-PET-PDRP-z-score decreases from 1.02 to 0.30 after 18 months of ADLL-treatment. These results support exploration of whether ADLL may have disease-modifying properties in prodromal PD. Clinical trials with N-acetyl-L-leucine showed beneficial effects in lysosomal diseases. Here, the authors investigate a disease modifying effect of acetyl-DL-leucine in 2 patients with REM sleep behavior disorder, a prodrome of Parkinson's disease, and report improvements in neurological symptoms and imaging biomarkers. [ABSTRACT FROM AUTHOR]

Objectives Epigenetically modified fibroblasts contribute to chronicity in inflammatory diseases. Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.68Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis. Methods Eight LVV patients with aortitis and eight age- and gender-matched controls were included. The distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared with MRI inflammatory activity scores. Imaging results were compared with clinical parameters such as serum inflammatory markers, time of remission and medication. Results Three aortitis patients were clinically active and five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared with controls. Patients in remission had a mean duration of remission of 2.8 years (range 1–4 years), yet significant FAPI uptake in the vessel wall was found. In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed. Conclusions This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV. [ABSTRACT FROM AUTHOR]

The aim of this prospective, observational cohort study was to investigate and assess diverse neuroimaging biomarkers to predict patients' neurological recovery after coma. 32 patients (18–76 years, M = 44.8, SD = 17.7) with disorders of consciousness participated in the study. Multimodal neuroimaging data acquired during the patient's hospitalization were used to derive cortical glucose metabolism (18F-fluorodeoxyglucose positron emission tomography/computed tomography), and structural (diffusion-weighted imaging) and functional connectivity (resting-state functional MRI) indices. The recovery outcome was defined as a continuous composite score constructed from a multivariate neurobehavioral recovery assessment administered upon the discharge from the hospital. Fractional anisotropy-based white matter integrity in the anterior forebrain mesocircuit (r = 0.72, p <.001, 95% CI: 0.87, 0.45), and the functional connectivity between the antagonistic default mode and dorsal attention resting-state networks (r = − 0.74, p < 0.001, 95% CI: − 0.46, − 0.88) strongly correlated with the recovery outcome. The association between the posterior glucose metabolism and the recovery outcome was moderate (r = 0.38, p = 0.040, 95% CI: 0.66, 0.02). Structural (adjusted R2 = 0.84, p = 0.003) or functional connectivity biomarker (adjusted R2 = 0.85, p = 0.001), but not their combination, significantly improved the model fit to predict the recovery compared solely to bedside neurobehavioral evaluation (adjusted R2 = 0.75). The present study elucidates an important role of specific MRI-derived structural and functional connectivity biomarkers in diagnosis and prognosis of recovery after coma and has implications for clinical care of patients with severe brain injury. [ABSTRACT FROM AUTHOR]

Background: Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. Methods: Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2–4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. Results: Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3 years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. Conclusions: The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries. [ABSTRACT FROM AUTHOR]

Background: The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed Objective: This study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning. Methods: Former contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [18F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels). Results: 47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (− 0.37 ± 0.41 vs. − 0.31 ± 0.37, paired p =.006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r = −.366, p =.02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played. Conclusion: A higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration. [ABSTRACT FROM AUTHOR]

This review article discusses the most significant aspects related to the conventional positron emitting radionuclides such as nitrogen-13, oxygen-15, and carbon-11. It is based on a comprehensive forty-year literature review and provides a through overview of the various production methods of these radionuclides, their use in the synthesis of radiopharmaceuticals, and their applications in nuclear imaging. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Modelling [18F]LW223 PET data using simplified imaging protocols for quantification of TSPO expression in the rat heart and brain" published in the European Journal of Nuclear Medicine & Molecular Imaging. The correction notice addresses errors in the original article and provides the accurate information. The corrections include changes to numerical values and clarifications in the text. Additionally, some figures in the original article were incorrect and have been corrected in the notice. The publisher, Springer Nature, remains neutral and unbiased in relation to jurisdictional claims and institutional affiliations. [Extracted from the article]

