Imaging demyelinated axons after spinal cord injuries with PET tracer [ F]3F4AP.

Spinal cord injuries (SCI) often lead to lifelong disability. Among the various types of injuries, incomplete and discomplete injuries, where some axons remain intact, offer potential for recovery. However, demyelination of these spared axons can worsen disability.

Common anesthetic used in preclinical PET imaging inhibits metabolism of the PET tracer [ F]3F4AP.

PET imaging studies in laboratory animals are almost always performed under isoflurane anesthesia to ensure that the subject stays still during the image acquisition. Isoflurane is effective, safe, and easy to use, and it is generally assumed to not have an impact on the imaging results. Motivated by marked differences observed in [ F]3F4AP brain uptake and metabolism between human and nonhuman primate studies, this study investigates the possible effect of isoflurane on [ F]3F4AP metabolism and brain uptake.

Metabolic Stability of the Demyelination Positron Emission Tomography Tracer [F]3-Fluoro-4-Aminopyridine and Identification of Its Metabolites.

[F]3-fluoro-4-aminopyridine ([F]3F4AP) is a positron emission tomography (PET) tracer for imaging demyelination based on the multiple sclerosis drug 4-aminopyridine (4AP, dalfampridine). This radiotracer was found to be stable in rodents and nonhuman primates imaged under isoflurane anesthesia. However, recent findings indicate that its stability is greatly decreased in awake humans and mice.

Broad-scope Syntheses of [ C/ F]Trifluoromethylarenes from Aryl(mesityl)iodonium Salts.

Efficient methods for labeling aryl trifluoromethyl groups to provide novel radiotracers for use in biomedical research with positron emission tomography (PET) are keenly sought. We report a broad-scope method for labeling trifluoromethylarenes with either carbon-11 (t =20.4 min) or fluorine-18 (t =109.

Syntheses of [C]2- and [C]3-trifluoromethyl-4-aminopyridine: potential PET radioligands for demyelinating diseases.

Trifluoromethyl groups are of great interest in PET radiopharmaceuticals. Radiolabelled 4-aminopyridine (4AP) derivatives have been proposed for imaging demyelinating diseases. Here, we describe methods for producing C-trifluoromethylated derivatives of 4AP and present early imaging results with [C]3-trifluoromethyl-4AP in a rhesus macaque.

Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler.

Background: We recently reported a method using positron emission tomography (PET) and the tracer F-labeled tetraphenylphosphonium (F-TPP) for mapping the tissue (i.e., cellular plus mitochondrial) membrane potential (ΔΨ) in the myocardium.

Structure-activity relationship studies of four novel 4-aminopyridine K channel blockers.

4-Aminopyridine (4AP) is a specific blocker of voltage-gated potassium channels (K1 family) clinically approved for the symptomatic treatment of patients with multiple sclerosis (MS). It has recently been shown that [F]3F4AP, a radiofluorinated analog of 4AP, also binds to K1 channels and can be used as a PET tracer for the detection of demyelinated lesions in rodent models of MS. Here, we investigate four novel 4AP derivatives containing methyl (-CH), methoxy (-OCH) as well as trifluoromethyl (-CF) in the 2 and 3 position as potential candidates for PET imaging and/or therapy.

Tuning the Color Palette of Fluorescent Copper Sensors through Systematic Heteroatom Substitution at Rhodol Cores.

Copper is an essential nutrient for sustaining life, and emerging data have expanded the roles of this metal in biology from its canonical functions as a static enzyme cofactor to dynamic functions as a transition metal signal. At the same time, loosely bound, labile copper pools can trigger oxidative stress and damaging events that are detrimental if misregulated. The signal/stress dichotomy of copper motivates the development of new chemical tools to study its spatial and temporal distributions in native biological contexts such as living cells.

Stage specific effects of soluble copper and copper oxide nanoparticles during sea urchin embryo development and their relation to intracellular copper uptake.

The effects of exposure to either soluble copper (copper sulfate) or copper oxide nanoparticles (nano-CuO) during specific early developmental stages of sea urchin embryos were analyzed. Soluble copper caused significant malformations in embryos (skeletal malformations, delayed development or gut malformations) when present at any given stage, while cleavage stage was the most sensitive to nano-CuO exposure causing skeletal malformations and decreased total antioxidant capacity. The stage specificity was linked to higher endocytic activity during the first hours of development that leads to higher accumulation of copper in specific cells critical for development.

Cell-surface copper transporters and superoxide dismutase 1 are essential for outgrowth during fungal spore germination.

During fungal spore germination, a resting spore returns to a conventional mode of cell division and resumes vegetative growth, but the requirements for spore germination are incompletely understood. Here, we show that copper is essential for spore germination in Germinating spores develop a single germ tube that emerges from the outer spore wall in a process called outgrowth. Under low-copper conditions, the copper transporters Ctr4 and Ctr5 are maximally expressed at the onset of outgrowth.

Thioether Coordination Chemistry for Molecular Imaging of Copper in Biological Systems.

Copper is an essential element in biological systems. Its potent redox activity renders it necessary for life, but at the same time, misregulation of its cellular pools can lead to oxidative stress implicated in aging and various disease states. Copper is commonly thought of as a static cofactor buried in protein active sites; however, evidence of a more loosely bound, labile pool of copper has emerged.

Recognition- and reactivity-based fluorescent probes for studying transition metal signaling in living systems.

Metals are essential for life, playing critical roles in all aspects of the central dogma of biology (e.g., the transcription and translation of nucleic acids and synthesis of proteins).

Synthetic fluorescent probes for studying copper in biological systems.

The potent redox activity of copper is required for sustaining life. Mismanagement of its cellular pools, however, can result in oxidative stress and damage connected to aging, neurodegenerative diseases, and metabolic disorders. Therefore, copper homeostasis is tightly regulated by cells and tissues.