Publications by authors named "David L Alexoff"

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women.

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Article Synopsis
  • - The research focuses on measuring the specific activity (SA) of carbon-11 cyanide ([(11)C]CN¯) produced by an automated production system, while identifying sources of carbon-12 cyanide ((12)CN¯).
  • - The production of [(11)C]CN¯ involves using [(11)C]CO2 generated from a nuclear reaction, and the cyanide concentrations were measured with an affordable ion selective electrode (ISE) demonstrating the system's efficiency.
  • - Findings reveal that 30% of (12)CN¯ mass comes from system gases, while 70% is from the molecular sieve/nickel furnace unit, and the study is the first to successfully use an ISE for
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Unlabelled: Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with (11)C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aimed to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathologic situations can be studied.

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We constructed a hand-held device to efficiently trap [(11)C]CO2 from the cyclotron target, safely transport up to 3.7GBq (100mCi) doses to remote sites and release it without the need for a liquid cryogen. The system consists of a 180W furnace and a miniature molecular sieve trap (80-100mg; 80-100mesh 13×) placed inside a lead pig weighing 11.

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  • Selegiline (L-deprenyl) is primarily used to treat Parkinson's disease as a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) at standard doses, but higher doses show potential antidepressant effects by possibly inhibiting MAO-A as well.
  • Zydis selegiline (Zelapar) is a fast-dissolving version that allows for better absorption, leading to increased plasma levels and fewer metabolite effects compared to regular selegiline; however, its selectivity for MAO-B may diminish at higher dosages.
  • A study found that a 10 mg daily dose of Zydis selegiline significantly inhibited MAO-A in healthy men, providing the first direct
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An improved production procedure and formulation method for the carbon-11 radiolabeled phytohormone, 3-indolyl-[l-(11)C]acetic acid ([(11)C]IAA), was developed by modifying selected original reaction parameters. This updated procedure both doubled the yield (from 25.9±6.

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Introduction: PET imaging in plants is receiving increased interest as a new strategy to measure plant responses to environmental stimuli and as a tool for phenotyping genetically engineered plants. PET imaging in plants, however, poses new challenges. In particular, the leaves of most plants are so thin that a large fraction of positrons emitted from PET isotopes ((18)F, (11)C, (13)N) escape while even state-of-the-art PET cameras have significant partial-volume errors for such thin objects.

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Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-(11)C]vorozole, we characterized the tracer distribution and kinetics in the living human brain.

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Introduction: We reinvestigated the synthesis of [N-methyl-(11)C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl-(11)C]vorozole.

Methods: Norvorozole was alkylated with [(11)C]methyl iodide as previously described and also with unlabeled methyl iodide.

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We investigated an imaging strategy that provides simultaneous measurements of radiotracer binding and behavior in awake, freely moving animals. In this strategy, animals are injected intravenously (i.v.

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Introduction: Acetone is an ubiquitous ingredient in many household products (e.g., glue solvents, air fresheners, adhesives, nail polish, and paint) that is putatively abused; however, there is little empirical evidence to suggest that acetone alone has any abuse liability.

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Rationale: Children and adolescents will readily abuse household products that contain solvents such as toluene. It is likely that reinforcing exposures to toluene alter brain glucose metabolism.

Objective: Using an animal model of drug reinforcement, we sought to identify a metabolic signature of toluene abuse in the adolescent rodent brain.

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Despite the widespread use of chronic brain implants in experimental and clinical settings, the effects of these long-term procedures on brain metabolism and receptor expression remain largely unknown. Under the hypothesis that intracerebral microdialysis transiently alters tissue metabolism, we performed a series of 18FDG microPET scans prior to and following surgical implantation of microdialysis cannulae. Parallel microPET measures using the competitive dopamine (DA) D2 receptor antagonist, 11C-raclopride, provided an assay of DA stability in these same animals.

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Introduction: One strength of small animal imaging is the ability to obtain longitudinal measurements within the same animal, effectively reducing the number of animals needed and increasing statistical power. However, the variability of within-rodent brain glucose uptake after an intraperitoneal injection across an extended time has not been measured.

Methods: Small animal imaging with 2-deoxy-2-[(18)F]-fluoro-D-glucose ((18)FDG) was used to determine the variability of a 50-min brain (18)FDG uptake following an intraperitoneal injection over time in awake male and female Sprague-Dawley rodents.

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Anorexia nervosa is a life-threatening psychiatric disorder characterized by severe weight loss and high rates of comorbidity and mortality. The current study assessed the feasibility of using microPET imaging to study the effects of chronic food restriction in an animal model of anorexia nervosa. To establish preliminary support for this model, we hypothesized that chronic food restriction would decrease relative 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) uptake in the rat, in effect modeling cerebral glucose hypometabolism reported in the clinical population of anorexia nervosa.

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In the field of small animal positron emission tomography (PET), the assumptions underlying human and primate kinetic models may not be sustained in rodents. That is, the threshold dose at which a pharmacologic response occurs may be lower in small animals. In order to define this relationship, we combined microPET imaging using 11C-raclopride with microdialysis measures of extracellular fluid (ECF) dopamine (DA).

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Unlabelled: A new generation of commercial animal PET cameras may accelerate drug development by streamlining preclinical testing in laboratory animals. However, little information on the feasibility of using these machines for quantitative PET in small animals is available. Here we investigate the reproducibility of microPET imaging of (11)C-raclopride in the rat brain and the effects of tracer-specific activity and photon scatter correction on measures of D2 receptor (D2R) availability.

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Article Synopsis
  • The study investigates how handling stress affects the response of norepinephrine (NE) and dopamine (DA) levels in the medial prefrontal cortex (mPFC) after administering methylphenidate (MP), a common medication for ADHD.
  • Researchers used a method to measure changes in NE and DA levels in rat brains following a 15-minute handling stress, which increased these neurotransmitter levels.
  • Results showed that prior exposure to handling stress reduced the DA response to MP given later, but increased the DA response when MP was administered at the same time, indicating that short-term stress can change how the brain reacts to medication.
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