Performing [F]MFBG Long-Axial-Field-of-View PET/CT Without Sedation or General Anesthesia for Imaging of Children with Neuroblastoma.

Meta-[I]iodobenzylguanidine ([I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [I]MIBG with the new PET tracer meta-[F]fluorobenzylguanidine ([F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [F]MFBG LAFOV PET/CT and compare it with [I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children.

Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited.

Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is caused by progressive neurodegeneration and characterised by motor dysfunction. Neurodegeneration of dopaminergic neurons also causes aberrations within the cortico-striato-thalamo-cortical (CSTC) circuit, which has been hypothesised to lead to non-motor symptoms such as depression. Individuals with PD have both lower synaptic density and changes in neuronal metabolic function in the basal ganglia, as measured using [C]UCB-J and [F]FDG positron emission tomography (PET), respectively.

Insights into Elution of Anion Exchange Cartridges: Opening the Path toward Aliphatic F-Radiolabeling of Base-Sensitive Tracers.

Aliphatic nucleophilic substitution (S2) with [F]fluoride is the most widely applied method to prepare F-labeled positron emission tomography (PET) tracers. Strong basic conditions commonly used during F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from the tradition to trap [F]fluoride on anion exchange cartridges and elute it afterward with basic anions.

Direct Cu-mediated aromatic F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging.

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported.

Fully Automated GMP-Compliant Synthesis of [F]FE-PE2I.

In the struggle to understand and accurately diagnose Parkinson's disease, radiopharmaceuticals and medical imaging techniques have played a major role. By being able to image and quantify the dopamine transporter density, noninvasive diagnostic imaging has become the gold standard. In the shift from the first generation of SPECT tracers, the fluorine-18-labeled tracer [F]FE-PE2I has emerged as the agent of choice for many physicians.

Improved radiosynthesis and preliminary in vivo evaluation of the C-labeled tetrazine [C]AE-1 for pretargeted PET imaging.

Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a C-labeled tetrazine ([C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents.

Automatic delineation of brain regions on MRI and PET images from the pig.

Background: The increasing use of the pig as a research model in neuroimaging requires standardized processing tools. For example, extraction of regional dynamic time series from brain PET images requires parcellation procedures that benefit from being automated.

Comparison With Existing Methods: Manual inter-modality spatial normalization to a MRI atlas is operator-dependent, time-consuming, and can be inaccurate with lack of cortical radiotracer binding or skull uptake.

5-HT/5-HT Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism.

The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and 5-HT/5-HT receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT receptor agonist properties, all analogues had an intrinsic clearance above 1.

Synthesis and evaluation of (18)F-labeled 5-HT2A receptor agonists as PET ligands.

Introduction: The serotonin 2A receptor (5-HT2AR) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins and processes in the human brain and several 5-HT2AR PET antagonist radioligands are available. In contrast to an antagonist radioligand, an agonist radioligand should be able to image the population of functional receptors, i.

Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors.

Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers, and determination of absolute configuration via enantioselective synthesis showed that the pharmacological activity resided almost exclusively in the (R)-enantiomer.

Identification of a new metabolite of GHB: gamma-hydroxybutyric acid glucuronide.

Gamma-hydroxybutyric acid (GHB) is an important analyte in clinical and forensic toxicology with a narrow detection window of 3-6 h. In the search of improved detection methods, the existence in vivo of a glucuronated GHB metabolite (GHB-GLUC) was hypothesized. Chemically pure standards of GHB-GLUC and a deuterated analogue for chromatography were synthesized.

Total synthesis of ascididemin via anionic cascade ring closure.

A new and convergent synthesis of ascididemin is presented. Using an anionic cascade ring closure as the key step, this natural product is obtained in 45% overall yield in just 6 steps starting from 2'-fluoroacetophenone. This new approach was extended to the synthesis of a new isomer of ascididemin.