Toward AI-driven neuroepigenetic imaging biomarker for alcohol use disorder: A proof-of-concept study.

Alcohol use disorder (AUD) is a disorder of clinical and public health significance requiring novel and improved therapeutic solutions. Both environmental and genetic factors play a significant role in its pathophysiology. However, the underlying epigenetic molecular mechanisms that link the gene-environment interaction in AUD remain largely unknown.

Synthesis and characterization of a new Positron emission tomography probe for orexin 2 receptors neuroimaging.

The orexin receptors (OXRs) have been involved in multiple physiological and neuropsychiatric functions. Identification of PET imaging probes specifically targeting OXRs enables us to better understand the OX system. Seltorexant (JNJ-42847922) is a potent OXR antagonist with the potential to be an OXR PET imaging probe.

Preliminary studies of an imidazole-based alcohol derivative for imaging of Heme oxygenase 1.

Heme oxygenase-1 (HO-1) has been involved in the pathogenesis of Alzheimer's disease (AD), thus constituting a promising target for AD drug development. Positron emission tomography (PET) is a fully translational imaging technology, which will help us understand the role of HO-1 in the progression of AD, facilitating to validate promising HO-1 inhibitors in clinical trials. To our knowledge, there is no report on PET imaging probe targeting HO-1 in animals and humans.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis.

Objective: To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies.

Summary Background Data: Identifying PC impacts prognosis and management of multiple cancer types.

Methods: Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021.

Visualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography.

We report the development of the first positron emission tomography (PET) radiotracer, [F]CNY-07, based on a highly specific and potent RIPK1 inhibitor, Nec-1s, for RIPK1/necroptosis brain imaging in rodents. [F]CNY-07 was synthesized through copper-mediated F-radiolabeling from an aryl boronic ester precursor and studied PET imaging in rodents. PET imaging results showed that [F]CNY-07 can penetrate the blood-brain barrier with a maximum percent injected dose per unit volume of 3 at 10 min postinjection in the brain .

Design, Synthesis, and Evaluation of Thienodiazepine Derivatives as Positron Emission Tomography Imaging Probes for Bromodomain and Extra-Terminal Domain Family Proteins.

To better understand the role of bromodomain and extra-terminal domain (BET) proteins in epigenetic mechanisms, we developed a series of thienodiazepine-based derivatives and identified two compounds, and , as potent BET inhibitors. Further pharmacokinetic studies and analysis of metabolic stability of revealed excellent brain penetration and reasonable metabolic stability. Compounds and were radiolabeled with fluorine-18 in two steps and utilized in positron emission tomography (PET) imaging studies in mice.

Clinical impact of PET/MRI in oligometastatic colorectal cancer.

Background: Oligometastatic colorectal cancer (CRC) is potentially curable and demands individualised strategies.

Methods: This single-centre retrospective study investigated if positron emission tomography (PET)/magnetic resonance imaging (MR) had a clinical impact on oligometastatic CRC relative to the standard of care imaging (SCI). Adult patients with oligometastatic CRC on SCI who also underwent PET/MR between 3/2016 and 3/2019 were included.

Synthesis and Characterization of a Positron Emission Tomography Imaging Probe Selectively Targeting the Second Bromodomain of Bromodomain Protein BRD4.

Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effects. However, little is known about this disease-related target.

Discovery of a Positron Emission Tomography Radiotracer Selectively Targeting the BD1 Bromodomains of BET Proteins.

In this paper, we report the design, synthesis, and biological evaluation of the first selective bromodomain and extra-terminal domain (BET) BD1 bromodomains of the PET radiotracer [F]PB006. The standard compound PB006 showed high affinity and good selectivity toward BRD4 BD1 ( = 100 nM and 29-fold selectively for BD1 over BD2) in an binding assay. PET imaging experiments in rodents were performed to evaluate the bioactivity of [F]PB006 .

Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome.

We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy substituent amenable to labeling with carbon-11. PET/CT imaging studies indicated that [C]1 exhibited rapid blood-brain barrier (BBB) penetration and moderate brain uptake, as well as blockable uptake in the brain.

Impact of PET/MRI in the Treatment of Pancreatic Adenocarcinoma: a Retrospective Cohort Study.

Purpose: Imaging is central to the diagnosis and management of Pancreatic Ductal Adenocarcinoma (PDAC). This study evaluated if positron emission tomography (PET)/magnetic resonance imaging (MRI) elicited treatment modifications in PDAC when compared to standard of care imaging (SCI).

Procedures: This retrospective study included consecutive patients with PDAC who underwent 2-deoxy-2-[F]fluoro-D-glucose ([F]F-FDG) PET/MRI and SCI from May 2017 to January 2019.

Improving staging of rectal cancer in the pelvis: the role of PET/MRI.

Purpose: The role of positron emission tomography/magnetic resonance (PET/MR) in evaluating the local extent of rectal cancer remains uncertain. This study aimed to investigate the possible role of PET/MR versus magnetic resonance (MR) in clinically staging rectal cancer.

Methods: This retrospective two-center cohort study of 62 patients with untreated rectal cancer investigated the possible role of baseline staging PET/MR versus stand-alone MR in determination of clinical stage.

Molecular imaging of Alzheimer's disease-related gamma-secretase in mice and nonhuman primates.

The pathogenesis of Alzheimer's disease (AD) is primarily driven by brain accumulation of the amyloid-β-42 (Aβ42) peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. γ-Secretase is a prime drug target for AD; however, its brain regional expression and distribution remain largely unknown. Here, we are aimed at developing molecular imaging tools for visualizing γ-secretase.

Development of a Novel Positron Emission Tomography (PET) Radiotracer Targeting Bromodomain and Extra-Terminal Domain (BET) Family Proteins.

Bromodomain and extra-terminal domain (BET) family proteins have become a hot research area because of their close relationship with a variety of human diseases. The non-invasive imaging technique, such as positron emission tomography (PET), provides a powerful tool to visualize and quantify the BET family proteins that accelerating the investigation of this domain. Herein, we describe the development of a promising PET probe, , specifically targeting BET family proteins based on the potent BET inhibitor CF53.

Imaging assisted evaluation of antitumor efficacy of a new histone deacetylase inhibitor in the castration-resistant prostate cancer.

Purpose: Castration-resistant prostate cancer (CRPC) is the most common cause of death in men. The effectiveness of HDAC inhibitors has been demonstrated by preclinical models, but not in clinical studies, probably due to the ineffectively accumulation of HDACI in prostate cancer cells. The purpose of this work was to evaluate effects of a novel HDACI (CN133) on CRPC xenograft model and 22Rv1 cells, and develops methods, PET/CT imaging, to detect the therapeutic effects of CN133 on this cancer.

Radiosynthesis and in vivo evaluation of a new positron emission tomography radiotracer targeting bromodomain and extra-terminal domain (BET) family proteins.

Introduction: Bromodomain and extra-terminal domain (BET) family proteins play a vital role in the epigenetic regulation process by interacting with acetylated lysine (Ac-K) residues in histones. BET inhibitors have become promising candidates to treat various diseases through the inhibition of the interaction between BET bromodomains and Ac-K of histone tails. With a molecular imaging probe, noninvasive imaging such as positron emission tomography (PET) can visualize the distribution and roles of BET family proteins in vivo and enlighten our understanding of BET protein function in both healthy and diseased tissue.