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Sample records for cannabinoid-1 receptor pet

  1. Association between cerebral cannabinoid 1 receptor availability and body mass index in patients with food intake disorders and healthy subjects: a [(18)F]MK-9470 PET study.

    Science.gov (United States)

    Ceccarini, J; Weltens, N; Ly, H G; Tack, J; Van Oudenhove, L; Van Laere, K

    2016-07-12

    Although of great public health relevance, the mechanisms underlying disordered eating behavior and body weight regulation remain insufficiently understood. Compelling preclinical evidence corroborates a critical role of the endocannabinoid system (ECS) in the central regulation of appetite and food intake. However, in vivo human evidence on ECS functioning in brain circuits involved in food intake regulation as well as its relationship with body weight is lacking, both in health and disease. Here, we measured cannabinoid 1 receptor (CB1R) availability using positron emission tomography (PET) with [(18)F]MK-9470 in 54 patients with food intake disorders (FID) covering a wide body mass index (BMI) range (anorexia nervosa, bulimia nervosa, functional dyspepsia with weight loss and obesity; BMI range=12.5-40.6 kg/m(2)) and 26 age-, gender- and average BMI-matched healthy subjects (BMI range=18.5-26.6 kg/m(2)). The association between regional CB1R availability and BMI was assessed within predefined homeostatic and reward-related regions of interest using voxel-based linear regression analyses. CB1R availability was inversely associated with BMI in homeostatic brain regions such as the hypothalamus and brainstem areas in both patients with FID and healthy subjects. However, in FID patients, CB1R availability was also negatively correlated with BMI throughout the mesolimbic reward system (midbrain, striatum, insula, amygdala and orbitofrontal cortex), which constitutes the key circuit implicated in processing appetitive motivation and hedonic value of perceived food rewards. Our results indicate that the cerebral homeostatic CB1R system is inextricably linked to BMI, with additional involvement of reward areas under conditions of disordered body weight.

  2. Kinetic analysis of the cannabinoid-1 receptor PET tracer [{sup 18}F]MK-9470 in human brain

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    Sanabria-Bohorquez, Sandra Marina; Hamill, Terence G.; Burns, H.D. [Merck Research Laboratories, Imaging, West Point, PA (United States); Goffin, Karolien; Laere, Koen van [University Hospital and K.U. Leuven, Division of Nuclear Medicine, Leuven (Belgium); Lepeleire, Inge de [Merck Research Laboratories, Brussels (Belgium); Bormans, Guy [K.U. Leuven, Laboratory of Radiopharmacy, Leuven (Belgium)

    2010-05-15

    Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [{sup 18}F]MK-9470 in human brain. [{sup 18}F]MK-9470 data were analysed using reversible models and the distribution volume V{sub T} and V{sub ND} k{sub 3} (V{sub ND} k{sub 3} = K{sub 1} k{sub 2}) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K{sub i} and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined. A reversible two-tissue compartment model using a global k{sub 4} value was necessary to describe brain kinetics. Both V{sub T} and V{sub ND} k{sub 3} were estimated satisfactorily and their test-retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K{sub i}. The linear relationship between K{sub i} and V{sub ND} k{sub 3} demonstrated that K{sub i} or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test-retest variability of K{sub i} and FUR was <10% and estimates were independent of blood flow. Brain uptake can be used as a receptor availability index, albeit at the expense of potential bias due to between-subject differences in tracer plasma kinetics. [{sup 18}F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [{sup 18}F]MK-9470 plasma kinetics can be assessed using a few venous samples. (orig.)

  3. Peripheral cannabinoid 1 receptor blockade activates brown adipose tissue and diminishes dyslipidemia and obesity

    NARCIS (Netherlands)

    Boon, M.R.; Kooijman, S.; Dam, A.D. van; Pelgrom, L.R.; Berbée, J.F.P.; Visseren, C.A.R.; Aggele, R.C. van; Hoek, A.M. van den; Sips, H.C.M.; Lombès, M.; Havekes, L.M.; Tamsma, J.T.; Guigas, B.; Meijer, O.C.; Jukema, J.W.; Rensen, P.C.N.

    2014-01-01

    The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis, and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintenance of weight loss and reduction of dyslipidemia in experimental and human obesity. The m

  4. Peripheral cannabinoid 1 receptor blockade activates brown adipose tissue and diminishes dyslipidemia and obesity

    NARCIS (Netherlands)

    Boon, M.R.; Kooijman, S.; Dam, A.D. van; Pelgrom, L.R.; Berbée, J.F.P.; Visseren, C.A.R.; Aggele, R.C. van; Hoek, A.M. van den; Sips, H.C.M.; Lombès, M.; Havekes, L.M.; Tamsma, J.T.; Guigas, B.; Meijer, O.C.; Jukema, J.W.; Rensen, P.C.N.

    2014-01-01

    The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis, and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintenance of weight loss and reduction of dyslipidemia in experimental and human obesity. The m

  5. The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake

    OpenAIRE

    COOPER, MARTIN E.; Regnell, Simon E.

    2013-01-01

    The cannabinoid 1 receptor (CB1R) has a well-established role in appetite regulation. Central CB1R antagonists, notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals, but were discontinued due to psychiatric side-effects. The CB1R is also expressed peripherally, where its effects include promotion of liver fat accumulation, which consumes ATP. Type 2 diabetes in obese subjects is linked to excess liver fat, whilst there is a negative correlation betwe...

  6. Cannabinoid-1 receptor antagonists in type-2 diabetes.

    Science.gov (United States)

    Scheen, André J

    2007-12-01

    Type-2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a risk of major cardiovascular disease. Several animal and human observations suggest that the endocannabinoid system is over-active in the presence of abdominal obesity and/or diabetes. Both central and peripheral endocannabinoid actions, via the activation of CB1 receptors, promote weight gain and associated metabolic changes. Rimonabant, the first selective CB(1) receptor blocker in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance index and C-reactive protein levels, and to increase high-density lipoprotein (HDL) cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7% reduction in HbA1c levels was observed in metformin- or sulphonylurea-treated patients with type-2 diabetes and in drug-naïve diabetic patients. Almost half of the metabolic changes, including HbA1c reduction, could not be explained by weight loss, suggesting that there are direct peripheral effects. Rimonabant was generally well-tolerated, and the safety profile was similar in diabetic and non-diabetic patients, with a higher incidence of depressed mood disorders, nausea and dizziness. In conclusion, the potential role of rimonabant in overweight/obese patients with type-2 diabetes and at high risk of cardiovascular disease deserves much consideration.

  7. The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake.

    Science.gov (United States)

    Cooper, Martin E; Regnell, Simon E

    2014-01-01

    The cannabinoid 1 receptor (CB1R) has a well-established role in appetite regulation. Central CB1R antagonists, notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals, but were discontinued due to psychiatric side-effects. The CB1R is also expressed peripherally, where its effects include promotion of liver fat accumulation, which consumes ATP. Type 2 diabetes in obese subjects is linked to excess liver fat, whilst there is a negative correlation between hepatic ATP content and insulin resistance. A decreased hepatic ATP/AMP ratio increases food intake by signals via the vagus nerve to the brain. The hepatic cannabinoid system is highly upregulated in obesity, and the effects of hepatic CB1R activation include increased activity of lipogenic and gluconeogenic transcription factors. Thus, blockade of hepatic CB1Rs could contribute significantly to the weight-reducing and insulin-sensitizing effects of CB1R antagonists. Additionally, upregulation of the hepatic CB1R may contribute to chronic liver inflammation, fibrosis and cirrhosis from causes including obesity, alcoholism and viral hepatitis. Peripheral CB1R antagonists induce weight loss and metabolic improvements in obese rodents; however, as there is evidence that hepatic CB1Rs are predominately intracellular, due to high intrinsic clearance, many drugs may not effectively block these receptors and therefore have limited efficacy. Hepatoselective CB1R antagonists may be effective at reducing hepatic steatosis, insulin resistance and bodyweight in obese, diabetic patients, with far fewer side-effects than first-generation CB1R antagonists. Additionally, such compounds may be effective in treating inflammatory liver disease, such as non-alcoholic steatohepatitis, reducing the likelihood of disease progression to cirrhosis or cancer. © 2013 The British Pharmacological Society.

  8. Prospective therapeutic agents for obesity: molecular modification approaches of centrally and peripherally acting selective cannabinoid 1 receptor antagonists.

    Science.gov (United States)

    Sharma, Mayank Kumar; Murumkar, Prashant R; Kanhed, Ashish M; Giridhar, Rajani; Yadav, Mange Ram

    2014-05-22

    Presently, obesity is one of the major health problems in the developed as well as developing countries due to lack of physical work and increasing sedentary life style. Endocannabinoid system (ECS) and especially cannabinoid 1 (CB1) receptor play a key role in energy homeostasis. Food intake and energy storage is enhanced due to the stimulation of ECS hence, inhibition of ECS by blocking CB1 receptors could be a promising approach in the treatment of obesity. Rimonabant, a diaryl pyrazole was the first potent and selective CB1 receptor antagonist that was introduced into the market in 2006 but was withdrawn in 2008 due to its psychiatric side effects. Researchers all over the world are interested to develop peripherally acting potent and selective CB1 receptor antagonists having a better pharmacokinetic profile and therapeutic index. In this development process, pyrazole ring of rimonabant has been replaced by different bioisosteric scaffolds like pyrrole, imidazole, triazole, pyrazoline, pyridine etc. Variations in substituents around the pyrazole ring have also been done. New strategies were also employed for minimizing the psychiatric side effects by making more polar and less lipophilic antagonists/inverse agonists along with neutral antagonists acting peripherally. It has been observed that some of the peripherally acting compounds do not show adverse effects and could be used as potential leads for the further design of selective CB1 receptor antagonists. Chemical modification strategies used for the development of selective CB1 receptor antagonists are discussed here in this review. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Predicting the CRIP1a-cannabinoid 1 receptor interactions with integrated molecular modeling approaches

    Science.gov (United States)

    Ahmed, Mostafa H.; Kellogg, Glen E.; Selley, Dana E.; Safo, Martin; Zhang, Yan

    2015-01-01

    Cannabinoid receptors are a family of G-protein coupled receptors that are involved in a wide variety of physiological processes and diseases. One of the key regulators that are unique to cannabinoid receptors is the cannabinoid receptor interacting proteins (CRIPs). Among them CRIP1a was found to decrease the constitutive activity of the cannabinoid type-1 receptor (CB1R). The aim of this study is to gain an understanding of the interaction between CRIP1a and CB1R through using different computational techniques. The generated model demonstrated several key putative interactions between CRIP1a and CB1R, including those involving Lys130 of CRIP1a. PMID:24461351

  10. Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice.

    Science.gov (United States)

    von Rüden, E L; Bogdanovic, R M; Wotjak, C T; Potschka, H

    2015-05-01

    Endocannabinoids, including 2-arachidonoylglycerol (2-AG), activate presynaptic cannabinoid type 1 receptors (CB1R) on inhibitory and excitatory neurons, resulting in a decreased release of neurotransmitters. The event-specific activation of the endocannabinoid system by inhibition of the endocannabinoid degrading enzymes may offer a promising strategy to selectively activate CB1Rs at the site of excessive neuronal activation with the overall goal to prevent the development epilepsy. The aim of this study was to investigate the impact of monoacylglycerol lipase (MAGL) inhibition on the development and progression of epileptic seizures in the kindling model of temporal lobe epilepsy. Therefore, we selectively blocked MAGL by JZL184 (8mg/kg, i.p.) in mice to analyze the effects of increased 2-AG levels on kindling acquisition and to exclude an anticonvulsive potential. Our results showed that JZL184 treatment significantly delayed the development of generalized seizures (p=0.0066) and decreased seizure (pkindling model of temporal lobe epilepsy, but caused only modest effects in fully kindled mice. Moreover, we proved that JZL184 treatment had no effects in conditional CB1R knockout mice lacking expression of the receptor in principle neurons of the forebrain. In conclusion, the data demonstrate that indirect CB1R agonism delays the development of generalized epileptic seizures but has no relevant acute anticonvulsive effects. Furthermore, we confirmed that the effects of JZL184 on kindling progression are CB1R mediated. Thus, the data indicate that the endocannabinoid 2-AG might be a promising target for an anti-epileptogenic approach.

  11. Lower levels of cannabinoid 1 receptor mRNA in female eating disorder patients: association with wrist cutting as impulsive self-injurious behavior.

    Science.gov (United States)

    Schroeder, Marc; Eberlein, Christian; de Zwaan, Martina; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge

    2012-12-01

    The cannabinoid 1 (CB 1) receptor as the primary mediator of the endocannabinoid (EC) system was found to play a role in eating disorders (EDs), depression, anxiety, and suicidal behavior. The CB 1 receptor is assumed to play a crucial role in the central reward circuitry with impact on body weight and personality traits like novelty-seeking behavior. In a previous study we found higher levels of CB 1 receptor mRNA in patients with anorexia nervosa (AN) and bulimia nervosa (BN) compared to healthy control women (HCW). The aim of the present study was to investigate the possible influence of the EC and the CB 1 receptor system on wrist cutting as self-injurious behavior (SIB) in women with EDs (n=43; AN: n=20; BN: n=23). Nine ED patients with repetitive wrist cutting (AN, n=4; BN, n=5) were compared to 34 ED patients without wrist cutting and 26 HCW. Levels of CB 1 receptor mRNA were determined in peripheral blood samples using quantitative real-time PCR. ED patients with self-injurious wrist cutting exhibited significantly lower CB 1 receptor mRNA levels compared with ED patients without wrist cutting and HCW. No significant differences were found between ED patients without a history of wrist cutting and HCW. Furthermore, a negative association was detected between CB 1 receptor mRNA levels and Beck Depression Inventory (BDI) scores. To our knowledge, this is the first study reporting a down-regulation of CB 1 receptor mRNA in patients with EDs and wrist cutting as SIB. Due to the small sample size, our results should be regarded as preliminary and further studies are warranted to reveal the underlying mechanisms.

  12. Predicting the molecular interactions of CRIP1a-cannabinoid 1 receptor with integrated molecular modeling approaches.

    Science.gov (United States)

    Ahmed, Mostafa H; Kellogg, Glen E; Selley, Dana E; Safo, Martin K; Zhang, Yan

    2014-02-15

    Cannabinoid receptors are a family of G-protein coupled receptors that are involved in a wide variety of physiological processes and diseases. One of the key regulators that are unique to cannabinoid receptors is the cannabinoid receptor interacting proteins (CRIPs). Among them CRIP1a was found to decrease the constitutive activity of the cannabinoid type-1 receptor (CB1R). The aim of this study is to gain an understanding of the interaction between CRIP1a and CB1R through using different computational techniques. The generated model demonstrated several key putative interactions between CRIP1a and CB1R, including the critical involvement of Lys130 in CRIP1a.

  13. In vitro and non-invasive in vivo effects of the cannabinoid-1 receptor (CB1R) agonist AM841 on gastrointestinal motor function in the rat

    Science.gov (United States)

    Abalo, R; Chen, C; Vera, G; Fichna, J; Thakur, GA; López-Pérez, AE; Makriyannis, A; Martín-Fontelles, MI; Storr, M

    2015-01-01

    Background Cannabinoids have been traditionally used for the treatment of gastrointestinal (GI) symptoms, but the associated central effects, through cannabinoid-1 receptors (CB1R), constitute an important drawback. Our aims were to characterize the effects of the recently developed highly potent long-acting megagonist AM841 on GI motor function and to determine its central effects in rats. Methods Male Wistar rats were used for in vitro and in vivo studies. The effect of AM841 was tested on electrically-induced twitch contractions of GI preparations (in vitro) and on GI motility measured radiographically after contrast administration (in vivo). Central effects of AM841 were evaluated using the cannabinoid tetrad. The non-selective cannabinoid agonist WIN 55,212-2 (WIN) was used for comparison. The CB1R (AM251) and CB2R (AM630) antagonists were used to characterize cannabinoid receptor-mediated effects of AM841. Key results AM841 dose-dependently reduced in vitro contractile activity of rat GI preparations via CB1R, but not CB2R or opioid receptors. In vivo, AM841 acutely and potently reduced gastric emptying and intestinal transit in a dose-dependent and AM251-sensitive manner. The in vivo GI effects of AM841 at 0.1 mg kg−1 were comparable to those induced by WIN at 5 mg kg−1. However, at this dose, AM841 did not induce any sign of the cannabinoid tetrad, whereas WIN induced significant central effects. Conclusions & Inferences The CB1R megagonist AM841 may potently depress GI motor function in the absence of central effects. This effect may be mediated peripherally and may be useful in the treatment of GI motility disorders. PMID:26387676

  14. Bivalent ligands that target μ opioid (MOP) and cannabinoid1 (CB1) receptors are potent analgesics devoid of tolerance.

    Science.gov (United States)

    Le Naour, Morgan; Akgün, Eyup; Yekkirala, Ajay; Lunzer, Mary M; Powers, Mike D; Kalyuzhny, Alexander E; Portoghese, Philip S

    2013-07-11

    Given that μ opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP-CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both μ agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo. Immunofluorescent studies on HEK293 cells coexpressing both receptors suggested 5 (20-atom spacer) to be the only member of the series that bridges the protomers of the heteromer. Antinociceptive testing in mice revealed 5 to be the most potent member of the series. As neither a mixture of monovalent ligands 9 + 10 nor bivalents 2-5 produced tolerance in mice, MOR-CB1 apparently is not an important target for reducing tolerance.

  15. Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity.

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    Lisa K Brents

    Full Text Available BACKGROUND: K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R. METHODS/PRINCIPAL FINDINGS: JWH-018, five potential monohydroxylated metabolites (M1-M5, and one carboxy metabolite (M6 were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i values that were lower than or equivalent to Δ(9-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251. CONCLUSIONS/SIGNIFICANCE: Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations

  16. Altered dendritic distribution of dopamine D2 receptors and reduction in mitochondrial number in parvalbumin-containing interneurons in the medial prefrontal cortex of cannabinoid-1 (CB1) receptor knockout mice.

    Science.gov (United States)

    Fitzgerald, Megan L; Chan, June; Mackie, Kenneth; Lupica, Carl R; Pickel, Virginia M

    2012-12-01

    The prelimbic prefrontal cortex (PL) is a brain region integral to complex behaviors that are highly influenced by cannabinoids and by dopamine D2 receptor (D2R)-mediated regulation of fast-firing parvalbumin-containing interneurons. We have recently shown that constitutive deletion of the cannabinoid-1 receptor (CB1R) greatly reduces parvalbumin levels in these neurons. The effects of CB1R deletion on PL parvalbumin interneurons may be ascribed to loss of CB1R-mediated retrograde signaling on mesocortical dopamine transmission, and, in turn, altered expression and/or subcellular distribution of D2R in the PL. Furthermore, diminished parvalbumin expression could indicate metabolic changes in fast-firing interneurons that may be reflected in changes in mitochondrial density in this population. We therefore comparatively examined electron microscopic dual labeling of D2R and parvalbumin in CB1 (-/-) and CB1 (+/+) mice to test the hypothesis that absence of CB1R produces changes in D2R localization and mitochondrial distribution in parvalbumin-containing interneurons of the PL. CB1 (-/-) mice had a significantly lower density of cytoplasmic D2R-immunogold particles in medium parvalbumin-labeled dendrites and a concomitant increase in the density of these particles in small dendrites. These dendrites received both excitatory and inhibitory-type synapses from unlabeled terminals and contained many mitochondria, whose numbers were significantly reduced in CB1 (-/-) mice. Non-parvalbumin dendrites showed no between-group differences in either D2R distribution or mitochondrial number. These results suggest that cannabinoid signaling provides an important determinant of dendritic D2 receptor distribution and mitochondrial availability in fast-spiking interneurons.

  17. Monohydroxylated metabolites of the K2 synthetic cannabinoid JWH-073 retain intermediate to high cannabinoid 1 receptor (CB1R) affinity and exhibit neutral antagonist to partial agonist activity.

    Science.gov (United States)

    Brents, Lisa K; Gallus-Zawada, Anna; Radominska-Pandya, Anna; Vasiljevik, Tamara; Prisinzano, Thomas E; Fantegrossi, William E; Moran, Jeffery H; Prather, Paul L

    2012-04-01

    K2 and several similar purported "incense products" spiked with synthetic cannabinoids are abused as cannabis substitutes. We hypothesized that metabolism of JWH-073, a prevalent cannabinoid found in K2, contributes to toxicity associated with K2 use. Competition receptor binding studies and G-protein activation assays, both performed by employing mouse brain homogenates, were used to determine the affinity and intrinsic activity, respectively, of potential monohydroxylated (M1, M3-M5) and monocarboxylated (M6) metabolites at cannabinoid 1 receptors (CB1Rs). Surprisingly, M1, M4 and M5 retain nanomolar affinity for CB1Rs, while M3 displays micromolar affinity and M6 does not bind to CB1Rs. JWH-073 displays equivalent efficacy to that of the CB1R full agonist CP-55,940, while M1, M3, and M5 act as CB1R partial agonists, and M4 shows little or no intrinsic activity. Further in vitro investigation by Schild analysis revealed that M4 acts as a competitive neutral CB1R antagonist (K(b)∼40nM). In agreement with in vitro studies, M4 also demonstrates CB1R antagonism in vivo by blunting cannabinoid-induced hypothermia in mice. Interestingly, M4 does not block agonist-mediated responses of other measures in the cannabinoid tetrad (e.g., locomotor suppression, catalepsy or analgesia). Finally, also as predicted by in vitro results, M1 exhibits agonist activity in vivo by inducing significant hypothermia and suppression of locomotor activity in mice. In conclusion, the present study indicates that further work examining the physiological effects of synthetic cannabinoid metabolism is warranted. Such a complex mix of metabolically produced CB1R ligands may contribute to the adverse effect profile of JWH-073-containing products.

  18. Effects of the cannabinoid 1 receptor peptide ligands hemopressin, (m)RVD-hemopressin(α) and (m)VD-hemopressin(α) on memory in novel object and object location recognition tasks in normal young and Aβ1-42-treated mice.

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    Zhang, Rui-San; He, Zhen; Jin, Wei-Dong; Wang, Rui

    2016-10-01

    The cannabinoid system plays an important role in memory processes, many studies have indicated that cannabinoid receptor ligands have ability to modulate memory in rodents. A nonapeptide hemopressin (Hp) derived from rat brain, acts as a peptide antagonist or selective inverse peptide agonist of cannabinoid 1 (CB1) receptor. N-terminally extended forms of Hp isolated from mouse brain, (m)RVD-hemopressin(α) (RVD) and (m)VD-hemopressin(α) (VD) also bind CB1 receptor, however, as peptide agonists. Here, we investigated the roles of Hp, RVD, and VD on memory in mice using novel object recognition (NOR) and object location recognition (OLR) tasks. In normal young mice, intracerebroventricular (i.c.v.) infusion of Hp before training not only improved memory formation, but also prolonged memory retention in the tasks, these effects could be inhibited by RVD or VD at the same dose and intraperitoneal (i.p.) injection of a small molecule agonist of CB1 receptor WIN55, 212-2 15min before administration of Hp inhibited the memory-improving effect of Hp. In addition, under the same experimental conditions, i.c.v. RVD or VD displayed memory-impairing effects, which could be prevented by Hp (i.c.v.) or AM251 (i.p.), a small molecule antagonist of CB1 receptor. Infusion of amyloid-β (1-42) (Aβ1-42) 14days before training resulted in impairment of memory in mice which could be used as animal model of Alzheimer's disease (AD). In these mice, RVD or VD (i.c.v.) reversed the memory impairment induced by Aβ1-42, and the effects of RVD and VD could be suppressed by Hp (i.c.v.) or AM251 (2mg/kg, i.p.). Separate administration of Hp had no effect in Aβ1-42-treated mice. The above results suggested that Hp, RVD and VD, as CB1 receptor peptide ligands, may be potential drugs to treatment of the memory deficit-involving disease, just as AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Analysis in conditional cannabinoid 1 receptor-knockout mice reveals neuronal subpopulation-specific effects on epileptogenesis in the kindling paradigm.

    Science.gov (United States)

    von Rüden, E L; Jafari, M; Bogdanovic, R M; Wotjak, C T; Potschka, H

    2015-01-01

    The endocannabinoid system serves as a retrograde negative feedback mechanism. It is thought to control neuronal activity in an epileptic neuronal network. The purpose of this study was to evaluate the impact of the endocannabinoid and endovanilloid systems on both epileptogenesis and ictogenesis. Therefore, we modulated the endocannabinoid and endovanilloid systems genetically and pharmacologically, and analyzed the subsequent impact on seizure progression in the kindling model of temporal lobe epilepsy in mice. In addition, the impact of seizures on associated cellular alterations was evaluated. Our principal results revealed that the endocannabinoid system affects seizure and afterdischarge duration dependent on the neuronal subpopulation being modulated. Genetic deletion of CB1-receptors (CB1Rs) from principal neurons of the forebrain and pharmacological antagonism with rimonabant (5 mg/kg) caused longer seizure duration. Deletion of CB1R from GABAergic forebrain neurons resulted in the opposite effect. Along with these findings, the CB1R density was elevated in animals with repetitively induced seizures. However, neither genetic nor pharmacological interventions had any impact on the development of generalized seizures. Other than CB1, genetic deletion or pharmacological blockade with SB366791 (1 mg/kg) of transient receptor potential vanilloid receptor 1 (TRPV1) had no effect on the duration of behavioral or electrographic seizure activity in the kindling model. In conclusion, we demonstrate that endocannabinoid, but not endovanilloid, signaling affects termination of seizure activity, without influencing seizure severity over time. These effects are dependent on the neuronal subpopulation. Thus, the data argue that the endocannabinoid system plays an active role in seizure termination but does not regulate epileptogenesis.

  20. PET imaging of human cardiac opioid receptors

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    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2002-10-01

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  1. Relationships between glucose, energy intake and dietary composition in obese adults with type 2 diabetes receiving the cannabinoid 1 (CB1 receptor antagonist, rimonabant

    Directory of Open Access Journals (Sweden)

    Heppenstall Charlotte

    2012-07-01

    Full Text Available Abstract Background Weight loss is often difficult to achieve in individuals with type 2 diabetes and anti-obesity drugs are often advocated to support dietary intervention. Despite the extensive use of centrally acting anti-obesity drugs, there is little evidence of how they affect dietary composition. We investigated changes in energy intake and dietary composition of macro- and micronutrients following therapy with the endocannabinoid receptor blocker, rimonabant. Methods 20 obese patients with type 2 diabetes were studied before and after 6 months dietary intervention with rimonabant. Dietary intervention was supervised by a diabetes dietician. Five-day food diaries were completed at baseline and at 6 months and dietary analysis was performed using computer software (Dietplan 6. Results After 6 months, (compared with baseline there were reductions in weight (107 ± 21Kg versus 112 ± 21, p  Conclusions In obese patients with type 2 diabetes, rimonabant in combination with dietary intervention led to reduced intake of energy and most macronutrients. Despite this, macronutrient composition of the diet was unaltered. These dietary changes (especially carbohydrate restriction were associated with weight loss and favourable metabolic effects.

  2. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid recepto

  3. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid

  4. Altered dendritic distribution of dopamine D2 receptors and reduction in mitochondrial number in parvalbumin-containing interneurons in the medial prefrontal cortex of cannabinoid-1 (CB1) receptor knockout mice

    OpenAIRE

    2012-01-01

    The prelimbic prefrontal cortex (PL) is a brain region integral to complex behaviors that are highly influenced by cannabinoids and by dopamine D2 receptor (D2R)-mediated regulation of fast-firing parvalbumin-containing interneurons. We have recently shown that constitutive deletion of the cannabinoid CB1 receptor (CB1R) greatly reduces parvalbumin levels in these neurons. The effects of CB1R deletion on PL parvalbumin interneurons may be ascribed to loss of CB1R-mediated retrograde signaling...

  5. Effects of a Cannabinoid1 receptor antagonist and Serotonin2C receptor agonist alone and in combination on motivation for palatable food: a dose-addition analysis study in mice.

    Science.gov (United States)

    Ward, Sara Jane; Lefever, Timothy W; Jackson, Cavario; Tallarida, Ronald J; Walker, Ellen A

    2008-05-01

    The cannabinoid and serotonin systems modulate feeding behavior in humans and laboratory animals. The present study assessed whether a cannabinoid (CB)(1) receptor antagonist and a serotonin (5-HT)(2C) receptor agonist alone and in combination attenuate motivation for the liquid nutritional drink Ensure as measured by a progressive ratio (PR) schedule of reinforcement in male C57BL/6 mice. Pretreatment (15 min i.p.) with either the CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716) (SR; Rimonabant or Acomplia) or the 5-HT(2C) receptor agonist m-chlorophenylpiperazine (mCPP) dose-dependently decreased the maximum ratio completed under the PR schedule (break point) in mice. ED(25) values for SR and mCPP to decrease break point were determined, and the relative potency of each drug alone was quantified. Fixed dose-ratio pairs of SR/mCPP based on their relative potency were then administered. Dose-addition analysis comparing the experimentally determined potency for SR/mCPP combinations with their predicted additive potency revealed that SR/mCPP combinations in 1:1 and 2:1 ratios based on relative potency produced significant synergistic attenuation of break point for Ensure. The ED(25) values for decreasing break point were consistently lower than ED(25) values for decreasing response rate, and synergistic effects of SR/mCPP combinations on break point were seen independent of synergistic effects on response rate. These results indicate that cannabinoid CB(1) and serotonin 5-HT(2C) receptors are involved in motivated feeding behavior in mice and that these compounds can synergistically modulate motivation for palatable food with the synergy dependent upon the ratio of SR/mCPP in the combination.

  6. Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis.

    Science.gov (United States)

    Pillai, Sekhar C; Gill, Deepak; Webster, Richard; Howman-Giles, Robert; Dale, Russell C

    2010-09-01

    N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2) with relapsing NMDA receptor encephalitis each had the classic clinical features of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia, and mild autonomic dysfunction. Both patients had persistent neuropsychiatric disability, despite immune therapies. Positron emission tomography (PET) scans were performed during clinical relapse at 6 weeks (case 1) and 5 months (case 2). In both cases, the scans demonstrated reduced fluorodeoxyglucose metabolism in the cerebral cortex, with the temporal regions being most affected. PET imaging was more sensitive than magnetic resonance imaging in these patients. In contrast, the one previous report of acute NMDA receptor encephalitis indicated cortical hypermetabolism. Thus, NMDA receptor encephalitis may be associated with variable PET findings, possibly dependent upon the timing of the study, or other factors. Future studies should investigate whether cortical hypometabolism is associated with a relapsing course, and whether it is predictive of a poorer outcome in NMDA receptor encephalitis.

  7. PET neuroimaging of extrastriatal dopamine receptors and prefrontal cortex functions.

    Science.gov (United States)

    Takahashi, Hidehiko

    2013-12-01

    The role of prefrontal dopamine D1 receptors in prefrontal cortex (PFC) functions, including working memory, is widely investigated. However, human (healthy volunteers and schizophrenia patients) positron emission tomography (PET) studies about the relationship between prefrontal D1 receptors and PFC functions are somewhat inconsistent. We argued that several factors including an inverted U-shaped relationship between prefrontal D1 receptors and PFC functions might be responsible for these inconsistencies. In contrast to D1 receptors, relatively less attention has been paid to the role of D2 receptors in PFC functions. Several animal and human pharmacological studies have reported that the systemic administration of D2 receptor agonist/antagonist modulates PFC functions, although those studies do not tell us which region(s) is responsible for the effect. Furthermore, while prefrontal D1 receptors are primarily involved in working memory, other PFC functions such as set-shifting seem to be differentially modulated by dopamine. PET studies of extrastriatal D2 receptors including ours suggested that orchestration of prefrontal dopamine transmission and hippocampal dopamine transmission might be necessary for a broad range of normal PFC functions. In order to understand the complex effects of dopamine signaling on PFC functions, measuring a single index related to basic dopamine tone is not sufficient. For a better understanding of the meanings of PET indices related to neurotransmitters, comprehensive information (presynaptic, postsynaptic, and beyond receptor signaling) will be required. Still, an interdisciplinary approach combining molecular imaging techniques with cognitive neuroscience and clinical psychiatry will provide new perspectives for understanding the neurobiology of neuropsychiatric disorders and their innovative drug developments.

  8. RGD-based PET tracers for imaging receptor integrin αv β3 expression.

    Science.gov (United States)

    Cai, Hancheng; Conti, Peter S

    2013-05-15

    Positron emission tomography (PET) imaging of receptor integrin αv β3 expression may play a key role in the early detection of cancer and cardiovascular diseases, monitoring disease progression, evaluating therapeutic response, and aiding anti-angiogenic drugs discovery and development. The last decade has seen the development of new PET tracers for in vivo imaging of integrin αv β3 expression along with advances in PET chemistry. In this review, we will focus on the radiochemistry development of PET tracers based on arginine-glycine-aspartic acid (RGD) peptide, present an overview of general strategies for preparing RGD-based PET tracers, and review the recent advances in preparations of (18) F-labeled, (64) Cu-labeled, and (68) Ga-labeled RGD tracers, RGD-based PET multivalent probes, and RGD-based PET multimodality probes for imaging receptor integrin αv β3 expression.