The article discusses the development and benefits of total body positron emission tomography (PET) scanners, which have an extended axial field of view and improved sensitivity compared to traditional scanners. These scanners allow for simultaneous imaging of the entire body, resulting in higher sensitivity, improved signal-to-noise ratio, shorter scan times, and the ability to conduct pediatric scans without anesthesia. The article highlights the clinical and research applications of total body PET scanners, including the quantification of mu-opioid receptors in the monkey brain, spinal cord, and peripheral organs. The study demonstrates the feasibility and advantages of using total body PET scanners for preclinical research. [Extracted from the article]

Purpose: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. Methods: Adult patients with untreated grade 1–3a FL/ stage II‐IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post‐induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1–3 was considered negative (CMR), whereas DS4‐5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). Results: Overall, 807 follicular lymphoma patients—52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3–5)—were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4–5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%–70%). The 5-yr PFS rate for PET neg (DS1–3) and PET pos (DS4–5) patients was 71% (95%CI: 67%–75%) and 36% (95%CI: 25%–46%), respectively, with HR 3.49 (95%CI: 2.57–4.72). Five-year PFS was worse as DS increased, with 74% (70%–78%), 58% (48%–67%; HR 1.71; p = 0.001)] and 36% (25%–46%; HR 3.88; p < 0.001) in DS1–2, DS3 and DS4–5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%–96%), with 96% (95%CI: 94–97) and 82% (95%CI: 72%–89%) in EOI PET negative (DS1–3) and positive (DS4–5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1–2 with high FLIPI-2 (3–5) experienced worse OS than patients with DS1–2 and low FLIPI-2 (1–2) (p = 0.003). Conclusion: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1–2 patients. [ABSTRACT FROM AUTHOR]

Purpose: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. Methods: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. Results: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 – 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 – 23.5) on [68Ga]Ga-FAPI-46 PET/CT. Conclusion: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively. [ABSTRACT FROM AUTHOR]

Purpose: Invasive fungal diseases, such as pulmonary aspergillosis, are common life-threatening infections in immunocompromised patients and effective treatment is often hampered by delays in timely and specific diagnosis. Fungal-specific molecular imaging ligands can provide non-invasive readouts of deep-seated fungal pathologies. In this study, the utility of antibodies and antibody fragments (Fab) targeting β-glucans in the fungal cell wall to detect Aspergillus infections was evaluated both in vitro and in preclinical mouse models. Methods: The binding characteristics of two commercially available β-glucan antibody clones and their respective antigen-binding Fabs were tested using biolayer interferometry (BLI) assays and immunofluorescence staining. In vivo binding of the Zirconium-89 labeled antibodies/Fabs to fungal pathogens was then evaluated using PET/CT imaging in mouse models of fungal infection, bacterial infection and sterile inflammation. Results: One of the evaluated antibodies (HA-βG-Ab) and its Fab (HA-βG-Fab) bound to β-glucans with high affinity (KD = 0.056 & 21.5 nM respectively). Binding to the fungal cell wall was validated by immunofluorescence staining and in vitro binding assays. ImmunoPET imaging with intact antibodies however showed slow clearance and high background signal as well as nonspecific accumulation in sites of infection/inflammation. Conversely, specific binding of [89Zr]Zr-DFO-HA-βG-Fab to sites of fungal infection was observed when compared to the isotype control Fab and was significantly higher in fungal infection than in bacterial infection or sterile inflammation. Conclusions: [89Zr]Zr-DFO-HA-βG-Fab can be used to detect fungal infections in vivo. Targeting distinct components of the fungal cell wall is a viable approach to developing fungal-specific PET tracers. [ABSTRACT FROM AUTHOR]

