Radionuclide Therapies in Molecular Imaging and Precision Medicine.

This article reviews recent advances and applications of radionuclide therapy. Individualized precision medicine, new treatments, and the evolving role of radionuclide therapy are discussed.

Optimization of benzoquinone and hydroquinone derivatives as potent inhibitors of human 5-lipoxygenase.

Aiming to assess the biological activities of synthetic 1,4-benzoquinones, we previously synthesized different libraries of benzoquinones with lipophilic and bulky alkyl- or aryl-substituents that inhibited 5-lipoxygenase (5-LO). The high potency of 4,5-dimethoxy-3-alkyl-1,2-benzoquinones on 5-LO led to the idea to further modify the structures and thus to improve the inhibitory potential in vitro and in vivo as well as to investigate SARs. Systematic structural optimization through accurate structure-based design resulted in compound 30 (3-tridecyl-4,5-dimethoxybenzene-1,2-diol), an ubiquinol derivative that exhibited the strongest anti-inflammatory effect, with a 10-fold improved 5-LO inhibitory activity (IC = 28 nM) in activated neutrophils.

PET Tracers Beyond FDG in Prostate Cancer.

Conventional anatomical imaging with CT and MRI has limitations in the evaluation of prostate cancer. PET is a powerful imaging technique, which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate-specific membrane antigen receptors, and skeletal osteoblastic activity. Although 2-deoxy-2-F-FDG-PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer.

Force Perception Thresholds in Cochlear Implantation Surgery.

Tissue trauma is a frequent complication of cochlear implantation (CI) surgery, but the relationship between intracochlear trauma, electrode insertion forces, and surgeons' ability to perceive these forces is poorly understood. In this study, we simulated CI surgery using a benchtop apparatus to repeatedly apply small forces to the subjects' hands while reducing the variability in their hand movements. We used a psychophysical testing procedure to estimate the force perception thresholds of 10 otologic surgeons and found a median threshold of 20.

Evaluation of tetrabromobisphenol A effects on human glucocorticoid and androgen receptors: A comparison of results from human- with yeast-based in vitro assays.

The incidence of immune-related diseases increased over the last years in industrialized countries, suggesting a contribution of environmental factors. Impaired glucocorticoid action has been associated with immune disorders. Thus, there is an increasing interest to identify chemicals disrupting glucocorticoid action.

Change in Salvage Radiotherapy Management Based on Guidance With FACBC (Fluciclovine) PET/CT in Postprostatectomy Recurrent Prostate Cancer.

Purpose: We explored the influence of FACBC (fluciclovine) PET/CT on the decision to offer radiotherapy and radiotherapy treatment field recommendations in postprostatectomy patients with recurrent prostate cancer.

Patients And Methods: After obtaining institutional review board approval and informed consent, 87 patients with detectable prostate-specific antigen (PSA) levels were recruited into a prospective clinical trial. After an initial provider-determined radiotherapy plan based on conventional imaging, 44 of 87 patients were randomized to additionally undergo fluciclovine PET/CT.

Multisite Experience of the Safety, Detection Rate and Diagnostic Performance of Fluciclovine (F) Positron Emission Tomography/Computerized Tomography Imaging in the Staging of Biochemically Recurrent Prostate Cancer.

Purpose: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine (F) after biochemical recurrence.

Materials And Methods: A total of 596 patients underwent fluciclovine (F) positron emission tomography/computerized tomography at 4 clinical sites.

Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs.

Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids.

Random Walk Based Segmentation for the Prostate on 3D Transrectal Ultrasound Images.

This paper proposes a new semi-automatic segmentation method for the prostate on 3D transrectal ultrasound images (TRUS) by combining the region and classification information. We use a random walk algorithm to express the region information efficiently and flexibly because it can avoid segmentation leakage and shrinking bias. We further use the decision tree as the classifier to distinguish the prostate from the non-prostate tissue because of its fast speed and superior performance, especially for a binary classification problem.

Combining Population and Patient-Specific Characteristics for Prostate Segmentation on 3D CT Images.

Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance.

Impact of F-Fluciclovine PET on Target Volume Definition for Postprostatectomy Salvage Radiotherapy: Initial Findings from a Randomized Trial.

The purpose of this study was to evaluate the role of the synthetic amino acid PET radiotracer F-fluciclovine in modifying the defined clinical and treatment-planning target volumes in postprostatectomy patients undergoing salvage radiotherapy and to evaluate the resulting dosimetric consequences to surrounding organs at risk. Ninety-six patients were enrolled in a randomized, prospective intention-to-treat clinical trial for potential salvage radiotherapy for recurrent prostate cancer after prostatectomy. The initial treatment plan was based on the results from conventional abdominopelvic CT and MRI.

