Radiosynthesis and evaluation of a novel F-labeled tracer for PET imaging of glycogen synthase kinase 3.

Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase family that regulates diverse biological processes including glucose metabolism, insulin activity and energy homeostasis. Dysregulation of GSK3 is implicated in the development of several diseases such as type 2 diabetes mellitus, Alzheimer's disease (AD), and various cancer types. In this study, we report the synthesis and evaluation of a novel positron emission tomography (PET) ligand compound 28 (codenamed [F]GSK3-2209).

Development of a Candidate C-Labeled Selective Phosphodiesterase 1 Radioligand for Positron Emission Tomography.

Phosphodiesterases (PDEs) constitute a superfamily of phosphohydrolytic enzymes that regulate intracellular second messenger signaling by hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate. Among the 11 subfamilies of PDEs, phosphodiesterase 1 (PDE1) stands out due to its broad implications in central and peripheral pathologies. There are three subtypes of PDE1: PDE1A, PDE1B, and PDE1C.

Identifying the bioimaging features of Alzheimer's disease based on pupillary light response-driven brain-wide fMRI in awake mice.

Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD) patients show potential as biomarkers for brain degeneration. To investigate AD-specific PLR and its underlying neuromodulatory sources, we combine high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( ) and post-illumination pupil dilation recovery (amplitude, , and time, T).

Discovery of F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor.

The histamine subtype 3 (H) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H receptor. In this study, we synthesized and evaluated the binding effects of [F]H3-2404 and [F]H3-2405 by modifying the structure of AZD5213, a selective H antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum.

Degradation of Amyloid-β Species by Multi-Copper Oxidases.

Background: Reduction of the production of amyloid-β (Aβ) species has been intensively investigated as potential therapeutic approaches for Alzheimer's disease (AD). However, the degradation of Aβ species, another potential beneficial approach, has been far less explored.

Objective: To investigate the potential of multi-copper oxidases (MCOs) in degrading Aβ peptides and their potential benefits for AD treatment.

Fabricating vascularized, anatomically accurate bone grafts using 3D bioprinted sectional bone modules, in-situ angiogenesis, BMP-2 controlled release, and bioassembly.

Bone grafting is the most common treatment for repairing bone defects. However, current bone grafting methods have several drawbacks. Bone tissue engineering emerges as a promising solution to these problems.

Half-Curcumin-Based Chemiluminescence Probes and Their Applications in Detecting Quasi-Stable Oxidized Proteins.

Numerous methods have been reported for detecting ROS/RNS in vitro and in vivo; however, detecting methods for the secondary products of the reactive oxygen species (ROS)/reactive nitrogen species (RNS) reactions, particularly quasi-stable oxidized products, have been much less explored. In this report, we observed that half-curcumins could generate chemiluminescence (CL). In contrast to other chemiluminescence scaffolds, the distinguishing feature of a half-curcumin is the formation of a carbanion intermediate of its acetylacetone moiety, opening unique avenues for applications.

Iterative Design of Near-Infrared Fluorescent Probes for Early Diagnosis of Alzheimer's Disease by Targeting Aβ Oligomers.

Amyloid-β oligomers (AβOs), crucial toxic proteins in early Alzheimer's disease (AD), precede the formation of Aβ plaques and cognitive impairment. In this context, we present our iterative process for developing novel near-infrared fluorescent (NIRF) probes specifically targeting AβOs, aimed at early AD diagnosis. An initial screening identified compound as being highly selective for AβOs.

Mapping the bioimaging marker of Alzheimer's disease based on pupillary light response-driven brain-wide fMRI in awake mice.

Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD) patients may be used as biomarkers of brain degeneration. To characterize AD-specific PLR and its underlying neuromodulatory sources, we combined high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( ) and post-illumination pupil dilation recovery (amplitude, , and time, ).

In vivo three-dimensional brain imaging with chemiluminescence probes in Alzheimer's disease models.

Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields, relatively long emission wavelengths, and high signal-to-noise ratios to fulfill the requirements for 3D brain imaging in vivo.

Molecularly generated light and its biomedical applications.

Molecularly generated light, referred to here as "molecular light", mainly includes bioluminescence, chemiluminescence, and Cerenkov luminescence. Molecular light possesses unique dual features of being both a molecule and a source of light. Its molecular nature enables it to be delivered as molecules to regions deep within the body, overcoming the limitations of natural sunlight and physically generated light sources like lasers and LEDs.

The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption.