Purpose: Here, we evaluate a PET displacement model with a Single-step and Numerical solution in healthy individuals using the synaptic vesicle glycoprotein (SV2A) PET-tracer [11C]UCB-J and the anti-seizure medication levetiracetam (LEV). We aimed to (1) validate the displacement model by comparing the brain LEV-SV2A occupancy from a single PET scan with the occupancy derived from two PET scans and the Lassen plot and (2) determine the plasma LEV concentration-SV2A occupancy curve in healthy individuals. Methods: Eleven healthy individuals (five females, mean age 35.5 [range: 25–47] years) underwent two 120-min [11C]UCB-J PET scans where an LEV dose (5–30 mg/kg) was administered intravenously halfway through the first PET scan to partially displace radioligand binding to SV2A. Five individuals were scanned twice on the same day; the remaining six were scanned once on two separate days, receiving two identical LEV doses. Arterial blood samples were acquired to determine the arterial input function and plasma LEV concentrations. Using the displacement model, the SV2A-LEV target engagement was calculated and compared with the Lassen plot method. The resulting data were fitted with a single-site binding model. Results: SV2A occupancies and VND estimates derived from the displacement model were not significantly different from the Lassen plot (p = 0.55 and 0.13, respectively). The coefficient of variation was 14.6% vs. 17.3% for the Numerical and the Single-step solution in Bland-Altman comparisons with the Lassen plot. The average half maximal inhibitory concentration (IC50), as estimated from the area under the curve of the plasma LEV concentration, was 12.5 µg/mL (95% CI: 5–25) for the Single-Step solution, 11.8 µg/mL (95% CI: 4–25) for the Numerical solution, and 6.3 µg/mL (95% CI: 0.08-21) for the Lassen plot. Constraining Emax to 100% did not significantly improve model fits. Conclusion: Plasma LEV concentration vs. SV2A occupancy can be determined in humans using a single PET scan displacement model. The average concentration of the three computed IC50 values ranges between 6.3 and 12.5 µg/mL. The next step is to use the displacement model to evaluate LEV occupancy and corresponding plasma concentrations in relation to treatment efficacy. Clinical trial registration: NCT05450822. Retrospectively registered 5 July 2022 https://clinicaltrials.gov/ct2/results? term=NCT05450822&Search=Search. [ABSTRACT FROM AUTHOR]

Purpose: To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. Methods: Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. Results: Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2–3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. Conclusion: Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents. [ABSTRACT FROM AUTHOR]

Purpose: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. Method: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. Results: For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24 h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48 h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48 h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. Conclusions: Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu. [ABSTRACT FROM AUTHOR]

Purpose: Mu-opioid receptors (MORs) are widely expressed in the central nervous system (CNS), peripheral organs, and immune system. This study measured the whole body distribution of MORs in rhesus macaques using the MOR selective radioligand [11C]carfentanil ([11C]CFN) on the PennPET Explorer. Both baseline and blocking studies were conducted using either naloxone or GSK1521498 to measure the effect of the antagonists on MOR binding in both CNS and peripheral organs. Methods: The PennPET Explorer was used for MOR total-body PET imaging in four rhesus macaques using [11C]CFN under baseline, naloxone pretreatment, and naloxone or GSK1521498 displacement conditions. Logan distribution volume ratio (DVR) was calculated by using a reference model to quantitate brain regions, and the standard uptake value ratios (SUVRs) were calculated for peripheral organs. The percent receptor occupancy (%RO) was calculated to establish the blocking effect of 0.14 mg/kg naloxone or GSK1521498. Results: The %RO in MOR-abundant brain regions was 75–90% for naloxone and 72–84% for GSK1521498 in blocking studies. A higher than 90% of %RO were observed in cervical spinal cord for both naloxone and GSK1521498. It took approximately 4–6 min for naloxone or GSK1521498 to distribute to CNS and displace [11C]CFN from the MOR. A smaller effect was observed in heart wall in the naloxone and GSK1521498 blocking studies. Conclusion: [11C]CFN total-body PET scans could be a useful approach for studying mechanism of action of MOR drugs used in the treatment of acute and chronic opioid use disorder and their effect on the biodistribution of synthetic opioids such as CFN. GSK1521498 could be a potential naloxone alternative to reverse opioid overdose. [ABSTRACT FROM AUTHOR]

