Performance evaluation of HiPET, a high sensitivity and high resolution preclinical PET tomograph.

HiPET is a recently developed prototype preclinical PET scanner dedicated to high sensitivity and high resolution molecular imaging. The HiPET system employs a phoswich depth of interaction (DOI) detector design, which also allows identification of the large majority of the cross layer crystal scatter (CLCS) events. This work evaluates its performance characteristics following the National Electrical Manufacturers Association (NEMA) NU4-2008 protocol.

Rapid One-Step F-Labeling of Peptides via Heteroaromatic Silicon-Fluoride Acceptors.

A new class of organosilicon-based radiosynthons, heteroaromatic silicon-fluoride acceptors, namely, HetSiFAs, that readily undergo isotope exchange with dry [F]fluoride at room temperature in high radiochemical yield (up to 94%) with good molar activity is reported. Radiofluorination proceeds in a single step in 2 min without high-performance liquid chromatography purification to provide an operationally simple method for F-PET tracer production. This method was used to prepare an F-labeled commercial tetrapeptide, and positron emission tomography imaging confirmed stability.

Tri-functional platform for construction of modular antibody fragments for F-PET or NIRF molecular imaging.

Positron emission tomography (PET) molecular imaging is a powerful tool for interrogating physiological and biochemical processes to understand the biology of disease and advance therapeutic developments. Near-infrared fluorescence (NIRF) optical imaging has become increasingly popular for intraoperative staging to enable cellular resolution imaging of tumor margins during surgical resection. In addition, engineered antibody fragments have emerged as promising molecular imaging agents given their exquisite target selectivity, rapid systemic clearance and site-selective chemical modification.

Publisher Correction: In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET).

Background: Conventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources.

High-throughput radio-TLC analysis.

Introduction: Radio thin layer chromatography (radio-TLC) is commonly used to analyze purity of radiopharmaceuticals or to determine the reaction conversion when optimizing radiosynthesis processes. In applications where there are few radioactive species, radio-TLC is preferred over radio-high-performance liquid chromatography due to its simplicity and relatively quick analysis time. However, with current radio-TLC methods, it remains cumbersome to analyze a large number of samples during reaction optimization.

A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes.

Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes.

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells.

Elevated glucose consumption is fundamental to cancer, but selectively targeting this pathway is challenging. We develop a high-throughput assay for measuring glucose consumption and use it to screen non-small-cell lung cancer cell lines against bioactive small molecules. We identify Milciclib that blocks glucose consumption in H460 and H1975, but not in HCC827 or A549 cells, by decreasing SLC2A1 (GLUT1) mRNA and protein levels and by inhibiting glucose transport.

In vivo characterization of [F]AVT-011 as a radiotracer for PET imaging of multidrug resistance.

Purpose: Multidrug resistance (MDR) impedes cancer treatment. Two efflux transporters from the ATP-binding cassette (ABC) family, ABCB1 and ABCG2, may contribute to MDR by restricting the entry of therapeutic drugs into tumor cells. Although a higher expression of these transporters has been correlated with an unfavorable response to chemotherapy, transporter expression does not necessarily correlate with function.

The subgingival microbiome associated with periodontitis in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a systemic disease, predisposing patients to other inflammatory conditions including periodontitis. The subgingival microbiome, a key player in periodontitis pathogenesis, is not well characterized in T2DM population. To better understand whether the subgingival microbiome is different between T2DM and systemically healthy, nondiabetic (ND) subjects, we performed a longitudinal analysis of the subgingival microbiome in T2DM patients (n = 15) compared with ND subjects (n = 16).

In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer.

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP.

F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis.

Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism.

On-demand radiosynthesis of -succinimidyl-4-[F]fluorobenzoate ([F]SFB) on an electrowetting-on-dielectric microfluidic chip for F-labeling of protein.

An all-electronic, droplet-based batch microfluidic device, operated using the electrowetting on dielectric (EWOD) mechanism was developed for on-demand synthesis of -succinimidyl-4-[F]fluorobenzoate ([F]SFB), the most commonly used F-prosthetic group for biomolecule labeling. In order to facilitate the development of peptides, and proteins as new diagnostic and therapeutic agents, we have diversified the compact EWOD microfluidic platform to perform the three-step radiosynthesis of [F]SFB starting from the no carrier added [F]fluoride ion. In this report, we established an optimal microliter droplet reaction condition to obtain reliable yields and synthesized [F]SFB with sufficient radioactivity for subsequent conjugation to the anti-PSCA cys-diabody (A2cDb) and for small animal imaging.

Nanostructured Substrates for Detection and Characterization of Circulating Rare Cells: From Materials Research to Clinical Applications.