Chronic pain is highly prevalent and is linked to a broad range of comorbidities, including sleep disorders. Epidemiological and clinical evidence suggests that chronic sleep disruption (CSD) leads to heightened pain sensitivity, referred to as CSD-induced hyperalgesia. However, the underlying mechanisms are unclear.

A Photolabile Curcumin-Diazirine Analogue Enables Phototherapy with Physically and Molecularly Produced Light for Alzheimer's Disease Treatment.

The development of Alzheimer's disease (AD) drugs has recently witnessed substantial achievement. To further enhance the pool of drug candidates, it is crucial to explore non-traditional therapeutic avenues. In this study, we present the use of a photolabile curcumin-diazirine analogue, CRANAD-147, to induce changes in properties, structures (sequences), and neurotoxicity of amyloid beta (Aβ) species both in cells and in vivo.

Bioluminescence Imaging with Functional Amyloid Reservoirs in Alzheimer's Disease Models.

Bioluminescence imaging has changed the daily practice of preclinical research on cancer and other diseases over the last few decades; however, it has rarely been applied in preclinical research on Alzheimer's disease (AD). In this Article, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Aβ) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Aβ aggregates and plaques.

The Application of Bio-orthogonality for In Vivo Animal Imaging.

The application of bio-orthogonality has greatly facilitated numerous aspects of biological studies in recent years. In particular, bio-orthogonal chemistry has transformed biological research, including in vitro conjugate chemistry, target identification, and biomedical imaging. In this review, we highlighted examples of bio-orthogonal in vivo imaging published in recent years.

Imaging Cholinergic Receptors in the Brain by Positron Emission Tomography.

Cholinergic receptors represent a promising class of diagnostic and therapeutic targets due to their significant involvement in cognitive decline associated with neurological disorders and neurodegenerative diseases as well as cardiovascular impairment. Positron emission tomography (PET) is a noninvasive molecular imaging tool that has helped to shed light on the roles these receptors play in disease development and their diverse functions throughout the central nervous system (CNS). In recent years, there has been a notable advancement in the development of PET probes targeting cholinergic receptors.

Degradation of amyloid beta species by multi-copper oxidases.

Reduction of the production of amyloid beta (Aβ) species has been intensively investigated as potential therapeutic approaches for Alzheimer's disease (AD). However, the degradation of Aβ species, another potential beneficial approach, has been far less explored. In this study, we discovered that ceruloplasmin (CP), an important multi-copper oxidase (MCO) in human blood, could degrade Aβ peptides.

In Vivo Three-dimensional Brain Imaging with Chemiluminescence Probes in Alzheimer's Disease Models.

Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields (QY), relatively long emission wavelengths, and high signal-to-noise ratios (SNRs) to fulfill the requirements for 3D brain imaging in vivo.

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation.

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood.

Imaging Brown Adipose Tissue with TSPO PET Tracers in Preclinical Animal Studies.

Brown adipose tissue (BAT) is closely associated with thermogenesis and related to numerous diseases, including type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), and obesity. Using molecular imaging technologies to monitor BAT could facilitate etiology elucidation, disease diagnosis, and therapeutics development. Translocator protein (TSPO), an 18 kDa protein that mainly locates on the outer mitochondrial membrane, has been proven as a promising biomarker for monitoring BAT mass.

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation.

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood.

Measurements of cerebral microvascular blood flow, oxygenation, and morphology in a mouse model of whole-brain irradiation-induced cognitive impairment by two-photon microscopy and optical coherence tomography: evidence for microvascular injury in the cerebral white matter.

Whole-brain irradiation (WBI, also known as whole-brain radiation therapy) is a mainstay treatment modality for patients with multiple brain metastases. It is also used as a prophylactic treatment for microscopic tumors that cannot be detected by magnetic resonance imaging. WBI induces a progressive cognitive decline in ~ 50% of the patients surviving over 6 months, significantly compromising the quality of life.

Practical Guidance for Developing Small-Molecule Optical Probes for In Vivo Imaging.

The WMIS Education Committee (2019-2022) reached a consensus that white papers on molecular imaging could be beneficial for practitioners of molecular imaging at their early career stages and other scientists who are interested in molecular imaging. With this consensus, the committee plans to publish a series of white papers on topics related to the daily practice of molecular imaging. In this white paper, we aim to provide practical guidance that could be helpful for optical molecular imaging, particularly for small molecule probe development and validation in vitro and in vivo.