Background: The long axial field of view, combined with the high sensitivity of the Biograph Vision Quadra PET/CT scanner enables the precise deviation of an image derived input function (IDIF) required for parametric imaging. Traditionally, this requires an hour-long dynamic PET scan for [18F]-FDG, which can be significantly reduced by using a population-based input function (PBIF). In this study, we expand these examinations and include the scanner's ultra-high sensitivity (UHS) mode in comparison to the high sensitivity (HS) mode and evaluate the potential for further shortening of the scan time. Methods: Patlak Ki and DV estimates were determined by the indirect and direct Patlak methods using dynamic [18F]-FDG data of 6 oncological patients with 26 lesions (0–65 min p.i.). Both sensitivity modes for different number/duration of PET data frames were compared, together with the potential of using abbreviated scan durations of 20, 15 and 10 min by using a PBIF. The differences in parametric images and tumour-to-background ratio (TBR) due to the shorter scans using the PBIF method and between the sensitivity modes were assessed. Results: A difference of 3.4 ± 7.0% (Ki) and 1.2 ± 2.6% (DV) was found between both sensitivity modes using indirect Patlak and the full IDIF (0–65 min). For the abbreviated protocols and indirect Patlak, the UHS mode resulted in a lower bias and higher precision, e.g., 45–65 min p.i. 3.8 ± 4.4% (UHS) and 6.4 ± 8.9% (HS), allowing shorter scan protocols, e.g. 50–65 min p.i. 4.4 ± 11.2% (UHS) instead of 7.3 ± 20.0% (HS). The variation of Ki and DV estimates for both Patlak methods was comparable, e.g., UHS mode 3.8 ± 4.4% and 2.7 ± 3.4% (Ki) and 14.4 ± 2.7% and 18.1 ± 7.5% (DV) for indirect and direct Patlak, respectively. Only a minor impact of the number of Patlak frames was observed for both sensitivity modes and Patlak methods. The TBR obtained with direct Patlak and PBIF was not affected by the sensitivity mode, was higher than that derived from the SUV image (6.2 ± 3.1) and degraded from 20.2 ± 12.0 (20 min) to 10.6 ± 5.4 (15 min). Ki and DV estimate images showed good agreement (UHS mode, RC: 6.9 ± 2.3% (Ki), 0.1 ± 3.1% (DV), peak signal-to-noise ratio (PSNR): 64.5 ± 3.3 dB (Ki), 61.2 ± 10.6 dB (DV)) even for abbreviated scan protocols of 50–65 min p.i. Conclusions: Both sensitivity modes provide comparable results for the full 65 min dynamic scans and abbreviated scans using the direct Patlak reconstruction method, with good Ki and DV estimates for 15 min short scans. For the indirect Patlak approach the UHS mode improved the Ki estimates for the abbreviated scans. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the staging efficiency of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in nasopharyngeal carcinoma (NPC) patients. Methods: Thirty-nine patients with pathologically confirmed NPC were enrolled in this prospective study. Each patient underwent paired [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT on 2 successive days. The accuracy of two PET/CT for assessing T, N, and M stages was compared by using head-and-neck MRI, histopathologic diagnosis and follow-up results as reference standards. The radiotracer uptake derived from two PETs was also compared. Results: For treatment-naïve patients, [68Ga]Ga-DOTATATE PET/CT showed identical sensitivity for the primary tumours but clearer tumor delineation induced by higher tumour-to-background (TBR) ratio (19.1 ± 8.7 vs. 12.4 ± 7.7, P = 0.003), compared with [68Ga]Ga-FAPI PET/CT. Regarding cervical lymph node (CLN) metastases, [68Ga]Ga-DOTATATE PET had significantly better sensitivity and accuracy based on neck sides (98% vs. 82%, P < 0.001; 99% vs. 88% P = 0.008), neck levels (98% vs. 78%, 99% vs. 97%; both P < 0.001) and individual nodes (89% vs. 56%, 91% vs. 76%; both P < 0.001), and higher TBR (8.1 ± 4.1 vs. 6.3 ± 3.7, P < 0.001). Additionally, [68Ga]Ga-DOTATATE PET/CT revealed higher sensitivity and accuracy for distant metastases (96% vs. 53%, 95% vs. 52%; both P < 0.001), particularly in bone metastases (99% vs. 49%, 97% vs. 49%; both P < 0.001). For post-treatment patients, [68Ga]Ga-DOTATATE PET/CT identified one more true-negative case than [68Ga]Ga-FAPI PET/CT. Conclusion: [68Ga]Ga-DOTATATE PET/CT performed better than [68Ga]Ga-FAPI PET/CT in visualizing the primary tumours, detecting the metastatic lesions and identifying the local recurrence, suggesting [68Ga]Ga-DOTATATE PET/CT may be superior to [68Ga]Ga-FAPI PET/CT for NPC staging. [ABSTRACT FROM AUTHOR]

Purpose: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo. Methods: ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies. Results: The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo. Conclusion: [89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101. [ABSTRACT FROM AUTHOR]

Purpose: [18F]PI-2620 positron emission tomography (PET) detects misfolded tau in progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). We questioned the feasibility and value of absolute [18F]PI-2620 PET quantification for assessing tau by regional distribution volumes (VT). Here, arterial input functions (AIF) represent the gold standard, but cannot be applied in routine clinical practice, whereas image-derived input functions (IDIF) represent a non-invasive alternative. We aimed to validate IDIF against AIF and we evaluated the potential to discriminate patients with PSP and AD from healthy controls by non-invasive quantification of [18F] PET. Methods: In the first part of the study, we validated AIF derived from radial artery whole blood against IDIF by investigating 20 subjects (ten controls and ten patients). IDIF were generated by manual extraction of the carotid artery using the average and the five highest (max5) voxel intensity values and by automated extraction of the carotid artery using the average and the maximum voxel intensity value. In the second part of the study, IDIF quantification using the IDIF with the closest match to the AIF was transferred to group comparison of a large independent cohort of 40 subjects (15 healthy controls, 15 PSP patients and 10 AD patients). We compared VT and VT ratios, both calculated by Logan plots, with distribution volume (DV) ratios using simplified reference tissue modelling and standardized uptake value (SUV) ratios. Results: AIF and IDIF showed highly correlated input curves for all applied IDIF extraction methods (0.78 < r < 0.83, all p < 0.0001; area under the curves (AUC): 0.73 < r ≤ 0.82, all p ≤ 0.0003). Regarding the VT values, correlations were mainly found between those generated by the AIF and by the IDIF methods using the maximum voxel intensity values. Lowest relative differences (RD) were observed by applying the manual method using the five highest voxel intensity values (max5) (AIF vs. IDIF manual, avg: RD = -82%; AIF vs. IDIF automated, avg: RD = -86%; AIF vs. IDIF manual, max5: RD = -6%; AIF vs. IDIF automated, max: RD = -26%). Regional VT values revealed considerable variance at group level, which was strongly reduced upon scaling by the inferior cerebellum. The resulting VT ratio values were adequate to detect group differences between patients with PSP or AD and healthy controls (HC) (PSP target region (globus pallidus): HC vs. PSP vs. AD: 1.18 vs. 1.32 vs. 1.16; AD target region (Braak region I): HC vs. PSP vs. AD: 1.00 vs. 1.00 vs. 1.22). VT ratios and DV ratios outperformed SUV ratios and VT in detecting differences between PSP and healthy controls, whereas all quantification approaches performed similarly in comparing AD and healthy controls. Conclusion: Blood-free IDIF is a promising approach for quantification of [18F]PI-2620 PET, serving as correlating surrogate for invasive continuous arterial blood sampling. Regional [18F]PI-2620 VT show large variance, in contrast to regional [18F]PI-2620 VT ratios scaled with the inferior cerebellum, which are appropriate for discriminating PSP, AD and healthy controls. DV ratios obtained by simplified reference tissue modeling are similarly suitable for this purpose. [ABSTRACT FROM AUTHOR]