  9. In vivo PET imaging of brain nicotinic cholinergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Bottlaender, M.; Valette, H.; Saba, W.; Schollhorn-Peyronneau, M.A.; Dolle, F.; Syrota, A. [Service Hospitalier Frederic Joliot (CEA/DSV/DRM), 91 - Orsay (France)

    2006-07-01

    Neuronal acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system where they modulate a number of CNS functions including neurotransmitter release, cognitive function, anxiety, analgesia and control of cerebral blood flow. In the brain, a major subtype is composed of the {alpha}4{beta}2 subunit combination. Density of this subtype has been shown to be decreased in patients with neuro-degenerative disease such as Alzheimer and Parkinson's disease (AD and PD), and mutated receptors has been described in some familial epilepsy. Thus, in vivo mapping of the nicotinic nAChRs by Positron Emission Tomography (PET) are of great interest to monitor the evolution of these pathologies and changes in the neuronal biochemistry induced by therapeutic agents. Recently, a new compound, 3-[2(S)-2-azetidinyl-methoxy]pyridine (A-85380) has been synthesised and labelled with fluorine-18, [{sup 18}F]fluoro-A-85380 (Dolle et al., 1999). The [{sup 18}F]fluoro-A-85380 has been shown to bind with high affinity t o nAChRs in vitro (Saba et al., 2004), and its toxicity was low and compatible with it s use at tracer dose in human PET studies (Valette, 2002). PET studies in baboons showed that, after in vivo administration of [ {sup 18}F]fluoro-A-85380 at a tracer dose, the distribution of the radioactivity in the brain reflect the distribution of the < 4R2 nAChRs. Competition and pre-blocking studies, using nicotinic agonists, confirm that the radiotracer binds specifically to the heteromeric nAChRs in the brain (Valette et al., 1999). The in vivo, characteristics of the [{sup 18}F]fluoro-A-8538 0 combined with its low toxicity make possible the imaging of the nicotinic receptor s in human by PET (Bottlaender 2003). Studies were performed in healthy non-smoker volunteers to evaluate the brain kinetics of [{sup 18}F]fluoro-A-85380 and to assess the quantification of its nAChRs binding in the human brain with PET (Gallezot et a., 2005). The [{sup 18}F

  10. Small Molecule Receptor Ligands for PET Studies of the Central Nervous System-Focus on G Protein Coupled Receptors.

    Science.gov (United States)

    Mach, Robert H

    2017-09-01

    G protein-coupled receptors (GPRCs) are a class of proteins that are expressed in high abundance and are responsible for numerous signal transduction pathways in the central nervous system. Consequently, alterations in GPRC function have been associated with a wide variety of neurologic and neuropsychiatric disorders. The development of PET probes for imaging GPRCs has served as a major emphasis of PET radiotracer development and PET imaging studies over the past 30 years. In this review, a basic description of the biology of G proteins and GPRCs is provided. This includes recent evidence of the existence of dimeric and multimeric species of GPRCs that have been termed "receptor mosaics," with an emphasis on the different GPRCs that form complexes with the dopamine D2 receptor. An overview of the different PET radiotracers for imaging the component GPRC within these different multimeric complexes of the D2 receptor is also provided. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Effect of cannabinoid 1 receptor over-expression on immunomodulation in mice with experimental autoimmune encephalomyelitis%大麻素1型受体过表达对实验性自身免疫性脑脊髓炎小鼠的免疫调节

    Institute of Scientific and Technical Information of China (English)

    程洁; 楼之茵; 李琳; 赵忠新

    2016-01-01

    目的 探讨大麻素1型受体(cannabinoid 1 receptor,CB1R)过表达对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)小鼠细胞免疫调节的影响.方法 选用C57B/L6小鼠制备EAE小鼠模型,采用质粒转染技术制备CB1R过表达组.观察假手术组和CB1R过表达组小鼠的神经功能缺损症状和体质量变化;用ELISA法检测EAE小鼠脊髓、脾脏中细胞因子INF-γ、IL-6、IL-10、IL-17、IL-1β、TNF-α浓度的变化.结果 与相同时间点的假手术组相比,CB1R过表达组出现神经功能缺损的时间及症状严重程度和体质量减轻程度显著降低(P<0.05).假手术组和CB1R过表达组中,细胞因子在中枢神经系统和外周免疫组织的分布不相同.与假手术组相比,CB1R过表达组EAE小鼠脊髓组织中IL-10的浓度显著升高(P<0.01),而INF-γ、IL-6、IL-17、IL-1β、TNF-α的浓度显著降低(P<0.05).结论 CB1R过表达对EAE小鼠中枢神经系统炎性损伤的保护作用,可能通过上调抑炎因子,下调促炎因子的表达实现.

  12. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... these PET tracers further....

  13. Characterizing Tumors Using Metabolic Imaging: PET Imaging of Cellular Proliferation and Steroid Receptors

    Directory of Open Access Journals (Sweden)

    David A. Mankoff

    2000-01-01

    Full Text Available Treatment decisions in oncology are increasingly guided by information on the biologic characteristics of tumors. Currently, patient-specific information on tumor biology is obtained from the analysis of biopsy material. Positron emission tomography (PET provides quantitative estimates of regional biochemistry and receptor status and can overcome the sampling error and difficulty in performing serial studies inherent with biopsy. Imaging using the glucose metabolism tracer, 2-deoxy-2-fluoro-D-glucose (FDG, has demonstrated PET's ability to guide therapy in clinical oncology. In this review, we highlight PET approaches to imaging two other aspects of tumor biology: cellular proliferation and tumor steroid receptors. We review the biochemical and biologic processes underlying the imaging, positron-emitting radiopharmaceuticals that have been developed, quantitative image-analysis considerations, and clinical studies to date. This provides a basis for evaluating future developments in these promising applications of PET metabolic imaging.

  14. PET

    DEFF Research Database (Denmark)

    Mariager, Rasmus Mølgaard; Schmidt, Regin; Heiberg, Morten Rievers

    PET handler om den hemmelige tjenestes arbejde under den kolde krig 1945-1989. Her fortæller Regin Schmidt, Rasmus Mariager og Morten Heiberg om de mest dramatiske og interessante sager fra PET's arkiv. PET er på flere måder en udemokratisk institution, der er sat til at vogte over demokratiet....... Dens virksomhed er skjult for offentligheden, den overvåger borgernes aktiviteter, og den registrerer følsomme personoplysninger. Historien om PET rejser spørgsmålet om, hvad man skal gøre, når befolkningen i et demokrati er kritisk indstillet over for overvågningen af lovlige politiske aktiviteter......, mens myndighederne mener, at det er nødvendigt for at beskytte demokratiet. PET er på en gang en fortælling om konkrete aktioner og begivenheder i PET's arbejde og et stykke Danmarkshistorie. Det handler om overvågning, spioner, politisk ekstremisme og international terrorisme.  ...

  15. Dopamine D(3) receptor antagonists: The quest for a potentially selective PET ligand. Part two: Lead optimization.

    Science.gov (United States)

    Micheli, Fabrizio; Holmes, Ian; Arista, Luca; Bonanomi, Giorgio; Braggio, Simone; Cardullo, Francesca; Di Fabio, Romano; Donati, Daniele; Gentile, Gabriella; Hamprecht, Dieter; Terreni, Silvia; Heidbreder, Christian; Savoia, Chiara; Griffante, Cristiana; Worby, Angela

    2009-08-01

    The lead optimization process to identify new selective dopamine D(3) receptor antagonists is reported. DMPK parameters and binding data suggest that selective D(3) receptor antagonists as potential PET ligands might have been identified.

  16. 68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease.

    Science.gov (United States)

    Ambrosini, Valentina; Campana, Davide; Allegri, Vincenzo; Opocher, Giuseppe; Fanti, Stefano

    2011-01-01

    A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.

  17. Small-Animal PET Study of Adenosine A(1) Receptors in Rat Brain : Blocking Receptors and Raising Extracellular Adenosine

    NARCIS (Netherlands)

    Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A.; Kwizera, Chantal; Sijbesma, Jurgen W. A.; Ishiwata, Kiichi; Willemsen, Antoon T. M.; Elsinga, Philip H.; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2011-01-01

    Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-C-11-methyl-3-propyl-xanthine (C-11-MPDX) and PET. This study aims to test whether C-11-MPDX

  18. Small-Animal PET Study of Adenosine A(1) Receptors in Rat Brain : Blocking Receptors and Raising Extracellular Adenosine

    NARCIS (Netherlands)

    Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A.; Kwizera, Chantal; Sijbesma, Jurgen W. A.; Ishiwata, Kiichi; Willemsen, Antoon T. M.; Elsinga, Philip H.; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2011-01-01

    Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-C-11-methyl-3-propyl-xanthine (C-11-MPDX) and PET. This study aims to test whether C-11-MPDX c

  19. PET imaging for receptor occupancy: meditations on calculation and simplification.

    Science.gov (United States)

    Zhang, Yumin; Fox, Gerard B

    2012-03-01

    This invited mini-review briefly summarizes procedures and challenges of measuring receptor occupancy with positron emission tomography. Instead of describing the detailed analytic procedures of in vivo ligand-receptor imaging, the authors provide a pragmatic approach, along with personal perspectives, for conducting positron emission tomography imaging for receptor occupancy, and systematically elucidate the mathematics of receptor occupancy calculations in practical ways that can be understood with elementary algebra. The authors also share insights regarding positron emission tomography imaging for receptor occupancy to facilitate applications for the development of drugs targeting receptors in the central nervous system.

  20. Feasibility and predictability of perioperative PET and estrogen receptor ligand in patients with invasive breast cancer.

    Science.gov (United States)

    Gemignani, Mary L; Patil, Sujata; Seshan, Venkatraman E; Sampson, Michelle; Humm, John L; Lewis, Jason S; Brogi, Edi; Larson, Steven M; Morrow, Monica; Pandit-Taskar, Neeta

    2013-10-01

    The presence of estrogen receptor (ER) in breast cancer is a prognostic indicator for both disease-free and overall survival. 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) with PET is a noninvasive test for evaluation of ER expression and has been used for predicting response to endocrine therapy in patients with ER-positive metastatic breast cancer. The purpose of this study was to correlate (18)F-FES PET and ER expression in patients with primary, operable breast cancer. Forty-eight patients were prospectively enrolled in an institutional review board-approved protocol and signed an informed consent form. All patients had undergone (18)F-FES PET preoperatively. Clinical characteristics, tumor characteristics, and treatment outcomes were recorded. Immunohistochemical analysis for ER and progesterone receptor (PgR) percentage expression (46 surgical, 2 core biopsy specimens) was performed. (18)F-FES PET standardized uptake value (SUV) of the breast lesion was correlated with percentage immunohistochemistry ER and PgR expression. (18)F-FES PET SUV was quantified, with a value of 1.5 or more considered positive, and ER and PgR was quantified, with 1% or more considered positive. Formalin-fixed paraffin-embedded tissue was available for 44 patients (42 surgical, 2 core biopsy specimens). We used a microarray platform, and estrogen-related gene expression data (ESR1, ESR2, and PGR) were compared with (18)F-FES PET SUV (Spearman rank correlation). Tumor size, ductal histology, grade, HER2-neu overexpression, PgR expression, estradiol level, body mass index (BMI), and lean BMI were compared with (18)F-FES PET uptake using univariate and multivariate analysis. Forty-eight patients completed our protocol, and 2 patients did not undergo surgery because bone metastases were identified preoperatively on (18)F-FES PET. Eighty-three percent of our patients were stage I or II, with a median tumor size of 1.9 cm. Forty-one patients underwent a sentinel node biopsy. Twenty

  1. Positron Emission Tomography (PET Quantification of GABAA Receptors in the Brain of Fragile X Patients.

    Directory of Open Access Journals (Sweden)

    Charlotte D'Hulst

    Full Text Available Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS, a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.

  2. Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Gottingen minipig

    DEFF Research Database (Denmark)

    Kornum, B.R.; Lind, N.M.; Gillings, N.;

    2009-01-01

    model provides stable and precise estimates of the binding potential in all regions. The binding potentials calculated for striatum, midbrain, and cortex from the PET data were highly correlated with 5-HT(4) receptor concentrations determined in brain homogenates from the same regions, except...... for hippocampus where PET-measurements significantly underestimate the 5-HT(4) receptor binding, probably because of partial volume effects. This study validates the use of [(11)C]SB207145 as a promising PET radioligand for in vivo brain imaging of the 5-HT(4) receptor in humans Udgivelsesdato: 2009/1...

  3. Effects of cannabinoid 1 receptor on regulation of visceral sensitivity in rats with acute restraint stress%大麻素1型受体在应激大鼠内脏敏感性调节中的作用

    Institute of Scientific and Technical Information of China (English)

    沈蕾; 杨小军; 钱伟; 侯晓华

    2009-01-01

    目的 研究大麻素1型受体(CB1R)对急性部分束缚应激大鼠内脏敏感性的调节作用.方法 将30只Sprague-Dawley大鼠均分成空白对照组(假性应激)、应激对照组和激动剂组.于实验第1、2、5、8天以测定结直肠气囊扩张(CRD)后腹壁肌电图(EMG)放电频率表示大鼠内脏感觉功能的变化.通过RT-PCR方法 检测实验第8天各组肠道CBIR mRNA表达水平.结果 实验第1天,三组大鼠腹壁肌电放电频率基础值差异均无统计学意义(P值均>0.05).实验第2天,激动剂组大鼠在40、60、80 mm Hg(1 mm Hg=0.133 kPa)压力下的腹壁肌电放电频率[分别为(22.37±1.49)、(42.24±3.03)、(69.09±5.54)次/min]较应激对照组大鼠[分别为(39.71±1.84)、(84.45±8.85)、(112.56±11.66)次/min]显著降低(P0.05).应激对照组大鼠回盲部、近端结肠和远端结肠CB1R mRNA表达水平(分别为2.53±0.52、2.29±0.42、2.54±0.29)均显著高于空白对照组(分别为0.56±0.15、0.73±0.12、0.82±0.09),差异均有统计学意义(P值均<0.05).CB1R激动剂干预对大鼠肠道CB1RmRNA表达无影响.结论 CB1R在束缚应激所致大鼠内脏高敏感中起重要的保护性调节作用.%Objective To investigate the effects of cannabinoid 1 receptor (CB1R) on regulating visceral sensitivity in rats with acute partial restraint stress. Methods Thirty Sprague-Dawley rats were divided into blank control (sham stress), acute stress and CB1R groups with 10 each. The frequency of discharge of electromyogram (EMG) was recorded at the 1st, 2nd, 5th and 8th day to evaluate the visceral sensitivity to colorectal distension (CRD) in rats. The expression of the CB1R mRNA was determined by means of RT-PCR at day 8. Results There was no significant difference in baseline discharge frequency among three groups at the 1st day. But the discharge frequencies corresponding to CRD at 40,60,80 mm Hg at the 2nd day were significantly lower in CB1R group [(22.37±1.49)/min, (42.24±3

  4. Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT7 Receptor

    DEFF Research Database (Denmark)

    Herth, Matthias M; Andersen, Valdemar L; Hansen, Hanne D;

    2015-01-01

    We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent (11)C-labeling and in vivo...

  5. Multiparametric PET imaging in thyroid malignancy characterizing tumour heterogeneity: somatostatin receptors and glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Traub-Weidinger, Tatjana [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Putzer, Daniel; Bale, Reto [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Guggenberg, Elisabeth von; Dobrozemsky, Georg; Nilica, Bernhard; Kendler, Dorota; Virgolini, Irene Johanna [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

    2015-12-15

    Radiolabelled somatostatin (SST) analogues have proven useful in diagnosing tumours positive for SST receptor (SSTR). As different subtypes of SSTR are expressed on the tumour cell surface, the choice of appropriate therapeutic SST analogue is crucial. We evaluated the SSTR status of thyroid cancer patients who had signs of progressive disease comparing different SSTR ligands for PET imaging to evaluate possible further therapeutic options. PET with {sup 68}Ga-radiolabelled SSTR ligands DOTA lanreotide (DOTA-LAN), DOTA-Tyr{sup 3} octreotide (DOTA-TOC) and {sup 18}F-FDG was performed in 31 patients with thyroid cancer (TC). These 31 patients comprised 18 with radioiodine non-avid differentiated TC (DTC) including 6 papillary TC (PTC), 8 follicular TC (FTC) and 4 oxyphilic TC (oxyTC), 5 with anaplastic TC (ATC), and 8 with medullary TC (MTC). The PET results were compared in a region-based evaluation. All patients underwent a PET study with {sup 68}Ga-DOTA-LAN, 28 patients with {sup 68}Ga-DOTA-TOC and 28 patients with {sup 18}F-FDG. A lack of SSTR expression was found in 13 of the 31 patients (42 %) with negative results with both SSTR tracers in 12 patients. Ambiguous results with both SSTR tracers were observed in one patient. High tracer uptake in SSTR PET images was seen in seven DTC patients (39 %; two PTC, three FTC, two oxyTC), in four ATC patients (80 %) and in six MTC patients (75 %). Lesions showing aerobic glycolysis on {sup 18}F-FDG PET were found in 24 of 28 patients (86 %) with corresponding positive results with {sup 68}Ga-DOTA-LAN in 35 % and with {sup 68}Ga-DOTA-TOC in 29 %. The heterogeneous SSTR profile of TC tumour lesions needs to be evaluated using different SSTR PET tracers to characterize more closely the SSTR subtype affinities in patients with progressive TC in order to further stratify therapy with SSTR therapeutics. (orig.)

  6. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; McPherson, D.W.; Luo, H. [and others

    1995-06-01

    Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.

  7. Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone

    Energy Technology Data Exchange (ETDEWEB)

    Muhr, C.; Bergstroem, M.L.; Lundberg, P.O.; Bergstroem, K.H.; Hartvig, P.; Lundqvist, H.; Antoni, G.; Langstroem B2

    1986-03-01

    Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment.

  8. A pharmacokinetic PET study of NK{sub 1} receptor occupancy

    Energy Technology Data Exchange (ETDEWEB)

    Zamuner, Stefano [GlaxoSmithKline, Clinical Pharmacology Modeling and Simulation, Stockley Park (United Kingdom); Rabiner, Eugenii A. [Hammersmith Hospital, GlaxoSmithKline, Clinical Imaging Centre, London (United Kingdom); Fernandes, Sofia A.; Bani, Massimo; Ratti, Emilangelo [GlaxoSmithKline, Neurosciences CEDD, Verona (Italy); Gunn, Roger N. [Hammersmith Hospital, GlaxoSmithKline, Clinical Imaging Centre, London (United Kingdom); University of Oxford, Department of Engineering Science, Oxford (United Kingdom); Gomeni, Roberto [GlaxoSmithKline, Pharmacometrics, Upper Merion, PA (United States); Cunningham, Vincent J. [Hammersmith Hospital, GlaxoSmithKline, Clinical Imaging Centre, London (United Kingdom); University of Aberdeen, School of Medical Sciences, Aberdeen Biomedical Imaging Centre, Aberdeen, Scotland (United Kingdom)

    2012-02-15

    There is growing recognition of the importance of integrating drug occupancy data acquired by positron emission tomography (PET) with the plasma pharmacokinetics of the drug, in order to establish proper dose selection in subsequent clinical trials. Here we present a study in human subjects of the occupancy of NK{sub 1} receptors achieved following different doses of casopitant, a selective NK{sub 1} antagonist. Two PET scans were carried out in each of eight human subjects, with the PET radioligand [{sup 11}C]GR205171, a high-affinity and selective NK{sub 1} receptor antagonist. The first scan was under baseline conditions and the second 24 h after a single oral dose of casopitant (2-120 mg). Arterial blood was collected throughout the scans for determination of plasma and whole blood input functions. Venous blood samples were taken prior to and following oral dosing up to 24 h for a pharmacokinetic study of casopitant concentration in plasma. It was first necessary to establish a suitable kinetic model for the estimation of [{sup 11}C]GR205171 NK{sub 1} receptor binding parameters in human brain tissue. A three-tissue compartment model with simultaneous estimation of multiple regions sharing common variables across regions was found suitable for the analysis. Because of the injected cold mass of the tracer and the high affinity of [{sup 11}C]GR205171 a correction for tracer occupancy effects was also incorporated into the analysis. We then developed a pharmacokinetic-receptor occupancy (PK-RO) model of the relationship between casopitant plasma concentrations and receptor binding, using a population approach. These results indicate that after chronic dosing, casopitant can achieve a degree of NK{sub 1} receptor occupancy higher than those that have previously been tested in studies of clinical depression. (orig.)

  9. Multifocal Head and Neck Paraganglioma Evaluated with Different PET Tracers: Comparison Between Fluorine-18-Fluorodeoxyglucose Between Fluorine-18-Fluorodeoxyglucose and Gallium-68-Somatostatin Receptor PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Castaldi, Paola; Rufini, Vittoria [Catholic Univ. of the Sacred Heart, Rome (Italy); Treglia, G. [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

    2013-09-15

    We report the case of a 46-year-old woman with a succinate dehydrogenase subtype D (SDHD) gene mutation and multifocal head and neck paraganglioma evaluated with fluorine-18-fluorodeoxyglucose and gallium-68-somatostatin receptor positron emission tomography/computed tomography (PET/CT). Gallium-68-somatostatin receptor PET/CT correctly assessed the extent of the disease in this patient, detecting additional lesions compared with fluorine-18-fluorodeoxyglucose PET/CT and influencing the patient management. A 46-year-old woman was referred to our centre for surveillance of a gastrointestinal stromal tumour (GIST). The patient underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG-PET/CT), which demonstrated a focal area of increased radiopharmaceutical uptake corresponding to a lesion located between the right carotid vessels (yellow arrow; Fig. 1a). This F-18-FDG-PET/CT finding was suspicious for a paraganglioma of the neck. The patient underwent further examinations, including biochemical and genetic tests and a somatostatin receptor PET/CT using somatostatin analogues labelled with gallium-68 (Ga-68-DOTANOC-PET/CT). Laboratory data were suspicious for a non-functioning neuroendocrine tumour. Increased serum chromogranin A value and normal values of plasmatic and urinary catecholamines and their metabolites were found. The patient had no symptoms of a functioning tumour. Genetic tests demonstrated the presence of a succinate dehydrogenase subtype D (SDHD) gene mutation, which is associated with head and neck paragangliomas. Surprisingly, Ga-68-DOTANOC-PET/CT (Fig. 1b) showed multiple bilateral areas of increased radiopharmaceutical uptake in the head and neck region, corresponding to bilateral neuroendocrine lesions and suggesting the presence of bilateral paragangliomas (yellow arrows) with small cervical lymph nodal metastases with short axis less than 1 cm of diameter (red arrows). Physiological radiopharmaceutical

  10. Benzophenanthridine alkaloid, piperonyl butoxide and (S)-methoprene action at the cannabinoid-1 receptor (CB1-receptor) pathway of mouse brain: Interference with [(3)H]CP55940 and [(3)H]SR141716A binding and modification of WIN55212-2-dependent inhibition of synaptosomal l-glutamate release.

    Science.gov (United States)

    Dhopeshwarkar, Amey Sadashiv; Nicholson, Russell Alfred

    2014-01-15

    Benzophenanthridine alkaloids (chelerythrine and sanguinarine) inhibited binding of [(3)H]SR141716A to mouse brain membranes (IC50s: CB1 receptors versus spleen CB2 receptors. All compounds reduced Bmax of [(3)H]SR141716A binding to CB1 receptors, but only methoprene and piperonyl butoxide increased Kd (3-5-fold). Benzophenanthridines increased the Kd of [(3)H]CP55940 binding (6-fold), but did not alter Bmax. (S)-methoprene increased the Kd of [(3)H]CP55940 binding (by almost 4-fold) and reduced Bmax by 60%. Piperonyl butoxide lowered the Bmax of [(3)H]CP55940 binding by 50%, but did not influence Kd. All compounds reduced [(3)H]SR141716A and [(3)H]CP55940 association with CB1 receptors. Combined with a saturating concentration of SR141716A, only piperonyl butoxide and (S)-methoprene increased dissociation of [(3)H]SR141716A above that of SR141716A alone. Only piperonyl butoxide increased dissociation of [(3)H]CP55940 to a level greater than CP55940 alone. Binding results indicate predominantly allosteric components to the study compounds action. 4-Aminopyridine-(4-AP-) evoked release of l-glutamate from synaptosomes was partially inhibited by WIN55212-2, an effect completely neutralized by AM251, (S)-methoprene and piperonyl butoxide. With WIN55212-2 present, benzophenanthridines enhanced 4-AP-evoked l-glutamate release above 4-AP alone. Modulatory patterns of l-glutamate release (with WIN-55212-2 present) align with previous antagonist/inverse agonist profiling based on [(35)S]GTPγS binding. Although these compounds exhibit lower potencies compared to many classical CB1 receptor inhibitors, they may have potential to modify CB1-receptor-dependent behavioral/physiological outcomes in the whole animal.

  11. PET Imaging of the AT{sub 1} receptor with [{sup 11}C]KR31173

    Energy Technology Data Exchange (ETDEWEB)

    Zober, Tamas G. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Mathews, William B. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Seckin, Esen [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Yoo, Sung-eun [Center for Biological Modulators, Korea Research Institute of Chemical Technology, Daejeon 305-343 (Korea, Republic of); Hilton, John [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Xia Jinsong [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Sandberg, Kathryn [Department of Medicine, Georgetown University, Washington, DC 20057 (United States); Ravert, Hayden T. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Dannals, Robert F. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States); Szabo, Zsolt [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-0817 (United States)]. E-mail: zszabo@jhmi.edu

    2006-01-15

    Aim: The goal of this study was to investigate the binding characteristics of [{sup 11}C]KR31173 and its applicability for PET studies of the AT{sub 1} receptor (AT{sub 1}R). Methods: Ex vivo biodistribution and pharmacology were tested in mice. PET imaging was performed in mice, beagle dogs and a baboon. To assess nonspecific binding, PET imaging was performed both before and after pretreatment with a potent AT{sub 1}R antagonist. In the baboon, PET imaging was also performed with the previously developed radioligand [{sup 11}C]L-159,884 for comparison. Results: Ex vivo biodistribution studies in mice showed specific binding rates of 80-90% in the adrenals, kidneys, lungs and heart. Specific binding was confirmed in mice using small animal PET. In dogs, renal cortex tissue concentration at 75-95 min postinjection (pi) was 63 nCi/ml per millicurie at a specific binding rate of 95%. In the baboon renal cortex, tissue activity at 55-75 min pi was 345 nCi/ml per millicurie. In the baboon the specific binding of [{sup 11}C]KR31173 was higher (81%) than the specific binding of [{sup 11}C]L-159,884 (34%). Conclusion: [{sup 11}C]KR31173 shows accumulation and significant specific binding to the AT{sub 1}R in the kidneys of mice, dogs and baboon. These findings suggest that this radioligand is suited for imaging the renal cortical AT{sub 1}R in multiple species.

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

    DEFF Research Database (Denmark)

    Herth, Matthias M; Petersen, Ida Nymann; Hansen, Hanne Demant

    2016-01-01

    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...

  13. Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Volk, Balázs; Pallagi, Katalin

    2012-01-01

    The most recently discovered serotonin (5-HT) receptor subtype, 5-HT(7), is considered to be associated with several CNS disorders. Noninvasive in vivo positron emission tomography (PET) studies of cerebral 5-HT(7) receptors could provide a significant advance in the understanding of the neurobio...

  14. Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

    Energy Technology Data Exchange (ETDEWEB)

    Kronfeld, Andrea; Müller-Forell, Wibke [Institute of Neuroradiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz 55131 (Germany); Buchholz, Hans-Georg; Maus, Stephan; Reuss, Stefan; Schreckenberger, Mathias; Miederer, Isabelle, E-mail: isabelle.miederer@unimedizin-mainz.de [Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz 55131 (Germany); Lutz, Beat [Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, Mainz 55128 (Germany)

    2015-12-15

    Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawley rats were investigated for template construction using MRI and [{sup 18}F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL

  15. Inverse agonist histamine H3 receptor PET tracers labelled with carbon-11 or fluorine-18.

    Science.gov (United States)

    Hamill, Terence G; Sato, Nagaaki; Jitsuoka, Makoto; Tokita, Shigeru; Sanabria, Sandra; Eng, Waisi; Ryan, Christine; Krause, Stephen; Takenaga, Norihiro; Patel, Shil; Zeng, Zhizhen; Williams, David; Sur, Cyrille; Hargreaves, Richard; Burns, H Donald

    2009-12-01

    Two histamine H3 receptor (H3R) inverse agonist PET tracers have been synthesized and characterized in preclinical studies. Each tracer has high affinity for the histamine H3 receptor, has suitable lipophilicity, and neither is a substrate for the P-glycoprotein efflux pump. A common phenolic precursor was used to synthesize each tracer with high specific activity and radiochemical purity by an alkylation reaction using either [(11)C]MeI or [(18)F]FCD(2)Br. Autoradiographic studies in rhesus monkey and human brain slices showed that each tracer had a widespread distribution with high binding densities in frontal cortex, globus pallidus and striatum, and lower uptake in cerebellum. The specificity of this expression pattern was demonstrated by the blockade of the autoradiographic signal by either the H3R agonist R-alpha-methylhistamine or a histamine H3R inverse agonist. In vivo PET imaging studies in rhesus monkey showed rapid uptake of each tracer into the brain with the same distribution seen in the autoradiographic studies. Each tracer could be blocked by pretreatment with a histamine H3R inverse agonist giving a good specific signal. Comparison of the in vitro metabolism of each compound showed slower metabolism in human liver microsomes than in rhesus monkey liver microsomes, with each compound having a similar clearance rate in humans. The in vivo metabolism of 1b in rhesus monkey showed that at 60 min, approximately 35% of the circulating counts were due to the parent. These tracers are very promising candidates as clinical PET tracers to both study the histamine H3R system and measure receptor occupancy of H3R therapeutic compounds.

  16. Radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET

    DEFF Research Database (Denmark)

    Ettrup, Anders; Palner, Mikael; Gillings, Nicolas;

    2010-01-01

    PET brain imaging of the serotonin 2A (5-hydroxytryptamine 2A, or 5-HT(2A)) receptor has been widely used in clinical studies, and currently, several well-validated radiolabeled antagonist tracers are used for in vivo imaging of the cerebral 5-HT(2A) receptor. Access to 5-HT(2A) receptor agonist...... PET tracers would, however, enable imaging of the active, high-affinity state of receptors, which may provide a more meaningful assessment of membrane-bound receptors. In this study, we radiolabel the high-affinity 5-HT(2A) receptor agonist 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-[(11)C-OCH(3...

  17. Frightening music triggers rapid changes in brain monoamine receptors: a pilot PET study.

    Science.gov (United States)

    Zhang, Ying; Chen, Qiaozhen; Du, Fenglei; Hu, Yanni; Chao, Fangfang; Tian, Mei; Zhang, Hong

    2012-10-01

    Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited. We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated. Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex. Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.

  18. Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [{sup 18}F]FITM

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Tomoteru [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); Tohoku University, Graduate School of Pharmaceutical Sciences, Sendai (Japan); Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); Yoshida, Yuichiro [SHI Accelerator Service Co. Ltd., Tokyo (Japan); Zhang, Ming-Rong [National Institute of Radiological Sciences, Molecular Imaging Centre, Chiba (Japan); National Institute of Radiological Sciences, Department of Molecular Probes, Molecular Imaging Centre, Chiba (Japan)

    2012-04-15

    In this study, we evaluate the utility of 4-[{sup 18}F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([{sup 18}F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [{sup 18}F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V{sub T}) was detected in the cerebellum (V{sub T} = 11.5). [{sup 18}F ]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [{sup 18}F ]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains. (orig.)

  19. Mass dose effects and in vivo affinity in brain PET receptor studies--a study of cerebral 5-HT4 receptor binding with [11C]SB207145

    DEFF Research Database (Denmark)

    Madsen, Karine; Marner, Lisbeth; Haahr, Mette;

    2011-01-01

    Attention to tracer dose principles is crucial in positron emission tomography (PET), and deviations can induce serious errors. In this study, we devise a method for determining receptor occupancy of the mass dose of the radioligand itself and the in vivo affinity.......Attention to tracer dose principles is crucial in positron emission tomography (PET), and deviations can induce serious errors. In this study, we devise a method for determining receptor occupancy of the mass dose of the radioligand itself and the in vivo affinity....

  20. Quantitative PET of human urokinase-type plasminogen activator receptor with 64Cu-DOTA-AE105

    DEFF Research Database (Denmark)

    Persson, Morten; Madsen, Jacob; Østergaard, Søren

    2012-01-01

    Expression levels of the urokinase-type plasminogen activator receptor (uPAR) represent an established biomarker for poor prognosis in a variety of human cancers. The objective of the present study was to explore whether noninvasive PET can be used to perform a quantitative assessment of expressi...

  1. Gallium-68 DOTATOC PET/CT in vivo characterization of somatostatin receptor expression in the prostate.

    Science.gov (United States)

    Todorović-Tirnanić, Mila V; Gajić, Milan M; Obradović, Vladimir B; Baum, Richard P

    2014-04-01

    The aim was to investigate somatostatin receptor (sstr) expression in normal prostate by determining the maximum standardized uptake value (SUVmax) of (68)Ga-DOTATOC PET/CT in neuroendocrine tumor (NET) patients, without NET involvement of the prostate gland, for establishing the reference standard. Sixty-four NET patients underwent (68)Ga-DOTATOC PET/CT. SUVmax of the prostate gland, normal liver, testes, and gluteus muscles were evaluated. The prostate gland size was measured. Statistical analysis was performed using dedicated software (SPSS13). Mean/median (68)Ga-DOTATOC SUVmax values were as follows: normal prostate 2.6 ± 0.0, slightly enlarged prostate 4.2 ± 1.6, prostatic hypertrophy 4.9 ± 1.6, prostatic hyperplasia 5.0 ± 1.5, prostate cancer 9.5 ± 2.1, normal liver 7.3 ± 1.8, testes 1.8 ± 0.5, and gluteus 1.0 ± 0.2. The normal prostate gland had three times less sstr expression than normal liver tissue. Strong correlation was found between patient age and sstr expression in prostate/prostate size. No significant difference existed in sstr expression between prostatic hypertrophy and hyperplasia. Much higher sstr expression was found in prostatic cancer compared with normal prostate. (68)Ga-DOTATOC PET/CT defines the baseline sstr uptake in prostate not affected by NET (significantly lower than in the liver). Higher values were established in prostatic hyperplasia and hypertrophy. Only concomitant prostate cancer was associated with higher SUVmax in comparison with non-neoplastic liver.

  2. Metabolism of the A{sub 1} adenosine receptor PET ligand [{sup 18}F]CPFPX by CYP1A2: implications for bolus/infusion PET studies

    Energy Technology Data Exchange (ETDEWEB)

    Matusch, Andreas [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Meyer, Philipp T. [Department of Neurology, University Hospital Aachen, D-52074 Aachen (Germany); Bier, Dirk [Institute for Neuroscience and Biophysics (INB4)-Nuclear Chemistry, Research Center Juelich GmbH, D-52425 Juelich (Germany); Holschbach, Marcus H. [Institute for Neuroscience and Biophysics (INB4)-Nuclear Chemistry, Research Center Juelich GmbH, D-52425 Juelich (Germany); Woitalla, Dirk [Neurological Department, Ruhr-University Bochum, D-44791 Bochum (Germany); Elmenhorst, David [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Winz, Oliver H. [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Zilles, Karl [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany); Bauer, Andreas [Institute of Medicine, Research Center Juelich GmbH, D-52425 Juelich (Germany)]. E-mail: an.bauer@fz-juelich.de

    2006-10-15

    The A{sub 1} adenosine receptor positron emission tomography (PET) ligand 8-cyclopentyl-3-(3-[{sup 18}F]fluoropropyl)-1-propylxanthine ([{sup 18}F]CPFPX, ) undergoes a fast hepatic metabolism. An optimal design of PET quantitation approaches (e.g., bolus/infusion studies) necessitates the knowledge of factors that influence this metabolism. Metabolites of were separated by radio thin-layer chromatography. Metabolism in vivo, in pooled human liver microsomes and in recombinant human cytochrome isoenzyme preparations was studied. Dynamic PET studies using were performed on three controls and two patients, one treated with the antidepressant and inhibitor of cytochrome CYP1A2 fluvoxamine, the other suffering from liver cirrhosis. CPFPX is metabolized by cytochrome CYP1A2 with high selectivity [K {sub M}=1.1 {mu}M (95% confidence interval, or CI, 0.6-2.0 {mu}M) and V {sub max}=243 pmol min{sup -1} mg{sup -1} (95% CI, 112-373 pmol min{sup -1} mg{sup -1}) corresponding to 2.4 pmol min{sup -1} pmol{sup -1} cytochrome P-450]. This metabolism can competitively be inhibited by fluvoxamine with K {sub I}=68 nM (95% CI, 34-138 nM). At least eight compounds found in human plasma and in the CYP1A2 in vitro preparations have an identical migration pattern and account together for >90% and >80% of the respective metabolite yield. Metabolism was considerably delayed in the two patients. In conclusion, is metabolized by cytochrome CYP1A2. Its metabolism is therefore subdued to disease-related or xenobiotic-induced changes of CYP1A2 activity. The identification of the metabolic pathway of 1 allows to optimize image quantification in A{sub 1} adenosine receptor PET studies.

  3. Quantitative measurement of histamine H{sub 1} receptors in human brains by PET and [{sup 11}C]doxepin

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Hideki; Kimura, Yuichi E-mail: ukimura@ieee.org; Ishii, Kenji; Oda, Keiichi; Sasaki, Toru; Tashiro, Manabu; Yanai, Kazuhiko; Ishiwata, Kiichi

    2004-02-01

    The aim of this study is to establish a method for quantitative measurement of histamine H{sub 1} receptor (H1R) in human brain by PET and [{sup 11}C]doxepin ([{sup 11}C]DOX). The estimated parameters with a two-compartment model were stable for the initial values for parameter estimation but those with a three-compartment model were not. This finding suggests that the H1R measured by the [{sup 11}C]DOX and PET can be evaluated with a two-compartment model.

  4. Quantification of 5-HT{sub 1A} receptors in human brain using p-MPPF kinetic modelling and PET

    Energy Technology Data Exchange (ETDEWEB)

    Sanabria-Bohorquez, S.M.; Veraart, C. [Neural Rehabilitation Engineering Lab., Univ. Catholique de Louvain, Brussels (Belgium); Biver, F.; Damhaut, P.; Wikler, D.; Goldman, S. [PET/Biomedical Cyclotron Unit, Univ. Libre de Bruxelles (Belgium)

    2002-01-01

    Serotonin-1A (5-HT{sub 1A}) receptors are implicated in neurochemical mechanisms underlying anxiety and depression and their treatment. Animal studies have suggested that 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-[{sup 18}F]fluorobenzamido] ethyl] piperazine (p-MPPF) may be a suitable positron emission tomography (PET) tracer of 5-HT{sub 1A} receptors. To test p-MPPF in humans, we performed 60-min dynamic PET scans in 13 healthy volunteers after single bolus injection. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 25% of the total radioactivity in plasma corresponded to p-MPPF. Radioactivity concentration was highest in hippocampus, intermediate in neocortex and lowest in basal ganglia and cerebellum. The interactions between p-MPPF and 5-HT{sub 1A} receptors were described using linear compartmental models with plasma input and reference tissue approaches. The two quantification methods provided similar results which are in agreement with previous reports on 5-HT{sub 1A} receptor brain distribution. In conclusion, our results show that p-MPPF is a suitable PET radioligand for 5-HT{sub 1A} receptor human studies. (orig.)

  5. Preclinical Safety Assessment of the 5-HT(2A) Receptor Agonist PET Radioligand [ (11)C]Cimbi-36

    DEFF Research Database (Denmark)

    Ettrup, Anders; Holm, Søren; Hansen, Martin;

    2013-01-01

    PURPOSE: [(11)C]Cimbi-36 was recently developed as an agonist radioligand for brain imaging of serotonin 2A receptors (5-HT(2A)) with positron emission tomography (PET). This may be used to quantify the high-affinity state of 5-HT(2A) receptors and may have the potential to quantify changes...... in cerebral 5-HT levels in vivo. We here investigated safety aspects related to clinical use of [(11)C]Cimbi-36, including radiation dosimetry and in vivo pharmacology. PROCEDURES: [(11)C]Cimbi-36 was injected in rats or pigs, and radiation dosimetry was examined by ex vivo dissection or with PET scanning......, respectively. Based on animal data, the Organ Level INternal Dose Assessment software was used to estimate extrapolated human dosimetry for [(11)C]Cimbi-36. The 5-HT(2A) receptor agonist actions of [(11)C]Cimbi-36 in vivo pharmacological effects in mice elicited by increasing doses of Cimbi-36 were assessed...

  6. Radiosynthesis and in vivo evaluation of novel radioligands for PET imaging of cerebral 5-HT7 receptors

    DEFF Research Database (Denmark)

    Hansen, Hanne D; Herth, Matthias M; Ettrup, Anders;

    2014-01-01

    The serotonin (5-hydroxytryptamine [5-ΗΤ]) 7 receptor (5-HT7R) is the most recently discovered 5-HT receptor, and its physiologic and possible pathophysiologic roles are not fully elucidated. So far, no suitable 5-HT7R PET radioligand is available, thus limiting the investigation of this receptor...... in the living brain. Here, we present the radiosynthesis and in vivo evaluation of Cimbi-712 (3-{4-[4-(4-methylphenyl)piperazine-1-yl]butyl}p-1,3-dihydro-2H-indol-2-one) and Cimbi-717 (3-{4-[4-(3-methoxyphenyl)piperazine-1-yl]butyl}-1,3-dihydro-2H-indol-2-one) as selective 5-HT7R PET radioligands in the pig...... brain. The 5-HT7R distribution in the postmortem pig brain is also assessed....

  7. Synthesis and Biological Evaluation of Thiophene-Based Cannabinoid Receptor Type 2 Radiotracers for PET Imaging

    Directory of Open Access Journals (Sweden)

    Ahmed Haider

    2016-07-01

    Full Text Available Over the past two decades, our understanding of the endocannabinoid system has greatly improved due to the wealth of results obtained from exploratory studies. Currently, two cannabinoid receptor subtypes have been well characterized. The cannabinoid receptor type 1 (CB1 is widely expressed in the central nervous system, while the levels of the cannabinoid receptor type 2 (CB2 in the brain and spinal cord of healthy individuals are relatively low. However, recent studies demonstrated a CB2 upregulation on activated microglia upon neuroinflammation, an indicator of neurodegeneration. Our research group aims to develop a suitable positron emission tomography (PET tracer to visualize the CB2 receptor in patients suffering from neurodegenerative diseases. Herein we report two novel thiophene-based 11C-labeled PET ligands designated [11C]AAT-015 and [11C]AAT-778. The reference compounds were synthesized using Gewald reaction conditions to obtain the aminothiophene intermediates, followed by amide formation. Saponification of the esters provided their corresponding precursors. Binding affinity studies revealed Ki values of 3.3 ± 0.5 nM (CB2 and 1.0 ± 0.2 µM (CB1 for AAT-015. AAT-778 showed similar Ki values of 4.3 ± 0.7 nM (CB2 and 1.1 ± 0.1 µM (CB1. Radiosynthesis was carried out under basic conditions using [11C]iodomethane as methylating agent. After semi-preparative HPLC purification both radiolabeled compounds were obtained in 99% radiochemical purity and the radiochemical yields ranged from 12 to 37%. Specific activity was between 96 - 449 GBq/µmol for both tracers. In order to demonstrate CB2 specificity of [11C]AAT-015 and [11C]AAT-778, we carried out autoradiography studies using CB2-positive mouse/rat spleen tissues. The obtained results revealed unspecific binding in spleen tissue that was not blocked by an excess of CB2-specific ligand GW402833. For in vivo analysis, [11C]AAT-015 was administered to healthy rats via tail

  8. Synthesis and Biological Evaluation of Thiophene-Based Cannabinoid Receptor Type 2 Radiotracers for PET Imaging

    Science.gov (United States)

    Haider, Ahmed; Müller Herde, Adrienne; Slavik, Roger; Weber, Markus; Mugnaini, Claudia; Ligresti, Alessia; Schibli, Roger; Mu, Linjing; Mensah Ametamey, Simon

    2016-01-01

    Over the past two decades, our understanding of the endocannabinoid system has greatly improved due to the wealth of results obtained from exploratory studies. Currently, two cannabinoid receptor subtypes have been well-characterized. The cannabinoid receptor type 1 (CB1) is widely expressed in the central nervous system, while the levels of the cannabinoid receptor type 2 (CB2) in the brain and spinal cord of healthy individuals are relatively low. However, recent studies demonstrated a CB2 upregulation on activated microglia upon neuroinflammation, an indicator of neurodegeneration. Our research group aims to develop a suitable positron emission tomography (PET) tracer to visualize the CB2 receptor in patients suffering from neurodegenerative diseases. Herein we report two novel thiophene-based 11C-labeled PET ligands designated [11C]AAT-015 and [11C]AAT-778. The reference compounds were synthesized using Gewald reaction conditions to obtain the aminothiophene intermediates, followed by amide formation. Saponification of the esters provided their corresponding precursors. Binding affinity studies revealed Ki-values of 3.3 ± 0.5 nM (CB2) and 1.0 ± 0.2 μM (CB1) for AAT-015. AAT-778 showed similar Ki-values of 4.3 ± 0.7 nM (CB2) and 1.1 ± 0.1 μM (CB1). Radiosynthesis was carried out under basic conditions using [11C]iodomethane as methylating agent. After semi-preparative HPLC purification both radiolabeled compounds were obtained in 99% radiochemical purity and the radiochemical yields ranged from 12 to 37%. Specific activity was between 96 and 449 GBq/μmol for both tracers. In order to demonstrate CB2 specificity of [11C]AAT-015 and [11C]AAT-778, we carried out autoradiography studies using CB2-positive mouse/rat spleen tissues. The obtained results revealed unspecific binding in spleen tissue that was not blocked by an excess of CB2-specific ligand GW402833. For in vivo analysis, [11C]AAT-015 was administered to healthy rats via tail-vein injection

  9. EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2

    DEFF Research Database (Denmark)

    Van Laere, Koen; Varrone, Andrea; Booij, Jan

    2010-01-01

    The guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2...... receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, which will increase the impact of this technique in neurological practice.The present document is an update of the first guidelines for SPECT using D2 receptor ligands labelled with (123)I [1...

  10. STRATEGIES FOR QUANTIFYING PET IMAGING DATA FROM TRACER STUDIES OF BRAIN RECEPTORS AND ENZYMES.

    Energy Technology Data Exchange (ETDEWEB)

    Logan, J.

    2001-04-02

    A description of some of the methods used in neuroreceptor imaging to distinguish changes in receptor availability has been presented in this chapter. It is necessary to look beyond regional uptake of the tracer since uptake generally is affected by factors other than the number of receptors for which the tracer has affinity. An exception is the infusion method producing an equilibrium state. The techniques vary in complexity some requiring arterial blood measurements of unmetabolized tracer and multiple time uptake data. Others require only a few plasma and uptake measurements and those based on a reference region require no plasma measurements. We have outlined some of the limitations of the different methods. Laruelle (1999) has pointed out that test/retest studies to which various methods can be applied are crucial in determining the optimal method for a particular study. The choice of method will also depend upon the application. In a clinical setting, methods not involving arterial blood sampling are generally preferred. In the future techniques for externally measuring arterial plasma radioactivity with only a few blood samples for metabolite correction will extend the modeling options of clinical PET. Also since parametric images can provide information beyond that of ROI analysis, improved techniques for generating such images will be important, particularly for ligands requiring more than a one-compartment model. Techniques such as the wavelet transform proposed by Turkheimer et al. (2000) may prove to be important in reducing noise and improving quantitation.

  11. Folic acid derivatives for PET imaging and therapy addressing folate receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schieferstein, Hanno

    2013-07-01

    Folic acid, also known as vitamin B9, is the oxidized form of 5,6,7,8-tetrahydrofolate, which serves as methyl- or methylene donor (C1-building blocks) during DNA synthesis. Under physiological conditions the required amount of 5,6,7,8-tetrahydrofolate for survival of the cell is accomplished through the reduced folate carrier (RFC). In contrast, the supply of 5,6,7,8-tetrahydrofolate is insufficient under pathophysiological conditions of tumors due to an increased proliferation rate. Consequently, many tumor cells exhibit an (over)expression of the folate receptor. This phenomenon has been applied to diagnostics (PET, SPECT, MR) to image FR-positive tumors and on the other hand to treat malignancies related to a FR (over)expression. Based on this concept, a new {sup 18}F-labeled folate for PET imaging has been developed and was evaluated in vivo using tumor-bearing mice. The incorporation of oligoethylene spacers into the molecular structure led to a significant enhancement of the pharmacokinetics in comparison to previously developed {sup 18}F-folates. The liver uptake could be reduced by one sixth by remaining a tumor uptake of 3%ID/g leading to better contrast ratios. Encouraged by these results, a clickable {sup 18}F-labeled serine-based prosthetic group has been synthesized, again with the idea to improve the metabolic and pharmacokinetic profile of hydrophilic radiotracers. Therefore, an alkyne-carrying azido-functionalized serine derivative for coupling to biomolecules was synthesized and a chlorine leaving group for {sup 18}F-labeling, which could be accomplished using a microwave-assisted synthesis, a [K is contained in 2.2.2]{sup +}/carbonate system in DMSO. Radiochemical yields of 77±6% could be achieved. The promising results obtained from the FR-targeting concept in the diagnostic field have been transferred to the boron neutron capture therapy. Therefore, a folate derivative was coupled to different boron clusters and cell uptake studies were

  12. Radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET

    DEFF Research Database (Denmark)

    Ettrup, Anders; Palner, Mikael; Gillings, Nic;

    2010-01-01

    PET tracers would, however, enable imaging of the active, high-affinity state of receptors, which may provide a more meaningful assessment of membrane-bound receptors. In this study, we radiolabel the high-affinity 5-HT(2A) receptor agonist 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-[(11)C-OCH(3...

  13. GABAA receptor subtypes in the mouse brain: Regional mapping and diazepam receptor occupancy by in vivo [(18)F]flumazenil PET.

    Science.gov (United States)

    Müller Herde, Adrienne; Benke, Dietmar; Ralvenius, William T; Mu, Linjing; Schibli, Roger; Zeilhofer, Hanns Ulrich; Krämer, Stefanie D

    2017-02-10

    Classical benzodiazepines, which are widely used as sedatives, anxiolytics and anticonvulsants, exert their therapeutic effects through interactions with heteropentameric GABAA receptors composed of two α, two β and one γ2 subunit. Their high affinity binding site is located at the interface between the γ2 and the adjacent α subunit. The α-subunit gene family consists of six members and receptors can be homomeric or mixed with respect to the α-subunits. Previous work has suggested that benzodiazepine binding site ligands with selectivity for individual GABAA receptor subtypes, as defined by the benzodiazepine-binding α subunit, may have fewer side effects and may even be effective in diseases, such as schizophrenia, autism or chronic pain, that do not respond well to classical benzodiazepines. The distributions of the individual α subunits across the CNS have been extensively characterized. However, as GABAA receptors may contain two different α subunits, the distribution of the subunits does not necessarily reflect the distribution of receptor subtypes with respect to benzodiazepine pharmacology. In the present study, we have used in vivo [(18)F]flumazenil PET and in vitro [(3)H]flumazenil autoradiography in combination with GABAA receptor point-mutated mice to characterize the distribution of the two most prevalent GABAA receptor subtypes (α1 and α2) throughout the mouse brain. The results were in agreement with published in vitro data. High levels of α2-containing receptors were found in brain regions of the neuronal network of anxiety. The α1/α2 subunit combinations were predictable from the individual subunit levels. In additional experiments, we explored in vivo [(18)F]flumazenil PET to determine the degree of receptor occupancy at GABAA receptor subtypes following oral administration of diazepam. The dose to occupy 50% of sensitive receptors, independent of the receptor subtype(s), was 1-2mg/kg, in agreement with published data from ex vivo

  14. [18F]MK-9470 PET measurement of cannabinoid CB1 receptor availability in chronic cannabis users.

    Science.gov (United States)

    Ceccarini, Jenny; Kuepper, Rebecca; Kemels, Dieter; van Os, Jim; Henquet, Cécile; Van Laere, Koen

    2015-03-01

    Δ(9) -Tetrahydrocannabinol, the main psychoactive component of cannabis, exerts its central effects through activation of the cerebral type 1 cannabinoid (CB1 ) receptor. Pre-clinical studies have provided evidence that chronic cannabis exposure is linked to decreased CB1 receptor expression and this is thought to be a component underlying drug tolerance and dependence. In this study, we make first use of the selective high-affinity positron emission tomography (PET) ligand [(18) F]MK-9470 to obtain in vivo measurements of cerebral CB1 receptor availability in 10 chronic cannabis users (age = 26.0 ± 4.1 years). Each patient underwent [(18) F]MK-9470 PET within the first week following the last cannabis consumption. A population of 10 age-matched healthy subjects (age = 23.0 ± 2.9 years) was used as control group. Parametric modified standardized uptake value images, reflecting CB1 receptor availability, were calculated. Statistical parametric mapping and volume-of-interest (VOI) analyses of CB1 receptor availability were performed. Compared with controls, cannabis users showed a global decrease in CB1 receptor availability (-11.7 percent). VOI-based analysis demonstrated that the CB1 receptor decrease was significant in the temporal lobe (-12.7 percent), anterior (-12.6 percent) and posterior cingulate cortex (-13.5 percent) and nucleus accumbens (-11.2 percent). Voxel-based analysis confirmed this decrease and regional pattern in CB1 receptor availability in cannabis users. These findings revealed that chronic cannabis use may alter specific regional CB1 receptor expression through neuroadaptive changes in CB1 receptor availability, opening the way for the examination of specific CB1 -cannabis addiction interactions which may predict future cannabis-related treatment outcome.

  15. Muscarinic Receptor Occupancy and Cognitive Impairment: A PET Study with [11C](+)3-MPB and Scopolamine in Conscious Monkeys

    OpenAIRE

    Yamamoto, Shigeyuki; Nishiyama, Shingo; Kawamata, Masahiro; Ohba, Hiroyuki; Wakuda, Tomoyasu; Takei, Nori; Tsukada, Hideo; Domino, Edward F.

    2011-01-01

    The muscarinic cholinergic receptor (mAChR) antagonist scopolamine was used to induce transient cognitive impairment in monkeys trained in a delayed matching to sample task. The temporal relationship between the occupancy level of central mAChRs and cognitive impairment was determined. Three conscious monkeys (Macaca mulatta) were subjected to positron emission tomography (PET) scans with the mAChR radioligand N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB). The scan sequence was pre-, 2,...

  16. Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET

    Science.gov (United States)

    Lanzenberger, R; Baldinger, P; Hahn, A; Ungersboeck, J; Mitterhauser, M; Winkler, D; Micskei, Z; Stein, P; Karanikas, G; Wadsak, W; Kasper, S; Frey, R

    2013-01-01

    Electroconvulsive therapy (ECT) is a potent therapy in severe treatment-refractory depression. Although commonly applied in psychiatric clinical routine since decades, the exact neurobiological mechanism regarding its efficacy remains unclear. Results from preclinical and clinical studies emphasize a crucial involvement of the serotonin-1A receptor (5-HT1A) in the mode of action of antidepressant treatment. This includes associations between treatment response and changes in 5-HT1A function and density by antidepressants. Further, alterations of the 5-HT1A receptor are consistently reported in depression. To elucidate the effect of ECT on 5-HT1A receptor binding, 12 subjects with severe treatment-resistant major depression underwent three positron emission tomography (PET) measurements using the highly selective radioligand [carbonyl-11C]WAY100635, twice before (test–retest variability) and once after 10.08±2.35 ECT sessions. Ten patients (∼83%) were responders to ECT. The voxel-wise comparison of the 5-HT1A receptor binding (BPND) before and after ECT revealed a widespread reduction in cortical and subcortical regions (P<0.05 corrected), except for the occipital cortex and the cerebellum. Strongest reductions were found in regions consistently reported to be altered in major depression and involved in emotion regulation, such as the subgenual part of the anterior cingulate cortex (−27.5%), the orbitofrontal cortex (−30.1%), the amygdala (−31.8%), the hippocampus (−30.6%) and the insula (−28.9%). No significant change was found in the raphe nuclei. There was no significant difference in receptor binding in any region comparing the first two PET scans conducted before ECT. This PET study proposes a global involvement of the postsynaptic 5-HT1A receptor binding in the effect of ECT. PMID:22751491

  17. Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    Li Zizhong [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Gifford, Andrew [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Liu Qian [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Ding Yushin [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Makriyannis, Alexandros [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Gatley, S. John [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States)]. E-mail: s.gatley@neu.edu

    2005-05-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB{sub 1} receptors that respond to {delta}{sup 9}-tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB{sub 1} receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[{sup 18}F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[{sup 18}F]fluoroaniline. The labeled precursor was synthesized from 1-[{sup 18}F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/{mu}mol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB{sub 1} receptors, absolute uptake at <0.003% injected radioactivity per cubic centimeter was lower than the previously reported uptake of the radioiodinated pyrazole AM281. Conclusions: The relatively poor brain uptake of AM5144 and other pyrazole CB{sub 1} receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB{sub 1} receptor that may require very lipophilic ligands.

  18. Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from {sup 68}Ga-RGD PET/CT and {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai-Jeon [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Ewha Womans University School of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Chun, In Kook [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kangwon National University Hospital, Department of Nuclear Medicine, Chuncheon, Kangwon-Do (Korea, Republic of); Cho, Nariya [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Im, Seock-Ah [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Jeong, Sunjoo [Dankook University, Department of Molecular Biology, Yongin (Korea, Republic of); Lee, Song [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Jung, Kyeong Cheon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Lee, Yun-Sang [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul (Korea, Republic of); Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, The Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2014-08-15

    Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes. In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6 ± 7.5 years old). {sup 68}Ga-Labeled arginine-glycine-aspartic acid (RGD) and {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}) from RGD PET/CT and SUV{sub max} and SUV{sub avg} from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered. Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88 ± 8.73 vs 10.48 ± 6.01, p = 0.02 for SUV{sub max}; 9.40 ± 5.19 vs 5.92 ± 4.09, p = 0.02 for SUV{sub avg}) and the PR-negative group (8.37 ± 4.94 vs 4.79 ± 3.93, p = 0.03 for SUV{sub avg}). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42 ± 0.59 vs 2.90 ± 0.75, p = 0.04 for SUV{sub max}; 1.60 ± 0.38 vs 1.95 ± 0.53, p = 0.04 for SUV{sub avg}) and showed a significant positive correlation with the HER2/CEP17 ratio (r = 0.38, p = 0.03 for SUV{sub max} and r = 0.46, p < 0.01 for SUV{sub avg}). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER

  19. Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI.

    Science.gov (United States)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Mandeville, Joseph B

    2016-04-01

    This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization.

  20. Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma

    DEFF Research Database (Denmark)

    Persson, Morten; Nedergaard, Mette K; Brandt-Larsen, Malene

    2016-01-01

    an orthotopic xenograft model of glioblastoma. Tumor growth was monitored using bioluminescence imaging. Five to six weeks after inoculation, all mice were scanned with small-animal PET/CT using two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and, for comparison, O-(2-(18)F...

  1. Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor

    Directory of Open Access Journals (Sweden)

    Linjing Mu

    2014-03-01

    Full Text Available Cannabinoid receptor subtype 2 (CB2 has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted.

  2. Immediate and Persistent Effects of Salvinorin A on the Kappa Opioid Receptor in Rodents, Monitored In Vivo with PET.

    Science.gov (United States)

    Placzek, Michael S; Van de Bittner, Genevieve C; Wey, Hsiao-Ying; Lukas, Scott E; Hooker, Jacob M

    2015-12-01

    Monitoring changes in opioid receptor binding with positron emission tomography (PET) could lead to a better understanding of tolerance and addiction because altered opioid receptor dynamics following agonist exposure has been linked to tolerance mechanisms. We have studied changes in kappa opioid receptor (KOR) binding availability in vivo with PET following kappa opioid agonist administration. Male Sprague-Dawley rats (n=31) were anesthetized and treated with the (KOR) agonist salvinorin A (0.01-1.8 mg/kg, i.v.) before administration of the KOR selective radiotracer [(11)C]GR103545. When salvinorin A was administered 1 min prior to injection of the radiotracer, [(11)C]GR103545 binding potential (BPND) was decreased in a dose-dependent manner, indicating receptor binding competition. In addition, the unique pharmacokinetics of salvinorin A (half-life ~8 min in non-human primates) allowed us to study the residual impact on KOR after the drug had eliminated from the brain. Salvinorin A was administered up to 5 h prior to [(11)C]GR103545, and the changes in BPND were compared with baseline, 2.5 h, 1 h, and 1 min pretreatment times. At lower doses (0.18 mg/kg and 0.32 mg/kg) we observed no prolonged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding (BPND decreased by 40-49%) which persisted up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain. These data point towards an agonist-induced adaptive response by KOR, the dynamics of which have not been previously studied in vivo with PET.

  3. Diphtheria toxin treatment of Pet-1-Cre floxed diphtheria toxin receptor mice disrupts thermoregulation without affecting respiratory chemoreception

    Science.gov (United States)

    Cerpa, Verónica; Gonzalez, Amalia; Richerson, George B.

    2014-01-01

    In genetically-modified Lmx1bf/f/p mice, selective deletion of LMX1B in Pet-1 expressing cells leads to failure of embryonic development of serotonin (5-HT) neurons. As adults, these mice have a decreased hypercapnic ventilatory response and abnormal thermoregulation. This mouse model has been valuable in defining the normal role of 5-HT neurons, but it is possible that developmental compensation reduces the severity of observed deficits. Here we studied mice genetically modified to express diphtheria toxin receptors (DTR) on Pet-1 expressing neurons (Pet-1-Cre/Floxed DTR or Pet1/DTR mice). These mice developed with a normal complement of 5-HT neurons. As adults, systemic treatment with 2 – 35 μg diphtheria toxin (DT) reduced the number of tryptophan hydroxylase immunoreactive (TpOH-ir) neurons in the raphe nuclei and ventrolateral medulla by 80%. There were no effects of DT on baseline ventilation (VE) or the ventilatory response to hypercapnia or hypoxia. At an ambient temperature (TA) of 24°C, all Pet1/DTR mice dropped their body temperature (TB) below 35°C after DT treatment, but the latency was shorter in males than females (3.0 ± 0.37 vs 4.57 ± 0.29 days, respectively; p thermoregulation, in males more than females. In comparison to models with deficient embryonic development of 5-HT neurons, acute deletion of 5-HT neurons in adults leads to a greater defect in thermoregulation, suggesting that significant developmental compensation can occur. PMID:25171790

  4. Cerebral 5-HT release correlates with [11C]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain

    DEFF Research Database (Denmark)

    Jørgensen, Louise M; Weikop, Pia; Villadsen, Jonas;

    2017-01-01

    Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [(11)C]Cimbi-36, for its...... sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [(11)C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular...... 5-HT levels with microdialysis and [(11)C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5...

  5. Developing new PET tracers to image the growth hormone secretagogue receptor 1a (GHS-R1a).

    Science.gov (United States)

    Kawamura, Kazunori; Fujinaga, Masayuki; Shimoda, Yoko; Yamasaki, Tomoteru; Zhang, Yiding; Hatori, Akiko; Xie, Lin; Wakizaka, Hidekatsu; Kumata, Katsushi; Ohkubo, Takayuki; Kurihara, Yusuke; Ogawa, Masanao; Nengaki, Nobuki; Zhang, Ming-Rong

    2017-09-01

    `The growth hormone secretagogue receptor 1a (GHS-R1a) is the orphan G-protein-coupled receptor, and its endogenous ligand is ghrelin. GHS-R1a contributes to regulation of glucose homeostasis, memory and learning, food addiction, and neuroprotection. Several PET tracers for GHS-R1a have been developed, but none have been reported to be clinically applicable to GHS-R1a imaging. In this study, we developed three new PET tracers for GHS-R1a: (18)F-labeled 6-(4-chlorophenyl)-3-((1-(2-fluoroethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (1), (11)C-labeled 6-(4-chlorophenyl)-3-((1-(2-methoxyethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one (2), and (11)C-labeled (S)-(4-(1H-indole-6-carbonyl)-3-methylpiperazin-1-yl)(4'-methoxy-[1,1'-biphenyl]-4-yl)methanone (3). [(18)F]1 was synthesized by the (18)F-fluoroethylation; [(11)C]2 or [(11)C]3 was synthesized by the (11)C-methylation. Biodistribution studies and PET studies were conducted in mice. We successfully radiosynthesized [(18)F]1, [(11)C]2, and [(11)C]3 with appropriate radioactivity for the animal study. In the ex vivo biodistribution study, 60min following injection, the radioactivity level of [(18)F]1 was relatively high in the small intestine, that of [(11)C]2 was high in the liver, and that of [(11)C]3 was high in the pancreas. The radioactivity levels of the three PET tracers were relatively low in the brain. Under pretreatment with YIL781 (a selective and high affinity antagonist for GHS-R1a), the pancreas radioactivity level at 30min following [(11)C]3 injection was significantly reduced to 55% of control, but the radioactivity in the brain was not changed. In the PET study under control conditions, high radioactivity levels in the liver and pancreas were observed following [(11)C]3 injection. With YIL781 pretreatment, the accumulated radioactivity in the pancreas 15-60min after [(11)C]3 injection was significantly decreased to 78% of control. [(11)C]3 exhibited relatively high uptake

  6. 68Ga-DOTA-NOC PET and peptide receptor radionuclide therapy in management of bilateral ovarian metastases from gastrointestinal carcinoid.

    Science.gov (United States)

    Singla, Suhas; Gupta, Santosh; Reddy, Rama Mohan; Durgapal, Prashant; Bal, C S

    2012-12-01

    The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

  7. PET imaging of cannabinoid type 2 receptors with [(11)C]A-836339 did not evidence changes following neuroinflammation in rats.

    Science.gov (United States)

    Pottier, Geraldine; Gómez-Vallejo, Vanessa; Padro, Daniel; Boisgard, Raphaël; Dollé, Frédéric; Llop, Jordi; Winkeler, Alexandra; Martín, Abraham

    2017-03-01

    Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using positron emission tomography (PET) imaging. In this work, we report the evaluation of the in vivo expression of CB2R with [(11)C]A-836339 PET after cerebral ischemia and in two rat models of neuroinflammation, first by intrastriatal LPS and then by AMPA injection. PET images and in vitro autoradiography showed a lack of specific [(11)C]A-836339 uptake in these animal models demonstrating the limitation of this radiotracer to image CB2 receptor under neuroinflammatory conditions. Further, using immunohistochemistry, the CB2 receptor displayed a modest expression increase after cerebral ischemia, LPS and AMPA models. Finally, [(18)F]DPA-714-PET and immunohistochemistry demonstrated decreased neuroinflammation by a selective CB2R agonist, JWH133. Taken together, these findings suggest that [(11)C]A-836339 is not a suitable radiotracer to monitor in vivo CB2R expression by using PET imaging. Future studies will have to investigate alternative radiotracers that could provide an accurate binding to CB2 receptors following brain inflammation.

  8. A pictoral review on somatostatin receptor scintigraphy in neuroendocrine tumors: The role of multimodality imaging with SRS and GLUT receptor imaging with FDG PET-CT

    Directory of Open Access Journals (Sweden)

    Sneha Shah

    2012-01-01

    Full Text Available Somatostatin receptor scintigraphy is considered as a comprehensive imaging modality for many neuroendocrine tumors. Multiple radiotracers using combinations of gamma or positron emitting radionuclides and tracers are now available. Newer radiopharmaceuticals using 99m Tc labeled with TOC, TATE, NOC are good alternatives to the 68 - Gallium radiotracers where the PET facility is not available. The pictoral depicts the role of SRS using 99m TC - HYNIC -TOC radiotracers in staging and treatment planning of NETs. Characterization of the tumor biology using combined SRS and FDG PET/CT is also demonstrated with a proposed categorization method. The emerging role of SRS in tailored targeted radionuclide therapy is outlined in brief.

  9. Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with 68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy

    OpenAIRE

    Wolfgang Luboldt; Holger Hartmann; Bärbel Wiedemann; Klaus Zöphel; Hans-Joachim Luboldt

    2010-01-01

    The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) during the course of somatostatin receptor radionuclide therapy (SRRT). In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA) and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax) of normal liver and hepatic metastases we...

  10. Development of new peripheral benzodiazepine receptor ligands for SPECT and PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, A.; Fookes, C.; Pham, T.; Holmes, T.; Mattner, F.; Berghoffer, P.; Gregoire, M.C.; Loc' h, C.; Greguric, I. [Radiopharmaceuticas Research Institute, ANSTO, Menai, N.S.W. Sydney (Australia); Thominiaux, C.; Boutin, H.; Chauveau, F.; Gregoire, M.C.; Hantraye, Ph.; Tavitain, B.; Dolle, F. [Service Hospitalier Frederic Joliot, CEA/DSV, 91 - Orsay (France); Arlicot, N.; Chalon, S.; Guilloteau, D. [Universite Francois Rabelais, Inserm U619, 37 - Tours (France)

    2008-02-15

    This study aims to demonstrate that a number of radiolabelled ({sup 123}I,{sup 11}C, {sup 18}F) imidazo pyridines, imidazo pyridazines and indolglyoxylamides can be developed as potential tracers for SPECT and PET imaging. (N.C.)

  11. Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot.

    Science.gov (United States)

    Veronese, Mattia; Zanotti-Fregonara, Paolo; Rizzo, Gaia; Bertoldo, Alessandra; Innis, Robert B; Turkheimer, Federico E

    2016-04-15

    PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i

  12. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    Science.gov (United States)

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  13. Islet-selectivity of G-protein coupled receptor ligands evaluated for PET imaging of pancreatic {beta}-cell mass

    Energy Technology Data Exchange (ETDEWEB)

    Cline, Gary W., E-mail: gary.cline@yale.edu [Yale University School of Medicine (United States); Zhao, Xiaojian [Yale University School of Medicine (United States); Jakowski, Amy B.; Soeller, Walter C.; Treadway, Judith L. [Pfizer Global Research and Development, Pfizer Inc., Groton CT (United States)

    2011-09-02

    Highlights: {yields} We screened G-protein coupled receptors for imaging pancreatic. {yields} Database mining and immunohistochemistry identified GPCRs enriched in {beta}-cells. {yields} In vitro and in vivo assays were used to determine exocrine vs endocrine specificity. {yields} GPCR candidates for imaging of {beta}-cell mass are Prokineticin-1R, mGluR5, and GLP-1R. -- Abstract: A critical unmet need exists for methods to quantitatively measure endogenous pancreatic {beta}-cell mass (BCM) for the clinical evaluation of therapies to prevent or reverse loss of BCM and diabetes progression. Our objective was to identify G-protein coupled receptors (GPCRs) that are expressed with a high degree of specificity to islet {beta}-cells for receptor-targeted imaging of BCM. GPCRs enriched in pancreatic islets relative to pancreas acinar and hepatic tissue were identified using a database screen. Islet-specific expression was confirmed by human pancreas immunohistochemistry (IHC). In vitro selectivity assessment was determined from the binding and uptake of radiolabeled ligands to the rat insulinoma INS-1 832/13 cell line and isolated rat islets relative to the exocrine pancreas cell-type, PANC-1. Tail-vein injections of radioligands into rats were used to determine favorable image criteria of in vivo biodistribution to the pancreas relative to other internal organs (i.e., liver, spleen, stomach, and lungs). Database and IHC screening identified four candidate receptors for further in vitro and in vivo evaluation for PET imaging of BCM: prokineticin-1 receptor (PK-1R), metabotropic glutamate receptor type-5 (mGluR5), neuropeptide Y-2 receptor (NPY-2R), and glucagon-like peptide 1 receptor (GLP-1R). In vitro specificity ratios gave the following receptor rank order: PK-1R > GLP-1R > NPY-2R > mGluR5. The biodistribution rank order of selectivity to the pancreas was found to be PK-1R > VMAT2 {approx} GLP-1R > mGluR5. Favorable islet selectivity and biodistribution

  14. Molecular imaging of neuroendocrine tumors using {sup 68}Ga-labeled peptides (Somatostatin receptor PET/CT); Molekulare Bildgebung neuroendokriner Tumoren mit {sup 68}Ga-markierten Peptiden (Somatostatinrezeptor-PET/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R.P.; Prasad, V. [Zentralklinik Bad Berka GmbH (Germany). Klinik fuer Nuklearmedizin/PET-Zentrum; Hoersch, D. [Zentralklinik Bad Berka GmbH (Germany). Klinik fuer Innere Medizin, Gastroenterologie, Onkologie, Endokrionologie

    2009-06-15

    Receptor PET/CT using {sup 68}Ga-labeled somatostatin analogues (DOTA-NOC, DOTA-TOC or DOTA-TATE) enables the highly sensitive molecular imaging of neuroendocrine tumors (NETs) based on the expression of somatostatin receptors and even the detection of receptor subtypes. Our experience after more than 3000 studies shows that receptor PET/CT has a significantly higher tumor detection rate than conventional scintigraphy (even in SPECT/CT technique), and that tumor lesions can be very accurately localized. By calculating standardized uptake values (SUV) - which are reproducible and investigator-independent - patients can be selected for peptide receptor radiotherapy and also the course after therapy can be controlled. Receptor-PET/CT is the most sensitive imaging modality for the detection of unknown primary tumors (CUP syndrome), which is especially true for the detection of neuroendocrine tumors of the pancreas and small bowel; whole-body staging (''one stop shop'') as well as restaging and selection of patients for peptide receptor radiotherapy can be performed using a patient-friendly procedure (examination finished within one hour) exposing the patient to less radiation than whole-body CT scanning. The {sup 68}Ge/{sup 68}Ga generator has proved very reliable over the years - even in a hospital environment. The effective costs for {sup 68}Ga labeled somatostatin analogues might be less than for scintigraphic agents, provided a certain number of studies per year are performed. The development of new tumor-specific peptides as well as of other DOTA- or NOTA-coupled radiopharmaceuticals opens a new avenue into the future: finally, the {sup 68}Ga generator could play a similar important role for PET/CT as did the {sup 99m}Tc-Generator for conventional gamma camera imaging over the last decades. (orig.)

  15. Characterization of [(11)C]Cimbi-36 as an agonist PET radioligand for the 5-HT(2A) and 5-HT(2C) receptors in the nonhuman primate brain

    DEFF Research Database (Denmark)

    Finnema, Sjoerd J; Stepanov, Vladimir; Ettrup, Anders

    2014-01-01

    a more meaningful assessment of available receptors than antagonist radioligands. In the current study we characterized [(11)C]Cimbi-36 receptor binding in the primate brain. On five experimental days, a total of 14 PET measurements were conducted in three female rhesus monkeys. On each day, PET...... agonist radioligand suitable for examination of 5-HT2A receptors in the cortical regions and of 5-HT2C receptors in the choroid plexus of the primate brain....

  16. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs;

    2011-01-01

    Small-molecule α(7) nicotinic acetylcholine receptor (α(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled α(7)nAChR PET tracer would be important for in vivo quantification of α(7)nAChR bind......Small-molecule α(7) nicotinic acetylcholine receptor (α(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled α(7)nAChR PET tracer would be important for in vivo quantification of α(7)n...

  17. Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Göttingen minipig

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Lind, Nanna M; Gillings, Nic;

    2009-01-01

    This study investigates 5-hydroxytryptamine 4 (5-HT(4)) receptor binding in the minipig brain with positron emission tomography (PET), tissue homogenate-binding assays, and autoradiography in vitro. The cerebral uptake and binding of the novel 5-HT(4) receptor radioligand [(11)C]SB207145 in vivo...... autoradiographic 5-HT(4) receptor distribution resembles the human 5-HT(4) receptor distribution with the highest binding in the striatum and no detectable binding in the cerebellum. We found that in the minipig brain [(11)C]SB207145 follows one-tissue compartment kinetics, and the simplified reference tissue...... model provides stable and precise estimates of the binding potential in all regions. The binding potentials calculated for striatum, midbrain, and cortex from the PET data were highly correlated with 5-HT(4) receptor concentrations determined in brain homogenates from the same regions, except...

  18. Initial investigation of three selective and potent small molecule oxytocin receptor PET ligands in New World monkeys.

    Science.gov (United States)

    Smith, Aaron L; Freeman, Sara M; Barnhart, Todd E; Abbott, David H; Ahlers, Elizabeth O; Kukis, David L; Bales, Karen L; Goodman, Mark M; Young, Larry J

    2016-07-15

    The neuropeptide oxytocin is part of a neuroendocrine system that has physiological effects ranging from ensuring uterine myometrial contractions at parturition and post-partum mammary gland milk ejection to the modulation of neural control of social relationships. This initial study was performed to investigate the potential use of positron emission tomography (PET) for localizing oxytocin receptors in two New World primates. Three biomarkers for PET (1-3) that are known to have high affinity and selectivity for the human oxytocin receptor were investigated in the common marmoset (Callithrix jacchus) via PET imaging. Brain penetration, and uptake in the salivary gland area were both observed with biomarkers 2 and 3. No brain penetration was observed with 1, but uptake was observed more specifically in several peripheral endocrine glands compared to 2 or 3. Biomarker 2, which displayed the best brain penetration of the three biomarkers in the marmoset, was then investigated in the monogamous coppery titi monkey (Callicebus cupreus) in a brain scan and a limited full body scan. No significant brain penetration of 2 was observed in the titi monkey, but significant uptake was observed in various locations throughout the periphery. Metabolism of 2 was suspected to have been significant based upon HPLC analysis of blood draws, but parent compound was still present near the end of the scan. Follow-up investigations will focus on next generation biomarkers bearing improved binding characteristics and brain penetrability as well as investigating tissue in regions where biomarker uptake was observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

    Energy Technology Data Exchange (ETDEWEB)

    Vandeputte, Caroline; Casteels, Cindy; Koole, Michel; Gerits, Anneleen [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); Struys, Tom [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Veghel, Daisy van; Evens, Nele; Bormans, Guy [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Laboratory of Radiopharmacy, Leuven (Belgium); Dresselaers, Tom; Himmelreich, Uwe [KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); KU Leuven, Biomedical NMR Unit, Leuven (Belgium); Lambrichts, Ivo [Hasselt University, Laboratory of Histology, Biomedical Research Institute, Hasselt (Belgium); Laere, Koen van [KU Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, Molecular Small Animal Imaging Center, MoSAIC, Leuven (Belgium); UZ Leuven, Division of Nuclear Medicine, Leuven (Belgium)

    2012-11-15

    Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB{sub 1} and CB{sub 2}) have been suggested. The purpose of this study was to evaluate CB{sub 1} and CB{sub 2} receptor binding over time in vivo in a rat photothrombotic stroke model using PET. CB{sub 1} and CB{sub 2} microPET imaging was performed at regular time-points up to 2 weeks after stroke using [{sup 18}F]MK-9470 and [{sup 11}C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB{sub 1} and CB{sub 2}. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68). [{sup 18}F]MK-9470 PET showed a strong increase in CB{sub 1} binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB{sub 1} immunohistochemical staining. [{sup 11}C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB{sub 2} revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB{sub 1} {sup +} and CB{sub 2} {sup +} cells showed minor immunoreactivity for CD68. Time-dependent and regionally strongly increased CB{sub 1}, but not CB{sub 2}, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB{sub 1} signalling as the role of CB{sub 2} seems minor in the acute and subacute phases of stroke. (orig.)

  20. Adenosine A{sub 2A} receptor imaging with [{sup 11}C]KF18446 PET in the rat brain after quinolinic acid lesion. Comparison with the dopamine receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi; Ogi, Nobuo; Hayakawa, Nobutaka [Tokyo Metropolitan Inst. of Gerontology, Tokyo (Japan). Positron Medical Center] [and others

    2002-11-01

    We proposed [{sup 11}C]KF18446 as a selective radioligand for mapping the adenosine A{sub 2A} receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [{sup 11}C]KF18446 PET can detect the change in the striatal adenosine A{sub 2A} receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [{sup 11}C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [{sup 11}C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [{sup 11}C] raclopride binding to dopamine D{sub 2} receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [{sup 11}C]SCH23390 binding to dopamine D{sub 1} receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [{sup 11}C]KF18446 PET can detect change in the adenosine A{sub 2A} receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum. (author)

  1. Adenosine A(2A receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Masahiro Mishina

    Full Text Available Adenosine A(2A receptors (A2ARs are thought to interact negatively with the dopamine D(2 receptor (D2R, so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD. However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET with [7-methyl-(11C]-(E-8-(3,4,5-trimethoxystyryl-1,3,7-trimethylxanthine ([(11C]TMSX in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test. In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test. In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an

  2. A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Zavaleta, Cristina L

    2012-01-01

    ]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/µmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [(18)F]13 in mice showed high uptake...

  3. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform...

  4. The Impact of Somatostatin Receptor-Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Barrio, Martin; Czernin, Johannes; Fanti, Stefano; Ambrosini, Valentina; Binse, Ina; Du, Lin; Eiber, Matthias; Herrmann, Ken; Fendler, Wolfgang P

    2017-05-01

    Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. (68)Ga-DOTATATE approval by the U.S. Food and Drug Administration has triggered widespread clinical interest in SSTR PET/CT throughout the United States. Here, we performed a systematic review and meta-analysis to evaluate the impact of SSTR PET/CT on the management of patients with NETs. Methods: A comprehensive literature search was performed using The National Center for Biotechnology Information PubMed online database, applying the following key words: "management" AND "PET" AND "neuroendocrine". Fourteen of 190 studies were deemed suitable based on the following inclusion criteria: original research, cohort study, number of patients 10 or more, and reported change in management after SSTR PET/CT. Change in management across studies was determined by a random-effects model. Results: A total of 1,561 patients were included. Overall, change in management occurred in 44% (range, 16%-71%) of NET patients after SSTR PET/CT. In 4 of 14 studies, SSTR PET/CT was performed after an (111)In-Octreotide scan. In this subgroup, additional information by SSTR PET/CT led to a change in management in 39% (range, 16%-71%) of patients. Seven of 14 studies differentiated between inter- and intramodality changes, with most changes being intermodality (77%; intramodality, 23%). Conclusion: The management was changed in more than one third of patients undergoing SSTR PET/CT even when performed after an (111)In-Octreotide scan. Intermodality changes were 3 times more likely than intramodality changes, underlining the clinical impact of SSTR PET/CT. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  5. Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach

    DEFF Research Database (Denmark)

    Haugbøl, Steven; Pinborg, Lars H; Arfan, Haroon M

    2006-01-01

    PURPOSE: To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach. Further, to estimate the sample size needed to detect regional differences between two groups and, finally, to evaluate how partial volume correction affects...... reproducibility and the required sample size. METHODS: For assessment of the variability, six subjects were investigated with [18F]altanserin PET twice, at an interval of less than 2 weeks. The sample size required to detect a 20% difference was estimated from [18F]altanserin PET studies in 84 healthy subjects......% (range 5-12%), whereas in regions with a low receptor density, BP1 reproducibility was lower, with a median difference of 17% (range 11-39%). Partial volume correction reduced the variability in the sample considerably. The sample size required to detect a 20% difference in brain regions with high...

  6. Biokinetics and imaging with the somatostatin receptor PET radioligand {sup 68}Ga-DOTATOC: preliminary data

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, M.; Boerner, A.R.; Weckesser, E.; Oei, M.L.; Meyer, G.J.; Knapp, W.H. [Dept. of Nuclear Medicine, Hannover University Medical School (Germany); Maecke, H.; Heppeler, A. [Dept. of Radiology, Kantonspittal, Basel (Switzerland); Schoeffski, P. [Dept. of Haematology and Oncology, Hannover University Medical School (Germany); Schumacher, J.; Henze, M. [German Cancer Research Centre, Heidelberg (Germany)

    2001-12-01

    Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of {sup 68}Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to {sup 68}Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 ({+-}0.3) min and 48 ({+-}7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70{+-}20 min post injection. Kidney uptake averaged <50% compared with spleen uptake. Of 40 lesions predefined by computed tomography and/or magnetic resonance imaging, {sup 68}Ga-DOTATOC PET identified 100%, whereas {sup 111}In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ({sup 111}In-octreotide: 1.5:1) to 100:1 for CNS ({sup 111}In-octreotide: 10:1). With {sup 68}Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using {sup 68}Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with {sup 111}In-octreotide scintigraphy. (orig.)

  7. Biokinetics and imaging with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data.

    Science.gov (United States)

    Hofmann, M; Maecke, H; Börner, R; Weckesser, E; Schöffski, P; Oei, L; Schumacher, J; Henze, M; Heppeler, A; Meyer, J; Knapp, H

    2001-12-01

    Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of (68)Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to (68)Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 (+/-0.3) min and 48 (+/-7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70+/-20 min post injection. Kidney uptake averaged 68)Ga-DOTATOC PET identified 100%, whereas (111)In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ((111)In-octreotide: 1.5:1) to 100:1 for CNS ((111)In-octreotide: 10:1). With (68)Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using (68)Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with (111)In-octreotide scintigraphy.

  8. Molecular imaging with {sup 68}Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kaemmerer, Daniel; Haugvik, Sven-Petter; Hommann, Merten [Zentralklinik Bad Berka GmbH, Department of General and Visceral Surgery, Bad Berka (Germany); Peter, Luisa; Lupp, Amelie; Schulz, Stefan [University of Jena, Department of Pharmacology and Toxicology, Jena (Germany); Saenger, Joerg [Laboratory of Pathology and Cytology, Bad Berka (Germany); Prasad, Vikas; Kulkarni, Harshad; Baum, Richard Paul [Zentralklinik Bad Berka, Department of Nuclear Medicine and Center for PET, Bad Berka (Germany)

    2011-09-15

    Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5. Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative {sup 68}Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV{sub max} and SUV{sub mean}) were used for PET/CT. The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV{sub max} on the PET/CT (p < 0.001; p < 0.05) and the IRS for SSTR2A with the SUV{sub mean} (p < 0.013). The level of SSTR2A score correlated significantly with chromogranin A staining and indirectly to the tumour grading. The highly significant correlation between SSTR2A and SSTR5 and the SUV{sub max} on the {sup 68}Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of {sup 68}Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using {sup 68}Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy. (orig.)

  9. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs

    2011-01-01

    Small-molecule a(7) nicotinic acetylcholine receptor (a(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled a(7)nAChR PET tracer would be important for in vivo quantification of a(7)n...

  10. Gender dependent rate of metabolism of the opioid receptor-PET ligand [{sup 18}F]fluoroethyl-diprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, G.; Spilker, M.E.; Hauser, A.I.; Boecker, H.; Schwaiger, M.; Wester, H.J. [Technische Univ. Muenchen, Garching (Germany). Dept. of Nuclear Medicine; Sprenger, T.; Platzer, S.; Toelle, T.R. [Technische Univ. Muenchen, Garching (Germany). Klinikum rechts der Isar, Neurology

    2006-07-01

    Aim: The morphinane-derivate 6-O-(2-[{sup 18}F]fluoroethyl)-6-O-desmethyldiprenorphine ([{sup 18}F]FDPN) is a non-selective opioid receptor ligand currently used in positron emission tomography (PET). Correction for plasma metabolites of the arterial input function is necessary for quantitative measurements of [{sup 18}]FDPN binding. A study was undertaken to investigate if there are gender dependent differences in the rate of metabolism of [{sup 18}F]FDPN. Methods: The rate of metabolism of [{sup 18}F]FDPN was mathematically quantified by fitting a bi-exponential function to each individual's dynamic metabolite data. Results: No statistically significant gender differences were found for age, weight, body mass index or dose. However, significant differences (p<0.01) in two of the four kinetic parameters describing the rate of metabolism were found between the two groups, with women metabolizing [{sup 18}F]FDPN faster than men. These differences were found in the contribution of the fast and slow kinetic components of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of [{sup 18}F]FDPN in women than in men. Conclusion: The findings reinforce the need for individualized metabolite correction during [{sup 18}F]FDPN-PET scans and also indicate that in certain cases, grouping according to gender could be performed in order to minimize methodological errors of the input function prior to kinetic analyses. (orig.)

  11. Verbal memory and 5-HT1A receptors in healthy volunteers--A PET study with [carbonyl-(11)C]WAY-100635.

    Science.gov (United States)

    Penttilä, Jani; Hirvonen, Jussi; Tuominen, Lauri; Lumme, Ville; Ilonen, Tuula; Någren, Kjell; Hietala, Jarmo

    2016-03-01

    The serotonin 5-HT1A receptor is a putative drug development target in disorders with cognitive and in particular memory deficits. However, previous human positron emission tomography (PET) studies on 5-HT1A receptor binding and memory functions have yielded discrepant results. We explored the association between verbal memory and 5-HT1A receptor binding in 24 healthy subjects (14 male, 10 female, aged 18-41 years). The cognitive tests included the Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Wisconsin Card Sorting Test (WCST). 5-HT1A receptor binding was measured with PET and the radioligand [carbonyl-(11)C]WAY-100635, which was quantified with the gold standard method based on kinetic modeling using arterial blood samples. We found that global 5-HT1A receptor binding was positively correlated with measures of verbal memory, such that subjects who had higher receptor binding tended to have better verbal memory than subjects who had lower receptor binding. Regional analyses suggested significant correlations in multiple neocortical brain regions and the raphe nuclei. We did not find significant correlations between 5-HT1A receptor binding and executive functions as measured with WCST. We conclude that neocortical as well as raphe 5-HT1A receptors are involved in verbal memory function in man.

  12. Determination of receptor occupancy in the presence of mass dose: [(11)C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746.

    Science.gov (United States)

    Gallezot, Jean-Dominique; Planeta, Beata; Nabulsi, Nabeel; Palumbo, Donna; Li, Xiaoxi; Liu, Jing; Rowinski, Carolyn; Chidsey, Kristin; Labaree, David; Ropchan, Jim; Lin, Shu-Fei; Sawant-Basak, Aarti; McCarthy, Timothy J; Schmidt, Anne W; Huang, Yiyun; Carson, Richard E

    2017-03-01

    Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds "tracer" levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [(11)C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [(11)C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%-97% and 30%-93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%-15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

  13. [68Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - Comparison to [18F]FDG and laboratory values

    Science.gov (United States)

    Lapa, Constantin; Schreder, Martin; Schirbel, Andreas; Samnick, Samuel; Kortüm, Klaus Martin; Herrmann, Ken; Kropf, Saskia; Einsele, Herrmann; Buck, Andreas K.; Wester, Hans-Jürgen; Knop, Stefan; Lückerath, Katharina

    2017-01-01

    Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [68Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [68Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [18F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [68Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [18F]FDG was available, [68Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [18F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [18F]FDG-PET positivity correlated with [68Ga]Pentixafor-PET positivity (p=0.018). [68Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma. PMID:28042328

  14. Synthesis of carbon-11 labelled SCH 39166, a new selective dopamine D-1 receptor ligand, and preliminary PET investigations

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Farde, Lars; Sedvall, Goeran (Karolinska Hospital, Stockholm (Sweden). Dept. of Psychiatry and Psychology); Barnett, Allen (Schering-Plough Corp., Bloomfield, NJ (USA))

    1991-01-01

    SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo(d)naphtho-(2,1-b)azepine ) is a new more selective dopamine D-1 receptor antagonist than the widely used SCH 23390. ({sup 11}C)SCH 39166 was prepared by N-methylation of the desmethyl compound SCH 40853 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-5H-benzo(d)naphtho -(2,1-b)azepine) with ({sup 11}C)methyl iodide. Reaction in acetone with subsequent straight-phase semi-preparative HPLC resulted in 20-30% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 35-40 min and a radiochemical purity >99%. The specific activity obtained at EOS was about 1500 Ci/mmol (55 GBq/{mu}mol). ({sup 11}C)SCH 39166 was injected into a Cynomolgus monkey. PET-analysis demonstrated accumulation in the striatum, a region known to have a high density of dopamine D-1 receptors. In a displacement experiment, radioactivity in the striatum was markedly reduced after injection of 6 mg unlabelled SCH 23390, thus demonstrating the specificity and reversibility of ({sup 11}C)SCH 39166 binding to dopamine D-1 receptors. (author).

  15. In vitro and in vivo evaluation of [{sup 11}C]MPEPy as a potential PET ligand for mGlu{sub 5} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Severance, Alin J. [Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States); Parsey, Ramin V. [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States)]. E-mail: rparsey@neuron.cpmc.columbia.edu; Kumar, J.S. Dileep [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States); Underwood, Mark D.; Arango, Victoria [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States); Majo, Vattoly J.; Prabhakaran, Jaya [Dept. of Psychiatry, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States); Simpson, Norman R.; Heertum, Ronald L. van [Dept. of Radiology, New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States); Mann, J. John [New York State Psychiatric Inst., Columbia Univ. College of Physicians and Surgeons, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Inst., New York, NY 10032 (United States)

    2006-11-15

    Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR{sub 5}) has been implicated in depression, neuropathic pain and other psychiatric, neurological and neurodegenerative diseases. A mGluR{sub 5} radioligand for in vivo quantification by positron emission tomography (PET) would facilitate studies of the role of this receptor in disease and treatment. 3-Methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity antagonist at the mGluR{sub 5} receptor was selected as a candidate ligand; a recent publication by Yu et al. [Nucl Med Biol 32 (2005) 631-640] presented initial micro-PET results for [{sup 11}C]MPEPy with enthusiasm. Building on their efforts, we report as unique contributions (1) an improved chemical synthesis method, (2) the first data using human tissue, (3) phosphor images for rat brain preparations, (4) a novel comparison of anesthetic agents and (5) in vivo data in baboon. In vitro phosphor imaging studies of this ligand using human and rat brain tissue demonstrated high specific binding in the hippocampus, striatum and cortex with minimal specific binding in the cerebellum. In contrast, in vivo micro-PET studies in rats using urethane anesthesia, PET studies in baboons using isoflurane anesthesia and ex vivo micro-PET studies in unanesthetized rats each showed little specific binding in the brain. Despite the promising in vitro results, the low signal-to-noise ratio found in vivo does not justify the use of [{sup 11}C]MPEPy as a PET radiotracer in humans.

  16. PET studies in epilepsy

    OpenAIRE

    Sarikaya, Ismet

    2015-01-01

    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. 18Fluoro-2-deoxyglucose (18F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients...

  17. Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D{sub 2} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer E-mail: christer.halldin@neuro.ks.se; Dolle, Frederic; Swahn, Carl-Gunnar; Olsson, Hans; Lundkvist, Per Karlsson; Hall, Haakan; Sandell, Johan; Vaufrey, Camilla; Loc' h, Christian; Franzoise; Crouzel, Christian; Maziere, Bernard; Farde, Lars

    1999-07-01

    Epidepride {l_brace}(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide= {r_brace} binds with a picomolar affinity (K{sub i}=24 pM) to the dopamine D{sub 2} receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D{sub 2} receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [{sup 11}C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/{mu}mol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [{sup 11}C]epidepride binding. The fraction of unchanged [{sup 11}C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [{sup 11}C]epidepride. The availability of [{sup 11}C]epidepride allows the PET-verification of the data obtained from quantitation studies with

  18. Synthesis of (R)- and (S)-[C-11]L-365,260 for PET studies of brain cholecystokinin (CCK) receptors

    Energy Technology Data Exchange (ETDEWEB)

    Haradahira, T. [Research Development Corporation of Japan, Tokyo (Japan); Suzuki, K.; Inoue, O. [National Institute of Radiological Sciences, Chiba (Japan)

    1994-05-01

    Cholecystokinin (CCK) is a recognized peptide hormone in the gut and proposed as a neurotransmitter or neuromodulator in the central nervous system. Two distinct CCK receptors termed CCK-A and CCK-B have been characterized. CCK-A receptor is primarily distributed in the peripheral tissues including pancreas and gallbladder and also known to be distributed in a few brain regions. CCK-B receptor is widely distributed in the brain and has been proposed to be involved in anxiety, satiety and nociception. To investigate the functional roles of the CCK receptors in the brain by positron emission tomography, we have synthesized an enantiomeric pair of C-11 labeled non-peptide antagonists against the CCK receptors. L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl)-N`-(3-methylpheny lurea)] is a potent CCK-B selective non-peptide antagonist (CCK-A/CCK-B ratio of IC50, 140), whereas its (S)-enantiomer is selective toward CCK-A receptor (CCK-A/CCK-B ratio of IC50, 0.02). We have synthesized the (R)- and (S)-enantiomers of [C-11]-365,260 by N-methylation (50{degrees}C for 5 min) of the racemic desmethyl precursor with [C-11]iodomethane using sodium hydride as a base and subsequent optical resolution with HPLC (column: ChiraSpher, 250 x 10 mm, Merck; eluent: n-hexane / 1,4-dioxane / 2-propanol / triethylamine = 70 / 25 / 5 / 0.1). Radiochemical yields (decay corrected) and optical purities were 34%, 99% for R-enantiomer and 36%, 99% for S-enantiomer, respectively. The total synthesis time was 40 min and specific activity was about 37 GBq/{mu}mol. In PET studies on rhesus monkey (R)-enantiomer showed a high uptake of radioactivity in the cerebral cortex, region known to have a high concentration of CCK-B receptor.

  19. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

    DEFF Research Database (Denmark)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian;

    2013-01-01

    responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide...

  20. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Tatsuro [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)]. E-mail: tsucchy@fmsrsa.fukui-med.ac.jp; Okazawa, Hidehiko [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Kobayashi, Masato [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Yoshida, Yoshio [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Itoh, Harumi [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)

    2007-02-15

    Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16{alpha}-[{sup 18}F]fluoro-17{beta}-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03{+-}1.05 vs. 3.97{+-}1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration.

  1. Test-retest measurements of dopamine D{sub 1}-type receptors using simultaneous PET/MRI imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kaller, Simon; Patt, Marianne; Becker, Georg-Alexander; Luthardt, Julia; Meyer, Philipp M.; Werner, Peter; Barthel, Henryk; Bresch, Anke; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Girbardt, Johanna [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); Fritz, Thomas H. [Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig (Germany); University of Gent, Institute for Psychoacoustics and Electronic Music (IPEM), Ghent (Belgium); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Integrated Research and Treatment Centre (IFB) Adiposity Diseases, Leipzig (Germany)

    2017-06-15

    The role of dopamine D{sub 1}-type receptor (D{sub 1}R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D{sub 1}-mediated neuronal network regulation using simultaneous PET/MRI and D{sub 1}R-selective [{sup 11}C]SCH23390, this study investigated the stability of central D{sub 1}R measurements between two independent PET/MRI sessions under baseline conditions. Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [{sup 11}C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of D{sub 1}R distribution volume ratio (DVR) and binding potential (BP{sub ND}) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low D{sub 1}R density. The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high D{sub 1}R density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low D{sub 1}R density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BP{sub ND} values. Accordingly, the absolute variability of BP{sub ND} ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low D{sub 1}R content, such as the occipital cortex, with higher mean variability. The test-retest reliability of D{sub 1}R measurements in this study was very high. This was the case not only for D{sub 1}R-rich brain areas, but

  2. Test-retest variability of high resolution positron emission tomography (PET imaging of cortical serotonin (5HT2A receptors in older, healthy adults

    Directory of Open Access Journals (Sweden)

    Graff-Guerrero Ariel

    2009-07-01

    Full Text Available Abstract Background Position emission tomography (PET imaging using [18F]-setoperone to quantify cortical 5-HT2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT2A receptor (5HT2AR binding potential. The purpose of this study was to assess the test-retest variability of [18F]-setoperone PET with a high resolution scanner (HRRT for measuring 5HT2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65–78 years completed two [18F]-setoperone PET scans on two separate occasions 5–16 weeks apart. Results The average difference in the binding potential (BPND as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. Conclusion We conclude that the test-retest variability of [18F]-setoperone PET in elderly subjects is comparable to that of [18F]-setoperone and other 5HT2AR radiotracers in younger subject samples.

  3. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Jakobsen, Annika Loft

    2010-01-01

    Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In-diethylenetriamin......Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In......-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with (123)I-metaiodobenzylguanidine (MIBG), and (18)F-FDG PET. METHODS: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET on average within 40 d. The functional images were fused with low......-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. RESULTS: The overall sensitivity of SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were (18)F-FDG PET...

  4. Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [(11)C](+)PHNO.

    Science.gov (United States)

    Gaiser, Edward C; Gallezot, Jean-Dominique; Worhunsky, Patrick D; Jastreboff, Ania M; Pittman, Brian; Kantrovitz, Lauren; Angarita, Gustavo A; Cosgrove, Kelly P; Potenza, Marc N; Malison, Robert T; Carson, Richard E; Matuskey, David

    2016-12-01

    Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (D2/3R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D2/3Rs when compared with normal weight (NW) individuals. A D3-preferring D2/3R agonist tracer, [(11)C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D2/3R availability within striatal reward regions. To date, OB individuals have not been studied with [(11)C](+)PHNO. We assessed D2/3R availability in striatal and extrastriatal reward regions in 14 OB and 14 age- and gender-matched NW individuals with [(11)C](+)PHNO PET utilizing a high-resolution research tomograph. Additionally, in regions where group D2/3R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D2/3R availability in those respective regions. A group-by-brain region interaction effect (F7, 182=2.08, p=0.047) was observed. Post hoc analyses revealed that OB individuals exhibited higher tracer binding in D3-rich regions: the substantia nigra/ventral tegmental area (SN/VTA) (+20%; p=0.02), ventral striatum (VST) (+14%; pD2/3R availability in the SN/VTA (r=0.34, p=0.03), VST (r=0.36, p=0.02), and pallidum (r=0.30, p=0.05) across all subjects. These data suggest that individuals who are obese have higher D2/3R availability in brain reward regions densely populated with D3Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.

  5. PET and SPECT in medically non-refractory complex partial seizures. Temporal asymmetries of glucose consumption, Benzodiazepine receptor density

    Energy Technology Data Exchange (ETDEWEB)

    Matheja, P.; Kuwert, T.; Wolf, K.; Schober, O. [Muenster Univ. (Germany). Kliniken und Polikliniken fuer Nuklearmedizin; Stodieck, S.R.G.; Diehl, B.; Ringelstein, E.B. [Muenster Univ. (Germany). Klinik fuer Neurologie; Schuierer, G. [Muenster Univ. (Germany). Inst. fuer Klinische Radiologie

    1998-12-31

    Aim: In contrast to medically refractory complex partial seizures (CPS), only limited knowledge exists on cerebral perfusion and metabolism in medically non-refractory CPS. The aim of this study was to investigate the frequency of temporal asymmetries in regional cerebral glucose consumption (rCMRGlc), regional cerebral blood flow (rCBF), and regional cerebral benzodiazepine receptor density (BRD) in this group of patients. Methods: The study included 49 patients with medically non-refractory cryptogenic CPS (age: 36.0{+-}16.1 years). rCMRGlc was studied with F-18-FDG-PET (FDG), rCBF with Tc-99m-ECD-SPECT (ECD), and BRD with I-123-iomazenil-SPECT (IMZ). All studies were performed interictally and within four weeks in each patient. Duration of epilepsy ranged from 0.1 to 42 years (median 4.0 years). SPECT was performed with the triple-headed SPECT camera Multispect 3, PET with the PET camera ECAT EXACT 47. Using linear profiles, glucose consumption, as well as uptake of ECD and IMZ, were measured in four temporal regions of interest (ROIs), and asymmetry indices were calculated (ASY). The results were compared to 95% confidence intervals determined in control subjects. Results: Thirty-five of the 49 (71%) patients had at least one significantly elevated ASY; temporal rCMRGlc was asymmetrical in 41% of the patients, temporal BRD in 29%, and temporal rCBF in 24%. One patient had an asymmetry of all three variables, two of temporal rCMRGlc and BRD, three of temporal rCMRGlc and rCBF, and another four of rCBF and BRD. Fourteen patients had an isolated temporal asymmetry in rCMRGlc, seven in BRD, and four in rCBF. A discrepancy in lateralization between the three modalities was not observed. Conclusion: The majority of patients with medically non-refractory CPS have focal abnormalities of blood flow and metabolism in their temporal lobe. In this group of patients, FDG-PET demonstrates abnormalities with the highest frequency of the three modalities studied, followed by

  6. The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-{sup 11}C]WAY-100635

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Patrycja; Savli, Markus; Fink, Martin; Spindelegger, Christoph; Moser, Ulrike; Kasper, Siegfried; Lanzenberger, Rupert [Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna (Austria); Wadsak, Wolfgang; Dudczak, Robert; Kletter, Kurt [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Mitterhauser, Markus; Mien, Leonhard-Key [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); University of Vienna, Department of Pharmaceutical Technology, Vienna (Austria)

    2008-12-15

    The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT{sub 1A}) receptor. Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl-{sup 11}C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT{sub 1A} receptor BP{sub ND} was quantified using (1) the 'gold standard' manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling. The 5-HT{sub 1A} receptor BP{sub ND} was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP{sub ND} values in every region investigated, with a borderline significant sex difference in the hypothalamus (p=0.012, uncorrected). There was a high intersubject variability of the 5-HT{sub 1A} receptor BP{sub ND} within both sexes compared to the small mean differences between men and women. To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT{sub 1A} receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT{sub 1A} receptor expression. (orig.)

  7. Biological evaluation of 2'-[{sup 18}F]fluoroflumazenil ([{sup 18}F]FFMZ), a potential GABA receptor ligand for PET

    Energy Technology Data Exchange (ETDEWEB)

    Mitterhauser, Markus E-mail: markus.mitterhauser@akh-wien.ac.at; Wadsak, Wolfgang; Wabnegger, Leila; Mien, Leonhard-Key; Toegel, Stefan; Langer, Oliver; Sieghart, Werner; Viernstein, Helmut; Kletter, Kurt; Dudczak, Robert

    2004-02-01

    [{sup 11}C]Flumazenil, a highly selective benzodiazepine antagonist is the most extensively used GABA{sub A} ligand for PET so far. To overcome half life disadvantages of {sup 11}C a [{sup 18}F]-labeled flumazenil derivative, 2'-[{sup 18}F]fluoroflumazenil (FFMZ) was developed and biologically evaluated with respect to the GABA{sub A} receptor. Organ with the highest uptake was the pituitary gland. Brain uptake was high and followed the order cortex>thalamus>cerebellum>rest brain. Fluoroflumazenil displaced [{sup 3}H]flumazenil binding from membrane GABA{sub A} receptors with an IC{sub 50}value (3.5 nM) comparable to that of Flumazenil (2.8 nM). The presented data confirm the potential of [{sup 18}F]FFMZ for PET imaging of the GABA-ergic system.

  8. In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

    Directory of Open Access Journals (Sweden)

    Natascha Nebel

    2016-08-01

    Full Text Available Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled D3 subtype selective radioligand would be beneficial for this purpose; however, as yet, there is no such tracer available. The three candidates [18F]1, [18F]2a and [18F]2b were chosen for in vitro and in vivo characterization as radioligands suitable for selective PET imaging of the D3 receptor. Their evaluation included the analysis of radiometabolites and the assessment of non-specific binding by in vitro rat brain autoradiography. While [18F]1 and [18F]2a revealed high non-specific uptake in in vitro rat brain autoradiography, the D3 receptor density was successfully determined on rat brain sections (n = 4 with the candidate [18F]2b offering a Bmax of 20.38 ± 2.67 pmol/g for the islands of Calleja, 19.54 ± 1.85 pmol/g for the nucleus accumbens and 16.58 ± 1.63 pmol/g for the caudate putamen. In PET imaging studies, the carboxamide 1 revealed low signal/background ratios in the rat brain and relatively low uptake in the pituitary gland, while the azocarboxamides [18F]2a and [18F]2b showed binding that was blockable by the D3 receptor ligand BP897 in the ventricular system and the pituitary gland in PET imaging studies in living rats.

  9. Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ikuko, E-mail: nakamuri@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Cardiovascular Medicine, Saga University, Saga (Japan); Hasegawa, Koki [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Pathology and Experimental Medicine, Kumamoto University, Kumamoto (Japan); Wada, Yasuhiro [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Hirase, Tetsuaki; Node, Koichi [Department of Cardiovascular Medicine, Saga University, Saga (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [RIKEN Center for Molecular Imaging Science, Kobe (Japan)

    2013-03-29

    Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectin mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin m

  10. Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Foged, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm (Sweden)]|[Novo Nordisk A/S, Health Care Discovery and Development, Maaloev (Denmark); Halldin, C.; Pauli, S.; Suhara, T.; Swahn, C.G.; Karlsson, P.; Farde, L. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm (Sweden); Loc`h, C.; Maziere, B.; Maziere, M. [Service Hospitalier Frederic Joliot, CEA, Orsay (France); Hansen, H.C. [Novo Nordisk A/S, Health Care Discovery and Development, Maaloev (Denmark)

    1997-10-01

    NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared {sup 76}Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [{sup 11}C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [{sup 76}Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [{sup 76}Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. (orig.) With 8 figs., 28 refs.

  11. Current radiosynthesis strategies for 5-HT2A receptor PET tracers

    DEFF Research Database (Denmark)

    Herth, Matthias M; Knudsen, Gitte M

    2015-01-01

    Serotonin 2A receptors have been implicated in various psychophysiological functions and disorders such as depression, Alzheimer's disease, or schizophrenia. Therefore, neuroimaging of this specific receptor is of significant clinical interest, and it is not surprising that many attempts have been...... made to develop a suitable 5-HT2A R positron emission tomography-tracer. In this review, we give an overview on the precursor, reference compound synthesis, and the preparation of promising 5-HT2A R radiopharmaceuticals applied in positron emission tomography. We also highlight possible learning...

  12. AZD5213: a novel histamine H3 receptor antagonist permitting high daytime and low nocturnal H3 receptor occupancy, a PET study in human subjects.

    Science.gov (United States)

    Jucaite, Aurelija; Takano, Akihiro; Boström, Emma; Jostell, Karl-Gustav; Stenkrona, Per; Halldin, Christer; Segerdahl, Märta; Nyberg, Svante

    2013-07-01

    The histamine H3 receptor represents an appealing central nervous system drug target due to its important role in the neurobiology of cognition and wake-sleep regulation. The therapeutic benefit of H3 antagonists/inverse agonists may be hampered by disruption of sleep that has been observed in humans with prolonged high H3 receptor occupancy (H3RO), extending into night-time. AZD5213 is a highly selective H3 antagonist (in vitro inverse agonist) developed to achieve a pharmacokinetic profile permitting circadian fluctuations of H3RO. Its efficacy has been demonstrated in rodent behavioural models of cognition. In human subjects, AZD5213 was safe and well tolerated following repeated doses (1-14 mg/d) and demonstrated a short (∼5 h) half-life. In this PET study H3RO was measured using the radioligand [11C]GSK189254 ([11C]AZ12807110) in seven young male volunteers following single doses of AZD5213 (0.05-30 mg). H3RO was calculated using the Lassen plot method. The plasma concentrations and the affinity constant (K i,pl 1.14 nmol/l, corresponding to the plasma concentration required to occupy 50% of available receptors) were used to estimate the H3RO time-course. AZD5213 showed dose and concentration dependent H3RO ranging from 16 to 90%. These binding characteristics and the pharmacokinetic profile of AZD5213 indicate that high daytime and low night-time H3RO could be achieved following once daily oral dosing of AZD5213. Fluctuations of H3RO following circadian rhythm of the histamine system may be expected to reduce the risk of sleep disruption while maintaining daytime efficacy. AZD5213 may thus be an optimal compound to evaluate the clinical benefit of selective H3 antagonism in cognitive disorders.

  13. PET Imaging of Steroid Receptor Expression in Breast and Prostate Cancer

    NARCIS (Netherlands)

    Hospers, G. A. P.; Helmond, F. A.; Dierckx, R. A.; de Vries, Emma; de Vries, Erik

    2008-01-01

    The vast majority of breast and prostate cancers express specific receptors for steroid hormones, which play a pivotal role in tumor progression. Because of the efficacy of endocrine therapy combined with its relatively mild side-effects, this intervention has nowadays become the treatment of choice

  14. PET Imaging of Steroid Receptor Expression in Breast and Prostate Cancer

    NARCIS (Netherlands)

    Hospers, G. A. P.; Helmond, F. A.; Dierckx, R. A.; de Vries, Emma; de Vries, Erik

    2008-01-01

    The vast majority of breast and prostate cancers express specific receptors for steroid hormones, which play a pivotal role in tumor progression. Because of the efficacy of endocrine therapy combined with its relatively mild side-effects, this intervention has nowadays become the treatment of choice

  15. A small-animal pharmacokinetic/pharmacodynamic PET study of central serotonin 1A receptor occupancy by a potential therapeutic agent for overactive bladder.

    Directory of Open Access Journals (Sweden)

    Yosuke Nakatani

    Full Text Available Serotonin 1A (5-HT1A receptors have been mechanistically implicated in micturition control, and there has been a need for an appropriate biomarker surrogating the potency of a provisional drug acting on this receptor system for developing a new therapeutic approach to overactive bladder (OAB. Here, we analyzed the occupancy of 5-HT1A receptors in living Sprague-Dawley rat brains by a novel candidate drug for OAB, E2110, using positron emission tomography (PET imaging, and assessed the utility of a receptor occupancy (RO assay to establish a pharmacodynamic index translatable between animals and humans. The plasma concentrations inducing 50% RO (EC50 estimated by both direct and effect compartment models were in good agreement. Dose-dependent therapeutic effects of E2110 on dysregulated micturition in different rat models of pollakiuria were also consistently explained by achievement of 5-HT1A RO by E2110 in a certain range (≥ 60%. Plasma drug concentrations inducing this RO range and EC50 would accordingly be objective indices in comparing pharmacokinetics-RO relationships between rats and humans. These findings support the utility of PET RO and plasma pharmacokinetic assays with the aid of adequate mathematical models in determining the in vivo characteristics of a drug acting on 5-HT1A receptors and thereby counteracting OAB.

  16. The GABA-A benzodiazepine receptor complex: Role of pet and spect in neurology and psychiatry; Der GABA-A-benzodiazepinrezeptorkomplex: Rolle von PET und SPECT in Neurologie und Psychiatrie

    Energy Technology Data Exchange (ETDEWEB)

    Juengling, F.D. [Abt. fuer Nuklearmedizin, Radiologie III, Universitaetsklinik Ulm (Germany); Schaefer, M.; Heinz, A. [Klinik fuer Psychiatrie und Psychotherapie, Charite, Humboldt-Univ. zu Berlin (Germany)

    2002-09-01

    Nuclear medicine imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) for selective depiction of GABA-A-benzodiazepine receptor (GBZR) binding are complementary investigations in the diagnostic process of neurological and psychiatric disorders. This review summarizes the current knowledge about options and limitations of PET and SPECT for in vivo diagnostics in neurology and psychiatry. The growing importance of GBZR-imaging for the understanding of pathophysiology and pharmacological treatment in different psychiatric syndromes is discussed. (orig.) [German] Mit der Entwicklung selektiver Liganden fuer den GABA-A-Benzodiazepinrezeptorkomplex (GBZR) hat die nuklearmedizinische Bildgebung mittels positronen-emissionstomographie (PET) und single-photon-emissionscomputertomographie (SPECT) einen festen Stellenwert fuer Klinik und Forschung in der Neurologie und Psychiatrie erlangt. Die vorliegende Ueberblicksarbeit fasst den aktuellen Wissensstand von Anwendungsmoeglichkeiten und -grenzen der nuklearmedizinischen Bildgebung der GBZR in vivo zusammen und beleuchtet ihren klinischen Nutzen. Die wachsende Bedeutung fuer das Verstaendnis der Pathophysiologie und pharmakotherapeutischer Konzepte unterschiedlicher psychiatrischer Erkrankungen wird herausgestellt. (orig.)

  17. (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M;

    2015-01-01

    Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C......]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs....... However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs....

  18. Somatostatin receptor PET in neuroendocrine tumours: {sup 68}Ga-DOTA{sup 0},Tyr{sup 3}-octreotide versus {sup 68}Ga-DOTA{sup 0}-lanreotide

    Energy Technology Data Exchange (ETDEWEB)

    Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Uprimny, Christian; Guggenberg, Elisabeth von; Decristoforo, Clemens; Warwitz, Boris; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Traub-Weidinger, Tatjana [Vienna Medical University, Department of Nuclear Medicine, Vienna (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-03-15

    The aim of this study was to evaluate the impact of {sup 68}Ga-labelled DOTA{sup 0}-lanreotide ({sup 68}Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or {sup 68}Ga-labelled DOTA{sup 0},Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or {sup 68}Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent {sup 68}Ga-DOTA-LAN PET to evaluate a treatment option with {sup 90}Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 {+-} 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. {sup 68}Ga-DOTA-LAN and {sup 68}Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of {sup 68}Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for {sup 68}Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. {sup 68}Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV{sub max}) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to {sup 68}Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. {sup 68}Ga

  19. Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide.

    Science.gov (United States)

    Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Traub-Weidinger, Tatjana; Uprimny, Christian; von Guggenberg, Elisabeth; Decristoforo, Clemens; Warwitz, Boris; Widmann, Gerlig; Virgolini, Irene Johanna

    2013-02-01

    The aim of this study was to evaluate the impact of (68)Ga-labelled DOTA(0)-lanreotide ((68)Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or (68)Ga-labelled DOTA(0),Tyr(3)-octreotide ((68)Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or (68)Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent (68)Ga-DOTA-LAN PET to evaluate a treatment option with (90)Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 ± 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. (68)Ga-DOTA-LAN and (68)Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of (68)Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for (68)Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. (68)Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV(max)) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to (68)Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. (68)Ga-DOTA-TOC revealed more tumour sites than (68)Ga

  20. MicroPET imaging of 5-HT{sub 1A} receptors in rat brain: a test-retest [{sup 18}F]MPPF study

    Energy Technology Data Exchange (ETDEWEB)

    Aznavour, Nicolas [McGill University, Department of Psychiatry, Montreal, QC (Canada)]|[Laboratory of Neuroenergetics and Cellular Dynamics, EPFL, SV, BMI, Lausanne (Switzerland); Benkelfat, Chawki; Gravel, Paul [McGill University, Department of Psychiatry, Montreal, QC (Canada)]|[McGill University, Department of Neurology and Neurosurgery, Montreal, QC (Canada); Aliaga, Antonio [McGill University, Department of Small Animal Imaging Laboratory, Montreal, QC (Canada); Rosa-Neto, Pedro [Douglas Hospital, Molecular NeuroImaging Laboratory, Montreal, QC (Canada); Bedell, Barry [McGill University, Department of Neurology and Neurosurgery, Montreal, QC (Canada)]|[McGill University, Department of Small Animal Imaging Laboratory, Montreal, QC (Canada); Zimmer, Luc [CERMEP, ANIMAGE Department, Lyon (France)]|[Universite Lyon 1 and CNRS, Lyon (France); Descarries, Laurent [Universite de Montreal, Department of Pathology and Cell Biology, Montreal, QC (Canada)]|[Universite de Montreal, Department of Physiology, Montreal, QC (Canada)]|[Universite de Montreal, GRSNC, Montreal, QC (Canada)

    2009-01-15

    Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [{sup 18}F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptors in different regions of animal and human brain, including that of 5-HT{sub 1A} autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems). Scans from isoflurane-anaesthetised rats (n = 18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model. Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei. MicroPET brain imaging of 5-HT{sub 1A} receptors with [{sup 18}F]MPPF thus represents a promising avenue for investigating 5-HT{sub 1A} receptor function in rat. (orig.)

  1. Effects of dopamine D2 receptor partial agonist antipsychotic aripiprazole on dopamine synthesis in human brain measured by PET with L-[β-11C]DOPA.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ito

    Full Text Available Dopamine D(2 receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2 receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11C]raclopride and L-[β-(11C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2 receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2 receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

  2. Development of a PET radioligand for the central 5-HT{sub 1B} receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Jan D., E-mail: j.d.andersson@ki.s [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Pierson, M. Edward [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Finnema, Sjoerd J.; Gulyas, Balazs [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Heys, Richard; Elmore, Charles S. [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Farde, Lars [AstraZeneca Pharmaceuticals, Neuroscience Clinical, SE-15185 Soedertaelje (Sweden); Halldin, Christer [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden)

    2011-02-15

    Introduction: The serotonin 1B (5-HT{sub 1B}) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT{sub 1B} receptor in the primate brain in vivo. Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [{sup 11}C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography. Results: In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/{mu}mol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [{sup 11}C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT{sub 1B} receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics. Conclusion: Candidate [{sup 11}C]6, i.e., [{sup 11}C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT{sub 1B} receptors and was nominated for further preclinical characterization and PET examination in human subjects.

  3. [{sup 18}F]F15599, a novel 5-HT{sub 1A} receptor agonist, as a radioligand for PET neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemoine, Laetitia; Verdurand, Mathieu [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian [Centre de Recherches Pierre Fabre, Castres (France); Le Bars, Didier [CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Zimmer, Luc [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); CERMEP - Imagerie du Vivant, ANIMAGE Department, Lyon (France)

    2010-03-15

    The serotonin-1A (5-HT{sub 1A}) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT{sub 1A} receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT{sub 1A} receptors. Since all clinical PET 5-HT{sub 1A} radiopharmaceuticals are antagonists, it is of great interest to develop a{sup 18}F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{l_brace}[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl{r_brace}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT{sub 1A} receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT{sub 1A} receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [{sup 18}F]MPPF, a validated 5-HT{sub 1A} antagonist radiopharmaceutical. The chemical and radiochemical purities of [{sup 18}F]F15599 were >98%. In vitro [{sup 18}F ]F15599 binding was consistent with the known 5-HT{sub 1A} receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [{sup 18}F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [{sup 18}F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT{sub 1A} antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer

  4. 5-HTT and 5-HT(1A) receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects.

    Science.gov (United States)

    Stenkrona, Per; Halldin, Christer; Lundberg, Johan

    2013-10-01

    Vortioxetine (Lu AA21004) is a new potential substance for the treatment of anxiety and mood disorders. It has high affinity for the 5-HT transporter (5-HTT) and moderate affinity for the 5-HT1A receptor in vitro. Positron emission tomography (PET) has commonly been used to examine the relation between dose/plasma concentration and occupancy to predict relevant dose intervals in a clinical setting. In this study 11 control subjects were examined with PET and [¹¹C]MADAM at baseline, after a single dose and after 9 days of dosing with Lu AA21004 (2.5, 10 or 60 mg) for quantification of 5-HTT occupancy. Four subjects were examined with PET and [¹¹C]WAY 100635 at baseline, after a single dose and after 9 days of dosing of Lu AA21004 (30 mg) for quantification of 5-HT(1A) occupancy. To allow for quantification of binding in the raphe nuclei, PET data were analyzed using wavelet aided parametric imaging. 5-HTT occupancy ranged from 2 (mean, 2.5 mg day 1) to 97% (60 mg day 9). The apparent affinity of Lu AA21004 binding to 5-HTT (KD(ND)) was calculated to 16.7 nM (R=0.95), and the corresponding oral dose (KD(ND)-dose) to 8.5 mg (R=0.91). No significant occupancy of 5-HT(1A) receptors was found after dosing of 30 mg Lu AA21004. Based on the literature and the present [¹¹C]MADAM binding data, a dose of 20-30 mg Lu AA21004 is suggested to give clinically relevant occupancy of the 5-HTT.

  5. Improved Estrogen Receptor Assessment by PET Using the Novel Radiotracer 4FMFES in ER+ Breast Cancer Patients: an Ongoing Phase II Clinical Trial.

    Science.gov (United States)

    Paquette, Michel; Lavallée, Éric; Phoenix, Serge; Ouellet, René; Senta, Helena; van Lier, Johan E; Guérin, Brigitte; Lecomte, Roger; Turcotte, Éric E

    2017-08-10

    Following encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) positron emission tomography (PET) radiotracer 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of 4FMFES to 16α-[(18)F]fluoroestradiol (FES) in ER positive (ER+) breast cancer patients. Methods: Patients diagnosed with ER+ breast cancer (n = 31) were recruited for this study, including six patients that undertook mastectomy and/or axillary node dissection. For each patient, FES- and 4FMFES-PET/CT scans were done sequentially (within a week) and in random order. One hour following injection of either radiotracer, a head-to-thigh static scan with 2 minutes acquisition per bed position was obtained. Blood samples were taken at different times following injection to assess each tracer metabolism by reverse-phase thin-layer chromatography (TLC). The mean standardized uptake values (SUVMean) of non-specific tissues and the maximum SUV (SUVMax) of the tumor were evaluated for each detected lesion, and tumor-to-non-specific organs ratios were calculated. Results: Blood metabolite analysis 60 minutes after injection of the tracer showed a 2.5-fold increase in metabolic stability of 4FMFES over FES. While for most foci 4FMFES-PET scored similar SUVMax values as compared to FES-PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in non-specific tissues for 4FMFES, notably a 4-fold decrease in blood pool activity as compared to FES. Consequently, image quality was considerably improved using 4FMFES, with lower overall background. As a result, 4FMFES successfully identified 9 more lesions than FES. Conclusion: This phase II study with ER+ breast cancer patients shows that 4FMFES-PET achieves lower non-specific signal and better tumor contrast than FES-PET resulting in improved diagnostic confidence and lower false negative diagnoses

  6. Synthesis and PET imaging of the benzodiazepine receptor tracer [N-methyl-{sup 11}C]iomazenil

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, Ronald M.; Horti, Andrew G.; Bremner, J. Douglas; Stratton, Morgan D.; Dannals, Robert F.; Ravert, Hayden T.; Zea-Ponce, Yolanda; Ng, Chin K.; Dey, Holley M.; Soufer, Robert; Charney, Dennis S.; Mazza, Samuel M.; Sparks, Richard B.; Stubbs, James B.; Innis, Robert B

    1995-07-01

    The central benzodiazepine receptor tracer [N-methyl-{sup 11}C]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with [{sup 11}C]methyl iodide. The [{sup 11}C]CH{sub 3}I (prepared by reduction of [{sup 11}C]CO{sub 2} with LiAlH{sub 4} followed by reaction with HI) was reacted with noriomazenil inN,N -dimethylformamide and Bu{sub 4}N{sup +}OH{sup -} for 1 min at 80 deg. C and purified by HPLC (C{sub 18}, 34% CH{sub 3}CN/H{sub 2}O, 7 mL/min). The product was obtained with synthesis time 35 {+-} 5 min (mean {+-} SD, n = 7), radiochemical yield (EOB) 36 {+-} 16%, radiochemical purity 99 {+-} 1%, and specific activity 5100 {+-} 2800 mCi/{mu}mol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of [{sup 11}C]iomazenil in an adult baboon or healthy human volunteer, radioactivity accumulated in the cortex with time-activity curves in agreement with results obtained with [{sup 11}C]flumazenil PET and [{sup 123}I]iomazenil SPECT studies. The count rate was sufficient to obtain quantitative images up to 2 h post-injection with a 14 mCi injection. These results suggest that [{sup 11}C]iomazenil will be a useful agent for measuring benzodiazepine receptorsin vivo by positron emission tomography.

  7. Evaluation in vitro and in animals of a new {sup 11}C-labeled PET radioligand for metabotropic glutamate receptors 1 in brain

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Clark, David T.; Morse, Cheryl; Pike, Victor W. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); Barth, Vanessa N.; Rhoads, Emily; Siuda, Edward; Heinz, Beverly A.; Nisenbaum, Eric; Dressman, Bruce; Joshi, Elizabeth; Luffer-Atlas, Debra; Fisher, Matthew J.; Masters, John J.; Goebl, Nancy; Kuklish, Steven L.; Tauscher, Johannes [Eli Lilly and Co., Indianapolis, IN (United States); Innis, Robert B. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States)

    2013-02-15

    Two allosteric modulators of the group I metabotropic glutamate receptors (mGluR1 and mGluR5) were evaluated as positron emission tomography (PET) radioligands for mGluR1. LY2428703, a full mGluR1 antagonist (IC{sub 50} 8.9 nM) and partial mGluR5 antagonist (IC{sub 50} 118 nM), and LSN2606428, a full mGluR1 and mGluR5 antagonist (IC{sub 50} 35.3 nM and 10.2 nM, respectively) were successfully labeled with {sup 11}C and evaluated as radioligands for mGluR1. The pharmacology of LY2428703 was comprehensively assessed in vitro and in vivo, and its biodistribution was investigated by liquid chromatography-mass spectrometry/mass spectrometry, and by PET imaging in the rat. In contrast, LSN2606428 was only evaluated in vitro; further evaluation was stopped due to its unfavorable pharmacological properties and binding affinity. {sup 11}C-LY2428703 showed promising characteristics, including: (1) high potency for binding to human mGluR1 (IC{sub 50} 8.9 nM) with no significant affinity for other human mGlu receptors (mGluR2 through mGluR8); (2) binding to brain displaceable by administration of an mGluR1 antagonist; (3) only one major radiometabolite in both plasma and brain, with a negligible brain concentration (with 3.5 % of the total radioactivity in cerebellum) and no receptor affinity; (4) a large specific and displaceable signal in the mGluR1-rich cerebellum with no significant in vivo affinity for mGluR5, as shown by PET studies in rats; and (5) lack of substrate behavior for efflux transporters at the blood-brain barrier, as shown by PET studies conducted in wild-type and knockout mice. {sup 11}C-LY2428703, a new PET radioligand for mGluR1 quantification, displayed promising characteristics both in vitro and in vivo in rodents. (orig.)

  8. PET studies in epilepsy.

    Science.gov (United States)

    Sarikaya, Ismet

    2015-01-01

    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. (18)Fluoro-2-deoxyglucose ((18)F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced (11)C-flumazenil (GABAA-cBDZ) and (18)F-MPPF (5-HT1A serotonin) and increased (11)C-cerfentanil (mu opiate) and (11)C-MeNTI (delta opiate) bindings in the area of seizure. (11)C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that (11)C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous

  9. N1'-fluoroethyl-naltrindole (BU97001) and N1'-fluoroethyl-(14-formylamino)-naltrindole (BU97018) potential {delta}-opioid receptor PET ligands

    Energy Technology Data Exchange (ETDEWEB)

    Tyacke, Robin J.; Robinson, Emma S.J.; Schnabel, Rebecca; Lewis, John W.; Husbands, Stephen M.; Nutt, David J.; Hudson, Alan L. E-mail: a.l.hudson@bristol.ac.uk

    2002-05-01

    The properties of two prospective positron emission tomography (PET) ligands for the {delta}-opioid receptor, N1'-fluoroethyl-naltrindole (BU97001) and N1'-fluoroethyl-(14-formylamino)-naltrindole (BU97018) were investigated. Both were antagonists in the mouse vas deferens, and showed high affinity and selectivity, 1.81 nM and 3.09 nM respectively. [{sup 3}H]BU97001 binding to rat whole brain was also of high affinity, K{sub D} of 0.42 nM of and B{sub MAX} of 59.95 fmol mg of protein{sup -1}. In autoradiographic studies, it was found to bind to brain areas previously shown to be associated with the {delta}-opioid receptor and good correlations were found to exist with naltrindole and DPDPE. BU97018 and especially BU97001 appear to show good potential as {delta}-opioid receptor PET ligands with the incorporation of {sup 18}F.

  10. Kinetic modeling of 11C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans

    OpenAIRE

    Naganawa, Mika; Zheng, Ming-Qiang; Nabulsi, Nabeel; Tomasi, Giampaolo; Henry, Shannan; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E.; Huang, Yiyun

    2014-01-01

    11C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of 11C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the bes...

  11. PET radiopharmaceuticals for neuroreceptor imaging

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Routine clinical PET radiopharmaceuticals for the noninvasive imaging of brain receptors, transporters,and enzymes are commonly labeled with positron emitting nuclides such as carbon-11 or fluorine-18. Certain minimal conditions need to be fulfilled for these PET ligands to be used as imaging agents in vivo. Some of these prerequisites are discussed and examples of the most useful clinical PET radiopharmaceuticals that have found application in the central nervous system are reviewed.

  12. Preclinical evaluation of [{sup 11}C]SA4503. Radiation dosimetry, in vivo selectivity and PET imaging of sigma{sub 1} receptors in the cat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori; Ishiwata, Kiichi; Shimada, Yuhei; Kimura, Yuichi; Senda, Michio [Tokyo Metropolitan Inst. of Gerontology (Japan). Positron Medical Center; Kobayashi, Tadayuki; Matsuno, Kiyoshi; Homma, Yoshio

    2000-08-01

    Our previous in vivo study with rats has demonstrated that {sup 11}C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([{sup 11}C]SA4503) is a potential radioligand for mapping central nervous system (CNS) sigma{sub 1} receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [{sup 11}C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [{sup 11}C]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4503 and haloperidol, but not by co-injection of any of six ligands for sigma{sub 2} or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for sigma{sub 1} receptor. In the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in the cortex and cerebellum at 76 min after tracer injection. We have concluded that [{sup 11}C]SA4503 has the potential for mapping sigma{sub 1} receptor by PET. (author)

  13. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Ianniello, Annarita; Sansovini, Maddalena; Severi, Stefano; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Unit, Meldola (Italy); Grana, Chiara Maria [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy); Massri, Katrin [Ospedale San Luca, Nuclear Medicine, Department of Radiology, Lucca (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Antonuzzo, Lorenzo [AOU Careggi, SC Oncologia Medica 1, Firenze (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela; Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2016-06-15

    Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and {sup 18}F-FDG PET as prognostic factors in patients with advanced TC or AC. A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients. The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group. Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of

  14. Clinical Translation of a Dual Integrin αvβ3- and Gastrin-Releasing Peptide Receptor-Targeting PET Radiotracer, 68Ga-BBN-RGD.

    Science.gov (United States)

    Zhang, Jingjing; Niu, Gang; Lang, Lixin; Li, Fang; Fan, Xinrong; Yan, Xuefeng; Yao, Shaobo; Yan, Weigang; Huo, Li; Chen, Libo; Li, Zhiyuan; Zhu, Zhaohui; Chen, Xiaoyuan

    2017-02-01

    This study aimed to document the first-in-human application of a (68)Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin αvβ3 and gastrin-releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnostic value of (68)Ga-BBN-RGD PET/CT in prostate cancer patients in comparison with (68)Ga-BBN. Five healthy volunteers (4 men and 1 woman; age range, 28-53 y) were enrolled to validate the safety of (68)Ga-BBN-RGD. Dosimetry was calculated using the OLINDA/EXM software. Thirteen patients with prostate cancer (4 newly diagnosed and 9 posttherapy) were enrolled. All the patients underwent PET/CT scans 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of (68)Ga-BBN-RGD and also accepted (68)Ga-BBN PET/CT within 2 wk for comparison. With a mean injected dose of 107.3 ± 14.8 MBq per patient, no side effect was found during the whole procedure and 2 wk follow-up, demonstrating the safety of (68)Ga-BBN-RGD. A patient would be exposed to a radiation dose of 2.90 mSv with an injected dose of 129.5 MBq (3.5 mCi), which is much lower than the dose limit set by the Food and Drug Administration. In 13 patients with prostate cancer diagnosed by biopsy, (68)Ga-BBN-RGD PET/CT detected 3 of 4 primary tumors, 14 metastatic lymph nodes, and 20 bone lesions with an SUVmax of 4.46 ± 0.50, 6.26 ± 2.95, and 4.84 ± 1.57, respectively. Only 2 of 4 primary tumors, 5 lymph nodes, and 12 bone lesions were positive on (68)Ga-BBN PET/CT, with the SUVmax of 2.98 ± 1.24, 4.17 ± 1.89, and 3.61 ± 1.85, respectively. This study indicates the safety and efficiency of a new type of dual integrin αvβ3- and GRPR-targeting PET radiotracer in prostate cancer diagnosis and staging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  15. Treatment with enalapril and not diltiazem ameliorated progression of chronic kidney disease in rats, and normalized renal AT1 receptor expression as measured with PET imaging.

    Science.gov (United States)

    Ismail, Basma; deKemp, Rob A; Croteau, Etienne; Hadizad, Tayebeh; Burns, Kevin D; Beanlands, Rob S; DaSilva, Jean N

    2017-01-01

    ACE inhibitors are considered first line of treatment in patients with many forms of chronic kidney disease (CKD). Other antihypertensives such as calcium channel blockers achieve similar therapeutic effectiveness in attenuating hypertension-related renal damage progression. Our objective was to explore the value of positron emission tomography (PET) imaging of renal AT1 receptor (AT1R) to guide therapy in the 5/6 subtotal-nephrectomy (Nx) rat model of CKD. Ten weeks after Nx, Sprague-Dawley rats were administered 10mg/kg/d enalapril (NxE), 30mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional 8-10 weeks. Kidney AT1R expression was assessed using in vivo [18F]fluoropyridine-losartan PET and in vitro autoradiography. Compared to shams, Nx rats exhibited higher systolic blood pressure that was reduced by both enalapril and diltiazem. At 18-20 weeks, plasma creatinine and albuminuria were significantly increased in Nx, reduced to sham levels in NxE, but enhanced in NxD rats. Enalapril treatment decreased kidney angiotensin II whereas diltiazem induced significant elevations in plasma and kidney levels. Reduced PET renal AT1R levels in Nx were normalized by enalapril but not diltiazem, and results were supported by autoradiography. Reduction of renal blood flow in Nx was restored by enalapril, while no difference was observed in myocardial blood flow amongst groups. Enhanced left ventricle mass in Nx was not reversed by enalapril but was augmented with diltiazem. Stroke volume was diminished in untreated Nx compared to shams and restored with both therapies. [18F]Fluoropyridine-Losartan PET allowed in vivo quantification of kidney AT1R changes associated with progression of CKD and with various pharmacotherapies.

  16. Drug action at the 5-HT{sub 1A} receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-{sup 11}C]WAY-100635

    Energy Technology Data Exchange (ETDEWEB)

    Rabiner, Eugenii A. E-mail: ilan@cu.rpms.ac.uk; Gunn, Roger N.; Wilkins, Martin R.; Sargent, Peter A.; Mocaer, Elizabeth; Sedman, Ewen; Cowen, Philip J.; Grasby, Paul M

    2000-07-01

    Serotonin{sub 1A} (5-HT{sub 1A}) receptors have been implicated in the pathophysiology and treatment of anxiety and depression and are a target for novel drug development. In this qualitative study, positron emission tomography (PET) and [carbonyl-{sup 11}C]WAY-100635 were used to assess 5-HT{sub 1A} autoreceptor and postsynaptic receptor occupancy in man in vivo by five different compounds with nanomolar affinity for this site. Occupancy by pindolol, penbutolol, buspirone, EMD 68843, and S 15535 was compared to test-retest data from 10 healthy volunteers. All drugs, apart from buspirone, displayed occupancy at the 5-HT{sub 1A} receptor site. Pindolol demonstrated a preferential occupancy at the autoreceptor compared to the postsynaptic receptor over a plasma range of about 10-20 ng/mL. Differential occupancy may be an important component of novel drug action. The level of autoreceptor or postsynaptic occupancy needed to achieve significant physiological effects is not known, although it is of note that none of the drugs in this study achieved occupancies beyond 60%. Overall this study demonstrates the utility of PET in aiding novel drug development.

  17. Methoxyphenylethynyl, methoxypyridylethynyl and phenylethynyl derivatives of pyridine: synthesis, radiolabeling and evaluation of new PET ligands for metabotropic glutamate subtype 5 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Yu Meixiang [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States)]. E-mail: myu@utmck.edu; Tueckmantel, Werner [Acenta Discovery Inc., Tucson, AZ 85747 (United States); Wang, Xukui [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States); Zhu Aijun [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States); Kozikowski, Alan P. [Acenta Discovery Inc., Tucson, AZ 85747 (United States); [Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612 (United States); Brownell, Anna-Liisa [Experimental PET Laboratory, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114 (United States)]. E-mail: abrownell@partners.org

    2005-08-01

    We have synthesized three different PET ligands to investigate the physiological function of metabotropic glutamate subtype 5 receptors (mGluR5) in vivo: 2-[{sup 11}C]methyl-6-(2-phenylethynyl)pyridine ([{sup 11}C]MPEP), 2-(2-(3-[{sup 11}C]methoxyphenyl)ethynyl)pyridine ([{sup 11}C]M-MPEP) and 2-(2-(5-[{sup 11}C]methoxypyridin-3-yl)ethynyl)pyridine ([{sup 11}C]M-PEPy). [{sup 11}C]Methyl iodide was used to label the compounds under basic conditions, and a Pd(0) catalyst was applied to label [{sup 11}C]MPEP in a Stille coupling reaction. In vivo microPET imaging studies of the functional accumulation of radiolabeled ligands were conducted in 35 rats (Sprague-Dawley, 8 weeks old male, weight of 300 g). Specific binding was tested using pre-administration of unlabeled mGluR5 antagonist 2-methyl-6-(2-phenylethynyl)pyridine (MPEP) (10 mg/kg iv 5 min before radioactivity injection). In the radiolabeling of [{sup 11}C]MPEP, [{sup 11}C]M-MPEP and [{sup 11}C]M-PEPy, a specific radioactivity of 700-1200 mCi/{mu}mol and over 97% radiochemical purity were obtained. The microPET studies showed these three radiolabeled mGluR5 antagonists having the highest binding in the olfactory bulb followed by striatum, hippocampus and cortex. Pre-administration of the mGluR5 antagonist MPEP induced a 45.1% decrease in [{sup 11}C]MPEP binding, a 59.7% decrease in [{sup 11}C]M-MPEP binding and an 84.6% decrease in [{sup 11}C]M-PEPy binding in the olfactory bulb at 5 min. The feasibility of synthesizing high-affinity and high-selectivity ligands for mGluR5 receptors and their suitability as PET imaging ligands for mGluR5 receptors in vivo are demonstrated.

  18. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    Science.gov (United States)

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M

    2007-12-01

    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  19. Measuring α4β2* nicotinic acetylcholine receptor density in vivo with [(18)F]nifene PET in the nonhuman primate.

    Science.gov (United States)

    Hillmer, Ansel T; Wooten, Dustin W; Slesarev, Maxim S; Ahlers, Elizabeth O; Barnhart, Todd E; Schneider, Mary L; Mukherjee, Jogeshwar; Christian, Bradley T

    2013-11-01

    [(18)F]Nifene is an agonist PET radioligand developed to image α4β2* nicotinic acetylcholine receptors (nAChRs). This work aims to quantify the receptor density (Bmax) of α4β2* nAChRs and the in vivo (apparent) dissociation constant (KDapp) of [(18)F]nifene. Multiple-injection [(18)F]nifene experiments with varying cold nifene masses were conducted on four rhesus monkeys with a microPET P4 scanner. Compartment modeling techniques were used to estimate regional Bmax values and a global value of KDapp. The fast kinetic properties of [(18)F]nifene also permitted alternative estimates of Bmax and KDapp at transient equilibrium with the same experimental data using Scatchard-like methodologies. Averaged across subjects, the compartment modeling analysis yielded Bmax values of 4.8±1.4, 4.3±1.0, 1.2±0.4, and 1.2±0.3 pmol/mL in the regions of antereoventral thalamus, lateral geniculate, frontal cortex, and subiculum, respectively. The KDapp of nifene was 2.4±0.3 pmol/mL. The Scatchard analysis based on graphical evaluation of the data after transient equilibrium yielded Bmax estimations comparable to the modeling results with a positive bias of 28%. These findings show the utility of [(18)F]nifene for measuring α4β2* nAChR Bmax in vivo in the rhesus monkey with a single PET experiment.

  20. Measurement of central {mu}-opioid receptor binding in vivo with PET and [{sup 11}C]carfentanil: a test-retest study in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Hirvonen, Jussi [Turku PET Centre, University of Turku and Turku University Central Hospital, Turku (Finland)]|[Turku PET Centre, Turku (Finland); Aalto, Sargo; Maksimow, Anu; Oikonen, Vesa; Naagren, Kjell [Turku PET Centre, University of Turku and Turku University Central Hospital, Turku (Finland); Hagelberg, Nora; Scheinin, Harry [Turku PET Centre, University of Turku and Turku University Central Hospital, Turku (Finland)]|[Turku University Central Hospital, Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku (Finland); Ingman, Kimmo [University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Virkkala, Jussi [Pirkanmaa Hospital District, Department of Clinical Neurophysiology, Medical Imaging Centre, Tampere (Finland)

    2009-02-15

    [{sup 11}C]Carfentanil has been widely used in positron emission tomography (PET) studies for measuring {mu}-opioid receptor binding in humans, but the reproducibility of the binding parameter estimates is unknown. Eight healthy volunteers were scanned twice during the same day with [{sup 11}C]carfentanil PET, and binding to receptors was assessed with both reference tissue and arterial plasma input-based models using region of interest (ROI) and voxel-based quantification. The two-tissue compartmental model distribution volume (V{sub T}) was highly reproducible as indicated by low variability (VAR < 6%) and high intraclass correlation coefficients (ICC > 0.93). BP{sub ND} (BP relative to the nondisplaceable tissue compartment) was also highly reproducible (VAR < 10%, ICC > 0.90) both at ROI- and voxel-level, and reference tissue-based models provided stable estimates after 40 min. The reproducibility of [{sup 11}C]carfentanil binding parameter estimates is excellent with outcome measures based on both arterial plasma and reference tissue input, and a scanning time of 40 min appears sufficient. (orig.)

  1. A [11C]Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced α5 benzodiazepine receptors in limbic regions.

    Science.gov (United States)

    Lingford-Hughes, Anne; Reid, Alastair G; Myers, James; Feeney, Adrian; Hammers, Alexander; Taylor, Lindsay G; Rosso, Lula; Turkheimer, Federico; Brooks, David J; Grasby, Paul; Nutt, David J

    2012-02-01

    Preclinical evidence suggests the α5 subtype of the GABA-benzodiazepine receptor is involved in some of the actions of alcohol and in memory. The positron emission tomography (PET) tracer, [(11)C]Ro15 4513 shows relative selectivity in labelling the α5 subtype over the other GABA-benzodiazepine receptor subtypes in limbic regions of the brain. We used this tracer to investigate the distribution of α5 subtype availability in human alcohol dependence and its relationship to clinical variables. Abstinent (>6 weeks) alcohol-dependent men and healthy male controls underwent an [(11)C]Ro15 4513 PET scan. We report [(11)C]Ro15 4513 brain uptake for 8 alcohol-dependent men and 11 healthy controls. We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens, parahippocampal gyri, right hippocampus and amygdala in the alcohol-dependent compared with the healthy control group. Levels of [(11)C]Ro15 4513 binding in both hippocampi were significantly and positively associated with performance on a delayed verbal memory task in the alcohol-dependent but not the control group. We speculate that the reduced limbic [(11)C]Ro15 4513 binding seen here results from the effects of alcohol, though we cannot currently distinguish whether they are compensatory in nature or evidence of brain toxicity.

  2. Regional distribution and behavioral correlates of 5-HT(2A) receptors in Alzheimer's disease with [(18)F]deuteroaltanserin and PET.

    Science.gov (United States)

    Santhosh, Lekshmi; Estok, Kristina M; Vogel, Rebecca S; Tamagnan, Gilles D; Baldwin, Ronald M; Mitsis, Effie M; Macavoy, Martha G; Staley, Julie K; van Dyck, Christopher H

    2009-09-30

    Postmortem studies show reductions in brain serotonin 2A (5-HT(2A)) receptors in Alzheimer's disease (AD). Converging evidence also suggests that serotonergic dysregulation may contribute to behavioral symptoms that frequently occur in AD. This study aimed to define regional reductions in 5-HT(2A) binding in AD patients and to examine their behavioral correlates. Nine patients with probable AD and eight elderly controls were studied using a constant infusion paradigm for equilibrium modeling of [(18)F]deuteroaltanserin with positron emission tomography (PET). Region of interest analyses were performed on PET images coregistered to MRI scans. The outcome measures BP(P) (ratio of specific brain uptake to total plasma parent concentration) and BP(ND) (ratio of specific to nondisplaceable uptake) were obtained for pertinent cortical and subcortical regions. AD patients showed a statistically significant decrease in the anterior cingulate in both BP(P) and BP(ND), but in no other region. Within the AD patient sample, no significant correlations were observed between regional 5-HT(2A) binding and behavioral measures, including depressive and psychotic symptoms. These results confirm a reduction in cortical 5-HT(2A) receptors in AD, specifically in the anterior cingulate. However, in a limited AD patient sample, they fail to demonstrate a relationship between regional 5-HT(2A) binding and major behavioral symptoms.

  3. Radiosynthesis and evaluation of [{sup 11}C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1

    Energy Technology Data Exchange (ETDEWEB)

    Yanamoto, Kazuhiko; Konno, Fujiko; Odawara, Chika; Yamasaki, Tomoteru; Kawamura, Kazunori; Hatori, Akiko; Yui, Joji; Wakizaka, Hidekatsu [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Nengaki, Nobuki [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan); Takei, Makoto [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan); Zhang Mingrong, E-mail: zhang@nirs.go.j [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)

    2010-07-15

    Introduction: Developing positron emission tomography (PET) ligands for imaging metabotropic glutamate receptor type 1 (mGluR1) is important for studying its role in the central nervous system. N-cyclohexyl-6-{l_brace}[N-(2-methoxyethyl)-N-methylamino]methyl{r_brace} -N-methylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-202074) exhibited high binding affinity for mGluR1 (K{sub i}=4.8 nM), and selectivity over other mGluRs in vitro. The purpose of this study was to label YM-202074 with carbon-11 and to evaluate in vitro and in vivo characteristics of [{sup 11}C]YM-202074 as a PET ligand for mGluR1 in rodents. Methods: [{sup 11}C]YM-202074 was synthesized by N-[{sup 11}C]methylation of its desmethyl precursor with [{sup 11}C]methyl iodide. The in vitro and in vivo brain regional distributions were determined in rats using autoradiography and PET, respectively. Results: [{sup 11}C]YM-202074 (262-630 MBq, n=5) was obtained with radiochemical purity of >98% and specific activity of 27-52 GBq/{mu}mol at the end of synthesis, starting from [{sup 11}C]CO{sub 2} of 19.3-21.5 GBq. In vitro autoradiographic results showed that the high specific binding of [{sup 11}C]YM-202074 for mGluR1 was presented in the cerebellum, thalamus and hippocampus, which are known as mGluR1-rich regions. In ex vivo autoradiography and PET studies, the radioligand was specifically distributed in the cerebellum, although the uptake was low. Furthermore, the regional distribution was fairly uniform in the whole brain by pretreatment with JNJ16259685 (a mGluR1 antagonist). However, radiometabolite(s) was detected in the brain. Conclusions: From these results, especially considering the low brain uptake and the influx of radiometabolite(s) into brain, [{sup 11}C]YM-202074 may not be a useful PET ligand for in vivo imaging of mGluR1 in the brain.

  4. The effects of lorazepam on extrastriatal dopamine D(2/3)-receptors-A double-blind randomized placebo-controlled PET study.

    Science.gov (United States)

    Vilkman, Harry; Kajander, Jaana; Aalto, Sargo; Vahlberg, Tero; Någren, Kjell; Allonen, Topias; Syvälahti, Erkka; Hietala, Jarmo

    2009-11-30

    Lorazepam is a widely used anxiolytic drug of the benzodiazepine class. The clinical actions of benzodiazepines are thought to be mediated via specific allosteric benzodiazepine binding sites and enhancement of GABAergic neurotransmission in the brain. However, the indirect effects of benzodiazepines on other neurotransmitter systems have not been extensively studied. Previous experimental evidence suggests that benzodiazepines inhibit striatal dopamine release by enhancing the GABAergic inhibitory effect on dopamine neurons whereas very little is known about cortical or thalamic gamma-amino-butyric (GABA)-dopamine interactions during benzodiazepine administration. We explored the effects of lorazepam (a single 2.5 mg dose) on cortical and thalamic D(2/3) receptor binding using Positron-Emission Tomography (PET) and the high-affinity D(2/3)-receptor ligand [(11)C]FLB 457 in 12 healthy male volunteers. We used a randomized, double-blind and placebo-controlled study design. Dopamine D(2)/D(3) receptor binding potential was measured with the reference tissue method in several extrastriatal D(2)-receptor areas including frontal, parietal, temporal cortices and thalamus. The main subjective effect of lorazepam was sedation. Lorazepam induced a statistically significant decrease of D(2)/D(3) receptor BP(ND) in medial temporal and dorsolateral prefrontal cortex (DLPFC) that was also confirmed by a voxel-level analysis. The sedative effect of lorazepam was associated with a decrease in D(2)/D(3) receptor BP(ND) in the DLPFC. In conclusion, lorazepam decreased [(11)C]FLB 457 binding in frontal and temporal cortex, suggesting that cortical GABA-dopamine interaction may be involved in the central actions of lorazepam in healthy volunteers. The correlation between lorazepam-induced sedation and D(2)/D(3) receptor binding potential (BP) change further supports this hypothesis.

  5. Giardia & Pets

    Science.gov (United States)

    ... body of water Young pets, like puppies and kittens, have a higher risk of illness than adult ... If your pet has persistent diarrhea, seek veterinary care. Diarrhea has different causes and could result in ...

  6. Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Nielsen, Carsten Haagen

    2014-01-01

    and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation. METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid...

  7. 5-HT(1A) receptor and 5-HTT binding during the menstrual cycle in healthy women examined with [(11)C] WAY100635 and [(11)C] MADAM PET.

    Science.gov (United States)

    Jovanovic, Hristina; Karlsson, Per; Cerin, Asta; Halldin, Christer; Nordström, Anna-Lena

    2009-04-30

    The aim of the present study was to explore the effects of the menstrual cycle phases on 5-HT(1A) receptor and 5-HTT binding potentials (BPs) in healthy women by using positron emission tomography (PET). Women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [(11)C]WAY10035 (n=13) and [(11)C]MADAM (n=8) to study 5-HT(1A) and 5-HTT BPs. The BPs values were quantified using the simplified reference tissue model. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TSV) and plasma levels of hormones estradiol (E(2)), progesterone (P(4)), follicle stimulating hormone (FSH) and luteinizing hormone (LH).The 5-HT(1A) receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between the change in E(2) or P(4) values with the change in 5-HT(1A) receptor or 5-HTT BPs. The results provide principally a new in vivo finding in human female biology, suggesting the absence of influence of menstrual cycle phase on 5-HT(1A) receptors or 5-HTT. The finding however does not preclude that gonadal hormones differentially influence central serotonin system inwomen and men, which might contribute to gender differences in serotonin-associated disorders.

  8. Pet Health

    Science.gov (United States)

    Pets can add fun, companionship and a feeling of safety to your life. Before getting a pet, think carefully about which animal is best for ... is each family member looking for in a pet? Who will take care of it? Does anyone ...

  9. Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor

    DEFF Research Database (Denmark)

    Hansen, Hanne Demant; Lacivita, Enza; Di Pilato, Pantaleo

    2014-01-01

    In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best com...

  10. Gastroenteropancreatic Neuroendocrine Tumors: Standardizing Therapy Monitoring with 68Ga-DOTATOC PET/CT Using the Example of Somatostatin Receptor Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Wolfgang Luboldt

    2010-11-01

    Full Text Available The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs during the course of somatostatin receptor radionuclide therapy (SRRT. In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax of normal liver and hepatic metastases were calculated. In addition, the volumes of hepatic metastases (volume of interest [VOI] were measured using four cut-offs to separate normal liver tissue from metastases (SUVmax of the normal liver plus 10% [VOIliver+10%], 20% [VOIliver+20%], 30% [VOIliver+30%] and SUV = 10 [VOI10SUV]. The SUVmaxof the normal liver was below 10 (7.2 ± 1.3 in all patients and without significant changes. Overall therapy changes (Δ per patient (mean [95% CI] were statistically significant with p < .01 for ΔCgA = −43 (−69 to −17, ΔSUVmax = −22 (−29 to −14, and ΔVOI10SUV = −53 (−68 to −38% and significant with p < .05 for ΔVOIliver+10% = −29 (−55 to −3%, ΔVOIliver+20% = −32 (−62 to −2 and ΔVOIliver+30% = −37 (−66 to −8. Correlations were found only between ΔCgA and ΔVOI10SUV (r = .595; p < .01, ΔSUVmax and ΔVOI10SUV (0.629, p < .01, and SUVmax and ΔSUVmax (r = .446; p < .05. 68Ga-DOTATOC PET/CT allows volumetric therapy monitoring via an SUV-based cut-off separating hepatic metastases from normal liver tissue (10 SUV recommended.

  11. Synthesis and evaluation of 6-[{sup 18}F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.-S. E-mail: ding@bnl.gov; Liu, N.; Wang, T.; Marecek, J.; Garza, V.; Ojima, I.; Fowler, J.S

    2000-05-01

    Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[{sup 18}F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[{sup 18}F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[{sup 18}F]fluoro-A-85380. Preliminary comparative PET studies of 6-[{sup 18}F]fluoro-A-85380 and 2-[{sup 18}F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system.

  12. Temporal Heterogeneity of Estrogen Receptor Expression in Bone-Dominant Breast Cancer: 18F-Fluoroestradiol PET Imaging Shows Return of ER Expression.

    Science.gov (United States)

    Currin, Erin; Peterson, Lanell M; Schubert, Erin K; Link, Jeanne M; Krohn, Kenneth A; Livingston, Robert B; Mankoff, David A; Linden, Hannah M

    2016-02-01

    Changes in estrogen receptor (ER) expression over the course of therapy may affect response to endocrine therapy. However, measuring temporal changes in ER expression requires serial biopsies, which are impractical and poorly tolerated by most patients. Functional ER imaging using (18)F-fluoroestradiol (FES)-PET provides a noninvasive measure of regional ER expression and is ideally suited to serial studies. Additionally, lack of measurable FES uptake in metastatic sites of disease predict tumor progression in patients with ER-positive primary tumors treated with endocrine therapy. This report presents a case of restored sensitivity to endocrine therapy in a patient with bone-dominant breast cancer who underwent serial observational FES-PET imaging over the course of several treatments at our center, demonstrating the temporal heterogeneity of regional ER expression. Although loss and restoration of endocrine sensitivity in patients who have undergone prior hormonal and cytotoxic treatments has been reported, this is, to our knowledge, the first time the accompanying changes in ER expression have been documented by molecular imaging.

  13. Dopamine D{sub 2} receptor occupancy in normal humans treated with a novel antipsychotic drug YKP1358 measured by PET and [11c]raclopride

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. S.; Kim, S. J.; Lee, K. J.; Kim, E.; Yu, K. S.; Jang, I. J.; Kwon, J. S.; Kang, W. J.; Jeong, J. M.; Lee, D. S.; Chung, J. K.; Lee, M. C. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    YKP1358 is a novel serotonin (5-HT{sub 2A}) and dopamine (D{sub 2}) antagonist, and fitted the general profile of an atypical neuroleptic agent in preclinical studies. The time course of D{sub 2} receptor occupancy in the brain of living human after a single oral dose of YKP1358 was measured using PET and related to the plasma drug levels. A single oral dose, dose escalation (100 mg, 200 mg, and 250 mg), open-label study was performed in 9 healthy male volunteers (3 per each dose) using the [{sup 11}C]raclopried PET. After the baseline scan, each subject was studied at 2, 5, and 10 hours after the single administration of YKP1358. Blood samples for evaluation of plasma concentration of YKP1358 were also taken at various time points (0-32 hours post-dose). Binding potential (BP) of [{sup 11}C]raclopride in the putamen was estimated with simplified reference tissue model and percent reduction of the BP was calculated to obtain the D{sub 2} receptor occupancy. BP parametric image was generated using a pixel-wise Logan noninvasive plot. T{sub max} of plasma concentration-time profiles was 0.67 hours, and elimination half-life was 5.71, 7.46, and 8.58 hours in 100 mg, 200 mg, and 250 mg dosing groups, respectively. D{sub 2} receptor occupancy of YKP1358 was 60 to 80% at 2 hours, 40 to 60% at 5 hours, and 20 to 50% at 10 hours. The relationship of plasma concentration and D{sub 2} receptor occupancy of YKP1358 was well predicted by Emax model, and Emax was 100 %, EC50 was 8.9 (=1.1) ng/mI, and Hills coefficient was 0.525. PK profile of YKP1358 showed individual variation, but the D{sub 2} receptor occupancy was less variable and well predicted by an Emax model. Since D{sub 2} antagonists show therapeutic effects at 50 to 80% D{sub 2} occupancy and the EC50 of YKP1358 is less than 10 ng/ml, doses of YKP1358 which maintain plasma concentrations above 10 ng/ml are expected to show therapeutic effects.

  14. Design and Synthesis of an 18F-Labeled Version of Phenylethyl Orvinol ([18F]FE-PEO for PET-Imaging of Opioid Receptors

    Directory of Open Access Journals (Sweden)

    Gjermund Henriksen

    2012-09-01

    Full Text Available The semisynthetic oripavine derivative phenethyl orvinol (PEO, a full agonist at opioid receptors (OR, is an attractive structural motif for developing 18F-labeled PET tracers with a high degree of sensitivity for competition between endogenous and exogenous OR-ligands. The target cold reference compound 6-O-(2-fluoroethyl-6-O-desmethylphenylethyl orvinol (FE-PEO was obtained via two separate reaction routes. A three-step synthesis was developed for the preparation of a tosyloxyethyl precursor (TE-TDPEO, the key precursor for a direct, nucleophilic radiofluorination to yield [18F]FE-PEO. The developed radiosynthesis provides the target compound in relevantly high yield and purity, and is adaptable to routine production.

  15. Synthesis and evaluation of [11C]Cimbi-806 as a potential PET ligand for 5-HT7 receptor imaging

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Hansen, Hanne Demant; Ettrup, Anders Janusz;

    2012-01-01

    2-(2',6'-Dimethoxy-[1,1'-biphenyl]-3-yl)-N,N-dimethylethanamine has been identified as a potent ligand for the serotonin 7 (5-HT(7)) receptor. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]2-(2',6'-dimethoxy-[1,1'-biphenyl]-3-yl......)-N,N-dimethylethanamine ([(11)C]Cimbi-806) as a radioligand for imaging brain 5-HT(7) receptors with positron emission tomography (PET). Precursor and reference compound was synthesized and subsequent (11)C-labelling with [(11)C]methyltriflate produced [(11)C]Cimbi-806 in specific activities ranging from 50 to 300 GBq......L/cm(3) in the cerebellum to 12 mL/cm(3) in the thalamus. Pretreatment with the 5-HT(7) receptor antagonist SB-269970 did not result in any significant changes in [(11)C]Cimbi-806 binding in any of the analyzed regions. Despite the high brain uptake and relevant distribution pattern, the absence...

  16. The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction:Combining preclinical evidence with human Positron Emission Tomography (PET studies

    Directory of Open Access Journals (Sweden)

    Sylvia eTerbeck

    2015-03-01

    Full Text Available In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5 activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET and combined the findings with preclinical animal research. This combined view of different methodological approaches — from basic neurobiological approaches to human studies — might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC. Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays in important role in systems for social functioning and the response to social stress. Finally, mGluR5’s important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC’s arousal and modulatory systems domain. Glutamate was previously mostly investigate in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

  17. Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism.

    Science.gov (United States)

    Lingford-Hughes, Anne; Myers, James; Watson, Ben; Reid, Alastair G; Kalk, Nicola; Feeney, Adrian; Hammers, Alexander; Riaño-Barros, Daniela A; McGinnity, Colm J; Taylor, Lindsay G; Rosso, Lula; Brooks, David J; Turkheimer, Federico; Nutt, David J

    2016-05-15

    The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.

  18. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

    Science.gov (United States)

    Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

  19. PET imaging evaluation of [{sup 18}F]DBT-10, a novel radioligand specific to α{sub 7} nicotinic acetylcholine receptors, in nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Hillmer, Ansel T.; Zheng, Ming-Qiang; Li, Songye; Lin, Shu-fei; Holden, Daniel; Labaree, David; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun [Yale University, PET Center, 801 Howard Ave, PO Box 208048, New Haven, CT (United States); Scheunemann, Matthias; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig (Germany)

    2016-03-15

    Positron emission tomography (PET) radioligands specific to α{sub 7} nicotinic acetylcholine receptors (nAChRs) afford in vivo imaging of this receptor for neuropathologies such as Alzheimer's disease, schizophrenia, and substance abuse. This work aims to characterize the kinetic properties of an α{sub 7}-nAChR-specific radioligand, 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-[{sup 18}F]-fluorodibenzo[b,d]thiophene 5,5-dioxide ([{sup 18}F]DBT-10), in nonhuman primates. [{sup 18}F]DBT-10 was produced via nucleophilic substitution of the nitro-precursor. Four Macaca mulatta subjects were imaged with [{sup 18}F]DBT-10 PET, with measurement of [{sup 18}F]DBT-10 parent concentrations and metabolism in arterial plasma. Baseline PET scans were acquired for all subjects. Following one scan, ex vivo analysis of brain tissue was performed to inspect for radiolabeled metabolites in brain. Three blocking scans with 0.69 and 1.24 mg/kg of the α{sub 7}-nAChR-specific ligand ASEM were also acquired to assess dose-dependent blockade of [{sup 18}F]DBT-10 binding. Kinetic analysis of PET data was performed using the metabolite-corrected input function to calculate the parent fraction corrected total distribution volume (V{sub T}/f{sub P}). [{sup 18}F]DBT-10 was produced within 90 min at high specific activities of 428 ± 436 GBq/μmol at end of synthesis. Metabolism of [{sup 18}F]DBT-10 varied across subjects, stabilizing by 120 min post-injection at parent fractions of 15-55 %. Uptake of [{sup 18}F]DBT-10 in brain occurred rapidly, reaching peak standardized uptake values (SUVs) of 2.9-3.7 within 30 min. The plasma-free fraction was 18.8 ± 3.4 %. No evidence for radiolabeled [{sup 18}F]DBT-10 metabolites was found in ex vivo brain tissue samples. Kinetic analysis of PET data was best described by the two-tissue compartment model. Estimated V{sub T}/f{sub P} values were 193-376 ml/cm{sup 3} across regions, with regional rank order of thalamus > frontal cortex > striatum

  20. Sigma-1 Receptor Imaging in the Brain : Cerebral sigma-1 receptors and cognition: Small-animal PET studies using 11C-SA4503

    NARCIS (Netherlands)

    Kuzhuppilly Ramakrishnan, Nisha

    2014-01-01

    The sigma-1 receptor is a unique orphan receptor, strongly expressed in neurons and glia. Sigma-1 receptors are involved in several central nervous system (CNS) disorders like depression, anxiety, psychosis, schizophrenia, Parkinson’s disease, Alzheimer’s disease, addiction and neuropathic pain. Sev

  1. Test-retest reliability of the novel 5-HT{sub 1B} receptor PET radioligand [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Saricicek, Aybala [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Izmir Katip Celebi University, Department of Psychiatry, Izmir (Turkey); Chen, Jason; Ruf, Barbara [Yale University, Department of Psychiatry, New Haven, CT (United States); Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun [Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Subramanyam, Kalyani; Maloney, Kathleen [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Matuskey, David [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Deserno, Lorenz [Charite - Universitaetsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin (Germany); Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Berlin (Germany); Neumeister, Alexander [Yale University, Department of Psychiatry, New Haven, CT (United States); Mount Sinai School of Medicine, Department of Psychiatry, New York, NY (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Krystal, John H. [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Carson, Richard E. [Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bhagwagar, Zubin [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bristol-Myers Squibb, Wallingford, CT (United States)

    2014-11-27

    [{sup 11}C]P943 is a novel, highly selective 5-HT{sub 1B} PET radioligand. The aim of this study was to determine the test-retest reliability of [{sup 11}C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP{sub ND} was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP{sub ND}, 0.5 % and 11.5 % for MA1 BP{sub P}, 16.7 % and 28.3 % for MA1 BP{sub F}, and between 0.2 % and 5.4 % for MRTM2 BP{sub ND}. The power analyses showed a greater number of subjects were required using MA1 BP{sub F} compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP{sub ND} and the lowest with MA1 BP{sub F} in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT{sub 1B} receptor binding can be obtained using the novel PET radioligand [{sup 11}C]P943. Quantification of 5-HT{sub 1B} receptor binding with MRTM2 BP{sub ND} and with MA1 BP{sub P

  2. Neurotransmission imaging by PET

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    2001-08-01

    PET studies on neurotransmission in psychological disorders to evaluate abnormal neurotransmission and therapeutic effects are thoroughly reviewed by type of major neurotransmitters. Studies on dopaminergic neurotransmission have focused on the function of dopamine D{sub 2} receptors, receptor subtypes, such as the D{sub 1} receptor, and ligands, such as transporters. PET studies of dopamine D{sub 2} receptor, which began in the early 1980s, have predominantly been performed in schizophrenia, and most have failed to detect any statistically significant differences between schizophrenia patients and controls. The studies in the early 1980s were performed by using [{sup 11}C]N-methyl-spiperone (NMSP) and [{sup 11}C]raclopride, ligands for striatal dopamine D{sub 2} receptors. [{sup 11}C]FLB457, which has much higher affinity for D{sub 2} receptors than raclopride, began to be used in the 1990s. Dopamine D{sub 2} occupancy after drug ingestion has also been investigated to clarify the mechanisms and effects of antipsychotic drugs, and there have also been studies on the effect of aging and personality traits on dopamine D{sub 2} receptor levels in healthy subjects. In studies on dopamine receptor subtypes other than D{sub 2}, dopamine D{sub 1} receptors have been studied in connection with assessments of cognitive functions. Most studies on dopamine transporters have been related to drug dependence. Serotonin 5-HT{sub 2A} receptors have been studied with [{sup 11}C]NMSP in schizophrenia patients, while studies of another serotonin receptor subtype, 5-HT{sub 1A} receptors, have been mainly conducted in patients with depression. [{sup 11}C]NMSP PET showed no difference between schizophrenia patients who had not undergone phamacotherapy and normal subjects. Because serotonin selective reuptake inhibitors (SSRIs) affect serotonin transporters, and abnormalities in serotonin transporters detected in mood disorders, PET ligands for serotonin transporters have increasingly

  3. PET and PET/CT in clinical cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Won, Kyoung Sook [Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2005-02-15

    Cardiac PET emerged as a powerful tool that allowed in vivo quantification of physiologic processes including myocardial perfusion and metabolism, as well as neuronal and receptor function for more than 25 years. Now PET imaging has been playing an important role in the clinical evaluation of patients with known or suspected ischemic heart disease. This important clinical role is expected to grow with the availability of PET/CT scanner that allow a true integration of structure and function. The objective of this review is to provide and update on the current and future role of PET in clinical cardiology with a special eye on the great opportunities now offered by PET/CT.

  4. In vivo imaging of insulin receptors by PET: preclinical evaluation of iodine-125 and iodine-124 labelled human insulin

    Energy Technology Data Exchange (ETDEWEB)

    Iozzo, P.; Osman, S.; Glaser, M.; Knickmeier, M.; Ferrannini, E.; Pike, V.W.; Camici, P.G.; Law, M.P. E-mail: marilyn.law@csc.mrc.ac.uk

    2002-01-01

    [A{sub 14}-*I]iodoinsulin was prepared for studies to assess the suitability of labeled iodoinsulin for positron emission tomography (PET). Iodine-125 was used to establish the methods and for preliminary studies in rats. Further studies and PET scanning in rats were carried out using iodine-124. Tissue and plasma radioactivity was measured as the uptake index (UI={l_brace}cpm{center_dot}(g tissue){sup -1}{r_brace}/{l_brace}cpm injected{center_dot}(g body weight){sup -1}{r_brace}) at 1 to 40 min after intravenous injection of either [A{sub 14}-{sup 125}I]iodoinsulin or [A{sub 14}-{sup 124}I]iodoinsulin. For both radiotracers, initial clearance of radioactivity from plasma was rapid (T{sub 1/2} {approx} 1 min), reaching a plateau (UI = 2.8) at {approx} 5 min which was maintained for 35 min. Tissue biodistributions of the two radiotracers were comparable; at 10 min after injection, UI for myocardium was 2.4, liver, 4.0, pancreas, 5.4, brain, 0.17, kidney, 22, lung, 2.3, muscle, 0.54 and fat, 0.28. Predosing rats with unlabelled insulin reduced the UI for myocardium (0.95), liver (1.8), pancreas (1.2) and brain (0.08), increased that for kidney (61) but had no effect on that for lung (2.5), muscle (0.50) or fat (0.34). Analysis of radioactivity in plasma demonstrated a decrease of [{sup 125}I]iodoinsulin associated with the appearance of labeled metabolites; the percentage of plasma radioactivity due to [{sup 125}I]iodoinsulin was 40% at 5 min and 10% at 10 min. The heart, liver and kidneys were visualized using [{sup 124}I]iodoinsulin with PET.

  5. Longitudinal assessment of cerebral 5-HT{sub 2A} receptors in healthy elderly volunteers: an [{sup 18}F]-altanserin PET study

    Energy Technology Data Exchange (ETDEWEB)

    Marner, Lisbeth; Knudsen, Gitte M.; Haugboel, Steven [University Hospital Rigshospitalet, Neurobiology Research Unit, N9201, Copenhagen O (Denmark); Holm, Soeren [Rigshospitalet, PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen (Denmark); Baare, William [Hvidovre Hospital, Danish Research Center for Magnetic Resonance, Copenhagen (Denmark); Hasselbalch, Steen G. [University Hospital Rigshospitalet, Neurobiology Research Unit, N9201, Copenhagen O (Denmark)]|[Memory Disorders Research Unit, The Neuroscience Center, Copenhagen (Denmark)

    2009-02-15

    The serotonin 2A (5-HT{sub 2A}) receptor is of interest in several psychiatric and neurological diseases. In the present study we investigated the longitudinal stability of 5-HT{sub 2A} receptors and the stability of the quantification procedure in the elderly in order to be able to study elderly patients with neuropsychiatric diseases on a longitudinal basis. [{sup 18}F]-Altanserin PET was used to quantify 5-HT{sub 2A} receptors in 12 healthy elderly individuals at baseline and at 2 years in six volumes of interest. A bolus/infusion protocol was used to achieve the binding potential, BP{sub P}. The reproducibility as assessed in terms of variability and the reliability as assessed in terms of intraclass correlation coefficient (ICC) were used to compare inter- and intraobserver stability and to evaluate the effects of increasing complexity of partial volume (PV) corrections. We also compared the stability of our measurements over 2 years with the stability of data from an earlier study with 2-week test-retest measurements. BP{sub P} was unaltered at follow-up without the use of PV correction and when applying two-tissue PV correction, test-retest reproducibility was 12-15% and reliability 0.45-0.67 in the large bilateral regions such as the parietal, temporal, occipital and frontal cortices, while orbitofrontal and anterior cingulate cortical regions were less stable. The use of PV correction decreased the variability but also decreased the between-subject variation, thereby worsening the reliability. In healthy elderly individuals, brain 5-HT{sub 2A} receptor binding remains stable over 2 years, and acceptable reproducibility and reliability in larger regions and high intra- and interobserver stability allow the use of [{sup 18}F]-altanserin in longitudinal studies of patients with neuropsychiatric disorders. (orig.)

  6. Type 1 cannabinoid receptor mapping with [{sup 18}F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Casteels, Cindy [KU Leuven and University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); University Hospital Gasthuisberg, Division of Nuclear Medicine, Leuven (Belgium); Martinez, Emili; Camon, Lluisa; Vera, Nuria de; Planas, Anna M. [IDIBAPS, Institute for Biomedical Research (IIBB-CSIC), Barcelona (Spain); Bormans, Guy [KU Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); KU Leuven, Laboratory for Radiopharmacy, Leuven (Belgium); Baekelandt, Veerle [KU Leuven, Laboratory for Neurobiology and Gene Therapy, Leuven (Belgium); Laere, Koen van [KU Leuven and University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); KU Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium)

    2010-12-15

    Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [{sup 18}F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB{sub 1}) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D{sub 2} receptor availability and amphetamine-induced turning behaviour. Twenty-one Wistar rats (11 QA and 10 shams) were investigated. Small animal PET acquisitions were conducted on a Focus 220 with approximately 18 MBq of [{sup 18}F]MK-9470, [{sup 18}F]FDG and [{sup 11}C]raclopride. Relative glucose metabolism and parametric CB{sub 1} receptor and D{sub 2} binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2). In the QA model, [{sup 18}F]MK-9470 uptake, glucose metabolism and D{sub 2} receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p < 2.10{sup -5}), while an increase for these markers was observed on the contralateral side (>5%, all p < 7.10{sup -4}). [{sup 18}F]MK-9470 binding was also increased in the cerebellum (p = 2.10{sup -5}), where it was inversely correlated to the number of ipsiversive turnings (p = 7.10{sup -6}), suggesting that CB{sub 1} receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p = 1.10{sup -6}). These data point to in vivo changes in endocannabinoid transmission, specifically for CB{sub 1} receptors in the QA model, with involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D{sub 2} and CB{sub 1} neurotransmission in the contralateral hemisphere. (orig.)

  7. Synthesis of [{sup 18}F]-labelled nebivolol as a β{sub 1}-adrenergic receptor antagonist for PET imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taek Soo; Park, Jeong Hoon; Lee, Jun Young; Yang, Seung Dae [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup (Korea, Republic of); Chang, Dong Jo [College of pharmacy, Sunchon National University, Suncheon (Korea, Republic of)

    2017-02-15

    Selective β{sub 1}-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective β{sub 1}-antagonists including nebivolol have high binding affinity on β{sub 1}-adrenergic receptor, not β{sub 2}-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective β{sub 1}-blockers in clinically used β{sub 1}- blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective β{sub 1}-blocker. Nebivolol is C{sub 2}-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of {sup 18}F. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for {sup 18}F-aromatic substitution, was synthesized in moderate yield which was readily subjected to {sup 18}F-aromatic substitution to give {sup 18}F-labelled nebivolol.

  8. Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1'-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine].

    Science.gov (United States)

    Wiese, Christian; Grosse Maestrup, Eva; Schepmann, Dirk; Grimme, Stefan; Humpf, Hans-Ulrich; Brust, Peter; Wünsch, Bernhard

    2011-02-01

    It was shown that racemic (±)-2 [1'-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine], WMS-1813] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ(1) receptors. To study the pharmacological activity of the enantiomers of 2, a preparative HPLC separation of (R)-2 and (S)-2 was performed. The absolute configuration of the enantiomers was determined by CD-spectroscopy together with theoretical calculations of the CD-spectrum of a model compound. In receptor binding studies with the radioligand [(3)H]-(+)-pentazocine, (S)-2 was thrice more potent than its (R)-configured enantiomer (R)-2. The metabolic degradation of the more potent (S)-enantiomer was considerably slower than the metabolism of (R)-2. The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap-LC-MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2. Copyright © 2010 Wiley-Liss, Inc.

  9. Diagnostic performances of the S.R.S. (scintigraphy of somatostatin receptors) and of the PET-F.D.G. in the extension situation of the well differentiated endocrine carcinomas at high Ki67; Performances diagnostiques de la SRS et de la TEP-FDG dans le bilan d'extension des carcinomes endocrines bien differencies a Ki67 eleve ({>=} 10%)

    Energy Technology Data Exchange (ETDEWEB)

    Abgrala, R.; Leboulleux, S.; Deandreis, D.; Lumbroso, J.; Schlumberger, M.; Baudin, E. [Medecine nucleaire, institut Gustave-Roussy, Villejuif, (France); Auperin, A. [Biostatistiques, Institut Gustave-Roussy, Villejuif, (France); Dromain, C. [radiologie, institut Gustave-Roussy, Villejuif, (France); Guigay, J. [pneumologie, institut Gustave-Roussy, Villejuif, (France); Ducreux, M. [hepato-gastroenterologie, Institut Gustave-Roussy, Villejuif, (France)

    2009-05-15

    The results suggest that among 90% of patients with well differentiated endocrine carcinomas at high Ki, the PET-F.D.G. is more noticeable or equivalent to the scintigraphy of somatostatin receptors (S.R.S.). (N.C.)

  10. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    Energy Technology Data Exchange (ETDEWEB)

    Sako, Takeo [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Senda, Michio [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)

    2013-12-06

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  11. Value of {sup 18}F-FDG uptake on PET/CT and CEA level to predict epidermal growth factor receptor mutations in pulmonary adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kai-Hsiung; Hsu, Hsian-He; Chang, Wei-Chou; Hsu, Yi-Chih; Chang, Tsun-Hou [Tri-Service General Hospital and National Defense Medical Center, Department of Radiology, Taipei 114 (China); Huang, Tsai-Wang; Chang, Hung [Tri-Service General Hospital and National Defense Medical Center, Department of Thoracic Surgery, Taipei (China); Gao, Hong-Wei [Tri-Service General Hospital and National Defense Medical Center, Department of Pathology, Taipei (China); Shen, Daniel H.Y. [Tri-Service General Hospital and National Defense Medical Center, Department of Nuclear medicine, Taipei (China); Chu, Chi-Ming [Institute of Public Health, National Defense Medical Center and University, Section of Health Informatics, Taipei (China); Ho, Ching-Liang [Tri-Service General Hospital and National Defense Medical Center, Division of Hematology-Oncology, Department of Internal Medicine, Taipei (China)

    2014-10-15

    The identification of the mutation status of the epidermal growth factor receptor (EGFR) is important for the optimization of treatment in patients with pulmonary adenocarcinoma. The acquisition of adequate tissues for EGFR mutational analysis is sometimes not feasible, especially in advanced-stage patients. The aim of this study was to predict EGFR mutation status in patients with pulmonary adenocarcinoma based on {sup 18}F-fluorodeoxyglucose (FDG) uptake and imaging features in positron emission tomography/computed tomography (PET/CT), as well as on the serum carcinoembryonic antigen (CEA) level. We retrospectively reviewed 132 pulmonary adenocarcinoma patients who underwent EGFR mutation testing, pretreatment FDG PET/CT and serum CEA analysis. The associations between EGFR mutations and patient characteristics, maximal standard uptake value (SUVmax) of primary tumors, serum CEA level and CT imaging features were analyzed. Receiver-operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. EGFR mutations were identified in 69 patients (52.2 %). Patients with SUVmax ≥6 (p = 0.002) and CEA level ≥5 (p = 0.013) were more likely to have EGFR mutations. The CT characteristics of larger tumors (≥3 cm) (p = 0.023) and tumors with a nonspiculated margin (p = 0.026) were also associated with EGFR mutations. Multivariate analysis showed that higher SUVmax and CEA level, never smoking and a nonspiculated tumor margin were the most significant predictors of EGFR mutation. The combined use of these four criteria yielded a higher area under the ROC curve (0.82), suggesting a good discrimination. The combined evaluation of FDG uptake, CEA level, smoking status and tumor margins may be helpful in predicting EGFR mutation status in patients with pulmonary adenocarcinoma, especially when the tumor sample is inadequate for genetic analysis or genetic testing is not available. Further large-scale prospective studies are

  12. Biodistribution and radiation dosimetry of the A{sub 1} adenosine receptor ligand {sup 18}F-CPFPX determined from human whole-body PET

    Energy Technology Data Exchange (ETDEWEB)

    Herzog, Hans; Elmenhorst, David; Winz, Oliver [Forschungszentrum Juelich GmbH, Institute of Neuroscience and Biophysics - Medicine, Juelich (Germany); Bauer, Andreas [Forschungszentrum Juelich GmbH, Institute of Neuroscience and Biophysics - Medicine, Juelich (Germany); University Hospital Duesseldorf, Department of Neurology, Duesseldorf (Germany)

    2008-08-15

    {sup 18}F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ({sup 18}F-CPFPX) is a potent radioligand to study human cerebral A{sub 1} adenosine receptors and their neuromodulatory and neuroprotective functions with positron emission tomography (PET). The purpose of this study was to determine the biodistribution and the radiation dose of {sup 18}F-CPFPX by whole-body scans in humans. Six normal volunteers were examined with 12 whole-body PET scans from 1.5 min to 4.5 h after injection. Volumes of interest were defined over all visually identifiable organs, i.e. liver, gallbladder, kidneys, small intestines, heart, and brain to obtain the organs' volumes and time-activity curves (TACs). TACs were fitted with exponential functions, extrapolated, multiplied with the physical decay and normalized to injected activities so that the residence times could be computed as area under the curve. Radiation doses were calculated using the OLINDA/EXM software for internal dose assessment in nuclear medicine. The liver uptake shows peak values (decay-corrected) of up to 35% of the injected radioactivity. About 30% is eliminated by bladder voiding. The highest radiation dose is received by the gallbladder (136.2 {+-} 66.1 {mu}Sv/MBq), followed by the liver (84.4 {+-} 10.6 {mu}Sv/MBq) and the urinary bladder (78.3 {+-} 7.1 {mu}Sv/MBq). The effective dose was 17.6 {+-} 0.5 {mu}Sv/MBq. With 300 MBq of injected {sup 18}F-CPFPX a subject receives an effective dose (ICRP 60) of 5.3 mSv. Thus the effective dose of an {sup 18}F-CPFPX study is comparable to that of other {sup 18}F-labelled neuroreceptor ligands. (orig.)

  13. The antipsychotic sultopride is overdosed--a PET study of drug-induced receptor occupancy in comparison with sulpiride.

    Science.gov (United States)

    Takano, Akihiro; Suhara, Tetsuya; Yasuno, Fumihiko; Suzuki, Kazutoshi; Takahashi, Hidehiko; Morimoto, Takuya; Lee, Young-Joo; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Okubo, Yoshiro

    2006-10-01

    Conventional antipsychotics tend to elicit extrapyramidal symptoms at clinical doses, but dose optimization could reduce the risk of such side-effects. In-vivo receptor-binding studies have suggested that 70-80% of dopamine D2 receptor occupancy provides the desired antipsychotic effects without extrapyramidal symptoms. In terms of dose optimization based on the occupancy, there has not been enough supporting data regarding the clinical doses of the respective antipsychotics. In this study, we measured dopamine D2 receptor occupancy of two conventional benzamide antipsychotics, sulpiride and sultopride, using positron emission tomography, to investigate the rationale of their clinical dose. Although they are prescribed at similar doses (300-1200 mg), the doses required to obtain similar receptor occupancy (70-80%) were quite different: 1010-1730 mg for sulpiride but 20-35 mg for sultopride. In terms of dose, sultopride has about 50 times greater potency than sulpiride based on dopamine D2 receptor occupancy. Evidence for the optimal doses of conventional antipsychotics based on dopamine D2 receptor occupancy would be helpful for rational antipsychotic therapy.

  14. Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.

    Science.gov (United States)

    Tateno, Amane; Arakawa, Ryosuke; Okumura, Masaki; Fukuta, Hajime; Honjo, Kazuyoshi; Ishihara, Keiichi; Nakamura, Hiroshi; Kumita, Shin-ichiro; Okubo, Yoshiro

    2013-04-01

    Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

  15. Adenosine A{sub 1} receptors in human sleep regulation studied by electroencephalography (EEG) and positron emission tomography (PET)[Dissertation 17227

    Energy Technology Data Exchange (ETDEWEB)

    Geissler, E

    2007-07-01

    Sleep is an essential physiological process. However, the functions of sleep and the endogenous mechanisms involved in sleep regulation are only partially understood. Convergent lines of evidence support the hypothesis that the build-up of sleep propensity during wakefulness and its decline during sleep are associated with alterations in brain adenosine levels and adenosine receptor concentrations. The non-selective A{sub 1} and A{sub 2A} adenosine receptor antagonist caffeine stimulates alertness and is known to attenuate changes in the waking and sleep electroencephalogram (EEG) typically observed after prolonged waking. Several findings point to an important function of the adenosine A{sub 1} receptor (A{sub 1}AR) in the modulation of vigilance states. The A{sub 1}AR is densely expressed in brain regions involved in sleep regulation, and pharmacological manipulations affecting the A{sub 1}AR were shown to influence sleep propensity and sleep depth. However, an involvement of the A{sub 2A} adenosine receptor (A{sub 2A}AR) is also assumed. The distinct functions of the A{sub 1} and A{sub 2A} receptor subtypes in sleep-wake regulation and in mediating the effects of caffeine have not been identified so far. The selective adenosine A{sub 1} receptor antagonist, 8-cyclopentyl-3-(3-{sup 18}Ffluoropropyl)- 1-propylxanthine ({sup 18}F-CPFPX), offers the opportunity to get further insights into adenosinergic mechanisms by in vivo imaging of the A{sub 1}AR subtype with positron emission tomography (PET). The aim of this thesis was to elucidate the role of adenosine A{sub 1} receptors in human sleep regulation, combining {sup 18}F-CPFPX PET brain imaging and EEG recordings, the gold standard in sleep research. It was hypothesized that sleep deprivation would induce adenosine accumulation and/or changes in A{sub 1}AR density. Thus, the question was addressed whether these effects of prolonged wakefulness can be visualized by altered {sup 18}F-CPFPX binding. Moreover, it was

  16. Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: design, synthesis, structure-activity relationships, physicochemical properties and biological activity

    NARCIS (Netherlands)

    Blaazer, A.R.; Lange, J.H.M.; van der Neut, M.A.W.; Mulder, A.; den Boon, F.S.; Werkman, T.R.; Kruse, C.G.; Wadman, W.J.

    2011-01-01

    The discovery, synthesis and structure-activity relationship (SAR) of a novel series of cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor ligands are reported. Based on the aminoalkylindole class of cannabinoid receptor agonists, a biphenyl moiety was introduced as novel lipophilic indole 3-acyl

  17. Preclinical evaluation and quantification of [{sup 18}F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Casteels, Cindy [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); University Hospital Gasthuisberg, Division of Nuclear Medicine, Leuven (Belgium); Koole, Michel; Laere, Koen van [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); Celen, Sofie; Bormans, Guy [K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); K.U. Leuven, Laboratory for Radiopharmacy, Leuven (Belgium)

    2012-09-15

    [{sup 18}F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [{sup 18}F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [{sup 18}F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V{sub T}) of [{sup 18}F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [{sup 18}F]MK-9470 in arterial plasma samples was 80 {+-} 23 % at 10 min, 38 {+-} 30 % at 40 min and 13 {+-} 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V{sub T} values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability ({<=}10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [{sup 18}F]MK-9470 V{sub T}, but was correlated. A correlation between [{sup 18}F]MK-9470 V{sub T} and SUV in the brain was also found (R {sup 2} = 0.26-0.33; p {<=} 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [{sup 18}F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  18. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET.

    Science.gov (United States)

    Jovanovic, Hristina; Lundberg, Johan; Karlsson, Per; Cerin, Asta; Saijo, Tomoyuki; Varrone, Andrea; Halldin, Christer; Nordström, Anna-Lena

    2008-02-01

    Women and men differ in serotonin associated psychiatric conditions, such as depression, anxiety and suicide. Despite this, very few studies focus on sex differences in the serotonin system. Of the biomarkers in the serotonin system, serotonin(1A) (5-HT(1A)) receptor is implicated in depression, and anxiety and serotonin transporter (5-HTT) is a target for selective serotonin reuptake inhibitors, psychotropic drugs used in the treatment of these disorders. The objective of the present study was to study sex related differences in the 5-HT(1A) receptor and 5-HTT binding potentials (BP(ND)s) in healthy humans, in vivo. Positron emission tomography and selective radioligands [(11)C]WAY100635 and [(11)C]MADAM were used to evaluate binding potentials for 5-HT(1A) receptors (14 women and 14 men) and 5-HTT (8 women and 10 men). The binding potentials were estimated both on the level of anatomical regions and voxel wise, derived by the simplified reference tissue model and wavelet/Logan plot parametric image techniques respectively. Compared to men, women had significantly higher 5-HT(1A) receptor and lower 5-HTT binding potentials in a wide array of cortical and subcortical brain regions. In women, there was a positive correlation between 5-HT(1A) receptor and 5-HTT binding potentials for the region of hippocampus. Sex differences in 5-HT(1A) receptor and 5-HTT BP(ND) may reflect biological distinctions in the serotonin system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result of the present study may help in understanding sex differences in drug treatment responses to drugs affecting the serotonin system.

  19. Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [{sup 68}Ga]SB3 and PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Maina, Theodosia; Charalambidis, David; Nock, Berthold A. [INRASTES, NCSR ' ' Demokritos' ' , Molecular Radiopharmacy, Athens (Greece); Bergsma, Hendrik; Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Kulkarni, Harshad R.; Mueller, Dirk; Baum, Richard P. [Zentralklinik, Molecular Radiotherapy and Molecular Imaging, Bad Berka (Germany); Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Radiology, Rotterdam (Netherlands)

    2016-05-15

    Gastrin-releasing peptide receptors (GRPR) represent attractive targets for tumor diagnosis and therapy because of their overexpression in major human cancers. Internalizing GRPR agonists were initially proposed for prolonged lesion retention, but a shift of paradigm to GRPR antagonists has recently been made. Surprisingly, radioantagonists, such as [{sup 99m}Tc]DB1 ({sup 99m}Tc-N{sub 4}'-DPhe{sup 6},Leu-NHEt{sup 13}BBN(6-13)), displayed better pharmacokinetics than radioagonists, in addition to their higher inherent biosafety. We introduce here [{sup 68}Ga]SB3, a [{sup 99m}Tc]DB1 mimic-carrying, instead of the {sup 99m}Tc-binding tetraamine, the chelator DOTA for labeling with the PET radiometal {sup 68}Ga. Competition binding assays of SB3 and [{sup nat}Ga]SB3 were conducted against [{sup 125}I-Tyr{sup 4}]BBN in PC-3 cell membranes. Blood samples collected 5 min postinjection (pi) of the [{sup 67}Ga]SB3 surrogate in mice were analyzed using high-performance liquid chromatography (HPLC) for degradation products. Likewise, biodistribution was performed after injection of [{sup 67}Ga]SB3 (37 kBq, 100 μL, 10 pmol peptide) in severe combined immunodeficiency (SCID) mice bearing PC-3 xenografts. Eventually, [{sup 68}Ga]SB3 (283 ± 91 MBq, 23 ± 7 nmol) was injected into 17 patients with breast (8) and prostate (9) cancer. All patients had disseminated disease and had received previous therapies. PET/CT fusion images were acquired 60-115 min pi. SB3 and [{sup nat}Ga]SB3 bound to the human GRPR with high affinity (IC{sub 50}: 4.6 ± 0.5 nM and 1.5 ± 0.3 nM, respectively). [{sup 67}Ga]SB3 displayed good in vivo stability (>85 % intact at 5 min pi). [{sup 67}Ga]SB3 showed high, GRPR-specific and prolonged retention in PC-3 xenografts (33.1 ± 3.9%ID/g at 1 h pi - 27.0 ± 0.9%ID/g at 24 h pi), but much faster clearance from the GRPR-rich pancreas (∼160%ID/g at 1 h pi to <17%ID/g at 24 h pi) in mice. In patients, [{sup 68}Ga]SB3 elicited no adverse effects and

  20. Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Tao; Tsui, Benjamin M. W.; Li, Xin; Vranesic, Melin; Lodge, Martin A.; Gulaldi, Nedim C. M.; Szabo, Zsolt, E-mail: zszabo@jhmi.edu [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287 (United States)

    2015-11-15

    Purpose: The radioligand {sup 11}C-KR31173 has been introduced for positron emission tomography (PET) imaging of the angiotensin II subtype 1 receptor in the kidney in vivo. To study the biokinetics of {sup 11}C-KR31173 with a compartmental model, the input function is needed. Collection and analysis of arterial blood samples are the established approach to obtain the input function but they are not feasible in patients with renal diseases. The goal of this study was to develop a quantitative technique that can provide an accurate image-derived input function (ID-IF) to replace the conventional invasive arterial sampling and test the method in pigs with the goal of translation into human studies. Methods: The experimental animals were injected with [{sup 11}C]KR31173 and scanned up to 90 min with dynamic PET. Arterial blood samples were collected for the artery derived input function (AD-IF) and used as a gold standard for ID-IF. Before PET, magnetic resonance angiography of the kidneys was obtained to provide the anatomical information required for derivation of the recovery coefficients in the abdominal aorta, a requirement for partial volume correction of the ID-IF. Different image reconstruction methods, filtered back projection (FBP) and ordered subset expectation maximization (OS-EM), were investigated for the best trade-off between bias and variance of the ID-IF. The effects of kidney uptakes on the quantitative accuracy of ID-IF were also studied. Biological variables such as red blood cell binding and radioligand metabolism were also taken into consideration. A single blood sample was used for calibration in the later phase of the input function. Results: In the first 2 min after injection, the OS-EM based ID-IF was found to be biased, and the bias was found to be induced by the kidney uptake. No such bias was found with the FBP based image reconstruction method. However, the OS-EM based image reconstruction was found to reduce variance in the subsequent

  1. [{sup 18}F]FE rate at SUPPY: a suitable PET tracer for the adenosine A3 receptor? An in vivo study in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Haeusler, Daniela; Zeilinger, Markus; Wadsak, Wolfgang; Hacker, Marcus; Mitterhauser, Markus [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Kuntner, Claudia; Wanek, Thomas; Langer, Oliver [AIT Austrian Institute of Technology GmbH, Biomedical Systems, Health and Environment Department, Seibersdorf (Austria); Nics, Lukas [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); University of Vienna, Department of Nutritional Sciences, Vienna (Austria); Savli, Markus; Lanzenberger, Rupert R. [Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna (Austria); Karagiannis, Panagiotis [King' s College London, Cutaneous Medicine and Immunotherapy, St. John' s Institute of Dermatology, Division of Genetics and Molecular Medicine King' s College London School of Medicine, Guy' s Hospital, London (United Kingdom); Shanab, Karem; Spreitzer, Helmut [University of Vienna, Department of Drug and Natural Product Synthesis, Vienna (Austria)

    2015-04-01

    The adenosine A{sub 3} receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [{sup 18}F]FE rate at SUPPY. Rats were injected with [{sup 18}F]FE rate at SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE rate at SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [{sup 18}F]FE rate at SUPPY and [{sup 18}F]FDG. Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice). In vitro stability of [{sup 18}F]FE rate at SUPPY in human and rat plasma was also evaluated. [{sup 18}F]FE rate at SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [{sup 18}F]FE rate at SUPPY uptake (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [{sup 18}F]FE rate at SUPPY uptake (p = 0.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [{sup 18}F]FE rate at SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [{sup 18}F]FDG uptake (p = 0.12), the xenograft model showed significantly increased uptake of [{sup 18}F]FE rate at SUPPY in the tissue masses from CHO cells expressing the human A3R (p = 0.03). [{sup 18}F

  2. (64)Cu- and (68)Ga-Based PET Imaging of Folate Receptor-Positive Tumors: Development and Evaluation of an Albumin-Binding NODAGA-Folate.

    Science.gov (United States)

    Farkas, Renáta; Siwowska, Klaudia; Ametamey, Simon M; Schibli, Roger; van der Meulen, Nicholas P; Müller, Cristina

    2016-06-06

    A number of folate-based radioconjugates have been synthesized and evaluated for nuclear imaging purposes of folate receptor (FR)-positive tumors and potential therapeutic application. A common shortcoming of radiofolates is, however, a significant accumulation of radioactivity in the kidneys. This situation has been faced by modifying the folate conjugate with an albumin-binding entity to increase the circulation time of the radiofolate, which led to significantly improved tumor-to-kidney ratios. The aim of this study was to develop an albumin-binding folate conjugate with a NODAGA-chelator (rf42) for labeling with (64)Cu and (68)Ga, allowing application for PET imaging. The folate conjugate rf42 was synthesized in 8 steps, with an overall yield of 5%. Radiolabeling with (64)Cu and (68)Ga was carried out at room temperature within 10 min resulting in (64)Cu-rf42 and (68)Ga-rf42 with >95% radiochemical purity. (64)Cu-rf42 and (68)Ga-rf42 were stable (>95% intact) in phosphate-buffered saline over more than 4 half-lives of the corresponding radionuclide. In vitro, the plasma protein-bound fraction of (64)Cu-rf42 and (68)Ga-rf42 was determined to be >96%. Cell experiments proved FR-specific uptake of both radiofolates, as it was reduced to 68)Ga-rf42 was found in KB tumors of mice (14.52 ± 0.99% IA/g and 11.92 ± 1.68% IA/g, respectively) at 4 h after injection. The tumor-to-kidney ratios were in the range of 0.43-0.55 over the first 4 h of investigation. At later time points (up to 72 h p.i. of (64)Cu-rf42) the tumor-to-kidney ratio increased to 0.73. High-quality PET/CT images were obtained 2 h after injection of (64)Cu-rf42 and (68)Ga-rf42, respectively, allowing distinct visualization of tumors and kidneys. Comparison of PET/CT images obtained with (64)Cu-rf42 and a (64)Cu-labeled DOTA-folate conjugate (cm10) clearly proved the superiority of NODAGA for stable coordination of (64)Cu. (64)Cu-cm10 showed high liver uptake, most probably as a consequence of

  3. Modification of dopamine D2 receptor activity by pergolide in Parkinson's disease : An in vivo study by PET

    NARCIS (Netherlands)

    Linazasoro, G; Obeso, JA; Gomez, JC; Martinez, M; Antonini, A; Leenders, KL

    1999-01-01

    It is well known that chronic administration of pergolide and other dopamine agonists may induce a downregulation of dopamine D2 receptors in the rat model of Parkinson's disease (PD). To our knowledge, this effect has not been demonstrated in vivo in patients with PD. At present, the status of

  4. Kinetic modeling of (11)C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans.

    Science.gov (United States)

    Naganawa, Mika; Zheng, Ming-Qiang; Nabulsi, Nabeel; Tomasi, Giampaolo; Henry, Shannan; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E; Huang, Yiyun

    2014-11-01

    (11)C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of (11)C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the best models to provide reliable measures of binding parameters. The rank order of (11)C-LY2795050 distribution volume (VT) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for (11)C-LY2795050. Three methods for calculation of the nondisplaceable distribution volume (VND) were assessed: (1) individual VND estimated from naltrexone occupancy plots, (2) mean VND across subjects, and (3) a fixed fraction of cerebellum VT. Approach (3) produced the lowest intersubject variability in the calculation of binding potentials (BPND, BPF, and BPP). Therefore, binding potentials of (11)C-LY2795050 can be determined if the specific binding fraction in the cerebellum is presumed to be unchanged by diseases and experimental conditions. In conclusion, results from the present study show the suitability of (11)C-LY2795050 to image and quantify KOR in humans.

  5. Kinetic modeling of 11C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans

    Science.gov (United States)

    Naganawa, Mika; Zheng, Ming-Qiang; Nabulsi, Nabeel; Tomasi, Giampaolo; Henry, Shannan; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E; Huang, Yiyun

    2014-01-01

    11C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of 11C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the best models to provide reliable measures of binding parameters. The rank order of 11C-LY2795050 distribution volume (VT) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for 11C-LY2795050. Three methods for calculation of the nondisplaceable distribution volume (VND) were assessed: (1) individual VND estimated from naltrexone occupancy plots, (2) mean VND across subjects, and (3) a fixed fraction of cerebellum VT. Approach (3) produced the lowest intersubject variability in the calculation of binding potentials (BPND, BPF, and BPP). Therefore, binding potentials of 11C-LY2795050 can be determined if the specific binding fraction in the cerebellum is presumed to be unchanged by diseases and experimental conditions. In conclusion, results from the present study show the suitability of 11C-LY2795050 to image and quantify KOR in humans. PMID:25182664

  6. Automated preparation of the dopamine D{sub 2/3} receptor agonist ligand [{sup 11}C]-(+)-PHNO for human PET imaging studies

    Energy Technology Data Exchange (ETDEWEB)

    Plisson, Christophe, E-mail: Christophe.2.plisson@gsk.com [GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London W12 0NN (United Kingdom); Huiban, Mickael; Pampols-Maso, Sabina; Singleton, Goerkem; Hill, Samuel P.; Passchier, Jan [GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London W12 0NN (United Kingdom)

    2012-02-15

    Carbon-11 labelled (+)-4-Propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([{sup 11}C]-(+)-PHNO) is used as a high-affinity state, dopamine D{sub 2/3} receptor ligand in clinical PET studies. To facilitate its use, robust, rapid, efficient and GMP compliant methods are required for the manufacturing and QC testing processes. Additionally, to allow for full quantification of the resulting signal in the CNS, a reliable method is required to establish the parent plasma concentration over the course of the scan. This paper provides high-quality methods to support clinical application of [{sup 11}C]-(+)-PHNO. - Highlights: Black-Right-Pointing-Pointer Fully automated synthesis of [{sup 11}C]-(+)-PHNO. Black-Right-Pointing-Pointer Rapid multi-step synthesis and QC analysis. Black-Right-Pointing-Pointer Reproducible synthesis process typically yielding more than 3 GBq of [{sup 11}C]-(+)-PHNO. Black-Right-Pointing-Pointer Very low failure rate.

  7. Cross sectional PET study of cerebral adenosine A{sub 1} receptors in premanifest and manifest Huntington's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matusch, Andreas; Elmenhorst, David [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Saft, Carsten; Kraus, Peter H.; Gold, Ralf [St. Josef Hospital, Ruhr University Bochum, Department of Neurology, Huntington Centre NRW, Bochum (Germany); Hartung, Hans-Peter [Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany); Bauer, Andreas [Institute of Neuroscience and Medicine (INM-2), Juelich (Germany); Heinrich Heine University Duesseldorf, Department of Neurology, Medical Faculty, Duesseldorf (Germany)

    2014-06-15

    To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). We quantified the cerebral binding potential (BP{sub ND}) of the A{sub 1}AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [{sup 18} F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36). Cerebral A{sub 1}AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p <.01, in the thalamus on average). Across stages a successive reduction of A{sub 1}AR BP{sub ND} was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p <.01, in the caudatus and amygdala. There was a strong correlation between A{sub 1}AR BP{sub ND} and years to onset. Before onset of HD, the assumed annual rates of change of A{sub 1}AR density were -1.2 % in the caudatus, -1.7 % in the thalamus and -3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively. Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism. (orig.)

  8. Pet Allergy Quiz

    Science.gov (United States)

    ... Treatments ▸ Allergies ▸ Pet Allergy ▸ Pet Allergy Quiz Share | Pet Allergy Quiz More than half of U.S. households ... cat family. Yet, millions of people suffer from pet allergies. Take this quiz to test your knowledge ...

  9. Utility of (18)F-fluoroestradiol ((18)F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.

    Science.gov (United States)

    Lin, Frank I; Gonzalez, E M; Kummar, S; Do, K; Shih, J; Adler, S; Kurdziel, K A; Ton, A; Turkbey, B; Jacobs, P M; Bhattacharyya, S; Chen, A P; Collins, J M; Doroshow, J H; Choyke, P L; Lindenberg, M L

    2017-03-01

    Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. (18)F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes (18)F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with (18)F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with (18)F-FES 1-5 days post administration of Z-endoxifen. Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

  10. Utility of {sup 18}F-fluoroestradiol ({sup 18}F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Frank I. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Gonzalez, E.M.; Kurdziel, K.A.; Ton, A.; Turkbey, B.; Choyke, P.L.; Lindenberg, M.L. [National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Kummar, S.; Do, K.; Collins, J.M.; Doroshow, J.H. [National Cancer Institute, Division of Cancer Treatment and Diagnosis and Center for Cancer Research, Bethesda, MD (United States); Shih, J. [National Cancer Institute, NIH, Biometric Research Program, Bethesda, MD (United States); Adler, S. [Leidos Biomedical Research, Inc., Clinical Research Directorate/Clinical Monitoring Research Program, Frederick, MD (United States); Jacobs, P.M. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); Bhattacharyya, S. [Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States); Chen, A.P. [National Cancer Institute, Early Clinical Trials Development Program, DCTD, Bethesda, MD (United States)

    2017-03-15

    Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. {sup 18}F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes {sup 18}F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with {sup 18}F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with {sup 18}F-FES 1-5 days post administration of Z-endoxifen. Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy. (orig.)

  11. Positron Emission Tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1990-01-01

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET. 22 figs.

  12. Positron Emission Tomography (PET)

    Science.gov (United States)

    Welch, M. J.

    1990-01-01

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET.

  13. Synthesis of a [2-pyridinyl-18F]-labelled fluoro derivative of (-)-cytisine as a candidate radioligand for brain nicotinic alpha4beta2 receptor imaging with PET.

    Science.gov (United States)

    Roger, Gaëlle; Lagnel, Béatrice; Rouden, Jacques; Besret, Laurent; Valette, Héric; Demphel, Stéphane; Gopisetti, JaganMohan; Coulon, Christine; Ottaviani, Michele; Wrenn, Lori A; Letchworth, Sharon R; Bohme, Georg A; Benavides, Jesus; Lasne, Marie-Claire; Bottlaender, Michel; Dollé, Frédéric

    2003-12-01

    In recent years, there has been considerable effort to design and synthesize radiotracers suitable for use in Positron Emission Tomography (PET) imaging of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) subtype. A new fluoropyridinyl derivative of (-)-cytisine (1), namely (-)-9-(2-fluoropyridinyl)cytisine (3, K(i) values of 24 and 3462 nM for the alpha4beta2 and alpha7 nAChRs subtypes, respectively) has been synthesized in four chemical steps from (-)-cytisine and labelled with fluorine-18 (T(1/2): 119.8 min) using an efficient two-step radiochemical process [(a). nucleophilic heteroaromatic ortho-radiofluorination using the corresponding N-Boc-protected nitro-derivative, (b). TFA removal of the Boc protective group]. Typically, 20-45 mCi (0.74-1.67 GBq) of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3, 2-3 Ci/micromol or 74-111 GBq/micromol) were easily obtained in 70-75 min starting from a 100 mCi (3.7 GBq) aliquot of a cyclotron-produced [18F]fluoride production batch (20-45% non decay-corrected yield based on the starting [18F]fluoride). The in vivo pharmacological profile of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) was evaluated in rats with biodistribution studies and brain radioactivity monitoring using intracerebral radiosensitive beta-microprobes. The observed in vivo distribution of the radiotracer in brain was rather uniform, and did not match with the known regional densities of nAChRs. It was also significantly different from that of the parent compound (-)-[3H]cytisine. Moreover, competition studies with (-)-nicotine (5 mg/kg, 5 min before the radiotracer injection) did not reduce brain uptake of the radiotracer. These experiments clearly indicate that (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) does not have the required properties for imaging nAChRs using PET.

  14. Evaluation of [methyl-{sup 3}H]L655,708 and [ethyl-{sup 3}H]RY80 as putative PET ligands for central GABA{sub A} receptors containing {alpha}5 subunit

    Energy Technology Data Exchange (ETDEWEB)

    Opacka-Juffry, J. E-mail: jolanta@cu.rpms.ac.uk; Hirani, E.; Dawson, G.R.; Luthra, S.K.; Hume, S.P

    1999-10-01

    Two selective radioligands of gamma aminobutyric acid (GABA){sub A} receptors containing the {alpha}5 subunit, [{sup 3}H]L655,708 and [{sup 3}H]RY80, were evaluated in rats as potential in vivo tracers for positron emission tomography (PET). Brain uptake index (BUI), a measure of first pass extraction, was moderate for [{sup 3}H]L655,708 (BUI of 59%) and good for [{sup 3}H]RY80 (BUI of 96%). This finding was consistent with their in vitro binding to plasma proteins of {approx}76% and 50%, respectively. Following intravenous injection of either radioligand, radioactivity in plasma was measured and uptake characteristics were assessed in brain within a time period relevant to PET scanning (up to 90 min). Discrete brain regions, such as frontal cortex, striatum, hypothalamus, thalamus, hippocampus, colliculi, medulla, and cerebellum, were sampled and the temporal distribution of radioactivity analysed. Despite the reasonable delivery to the brain, neither of the radioligands had sufficient retention in the tissues rich in {alpha}5-containing GABA{sub A} receptors to achieve a good selective signal. For both radioligands, a maximal tissue:cerebellum ratio of 1.5 was seen in hippocampus at 10 min after injection. Thus, neither of the compounds studied shows potential for further development as an in vivo PET ligand.

