Cardiotoxicity detection tool for breast cancer chemotherapy: a retrospective study.

Background: Patients with breast cancer undergoing biological therapy and/or chemotherapy perform multiple radionuclide angiography (RNA) or multigated acquisition (MUGA) scans to assess cardiotoxicity. The association between RNA imaging parameters and left ventricular (LV) ejection fraction (LVEF) remains unclear.

Objectives: This study aimed to extract and evaluate the association of several novel imaging biomarkers to detect changes in LVEF in patients with breast cancer undergoing chemotherapy.

Development and Validation of Prognostic Models Using Radiomic Features from Pre-Treatment Positron Emission Tomography (PET) Images in Head and Neck Squamous Cell Carcinoma (HNSCC) Patients.

High-dimensional radiomics features derived from pre-treatment positron emission tomography (PET) images offer prognostic insights for patients with head and neck squamous cell carcinoma (HNSCC). Using 124 PET radiomics features and clinical variables (age, sex, stage of cancer, site of cancer) from a cohort of 232 patients, we evaluated four survival models-penalized Cox model, random forest, gradient boosted model and support vector machine-to predict all-cause mortality (ACM), locoregional recurrence/residual disease (LR) and distant metastasis (DM) probability during 36, 24 and 24 months of follow-up, respectively. We developed models with five-fold cross-validation, selected the best-performing model for each outcome based on the concordance index (C-statistic) and the integrated Brier score (IBS) and validated them in an independent cohort of 102 patients.

Comparison of semi-automatic and manual segmentation methods for tumor delineation on head and neck squamous cell carcinoma (HNSCC) positron emission tomography (PET) images.

. Accurate and reproducible tumor delineation on positron emission tomography (PET) images is required to validate predictive and prognostic models based on PET radiomic features. Manual segmentation of tumors is time-consuming whereas semi-automatic methods are easily implementable and inexpensive.

A systematic review and meta-analysis of predictive and prognostic models for outcome prediction using positron emission tomography radiomics in head and neck squamous cell carcinoma patients.

Background: Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular levels. Therefore, PET radiomics-based prediction and prognostic models have the potentials to understand tumour heterogeneity and assist clinicians with diagnosis, prognosis and management of the disease. We conducted a systematic review of published modelling information to evaluate the usefulness of PET radiomics in the prediction and prognosis of HNSCC patients.

Metabolic alterations in a rat model of takotsubo syndrome.

Aims: Cardiac energetic impairment is a major finding in takotsubo patients. We investigate specific metabolic adaptations to direct future therapies.

Methods And Results: An isoprenaline-injection female rat model (vs.

Standardization of Preclinical PET/CT Imaging to Improve Quantitative Accuracy, Precision, and Reproducibility: A Multicenter Study.

Preclinical PET/CT is a well-established noninvasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially nonexistent. This study (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multicenter data, optimized for routine scanning in the preclinical PET/CT laboratory.

Design, synthesis, in vitro characterization and preliminary imaging studies on fluorinated bile acid derivatives as PET tracers to study hepatic transporters.

With the aim of identifying a fluorinated bile acid derivative that could be used as [F]-labeled Positron Emission Tomography (PET) tracer for imaging the in vivo functioning of liver transporter proteins, and particularly of OATP1B1, three fluorinated bile acid triazole derivatives of cholic, deoxycholic and lithocholic acid (CATD, DCATD and LCATD 4a-c, respectively) were synthesized and labeled with tritium. In vitro transport properties were studied with cell-based assays to identify the best substrate for OATP1B1. In addition, the lead compound, LCATD (4c), was tested as a substrate of other liver uptake transporters OATP1B3, NTCP and efflux transporter BSEP to evaluate its specificity of liver transport.

Neuronal human BACE1 knockin induces systemic diabetes in mice.

Aims: β-Secretase 1 (BACE1) is a key enzyme in Alzheimer's disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4).

Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate.

Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m², took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30% of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake.

Mapping changes in mouse brain metabolism with PET/CT.

Unlabelled: Because preclinical imaging offers challenges and opportunities, we set out to investigate and optimize image processing techniques to measure changes in mouse brain metabolism with preclinical (18)F-FDG PET/CT. In particular, we considered the effects of scan length, image registration methods, image quantification methods, and smoothing during statistical parametric mapping (SPM).

Methods: A cohort of 12 wild-type mice was scanned on 3 occasions at an average age of 6, 10, and 14 mo.

18F-barbiturates are PET tracers with diagnostic potential in Alzheimer's disease.

Three fluoro-barbiturates were synthesised, showing in vivo sedative efficacy. One of them, [(18)F], was synthesised in radiofluorinated form. PET/CT Imaging with [(18)F] identified β-amyloid over-expressing transgenic mice (βA mice) compared to wild type and tau lines.

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.

Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance. Global PTP1B deletion improves diet-induced obesity and glucose homeostasis via enhanced leptin signaling in the brain and increased insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes is unclear, with studies demonstrating beneficial, detrimental or no effect(s) of adipose-PTP1B-deficiency on body mass and insulin resistance.

Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1.

Late-stage neuropathological hallmarks of Alzheimer's disease (AD) are β-amyloid (βA) and hyperphosphorylated tau peptides, aggregated into plaques and tangles, respectively. Corresponding phenotypes have been mimicked in existing transgenic mice, however, the translational value of aggressive over-expression has recently been questioned. As controlled gene expression may offer animal models with better predictive validity, we set out to design a transgenic mouse model that circumvents complications arising from pronuclear injection and massive over-expression, by targeted insertion of human mutated amyloid and tau transgenes, under the forebrain- and neurone-specific CaMKIIα promoter, termed PLB1(Double).

FDG-PET imaging, EEG and sleep phenotypes as translational biomarkers for research in Alzheimer's disease.

The lack of reliable translational procedures applicable to both patients and experimental models are a major obstacle for the advancement of basic research as well as for the development of therapeutics. This is particularly relevant to neurodegenerative disorders such as AD (Alzheimer's disease), where the predictive validity of animal models and procedures applied preclinically have met with little success. Two approaches available for human diagnostics are currently experiencing major advancements in preclinical research: in vivo imaging using MRI (magnetic resonance imaging) or PET (positron-emission tomography) and recordings of brain electrical activity via surface EEG (electroencephalogram).

Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro.

Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18F]fluoro-2-deoxy-d-glucose (FDG) incorporation, as compared with sensitive cells.

Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells.

[Methyl-3H]-choline incorporation into MCF-7 cells: correlation with proliferation, choline kinase and phospholipase D assay.

Background: [Methyl-3H]-choline is a promising new positron emission tomography (PET) agent used for cancer imaging whose mechanism has still not fully been elucidated. In this study, whether [methyl-3H]-choline determined by measuring the activity of choline kinase (ChoK) and phospholipase D (PLD) in rapidly proliferating and confluent breast cancer MCF-7 cells is related to cell proliferation or not was investigated.

Materials And Methods: The activity of ChoK and PLD were determined using ion exchange chromatography and transphosphatidylation assay respectively.

[methyl-3H]Choline incorporation into MCF7 tumour cells: correlation with proliferation.

Purpose: The aim of the study was to investigate the intracellular location of [methyl-(3)H]choline in MCF7 tumour cells and to determine the relationship between [methyl-(3)H]choline incorporation and proliferation.

Methods: Tumour cells were incubated with [methyl-(3)H]choline for 10 min, and then in cold medium to simulate the rapid blood clearance of [methyl-(11)C]choline. Labelled metabolites were then extracted from cells by treating them with organic and aqueous solvents to determine the distribution of tracer between phospholipid and water-soluble metabolite pools.