Tachycardia detection in ICDs by Boston Scientific : Algorithms, pearls, and pitfalls.

Aim: The aim of this study was to summarize how implantable cardioverter defibrillators (ICDs) by Boston Scientific sense, detect, discriminate rhythms, and classify episodes.

Methods: Modern devices include multiple programming selections, diagnostic features, therapy options, memory functions, and device-related history features. Device operation includes logical steps from sensing, detection, discrimination, therapy delivery to history recording.

Evaluation of selected 3D virtual screening tools for the prospective identification of peroxisome proliferator-activated receptor (PPAR) γ partial agonists.

The peroxisome proliferator-activated receptor (PPAR) γ regulates the expression of genes involved in adipogenesis, lipid homeostasis, and glucose metabolism, making it a valuable drug target. However, full activation of the nuclear receptor is associated with unwanted side effects. Research therefore focuses on the discovery of novel partial agonists, which show a distinct protein-ligand interaction pattern compared to full agonists.

Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial.

Purpose: (18)F-Fluciclovine (anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of (18)F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes.

Methods And Materials: We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the (18)F-fluciclovine arm.

Leoligin, the major lignan from Edelweiss, inhibits 3-hydroxy-3-methyl-glutaryl-CoA reductase and reduces cholesterol levels in ApoE-/- mice.

The health benefit through the control of lipid levels in hyperlipidaemic individuals is evident from a large number of studies. The pharmacological options to achieve this goal shall be as specific and personalized as the reasons for and co-factors of hyperlipidaemia. It was the goal of this study to reveal the impact of leoligin on cholesterol levels and to define its mechanism of action.

Relationships between unilateral horizontal and vertical drop jumps and 20 m sprint performance.

Objectives: The purpose of this study was to compare the relationships between horizontal (HDJ) and vertical drop jumps (VDJ) to sprint performance.

Design: Exploratory Study.

Setting: Laboratory.

Teriparatide in patients with osteoporosis and type 2 diabetes.

Despite evidence for higher fracture risk, clinical effects of osteoporosis treatments in type 2 diabetes (T2D) are largely unknown. Post hoc analyses of the DANCE observational study compared T2D patients and patients without diabetes to assess the effect of teriparatide, an osteoanabolic therapy on skeletal outcomes and safety. Patients included ambulatory men and women with osteoporosis receiving teriparatide 20μg/day SQ up to 24months followed by observation up to 24months.

Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors.

Over the last twenty years, tocotrienol analogues raised great interest because of their higher level and larger domain of biological activities when compared with tocopherols. Amongst the most promising therapeutic application, anti-inflammatory potency has been evaluated through the inhibition of various mediators of inflammation. Here, we worked on the isolation of two natural isoforms of garcinoic acid (i.

Is There a Role for PET/CT Parameters to Characterize Benign, Malignant, and Metastatic Parotid Tumors?

Objective: Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity.

Initial radiographic tumor control is similar following single or multi-fractionated stereotactic radiosurgery for jugular paragangliomas.

Objective: To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS).

Study Design: Retrospective chart review.

Setting: Tertiary academic referral center.

The 5-lipoxygenase inhibitor RF-22c potently suppresses leukotriene biosynthesis in cellulo and blocks bronchoconstriction and inflammation in vivo.

5-Lipoxygenase (5-LO) catalyzes the first two steps in leukotriene (LT) biosynthesis. Because LTs play pivotal roles in allergy and inflammation, 5-LO represents a valuable target for anti-inflammatory drugs. Here, we investigated the molecular mechanism, the pharmacological profile, and the in vivo effectiveness of the novel 1,2-benzoquinone-featured 5-LO inhibitor RF-22c.

hERG Channel Blocking Ipecac Alkaloids Identified by Combined In Silico - In Vitro Screening.

Human ether-a-go-go-related gene channel blocking is associated with QT interval prolongation and increased risk of potentially fatal arrhythmias. As natural products keep increasing in popularity, there is an urgent need for studies assessing human ether-a-go-go-related gene channel-related cardiotoxic risks. We selected 49 plant species based on the results of a pharmacophore-based virtual screening campaign, in parallel with a literature data survey concerning highly consumed herbal medicines with reported cardiac liabilities.

Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer's disease.

Background: The burden on caregivers of patients with Alzheimer's disease (AD) is associated with the patient's functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed.

Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT.

Purpose: To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[(18)F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma.

Methods: This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated.