PET quantification of [18F]MPPF in the canine brain using blood input and reference tissue modelling

Abstract Background Currently, [18F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. Results The distribution of [18F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. Conclusions This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5-HT2A receptor in the canine brain.

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A generalized reference tissue model for quantification of dynamic PET with bolus plus continuous infusion tracer administration and pharmacological challenge

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0645 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S645-S645

Author(s):

Yun Zhou ◽

Weiguo Ye ◽

Mingkai Chen ◽

Anil Kumar ◽

Mohab Alexander ◽

...

Keyword(s):

Continuous Infusion ◽

Dynamic Pet ◽

Reference Tissue ◽

Tissue Model ◽

Pharmacological Challenge ◽

Reference Tissue Model

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Monte Carlo simulation for reference tissue-based linear analysis of [11C]MP4A AND [11C]MP4P: Assessment of optimal regions and optimization for precise measurement of brain AChE activity

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0644 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S644-S644

Author(s):

Koichi Sato ◽

Kiyoshi Fukushi ◽

Hitoshi Shinotoh ◽

Shin-ichiro Nagatsuka ◽

Noriko Tanaka ◽

...

Keyword(s):

Monte Carlo Simulation ◽

Monte Carlo ◽

Ache Activity ◽

Precise Measurement ◽

Linear Analysis ◽

Reference Tissue ◽

Brain Ache ◽

Brain Ache Activity

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Glucagon-like polypeptides in canine brain

Diabetes ◽

10.2337/diabetes.28.7.700 ◽

1979 ◽

Vol 28 (7) ◽

pp. 700-702 ◽

Cited By ~ 33

Author(s):

J. M. Conlon ◽

W. K. Samson ◽

R. E. Dobbs ◽

L. Orci ◽

R. H. Unger

Keyword(s):

Canine Brain

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Surgical removal of a sewing needle penetrated through the foramen lacerum into a canine brain

Journal of Small Animal Practice ◽

10.1111/jsap.13391 ◽

2021 ◽

Author(s):

S. Abed Alla ◽

A. Locatelli ◽

S. Losio ◽

G. Allevi

Keyword(s):

Surgical Removal ◽

Sewing Needle ◽

Canine Brain

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Central Noradrenergic Neurotransmission and Weight Loss 6 Months After Gastric Bypass Surgery in Patients with Severe Obesity

Obesity Surgery ◽

10.1007/s11695-021-05657-7 ◽

2021 ◽

Author(s):

J. Marvin Soeder ◽

Julia Luthardt ◽

Michael Rullmann ◽

Georg A. Becker ◽

Mohammed K. Hankir ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Severe Obesity ◽

Occipital Cortex ◽

Brain Regions ◽

General Tendency ◽

Strong Positive Correlation ◽

Reference Tissue ◽

Efficient Treatment ◽

Post Surgery

Abstract Purpose Roux-en-Y gastric bypass (RYGB) surgery is currently the most efficient treatment to achieve long-term weight loss in individuals with severe obesity. This is largely attributed to marked reductions in food intake mediated in part by changes in gut-brain communication. Here, we investigated for the first time whether weight loss after RYGB is associated with alterations in central noradrenaline (NA) neurotransmission. Materials and Methods We longitudinally studied 10 individuals with severe obesity (8 females; age 43.9 ± 13.1 years; body mass index (BMI) 46.5 ± 4.8 kg/m2) using (S,S)-[11C]O-methylreboxetine and positron emission tomography to estimate NA transporter (NAT) availability before and 6 months after surgery. NAT distribution volume ratios (DVR) were calculated by volume-of-interest analysis and the two-parameter multilinear reference tissue model (reference region: occipital cortex). Results The participants responded to RYGB surgery with a reduction in BMI of 12.0 ± 3.5 kg/m2 (p < 0.001) from baseline. This was paralleled by a significant reduction in DVR in the dorsolateral prefrontal cortex (pre-surgery 1.12 ± 0.04 vs. post-surgery 1.07 ± 0.04; p = 0.019) and a general tendency towards reduced DVR throughout the brain. Furthermore, we found a strong positive correlation between pre-surgery DVR in hypothalamus and the change in BMI (r = 0.78; p = 0.01). Conclusion Reductions in BMI after RYGB surgery are associated with NAT availability in brain regions responsible for decision-making and homeostasis. However, these results need further validation in larger cohorts, to assess whether brain NAT availability could prognosticate the outcome of RYGB on BMI. Graphical abstract

