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INTRODUCTION Tau‐positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis. METHODS Using head‐to‐head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed “CenTauR” [CTR]). JPM is a statistical model that simultaneously models the relationships between head‐to‐head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale. RESULTS A strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach. DISCUSSION Preliminary findings using the JPM support the development and adoption of a universal scale for tau‐PET quantification. Highlights Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed “CenTauRs”. Tested a Centiloid‐like linear regression approach. Using five cohorts with head‐to‐head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

INTRODUCTION Imaging biomarkers are fundamental in diagnosing neurodegenerative diseases, but their use in FTD remains limited. This study examines PET biomarkers in Argentine bvFTD patients. METHODS We studied a cohort of bvFTD patients (n = 20) and controls (n = 21) with three different PET radiotracers (18F‐FDG, 11C‐PiB, and 18F‐AV1451). RESULTS In bvFTD patients, 18F‐FDG PET showed significant hypometabolism in frontotemporal regions, along with hypermetabolism in the precentral gyrus, compared to normal controls. 11C‐PIB did not reveal a pattern typical of Alzheimer's disease, yet increased uptake was notably observed in the precentral region. We found 18F‐AV1451 uptake in frontal lobe, parietal, precuneus, cuneus, posterior cingulum, highly significant in bvFTD with respect to NCs. DISCUSSION PET biomarkers are a crucial tool in diverse real‐world clinical scenarios. However, their utility in revealing questions about the underlying pathology in FTD is still limited. Highlights First bvFTD study using 18F‐FDG, 11C‐PIB, and 18F‐AV1451 PET in a Latin American cohort. Frontotemporal hypometabolism with compensatory precentral hypermetabolism due to amyloid. Amyloid deposits observed in the precentral gyrus without an Alzheimer's‐like pattern. 18F‐AV1451 shows limitations in specificity for bvFTD pathology. Study provides new insights into PET biomarker utility for bvFTD clinical assessment.

This study sought to identify a reference tissue‐based quantification approach for improving the statistical power in detecting changes in brain glucose metabolism, amyloid, and tau deposition in Alzheimer's disease studies. A total of 794, 906, and 903 scans were included for 18F‐FDG, 18F‐florbetapir, and 18F‐flortaucipir, respectively. Positron emission tomography (PET) and T1‐weighted images of participants were collected from the Alzheimer's disease Neuroimaging Initiative database, followed by partial volume correction. The standardized uptake value ratios (SUVRs) calculated from the cerebellum gray matter, centrum semiovale, and pons were evaluated at both region of interest (ROI) and voxelwise levels. The statistical power of reference tissues in detecting longitudinal SUVR changes was assessed via paired t‐test. In cross‐sectional analysis, the impact of reference tissue‐based SUVR differences between cognitively normal and cognitively impaired groups was evaluated by effect sizes Cohen's d and two sample t‐test adjusted by age, sex, and education levels. The average ROI t values of pons were 86.62 and 38.40% higher than that of centrum semiovale and cerebellum gray matter in detecting glucose metabolism decreases, while the centrum semiovale reference tissue‐based SUVR provided higher t values for the detection of amyloid and tau deposition increases. The three reference tissues generated comparable d images for 18F‐FDG, 18F‐florbetapir, and 18F‐flortaucipir and comparable t maps for 18F‐florbetapir and 18F‐flortaucipir, but pons‐based t map showed superior performance in 18F‐FDG. In conclusion, the tracer‐specific reference tissue improved the detection of 18F‐FDG, 18F‐florbetapir, and 18F‐flortaucipir PET SUVR changes, which helps the early diagnosis, monitoring of disease progression, and therapeutic response in Alzheimer's disease. The reference tissue pons‐based 18F‐FDG SUVR and centrum semiovale‐based 18F‐florbetapir and 18F‐flortaucipir SUVR significantly improved the detection power of longitudinal PET changes in subjects with cognitive decline. The tracer‐specific reference tissue improved the detection of 18F‐FDG, 18F‐florbetapir, and 18F‐flortaucipir PET SUVR changes, which helps the early diagnosis, monitoring of disease progression, and therapeutic response in Alzheimer's disease.