Circulating rare cells in the blood are of great significance for both materials research and clinical applications. For example, circulating tumor cells (CTCs) have been demonstrated as useful biomarkers for "liquid biopsy" of the tumor. Circulating fetal nucleated cells (CFNCs) have shown potential in noninvasive prenatal diagnostics.

Noninvasive Prenatal Diagnostics: Recent Developments Using Circulating Fetal Nucleated Cells.

Purpose Of Review: The purpose of this review is to highlight recent research advances in noninvasive prenatal diagnostic methods.

Recent Findings: Recent studies developing noninvasive prenatal diagnostic (NIPD) methods have been focused on either fetal nucleated red blood cells (fNRBCs) or circulating trophoblasts (cTBs). Enriched cTBs were successfully utilized for whole genome profiling and short tandem repeat (STR) identification to confirm feto-maternal relationship.

Hyperoxia but not AOX expression mitigates pathological cardiac remodeling in a mouse model of inflammatory cardiomyopathy.

Constitutive expression of the chemokine Mcp1 in mouse cardiomyocytes creates a model of inflammatory cardiomyopathy, with death from heart failure at age 7-8 months. A critical pathogenic role has previously been proposed for induced oxidative stress, involving NADPH oxidase activation. To test this idea, we exposed the mice to elevated oxygen levels.

Ionic-surfactant-mediated electro-dewetting for digital microfluidics.

The ability to manipulate droplets on a substrate using electric signals-known as digital microfluidics-is used in optical, biomedical, thermal and electronic applications and has led to commercially available liquid lenses and diagnostics kits. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD); this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown, electric charging and biofouling.

A Tumor Agnostic Therapeutic Strategy for Hexokinase 1-Null/Hexokinase 2-Positive Cancers.

Since Warburg's observation that most cancers exhibit elevated glycolysis, decades of research have attempted to reduce tumor glucose utilization as a therapeutic approach. Hexokinase (HK) activity is the first glycolytic enzymatic step; despite many attempts to inhibit HK activity, none has reached clinical application. Identification of HK isoforms, and recognition that most tissues express only HK1 while most tumors express HK1 and HK2, stimulated reducing HK2 activity as a therapeutic option.

A linear mixed model approach to gene expression-tumor aneuploidy association studies.

Aneuploidy, defined as abnormal chromosome number or somatic DNA copy number, is a characteristic of many aggressive tumors and is thought to drive tumorigenesis. Gene expression-aneuploidy association studies have previously been conducted to explore cellular mechanisms associated with aneuploidy. However, in an observational setting, gene expression is influenced by many factors that can act as confounders between gene expression and aneuploidy, leading to spurious correlations between the two variables.

Current and Future Imaging Methods for Evaluating Response to Immunotherapy in Neuro-Oncology.

Imaging plays a central role in evaluating responses to therapy in neuro-oncology patients. The advancing clinical use of immunotherapies has demonstrated that treatment-related inflammatory responses mimic tumor growth via conventional imaging, thus spurring the development of new imaging approaches to adequately distinguish between pseudoprogression and progressive disease. To this end, an increasing number of advanced imaging techniques are being evaluated in preclinical and clinical studies.

Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells.

Well-preserved mRNA in circulating tumor cells (CTCs) offers an ideal material for conducting molecular profiling of tumors, thereby providing a noninvasive diagnostic solution for guiding treatment intervention and monitoring disease progression. However, it is technically challenging to purify CTCs while retaining high-quality mRNA.Here, we demonstrate a covalent chemistry-based nanostructured silicon substrate ("Click Chip") for CTC purification that leverages bioorthogonal ligation-mediated CTC capture and disulfide cleavage-driven CTC release.

The role of the skin microbiota in acne pathophysiology.

Background: The role of skin microbiota in acne remains to be fully elucidated. Initial culture-based investigations were hampered by growth rate and selective media bias. Even with less biased genomic methods, sampling, lysis and methodology, the task of describing acne pathophysiology remains challenging.

Pan-cancer Convergence to a Small-Cell Neuroendocrine Phenotype that Shares Susceptibilities with Hematological Malignancies.

Small-cell neuroendocrine cancers (SCNCs) are an aggressive cancer subtype. Transdifferentiation toward an SCN phenotype has been reported as a resistance route in response to targeted therapies. Here, we identified a convergence to an SCN state that is widespread across epithelial cancers and is associated with poor prognosis.

[Zr]A2cDb Immuno-PET of Prostate Cancer in a Human Prostate Stem Cell Antigen Knock-in (hPSCA KI) Syngeneic Model.

Purpose: A great challenge in the diagnosis and treatment of prostate cancer is distinguishing between indolent or local disease and aggressive or metastatic disease. Antibody-based positron emission tomography (immuno-PET) as a cancer-specific imaging modality could improve diagnosis of primary disease, aid the detection of metastases to regional lymph nodes as well as to distant sites (e.g.