Purpose: 68Ga-Trivehexin is an investigational PET radiopharmaceutical (NCT05799274) targeting αvβ6-integrin for PET imaging of carcinomas. 177Lu-D0301 is a structurally related therapeutic peptide tetramer. However, it showed considerable kidney uptake in rodents, impeding clinical applicability. We therefore evaluated the impact of different kidney protection strategies on the biodistribution of both agents in normal and tumor-bearing mice. Methods: Ex-vivo biodistribution of 68Ga-Trivehexin (90 min p.i.) and 177Lu-D0301 (90 min and 24 h p.i.) was determined in healthy C57BL/6N and H2009 (human lung adenocarcinoma) xenografted CB17-SCID mice without and with co-infusion of 100 µL of solutions containing 2.5% arginine + 2.5% lysine (Arg/Lys), 4% succinylated gelatin (gelofusine, gelo), or combinations thereof. Arg/Lys was injected either i.p. 30 min before and after the radiopharmaceutical, or i.v. 2 min before the radiopharmaceutical. Gelo was administered either i.v. 2 min prior activity, or pre-mixed and injected together with the radiopharmaceutical (n = 5 per group). C57BL/6N mice were furthermore imaged by PET (90 min p.i.) and SPECT (24 h p.i.). Results: Kidney uptake of 68Ga-Trivehexin in C57BL/6N mice was reduced by 15% (Arg/Lys i.p.), 25% (Arg/Lys i.v.), and 70% (gelo i.v.), 90 min p.i., relative to control. 177Lu-D0301 kidney uptake was reduced by 2% (Arg/Lys i.p.), 41% (Arg/Lys i.v.), 61% (gelo i.v.) and 66% (gelo + Arg/Lys i.v.) 24 h p.i., compared to control. Combination of Arg/Lys and gelo provided no substantial benefit. Gelo furthermore reduced kidney uptake of 177Lu-D0301 by 76% (90 min p.i.) and 85% (24 h p.i.) in H2009 bearing SCID mice. Since tumor uptake was not (90 min p.i.) or only slightly reduced (15%, 24 h p.i.), the tumor/kidney ratio was improved by factors of 3.3 (90 min p.i.) and 2.6 (24 h p.i.). Reduction of kidney uptake was demonstrated by SPECT, which also showed that the remaining activity was located in the cortex. Conclusions: The kidney uptake of both investigated radiopharmaceuticals was more efficiently reduced by gelofusine (61–85%) than Arg/Lys (25–41%). Gelofusine appears particularly suitable for reducing renal uptake of αvβ6-integrin targeted 177Lu-labeled peptide multimers because its application led to approximately three times higher tumor-to-kidney ratios. Since the incidence of severe adverse events (anaphylaxis) with succinylated gelatin products (reportedly 0.0062–0.038%) is comparable to that of gadolinium-based MRI or iodinated CT contrast agents (0.008% and 0.04%, respectively), clinical use of gelofusine during radioligand therapy appears feasible if similar risk management strategies as for contrast agents are applied. [ABSTRACT FROM AUTHOR]

Purpose: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. Methods: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. Results: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19–47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan–Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. Conclusion: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. Trial registration: : The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933). [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model. NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([18F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells. Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients. [ABSTRACT FROM AUTHOR]

