Imaging of Pain using Positron Emission Tomography.

Positron emission tomography (PET) is a noninvasive molecular imaging technique that utilizes biologically active radiolabeled compounds to image biochemical processes. As such, PET can provide important pathophysiological information associated with pain of different etiologies. As such, the information obtained using PET often combined with MRI or CT can provide useful information for diagnosing and monitoring changes associated with pain.

Chemical and biophysical characterization of novel potassium channel blocker 3-fluoro-5-methylpyridin-4-amine.

4-aminopyridine (4AP) is a potassium (K) channel blocker used clinically to improve walking in people with multiple sclerosis (MS). 4AP binds to exposed K channels in demyelinated axons, reducing the leakage of intracellular K and enhancing impulse conduction. Multiple derivatives of 4AP capable of blocking K channels have been reported including three radiolabeled with positron emitting isotopes for imaging demyelinated lesions using positron emission tomography (PET).

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.

Radiosynthesis automation, non-human primate biodistribution and dosimetry of K channel tracer [C]3MeO4AP.

Background: 4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high in vivo binding affinity.

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.

Evaluation of - and -4-[F]fluorogabapentin for brain PET imaging.

Gabapentin, a selective ligand for the α2δ subunit of voltage-dependent calcium channels, is an anticonvulsant medication used in the treatment of neuropathic pain, epilepsy and other neurological conditions. We recently described two radiofluorinated derivatives of gabapentin (4-[F]fluorogabapentin, [F]tGBP4F, and 4-[F]fluorogabapentin, [F]cGBP4F) and showed that these compounds accumulate in the injured nerves in a rodent model of neuropathic pain. Given the use of gabapentin in brain diseases, here we investigate whether these radiofluorinated derivatives of gabapentin can be used for imaging α2δ receptors in the brain.

Radiosynthesis automation, non-human primate biodistribution and dosimetry of K channel tracer [ C]3MeO4AP.

Purpose: 4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [ C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high binding affinity.

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.

Radiochemical Synthesis and Evaluation of 3-[C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS.

Demyelination, the loss of the insulating sheath of neurons, causes failed or slowed neuronal conduction and contributes to the neurological symptoms in multiple sclerosis, traumatic brain and spinal cord injuries, stroke, and dementia. In demyelinated neurons, the axonal potassium channels K1.1 and K1.

Development of a PET radioligand for α2δ-1 subunit of calcium channels for imaging neuropathic pain.

Neuropathic pain affects 7-10% of the adult population. Being able to accurately monitor biological changes underlying neuropathic pain will improve our understanding of neuropathic pain mechanisms and facilitate the development of novel therapeutics. Positron emission tomography (PET) is a noninvasive molecular imaging technique that can provide quantitative information of biochemical changes at the whole-body level by using radiolabeled ligands.

PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study.

Mitochondrial dysfunction plays a key role in doxorubicin-induced cardiotoxicity (DIC). In this proof-of-principle study, we investigated whether PET mapping of cardiac membrane potential, an indicator of mitochondrial function, could detect an acute cardiotoxic effect of doxorubicin (DOX) in a large animal model. Eight Yucatan pigs were imaged dynamically with [F](4-Fluorophenyl)triphenylphosphonium ([F]FTPP) PET/CT.

Radiolabeling with [C]HCN for Positron emission tomography.

Hydrogen cyanide (HCN) is a versatile synthon for generating carbon‑carbon and carbon-heteroatom bonds. Unlike other one-carbon synthons (i.e.

Radiochemical Synthesis and Evaluation in Non-Human Primates of 3-[C]methoxy-4-aminopyridine: A Novel PET Tracer for Imaging Potassium Channels in the CNS.

Demyelination, the loss of the protecting sheath of neurons, contributes to disability in many neurological diseases. In order to fully understand its role in different diseases and to monitor treatments aiming at reversing this process, it would be valuable to have PET radiotracers that can detect and quantify molecular changes involved in demyelination such as the uncovering and upregulation of the axonal potassium channels K1.1 and K1.

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.

Sensitivity to myelin using model-free analysis of the water resonance line-shape in postmortem mouse brain.

Purpose: Dysmyelinating diseases are characterized by abnormal myelin formation and function. Such microstructural abnormalities in myelin have been demonstrated to produce measurable effects on the MR signal. This work examines these effects on measurements of voxel-wise, high-resolution water spectra acquired using a 3D echo-planar spectroscopic imaging (EPSI) pulse sequence from both postmortem fixed control mouse brains and a dysmyelination mouse brain model.

Fifty Years of Radiopharmaceuticals.

To celebrate the 50th anniversary of the founding of the SNMMI Technologist Section in 1970, the Radiopharmaceutical Sciences Council board of directors is pleased to contribute to this celebratory supplement of the with a perspective highlighting major developments in the radiopharmaceutical sciences that have occurred in the last 50 years.