This study aims to investigate if vaginal bacteriology obtained prior to treatment influences the 3′-deoxy-3 18F-fluorothymidine (FLT) [18F]FLT and 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG) [18F]FDG parameters in positron emission tomography (PET/CT) in cervical cancer (CC) patients. Methods: Retrospective analysis was performed on 39 women with locally advanced histologically confirmed cervical cancer who underwent dual tracer PET/CT examinations. The [18F]FLT and [18F]FDG PET parameters in the primary tumor, including SUVmax, SUVmean, MTV, heterogeneity, before radiotherapy (RT) were analyzed, depending on the bacteriology. The p-values < 0.05 were considered statistically significant. Results: In the vaginal and/or cervical smears, there were 27 (79.4%) positive results. In seven (20.6%) cases, no opportunistic pathogen growth was observed (No Bacteria Group). In positive bacteriology, eleven (32%) Gram-negative bacilli (Bacteria group 2) and fifteen (44%) Gram-positive bacteria (Bacteria group 1) were detected. Five patients with unknown results were excluded from the analysis. Data analysis shows a statistically significant difference between the SUVmax, and SUVmin values for three independent groups for the [18F]FLT. Conclusions: The lowest values of SUVmax and SUVmin for [18F]FLT are registered in Gram-negative bacteria, higher are in Gram-positive, and the absence of bacteria causes the highest [18F]FLT values.

PurposeTo compare the diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) and 18F-fluoroestradiol (18F-FES) positron emission tomography/computed tomography (PET/CT) for initial staging of estrogen receptor (ER) positive breast cancer.MethodsTwenty-eight patients with ER-positive breast cancer underwent 18F-FDG and 18F-FES PET/CT for initial staging. Diagnostic performance and concordance rates were analyzed for both radiotracers. Semiquantitative parameters of maximum standardized uptake value (SUVmax) and tumor-to-normal ratio (T/N ratio) were compared using Wilcoxon signed-rank test. Factors potentially affecting the degree of radiotracer uptake were analyzed by multi-level linear regression analysis.ResultsThe overall diagnostic performance of 18F-FES was comparable to 18F-FDG, except for higher specificity and NPV, with sensitivity, specificity, PPV, NPV, and accuracy of 87.56%, 100%, 100%, 35.14%, and 88.35%, respectively, for 18F-FES and 83.94%, 30.77%, 94.74%, 11.43%, and 95.37%, respectively, for 18F-FDG. Diagnostic performance of strong ER expression was better in 18F-FES but worse for 18F-FDG. There was a correlation of mucinous cell type and Allred score 7–8 with 18F-FES uptake, with correlation coefficients of 26.65 (19.28, 34.02), 5.90 (− 0.005, 11.81), and p-value of < 0.001, 0.05, respectively. Meanwhile, luminal B and Ki-67 were related to 18F-FDG uptake, with correlation coefficients of 2.76 (1.10, 0.20), 0.11 (0.01, 0.2), and p-value of 0.018, 0.025, respectively.ConclusionDiagnostic performance of 18F-FES is comparable to 18F-FDG, but better for strongly ER-positive breast cancer. Combination of 18F-FES and 18F-FDG would potentially overcome the limitations of each tracer with more accurate staging.