Purpose: Brain functional and physiological plasticity is essential to combat dynamic environmental challenges. The rhythmic dopamine signaling pathway, which regulates emotion, reward and learning, shows seasonal patterns with higher capacity of dopamine synthesis and lower number of dopamine transporters during dark seasons. However, seasonal variation of the dopamine receptor signaling remains to be characterized. Methods: Based on a historical database of healthy human brain [11C]raclopride PET scans (n = 291, 224 males and 67 females), we investigated the seasonal patterns of D2/3 dopamine receptor signaling. Daylength at the time of scanning was used as a predictor for brain regional non-displaceable binding of the radiotracer, while controlling for age and sex. Results: Daylength was negatively correlated with availability of D2/3 dopamine receptors in the striatum. The largest effect was found in the left caudate, and based on the primary sample, every 4.26 h (i.e., one standard deviation) increase of daylength was associated with a mean 2.8% drop (95% CI -0.042 to -0.014) of the receptor availability. Conclusions: Seasonally varying D2/3 receptor signaling may also underlie the seasonality of mood, feeding, and motivational processes. Our finding suggests that in future studies of brain dopamine signaling, especially in high-latitude regions, the effect of seasonality should be considered. [ABSTRACT FROM AUTHOR]

The single nucleotide polymorphism (SNP)-rs6922617 in the triggering receptor expressed on myeloid cells (TREM) gene cluster is a potential risk factor for Alzheimer's disease (AD). Here, we examined whether rs6922617 is associated with AD-defining neuropathological hallmarks and memory performance. We assessed the interaction between the variant rs6922617 and levels of beta-amyloid (Aβ), tau pathology, neurodegeneration, namely amyloid-tau-neurodegeneration framework, and cognition functions in 660 healthy controls, 794 mild cognitively impaired, and 272 subjects with AD. We employed linear regression and linear mixed models to examine the association. Here we find that the SNP-rs6922617 in the TREM gene cluster is associated with a higher global amyloid-ligands positron emission tomography (Aβ-PET) burden and lower fluorodeoxyglucose positron emission tomography (FDG-PET) load. Interestingly, rs6922617 risk allele carriers exhibit a significantly reduced tau accumulation compared to the non-carriers, indicating a discrepant association with Aβ and tau pathologies. Though the participants carrying the rs6922617 risk allele do not show a correlation with poorer cognitive performance, stronger neuropathological phenotypes, and memory impairments are evident in ApoE ε4 carriers with the rs6922617 risk allele. These results support the notion that the SNP-rs6922617 in the TREM gene cluster is associated with AD-related neuropathological hallmarks, such as Aβ and FDG-mediated neurodegeneration, rather than tau accumulation. Although the direct association with memory impairment in the Alzheimer's continuum remains inconclusive, our findings suggest a potential role of rs6922617 in facilitating neuropathology hallmarks. [ABSTRACT FROM AUTHOR]

Background: Age represents the largest risk factor for Alzheimer's disease (AD) but is typically treated as a covariate. Still, there are similarities between brain regions affected in AD and those showing accelerated decline in normal aging, suggesting that the distinction between the two might fall on a spectrum. Objective: Our goal was to identify regions showing accelerated atrophy across the brain and investigate whether these overlapped with regions involved in AD or where related to amyloid. Methods: We used a longitudinal sample of 137 healthy older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), who underwent magnetic resonance imaging (MRI). In addition, a total of 79 participants also had longitudinal positron emission tomography (PET) data. We computed linear-mixed effects models for brain regions declining faster than the average to investigate variability in the rate of change. Results: 23 regions displayed a 0.5 standard deviation (SD) above average decline over 2 years. Of these, 52% overlapped with regions showing similar decline in a matched AD sample. Beyond this, the left precuneus, right superior frontal, transverse temporal, and superior temporal sulcus showed accelerated decline. Lastly, atrophy in the precuneus was associated with increased amyloid load. Conclusions: Accelerated decline in normal aging might contribute to the detection of early signs of AD among healthy individuals. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single‐photon emission computed tomography (SPECT) and 18F‐FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). Methods: A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). Results: After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008–1.052, p =.007). The cut‐off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p =.035). A sensitivity analysis restricting patients with single‐vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008–1.043, p =.005). Conclusion: HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO‐PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large‐scale studies. [ABSTRACT FROM AUTHOR]