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Aquaporin-4 protein expression in normal canine brains

BMC Veterinary Research ◽

10.1186/s12917-021-02745-9 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Patricia Álvarez ◽

Ester Blasco ◽

Martí Pumarola ◽

Annette Wessmann

Keyword(s):

White Matter ◽

Cancer Progression ◽

Aquaporin 4 ◽

Histopathological Study ◽

White Matter Tracts ◽

Aqp4 Expression ◽

Canine Brain ◽

Potential Marker ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded

Abstract Background Aquaporin-4 (AQP4) is in growing recognition as potential marker for cancer progression, differentiation and therapeutic intervention. No information is available about AQP4 expression in the normal canine brain. The aim of this histopathological study is to confirm the presence of AQP4 by immunohistochemistry technique in a group of non-pathological canine brains and to describe its expression and distribution across the brain. Results Twelve non-pathological canine brains of various ages (ranging from 21 days to 17 years) and breeds were included in the study. Immunohistochemical expression of AQP4 was analyzed using formalin-fixed paraffin-embedded brain tissue sections. The findings were correlated between AQP4 expressing cells and astrocytes using glial fibrillary acidic protein (GFAP). AQP4 expression was more marked in the astrocyte foot processes of subpial, perivascular and periventricular surfaces in all specimens. The majority of the canine brain sections (9/12) presented with an AQP4 predilection for white matter tracts. Interestingly, the two youngest dogs (21 days and 3 months old) were characterized by diffuse AQP4 labelling in both grey and white matter tracts. This result may suggest that brain development and ageing may play a role in the AQP4 distribution throughout the canine brain. Conclusions This is the first study to describe immunohistochemical distribution of AQP4 in normal canine brains. The AQP4 expression and distribution in non-pathological canine brains was comparable to other species. Larger studies are needed to substantiate the influence of breed and ageing on AQP4 expression in the normal canine brain.

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Acute acetate administration increases endogenous opioid levels in the human brain: A [11C]carfentanil molecular imaging study

Journal of Psychopharmacology ◽

10.1177/0269881120965912 ◽

2021 ◽

pp. 026988112096591

Author(s):

Abhishekh H Ashok ◽

Jim Myers ◽

Gary Frost ◽

Samuel Turton ◽

Roger N Gunn ◽

...

Keyword(s):

Human Brain ◽

Sodium Acetate ◽

Statistical Significance ◽

Imaging Study ◽

Pet Scan ◽

Endogenous Opioid ◽

Reference Tissue ◽

Healthy Human ◽

Fourfold Increase ◽

Positron Emission

Introduction: A recent study has shown that acetate administration leads to a fourfold increase in the transcription of proopiomelanocortin (POMC) mRNA in the hypothalamus. POMC is cleaved to peptides, including β-endorphin, an endogenous opioid (EO) agonist that binds preferentially to the µ-opioid receptor (MOR). We hypothesised that an acetate challenge would increase the levels of EO in the human brain. We have previously demonstrated that increased EO release in the human brain can be detected using positron emission tomography (PET) with the selective MOR radioligand [11C]carfentanil. We used this approach to evaluate the effects of an acute acetate challenge on EO levels in the brain of healthy human volunteers. Methods: Seven volunteers each completed a baseline [11C]carfentanil PET scan followed by an administration of sodium acetate before a second [11C]carfentanil PET scan. Dynamic PET data were acquired over 90 minutes, and corrected for attenuation, scatter and subject motion. Regional [11C] carfentanil BPND values were then calculated using the simplified reference tissue model (with the occipital grey matter as the reference region). Change in regional EO concentration was evaluated as the change in [11C]carfentanil BPND following acetate administration. Results: Following sodium acetate administration, 2.5–6.5% reductions in [11C]carfentanil regional BPND were seen, with statistical significance reached in the cerebellum, temporal lobe, orbitofrontal cortex, striatum and thalamus. Conclusions: We have demonstrated that an acute acetate challenge has the potential to increase EO release in the human brain, providing a plausible mechanism of the central effects of acetate on appetite in humans.

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