Diet-induced increase in body weight is a growing health concern worldwide. Often accompanied by a low-grade metabolic inflammation that changes systemic functions, diet-induced alterations may contribute to neurodegenerative disorder progression as well. This study aims to non-invasively investigate diet-induced metabolic and inflammatory effects in the brain of an APPPS1 mouse model of Alzheimer’s disease. [ 18 F]FDG, [ 18 F]FTHA, and [ 18 F]GE-180 were used for in vivo PET imaging in wild-type and APPPS1 mice. Ex vivo flow cytometry and histology in brains complemented the in vivo findings. 1 H- magnetic resonance spectroscopy in the liver, plasma metabolomics and flow cytometry of the white adipose tissue were used to confirm metaflammatory condition in the periphery. We found disrupted glucose and fatty acid metabolism after Western diet consumption, with only small regional changes in glial-dependent neuroinflammation in the brains of APPPS1 mice. Further ex vivo investigations revealed cytotoxic T cell involvement in the brains of Western diet-fed mice and a disrupted plasma metabolome. 1 H-magentic resonance spectroscopy and immunological results revealed diet-dependent inflammatory-like misbalance in livers and fatty tissue. Our multimodal imaging study highlights the role of the brain-liver-fat axis and the adaptive immune system in the disruption of brain homeostasis in amyloid models of Alzheimer’s disease.

•Assessment of inter-organ metabolic connectivity.•Automated and manual organ delineation.•Validation of metabolic connectivity approach.•Liver and kidney strongest connectivity with brain. The nervous and circulatory system interconnects the various organs of the human body, building hierarchically organized subsystems, enabling fine-tuned, metabolically expensive brain-body and inter-organ crosstalk to appropriately adapt to internal and external demands. A deviation or failure in the function of a single organ or subsystem could trigger unforeseen biases or dysfunctions of the entire network, leading to maladaptive physiological or psychological responses. Therefore, quantifying these networks in healthy individuals and patients may help further our understanding of complex disorders involving body-brain crosstalk. Here we present a generalized framework to automatically estimate metabolic inter-organ connectivity utilizing whole-body functional positron emission tomography (fPET). The developed framework was applied to 16 healthy subjects (mean age ± SD, 25 ± 6 years; 13 female) that underwent one dynamic 18F-FDG PET/CT scan. Multiple procedures of organ segmentation (manual, automatic, circular volumes) and connectivity estimation (polynomial fitting, spatiotemporal filtering, covariance matrices) were compared to provide an optimized thorough overview of the workflow. The proposed approach was able to estimate the metabolic connectivity patterns within brain regions and organs as well as their interactions. Automated organ delineation, but not simplified circular volumes, showed high agreement with manual delineation. Polynomial fitting yielded similar connectivity as spatiotemporal filtering at the individual subject level. Furthermore, connectivity measures and group-level covariance matrices did not match. The strongest brain-body connectivity was observed for the liver and kidneys. The proposed framework offers novel opportunities towards analyzing metabolic function from a systemic, hierarchical perspective in a multitude of physiological pathological states.

Imaging plays several key roles in managing brain tumors, including diagnosis, prognosis, and treatment response assessment. Ongoing challenges remain as new therapies emerge and there are urgent needs to find accurate and clinically feasible methods to noninvasively evaluate brain tumors before and after treatment. This review aims to provide an overview of several advanced imaging modalities including magnetic resonance imaging and positron emission tomography (PET), including advances in new PET agents, and summarize several key areas of their applications, including improving the accuracy of diagnosis and addressing the challenging clinical problems such as evaluation of pseudoprogression and anti-angiogenic therapy, and rising challenges of imaging with immunotherapy.

Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to d-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality. In this study, we used immunohistochemistry to examine the level of MG protein adducts, in a series of 102 CRC human tumors divided into four clinical stages. We consistently detected a high level of MG adducts and low GLO1 activity in high stage tumors compared to low stage ones suggesting a pro-tumor role for dicarbonyl stress. Accordingly, GLO1 depletion in CRC cells promoted tumor growth in vivo that was efficiently reversed using carnosine, a potent MG scavenger. Our study represents the first demonstration that MG adducts accumulation is a consistent feature of high stage CRC tumors. Our data point to MG production and detoxification levels as an important molecular link between exacerbated glycolytic activity and CRC progression.