  15. Facile labelling of an anti-epidermal growth factor receptor nanobody with {sup 68}Ga via a novel bifunctional desferal chelate for immuno-PET

    Energy Technology Data Exchange (ETDEWEB)

    Vosjan, Maria J.W.D.; Perk, Lars R.; Stigter van Walsum, Marijke [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); Roovers, Rob C.; Bergen en Henegouwen, Paul M.P. van [Utrecht University, Cellular Dynamics, Science Faculty, Utrecht (Netherlands); Visser, Gerard W.M. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Dongen, Guus A.M.S. van [VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands)

    2011-04-15

    The {proportional_to}15 kDa variable domains of camelid heavy-chain-only antibodies (called Nanobodies {sup registered}) have the flexibility to be formatted as monovalent, monospecific, multivalent or multispecific single chain proteins with either fast or slow pharmacokinetics. We report the evaluation of the fast kinetic anti-epidermal growth factor receptor (EGFR) Nanobody 7D12, labelled with {sup 68}Ga via the novel bifunctional chelate (BFC) p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS). Df-Bz-NCS has recently been introduced as the chelate of choice for {sup 89}Zr immuno-positron emission tomography (PET). Nanobody 7D12 was premodified with Df-Bz-NCS at pH 9. Radiolabelling with purified {sup 68}Ga was performed at pH 5.0-6.5 for 5 min at room temperature. For in vitro stability measurements in storage buffer (0.25 M NaOAc with 5 mg ml{sup -1} gentisic acid, pH 5.5) at 4 C or in human serum at 37 C, a mixture of {sup 67}Ga and {sup 68}Ga was used. Biodistribution and immuno-PET studies of {sup 68}Ga-Df-Bz-NCS-7D12 were performed in nude mice bearing A431 xenografts using {sup 89}Zr-Df-Bz-NCS-7D12 as the reference conjugate. The Df-Bz-NCS chelate was conjugated to Nanobody 7D12 with a chelate to Nanobody molar substitution ratio of 0.2:1. The overall {sup 68}Ga radiochemical yield was 55-70% (not corrected for decay); specific activity was 100-500 MBq/mg. Radiochemical purity of the conjugate was >96%, while the integrity and immunoreactivity were preserved. {sup 68/67}Ga-Df-Bz-NCS-7D12 was stable in storage buffer as well as in human serum during a 5-h incubation period (<2% radioactivity loss). In biodistribution studies the {sup 68}Ga-labelled Nanobody 7D12 showed high uptake in A431 tumours (ranging from 6.1 {+-} 1.3 to 7.2 {+-} 1.5%ID/g at 1-3 h after injection) and high tumour to blood ratios, which increased from 8.2 to 14.4 and 25.7 at 1, 2 and 3 h after injection, respectively. High uptake was also observed in the kidneys. Biodistribution was

  16. 5HT{sub 2} receptors in cerebral cortex of migraineurs studied using PET and {sup 18}F-fluorosetoperoene

    Energy Technology Data Exchange (ETDEWEB)

    Chabriat, H.; Tehindrazanarivelo, A.; Vera, P.; Samson, Y.; Pappata, S.; Boullais, N.; Bousser, M.G. [Hospital Saint Antoine, Paris (France)

    1995-04-01

    Since the brain 5HT{sub 2} might be implicated in migraine pathogenesis, the authors have used positron emission tomography and {sup 18}F-fluorosetoperone, a 5HT{sub 2} specific radioligand, to investigate in vivo the cortical 5HT{sub 2} receptors in migraine subjects. Nine migraineurs who had either migraine with and without aura or only migraine without aura were studied between attacks. 12 unmedicated healthy subjects of similar mean age were used as controls. Brain radioactivity was measured after {sup 18}F-setoperone IV injection for 90 min. A decrease of the regional specific distribution volumes (SDV) of the ligand was observed both in migraineurs and in controls. The age adjusted group means of SDV did not differ between patients and controls for the whole and for the right or left frontal, temporal, parietal and occipital cortex. These results suggest that cortical 5HT{sub 2} receptors may be unaltered between attacks in migraine sufferers. 30 refs., 4 figs., 2 tabs.

  17. Simplified PET measurement for evaluating histamine H{sub 1} receptors in human brains using [{sup 11}C]doxepin

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Hideki [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Kimura, Yuichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)]. E-mail: ukimura@ieee.org; Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Sasaki, Toru [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Tashiro, Manabu [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Yanai, Kazuhiko [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)

    2004-11-01

    The aim of this study was to develop simplified positron emission tomography measurement using [{sup 11}C]doxepin ([{sup 11}C]DOX) to evaluate histamine H{sub 1} receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [{sup 11}C]DOX, estimated quantitatively with a two-compartment model, and the [{sup 11}C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [{sup 11}C]DOX-H1R binding.

  18. Imaging of I{sub 2}-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-{sup 11}C]tolyl)-4,5-dihydro-1H-imidazole ([{sup 11}C]FTIMD)

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori, E-mail: kawamur@nirs.go.j [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Naganawa, Mika [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Konno, Fujiko; Yui, Joji [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Wakizaka, Hidekatsu [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Yamasaki, Tomoteru; Yanamoto, Kazuhiko; Hatori, Akiko [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Takei, Makoto [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Tokyo Nuclear Services Co., Ltd., Tokyo 110-0016 (Japan); Yoshida, Yuichiro [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); SHI Accelerator Service Ltd., Tokyo 141-0032 (Japan); Sakaguchi, Kazuya [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Fukumura, Toshimitsu [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Kimura, Yuichi [Department of Biophysics, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Zhang, Ming-Rong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2010-07-15

    Introduction: Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I{sub 1}R and I{sub 2}R). I{sub 2}Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I{sub 2}Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I{sub 2}Rs by PET. We labeled a selective I{sub 2}R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole (FTIMD) with {sup 11}C and performed the first imaging of I{sub 2}Rs by PET using 2-(3-fluoro-[4-{sup 11}C]tolyl)-4,5-dihydro-1H-imidazole ([{sup 11}C]FTIMD). Methods: [{sup 11}C]FTIMD was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [{sup 11}C]methyl iodide in the presence of tris(dibenzylideneacetone)dipalladium(0) and tri(o-tol)phosphine. Biodistribution was investigated in rats by tissue dissection. [{sup 11}C]FTIMD metabolites were measured in brain tissues and plasma. Dynamic PET scans were acquired in rats, and the kinetic parameters estimated. Results: [{sup 11}C]FTIMD was successfully synthesized with a suitable radioactivity for the injection. Co-injection with 0.1 mg/kg of cold FTIMD and BU224 induced a significant reduction in the brain-to-blood ratio 15 and 30 min after the injection. In metabolite analysis, unchanged [{sup 11}C]FTIMD in the brain was high (98%) 30 min after the injection. In PET studies, high radioactivity levels were observed in regions with a high density of I{sub 2}R. The radioactivity levels and V{sub T} values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control. Conclusion: [{sup 11}C]FTIMD showed specific binding to I{sub 2}Rs in rat brains with a high density of I{sub 2}R.

  19. Effect of tracer metabolism on PET measurement of [[sup 11]C]pyrilamine binding to histamine H[sub 1] receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Eun (Sungkyunkwan Univ., Seoul (Korea, Republic of). School of Medicine); Szabo, Z.; Seki, Chie; Ravert, H.T.; Scheffel, U.; Dannals, R.F.; Wagner, H.N. Jr.

    1999-04-01

    The present study was carried out to investigate the time course of [[sup 11]C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [[sup 11]C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [[sup 11]C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [[sup 11]C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [[sup 11]C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [[sup 11]C]pyrilamine. Based on the rat data, the contribution of [sup 11]C-labeled metabolites to total [[sup 11]C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [[sup 11]C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [[sup 11]C]pyrilamine by brain tissue itself. Therefore, [[sup 11]C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [[sup 11]C]pyrilamine binding to histamine H[sub 1] receptors. (author)

  20. Effect of tracer metabolism on PET measurement of [{sup 11}C]pyrilamine binding to histamine H{sub 1} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Eun [Sungkyunkwan Univ., Seoul (Korea, Republic of). School of Medicine; Szabo, Z.; Seki, Chie; Ravert, H.T.; Scheffel, U.; Dannals, R.F.; Wagner, H.N. Jr.

    1999-04-01

    The present study was carried out to investigate the time course of [{sup 11}C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [{sup 11}C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [{sup 11}C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [{sup 11}C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [{sup 11}C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [{sup 11}C]pyrilamine. Based on the rat data, the contribution of {sup 11}C-labeled metabolites to total [{sup 11}C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [{sup 11}C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [{sup 11}C]pyrilamine by brain tissue itself. Therefore, [{sup 11}C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [{sup 11}C]pyrilamine binding to histamine H{sub 1} receptors. (author)

  1. PARAMETRIC IMAGING AND TEST-RETEST VARIABILITY OF 11C-(+)-PHNO BINDING TO D2/D3 DOPAMINE RECEPTORS IN HUMANS ON THE HRRT PET SCANNER

    Science.gov (United States)

    Gallezot, Jean-Dominique; Zheng, Ming-Qiang; Lim, Keunpoong; Lin, Shu-fei; Labaree, David; Matuskey, David; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E.; Malison, Robert T.

    2014-01-01

    11C-(+)-PHNO is an agonist radioligand for imaging dopamine D2 and D3 receptors in the human brain with PET. In this study we evaluated the reproducibility of 11C-(+)-PHNO binding parameters using a within-day design and assessed parametric imaging methods. Methods Repeated studies were performed in eight subjects, with simultaneous measurement of the arterial input function and plasma free fraction. Two 11C-(+)-PHNO scans on the same subject were separated by 5.4±0.7 h. After evaluating compartment models, 11C-(+)-PHNO volumes of distribution VT and VT/fP and binding potentials BPND, BPP and BPF were quantified using the multilinear analysis MA1, with the cerebellum as reference region. Parametric images of BPND were also computed using SRTM and SRTM2. Results The test-retest variability of 11C-(+)-PHNO BPND was 9% in D2-rich regions (caudate and putamen). Among D3-rich regions, variability was low in pallidum (6%), but higher in substantia nigra (19%), thalamus (14%) and hypothalamus (21%). No significant mass carry-over effect was observed in D3-rich regions, although a trend in BPND was present in substantia nigra (−14±15%). Due to the relatively fast kinetics, low noise BPND parametric images were obtained with both SRTM and SRTM2 without spatial smoothing. Conclusion 11C-(+)-PHNO can be used to compute low noise parametric images in both D2 and D3 rich regions in humans. PMID:24732151

  2. Radiosynthesis of (S)-[(18)F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Sarasamkan, Jiradanai; Fischer, Steffen; Deuther-Conrad, Winnie; Ludwig, Friedrich-Alexander; Scheunemann, Matthias; Arunrungvichian, Kuntarat; Vajragupta, Opa; Brust, Peter

    2017-03-18

    Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a [(18)F]-labelled analog of the highly affine and selective α3β4 ligand (S)-3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)quinuclidine ((S)-T1). (S)-[(18)F]T1 was synthesized from ethynyl-4-[(18)F]fluorobenzene ([(18)F]5) and (S)-azidoquinuclidine by click reaction. After a synthesis time of 130min (S)-[(18)F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of (S)-[(18)F]T1 in mice at 30min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of (S)-[(18)F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001. These findings make (S)-[(18)F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET.

  3. In Vivo Stabilization of a Gastrin-Releasing Peptide Receptor Antagonist Enhances PET Imaging and Radionuclide Therapy of Prostate Cancer in Preclinical Studies.

    Science.gov (United States)

    Chatalic, Kristell L S; Konijnenberg, Mark; Nonnekens, Julie; de Blois, Erik; Hoeben, Sander; de Ridder, Corrina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; van Gent, Dik C; Nock, Berthold A; Maina, Theodosia; van Weerden, Wytske M; de Jong, Marion

    2016-01-01

    A single tool for early detection, accurate staging, and personalized treatment of prostate cancer (PCa) would be a major breakthrough in the field of PCa. Gastrin-releasing peptide receptor (GRPR) targeting peptides are promising probes for a theranostic approach for PCa overexpressing GRPR. However, the successful application of small peptides in a theranostic approach is often hampered by their fast in vivo degradation by proteolytic enzymes, such as neutral endopeptidase (NEP). Here we show for the first time that co-injection of a NEP inhibitor (phosphoramidon (PA)) can lead to an impressive enhancement of diagnostic sensitivity and therapeutic efficacy of the theranostic (68)Ga-/(177)Lu-JMV4168 GRPR-antagonist. Co-injection of PA (300 µg) led to stabilization of (177)Lu-JMV4168 in murine peripheral blood. In PC-3 tumor-bearing mice, PA co-injection led to a two-fold increase in tumor uptake of (68)Ga-/(177)Lu-JMV4168, 1 h after injection. In positron emission tomography (PET) imaging with (68)Ga-JMV4168, PA co-injection substantially enhanced PC-3 tumor signal intensity. Radionuclide therapy with (177)Lu-JMV4168 resulted in significant regression of PC-3 tumor size. Radionuclide therapy efficacy was confirmed by production of DNA double strand breaks, decreased cell proliferation and increased apoptosis. Increased survival rates were observed in mice treated with (177)Lu-JMV4168 plus PA as compared to those without PA. This data shows that co-injection of the enzyme inhibitor PA greatly enhances the theranostic potential of GRPR-radioantagonists for future application in PCa patients.

  4. Radiosynthesis and biological evaluation of a promising {sigma}{sub 2}-receptor ligand radiolabeled with fluorine-18 or iodine-125 as a PET/SPECT probe for imaging breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tu Zhude; Xu Jinbin; Jones, Lynne A.; Li Shihong; Zeng Dexing [Division of Radiological Sciences, Washington University School of Medicine, Campus Box 8225, 510 South Kingshighway Blvd., St. Louis, MO 63110 (United States); Kung Meiping; Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Mach, Robert H., E-mail: rhmach@mir.wustl.ed [Division of Radiological Sciences, Washington University School of Medicine, Campus Box 8225, 510 South Kingshighway Blvd., St. Louis, MO 63110 (United States)

    2010-12-15

    Sigma-2 receptors represent an endogenous marker for proliferation in solid tumors. The high affinity, high selectivity {sigma}{sub 2} receptor ligand N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl) -2-(2-fluoroethoxy)-5-iodo-3-methoxybenzamide (3) was separately radiolabeled with F-18 and I-125. The radiolabeling yield was 30% and 70% for [{sup 18}F]3 and [{sup 125}I]3, respectively. Studies of [{sup 125}I]3 using murine 66 breast tumor membrane homogenates and evaluation of [{sup 18}F]3 and [{sup 125}I]3 in 66 tumor-bearing mice indicate that this ligand has potential as a PET or a SPECT probe for imaging {sigma}{sub 2} receptors in breast cancer.

  5. [{sup 18}F]p-MPPF: A Radiolabeled Antagonist for the Study of 5-HT{sub 1A} Receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Plenevaux, A. E-mail: Alain.Plenevaux@ulg.ac.be; Lemaire, C.; Aerts, J.; Lacan, G.; Rubins, D.; Melega, W.P.; Brihaye, C.; Degueldre, C.; Fuchs, S.; Salmon, E.; Maquet, P.; Laureys, S.; Damhaut, P.; Weissmann, D.; Le Bars, D.; Pujol, J.-F.; Luxen, A

    2000-07-01

    This paper summarizes the present status of the researches conducted with [{sup 18}F]4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluoro benzamido]ethyl] -piperazine known as [{sup 18}F]p-MPPF, a new 5-HT{sub 1A} antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism.

  6. Senior Pets

    Science.gov (United States)

    ... by Animal/Species Browse by Topic Browse by Discipline Resources Tools for K-12 Educators You are here: Home | Public Resources | Pet ... to 6 years of age. Contrary to popular belief, dogs do not age at a rate of 7 human years for each year in dog years. Age ...

  7. Pet Therapy.

    Science.gov (United States)

    Kavanagh, Kim

    1994-01-01

    This resource guide presents information on a variety of ways that animals can be used as a therapeutic modality with people having disabilities. Aspects addressed include: pet ownership and selection criteria; dogs (including service dogs, hearing/signal dogs, seeing leader dogs, and social/specialty dogs); horseriding for both therapy and fun;…

  8. Radiosynthesis and initial evaluation of [{sup 18}F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Alan A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: alan.wilson@camhpet.ca; Garcia, Armando; Parkes, Jun [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); McCormick, Patrick [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Houle, Sylvain; Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8 (Canada)

    2008-04-15

    Introduction: A novel [{sup 18}F]-radiolabelled phenoxyanilide, [{sup 18}F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [{sup 18}F]-FEPPA and two other radiotracers for imaging PBR, namely [{sup 11}C]-PBR28 and [{sup 11}C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [{sup 18}F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [{sup 18}F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a K{sub i} of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [{sup 18}F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [{sup 18}F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [{sup 18}F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [{sup 18}F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models.

  9. The effects of d-amphetamine on extrastriatal dopamine D{sub 2}/D{sub 3} receptors: a randomized, double-blind, placebo-controlled PET study with [{sup 11}C]FLB 457 in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, Sargo [University of Turku, Turku PET Centre, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Hirvonen, Jussi; Kajander, Jaana; Naagren, Kjell; Rinne, Juha O. [University of Turku, Turku PET Centre, Turku (Finland); Kaasinen, Valtteri [University of Turku, Department of Neurology, P.O. Box 52, Turku (Finland); Hagelberg, Nora [University of Turku, Turku PET Centre, Turku (Finland); Turku University Central Hospital, Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku (Finland); Seppaelae, Timo [Drug Research Unit, National Public Health Institute, Helsinki (Finland); Scheinin, Harry [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Hietala, Jarmo [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Psychiatry, Turku (Finland)

    2009-03-15

    The dopamine D{sub 2}/D{sub 3} receptor ligand [{sup 11}C]FLB 457 and PET enable quantification of low-density extrastriatal D{sub 2}/D{sub 3} receptors, but it is uncertain whether [{sup 11}C]FLB 457 can be used for measuring extrastriatal dopamine release. We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [{sup 11}C]FLB 457 binding potential (BP{sub ND}) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. The effects of d-amphetamine on [{sup 11}C]FLB 457 BP{sub ND} and distribution volume (V{sub T}) in the frontal cortex were not different from those of placebo. Small decreases in [{sup 11}C]FLB 457 BP{sub ND} were observed only in the posterior cingulate and hippocampus. The regional changes in [{sup 11}C]FLB 457 BP{sub ND} did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria. This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D{sub 2}/D{sub 3} receptor binding. Our results indicate that [{sup 11}C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans. (orig.)

  10. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with {sup 18}F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Groheux, David [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France); Martineau, Antoine; Vercellino, Laetitia; Merlet, Pascal [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Teixeira, Luis; Espie, Marc [Saint-Louis Hospital, Breast Diseases Unit, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France)

    2017-07-15

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an {sup 18}F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV{sub max} and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV{sub max} and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV{sub max} and TLG were able to predict response to NAC, TFs failed. (orig.)

  11. Active cyamemazine metabolites in patients treated with cyamemazine (Tercian®): influence on cerebral dopamine D2 and serotonin 5-HT (2A) receptor occupancy as measured by positron emission tomography (PET).

    Science.gov (United States)

    Hodé, Yann; Benyamina, Amine; Arbus, Christophe; Reimold, Matthias

    2011-10-01

    Cyamemazine (Tercian®) is an antipsychotic agent blocking central dopamine D(2) receptors, which induces few extrapyramidal adverse effects, due to a potent antagonistic action at serotonin 5-HT(2A) receptors. In vitro studies showed that the desmethyl metabolite of cyamemazine (N-desmethyl cyamemazine) has similar affinity for 5-HT(2A) receptors as cyamemazine, whereas its D(2) receptor affinity is eight times lower (Benyamina et al. in Eur J Pharmacol 578(2-3):142-147, 2008). Moreover, cyamemazine sulfoxide showed modest affinity for 5-HT(2A) receptors. The objective of this study is to measure steady-state plasma levels of N-desmethyl cyamemazine and cyamemazine sulfoxide in patients treated with clinically relevant doses of cyamemazine and correlate them with dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) assessed by positron emission tomography (PET). Eight patients received Tercian® 37.5, 75, 150, or 300 mg/day according to their symptoms. Dopamine D(2) and serotonin 5-HT(2A) RO were assessed at steady-state cyamemazine plasma levels using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively, for PET. Plasma levels of cyamemazine metabolites were determined using a validated high-performance liquid chromatography (PerkinElmer) associated with a mass spectrometry detection (API 365, PE SCIEX). The apparent equilibrium inhibition constant (K (i)) was estimated by fitting RO with plasma levels of cyamemazine metabolites at the time of the PET scan. After 6 days of cyamemazine administration, plasma N-desmethyl cyamemazine reached steady-state levels at 2 to 12 times higher than those previously found for cyamemazine (Hode et al. in Psychopharmacology (Berl) 180:377-384, 2005). Plasma levels of N-desmethyl cyamemazine were closely related to striatal D(2) RO (r (2) = 0.942) and extrastriatal 5-HT(2A) RO (r (2) = 0.901). The estimated K (i(app)) value of N-desmethyl cyamemazine for striatal D(2) receptors was about fivefold

  12. Pet Disaster Preparedness

    Science.gov (United States)

    ... Safety Checklist – Arabic Pets and Disaster Safety Checklist – Chinese Pets and Disaster Safety Checklist – French Pets and ... Cross serves in the US, its territories and military installations around the world. Please try again. Your ...

  13. Your Pet's Medications

    Science.gov (United States)

    ... Care Animal Welfare Veterinary Careers Public Health Your Pet's Medications When your pet has a medical condition, ... authorized. What you can do to keep your pet safe When the medication is prescribed Let your ...

  14. The relationship between estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression of breast cancer and the retention index in dual phase {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Woo Chul; Kim, Hyun Ah; Kim, Eun Kyu [Dept.of Surgery, Korea Cancer Center HospitalKorea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of); and others

    2016-09-15

    This study investigates the correlation of retention index (RI) using the dual phase FDG PET/CT scan with the breast cancer biomarkers. A total of 55 patients with breast cancer underwent dual phase FDG PET/CT scans (60 and 120 min after FDG injection) before treatment. SUVmax and SUVmean of the primary breast tumors were measured, then the percent change of SUVmax and SUVmean between the two scans were calculated, and denoted as RImax and RImean, respectively. After the surgical resection of the breast tumor, the status of biomarkers (ER, PR, and HER-2) was evaluated in the postsurgical specimen. RImean was significantly higher in ER (−) (median, 16.2; IQR, 10.8–21.0) or HER-2 (+) (median, 16.1; IQR, 10.7–21.6) tumors than in ER (+) tumors (median, 9.9; IQR, 5.5–15.3) or HER-2 (−) tumors (median, 10.5; IQR, 5.5–16.1). However, there were no significant differences of SUVmax or RImax according to the ER or HER-2 status. There were no significant differences of any PET parameters between PR (+) and PR (−) tumors. Based off ROC curve analyses, RImean predicted the ER (+) tumors (AUC, 0.699; p = 0.006), and HER-2 (+) tumors (AUC, 0.674; p = 0.022), but not the PR (+) tumors. However, neither SUVmax nor RImax predicted ER (+), PR (+), or HER-2 (+) tumors. Retention index of SUVmean can reflect the ER and HER-2 status of breast cancers. Higher retention index of SUVmean might associate with lower ER expression and higher HER-2 expression.

  15. PET Molecular Probes Targeting Folate Receptor%靶向叶酸受体的正电子分子探针研究进展

    Institute of Scientific and Technical Information of China (English)

    尹吉林; 王成; 王欣璐

    2016-01-01

    叶酸能与多种肿瘤细胞膜表面的叶酸受体(FR)特异性结合,通过FR介导的内吞作用进入细胞,为放射性核素选择性载带提供良好的途径。基于受体和配体间的高度亲和性,可将多种放射性核素与叶酸分子及其衍生物偶联,制备核医学显像探针。本文主要对非金属正电子核素(18 F、124 I)和金属正电子核素(68 Ga、44 Sc、152 Tb)标记的叶酸及其衍生物PET显像探针与炎症PET显像探针进行综述,并展望其临床前景。%Folic acid can combine specifically with folate receptors (FRs) which are over‐expressed on the epithelial cells of the tumor .The FRs are confirmed to be the tumor‐associated antigens that bind folate and folate conjugates with very high affinity and shuttle these bound molecules inside cells via an endocytic mechanism .The FR‐αis a tar‐get of critical value for nuclear imaging through using folate‐based radiotracers as it is expressed on several tumor types .Moreover ,employment of folate radiopharmaceuti‐cals for imaging of inflammatory diseases by targeting at FR‐βon activated macrophages holds promise as a further field of application .Based on these ,more and more resear‐ches focus on folate conjugates labeled with radionuclides for nuclear medicine imaging (including single photon emission computed tomography (SPECT ) and positron emis‐sion tomography (PET ) .These folate molecular probes are applied not only in cancer imaging but also in inflammation imaging .Hence ,folate‐based imaging agents may be useful for selection of patients w ho could profit from such new therapy concepts and for monitoring response to a particular treatment .This review was focused on the prepara‐tion and preclinical biological evaluation of the molecular probes which were labeled by positron nuclides (18 F ,124I ,68Ga ,44Sc ,152 Tb) ,and the clinical application of these molecular probes were discussed .

  16. Quantitative projection of human brain penetration of the H3 antagonist PF-03654746 by integrating rat-derived brain partitioning and PET receptor occupancy.

    Science.gov (United States)

    Sawant-Basak, Aarti; Chen, Laigao; Shaffer, Christopher L; Palumbo, Donna; Schmidt, Anne; Tseng, Elaine; Spracklin, Douglas K; Gallezot, Jean-Dominique; Labaree, David; Nabulsi, Nabeel; Huang, Yiyun; Carson, Richard E; McCarthy, Timothy

    2017-02-01

    1. Unbound brain drug concentration (Cb,u), a valid surrogate of interstitial fluid drug concentration (CISF), cannot be directly determined in humans, which limits accurately defining the human Cb,u:Cp,u of investigational molecules. 2. For the H3R antagonist (1R,3R)-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-lmethyl)phenyl]cyclobutane-1-carboxamide (PF-03654746), we interrogated Cb,u:Cp,u in humans and nonhuman primate (NHP). 3. In rat, PF-03654746 achieved net blood-brain barrier (BBB) equilibrium (Cb,u:Cp,u of 2.11). 4. In NHP and humans, the PET receptor occupancy-based Cp,u IC50 of PF-03654746 was 0.99 nM and 0.31 nM, respectively, which were 2.1- and 7.4-fold lower than its in vitro human H3 Ki (2.3 nM). 5. In an attempt to understand this higher-than-expected potency in humans and NHP, rat-derived Cb,u:Cp,u of PF-03654746 was integrated with Cp,u IC50 to identify unbound (neuro) potency of PF-03654746, nIC50. 6. The nIC50 of PF-03654746 was 2.1 nM in NHP and 0.66 nM in human which better correlated (1.1- and 3.49-fold lower) with in vitro human H3 Ki (2.3 nM). 7. This correlation of the nIC50 and in vitro hH3 Ki suggested the translation of net BBB equilibrium of PF-03654746 from rat to NHP and humans, and confirmed the use of Cp,u as a reliable surrogate of Cb,u. 8. Thus, nIC50 quantitatively informed the human Cb,u:Cp,u of PF-03654746.

  17. American Pet Culture

    Institute of Scientific and Technical Information of China (English)

    海焰

    2007-01-01

    In America you can find dogs,cats, horses,monkeys, snakes and even pigs in almost every family.They are their pets.Americans love pets and look on them as a part of the family.Sometimes pet owners dress their pets in fashionable clothes.They even buy toys for their pets.Americans love their pets as their children, sometimes even better.

  18. Development of central 5-HT{sub 2A} receptor radioligands for PET: Comparison of [{sup 3}H]RP 62203 and [{sup 3}H]SR 46349B kinetics in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ashworth, Sharon; Hume, Susan P.; Lammertsma, Adriaan A.; Opacka-Juffry, Jolanta; Shah, Farah; Pike, Victor W

    1996-04-01

    [{sup 3}H]RP 62203 and [{sup 3}H]SR 46349B binding were assessed in rat brain after intravenous (iv) injection. The distribution of specific binding of each radioligand corresponded to the known distribution of 5-HT{sub 2A} receptor sites. The maximum signals (counts/g tissue over counts/g cerebellum) given by [{sup 3}H]RP 62203 and [{sup 3}H]SR 46349B were 9.0 {+-} 0.9 at 60 min and 3.2 {+-} 0.3 at 30 min, respectively, in frontopolar cortex. Specific binding was quantified using a reference-tissue compartment model. RP 62203 appears to be more suitable than SR 46349B for development as a PET radioligand on the basis of its higher receptor specific signal.

  19. Reduction of dopamine D2/3 receptor binding in the striatum after a single administration of esketamine, but not R-ketamine: a PET study in conscious monkeys.

    Science.gov (United States)

    Hashimoto, Kenji; Kakiuchi, Takeharu; Ohba, Hiroyuki; Nishiyama, Shingo; Tsukada, Hideo

    2017-03-01

    R-ketamine appears to be a potent, long-lasting and safer antidepressant, relative to esketamine (S-ketamine), since it might be free of psychotomimetic side effects. Using [(11)C]raclopride and positron emission tomography (PET), we investigated whether esketamine and R-ketamine can affect dopamine D2/3 receptor binding in the conscious monkey brain. A single infusion of esketamine (0.5 mg/kg), but not R-ketamine (0.5 mg/kg), caused a reduction of binding availability of dopamine D2/3 receptor in the monkey striatum. This study suggests that unlike to R-ketamine, esketamine can cause dopamine release in the striatum, and that its release might be associated with psychotomimetic effects of esketamine.

  20. Imaging of urokinase-type plasminogen activator receptor expression using a 64Cu-labeled linear peptide antagonist by microPET

    DEFF Research Database (Denmark)

    Li, Z.B.; Niu, G.; Wang, H.;

    2008-01-01

    for positron emission tomography (PET) imaging. A linear, high-affinity uPAR-binding peptide antagonist AE105 was conjugated with 1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA) and labeled with (64)Cu for microPET imaging of mice bearing U87MG human glioblastoma (uPAR positive) and MDA-MB-435...... human breast cancer (uPAR negative). RESULTS: Surface plasmon resonance measurements show that AE105 with DOTA conjugated at the alpha-amino group (DOTA-AE105) has high affinity toward uPAR. microPET imaging reveals a rapid and high accumulation of (64)Cu-DOTA-AE105 in uPAR-positive U87MG tumors (10...... translation of this class of radiopharmaceuticals for uPAR-positive cancer detection and patient stratification for uPA/uPAR system-based cancer therapy Udgivelsesdato: 2008/8/1...

  1. Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging.

    Science.gov (United States)

    Syvänen, Stina; Eriksson, Jonas; Genchel, Tove; Lindhe, Orjan; Antoni, Gunnar; Långström, Bengt

    2007-07-30

    The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/mumol and 270 GBq/mumol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S)-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)-2-phenylpiperidin-3-amine (I) and (2S,3S)-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)piperidin-3-amine (II) was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II) had no specific binding in striatum. Ligand (I) had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I) displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. The propyl-analogue (II) cannot be used for detecting changes in NK1-ligand levels, while further studies should be performed with the ethyl-analogue (I).

  2. Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging

    Directory of Open Access Journals (Sweden)

    Genchel Tove

    2007-07-01

    Full Text Available Abstract Background The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. Methods [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethyl-2-phenylpiperidin-3-amine (I and (2S,3S-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethylpiperidin-3-amine (II was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. Results All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II had no specific binding in striatum. Ligand (I had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. Conclusion The propyl-analogue (II cannot be used for detecting changes in NK1-ligand levels, while further studies should be

  3. Pet Problems at Home: Pet Problems in the Community.

    Science.gov (United States)

    Soltow, Willow

    1984-01-01

    Discusses problems of pets in the community, examining the community's role related to disruptive pets and pet overpopulation. Also discusses pet problems at home, offering advice on selecting a pet, meeting a pet's needs, and disciplining pets. Includes a list of books, films/filmstrips, teaching materials, and various instructional strategies.…

  4. Pet Problems at Home: Pet Problems in the Community.

    Science.gov (United States)

    Soltow, Willow

    1984-01-01

    Discusses problems of pets in the community, examining the community's role related to disruptive pets and pet overpopulation. Also discusses pet problems at home, offering advice on selecting a pet, meeting a pet's needs, and disciplining pets. Includes a list of books, films/filmstrips, teaching materials, and various instructional strategies.…

  5. Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of chemotherapy : An in vitro study in glioma cells

    NARCIS (Netherlands)

    van Waarde, Aren; Been, Lukas B.; Ishiwata, Kiichi; Dierckx, Rudi A.; Elsinga, Philip H.

    2006-01-01

    The significant presence of nontumor cell populations within tumors can complicate the assessment of in vivo tumor metabolism during therapy. To more clearly define the impact of cytotoxic agents, we compared early changes in the uptake of 6 PET tracers in cultured glioma cells. Doxorubicin (1 mu mo

  6. Novel Approach to Repeated Arterial Blood Sampling in Small Animal PET : Application in a Test-Retest Study with the Adenosine A1 Receptor Ligand [C-11]MPDX

    NARCIS (Netherlands)

    Sijbesma, Jürgen W A; Zhou, Xiaoyun; Vállez García, David; Houwertjes, Martin C; Doorduin, Janine; Kwizera, Chantal; Maas, Bram; Meerlo, Peter; Dierckx, Rudi A; Slart, Riemer H J A; Elsinga, Philip H; van Waarde, Aren

    2016-01-01

    Small animal positron emission tomography (PET) can be used to detect small changes in neuroreceptor availability. This often requires rapid arterial blood sampling. However, current catheterization procedures do not allow repeated blood sampling. We have developed a procedure which allows arterial

  7. Microfluidics for Synthesis of Peptide-Based PET Tracers

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2013-01-01

    Full Text Available Positron emission tomography (PET is a powerful noninvasive tool for acquisition of the physiological parameters in human and animals with the help of PET tracers. Among all the PET tracers, radiolabeled peptides have been widely explored for cancer-related receptor imaging due to their high affinity and specificity to receptors. But radiochemistry procedures for production of peptide-based PET tracers are usually complex, which makes large-scale clinical studies relatively challenging. New radiolabeling technologies which could simplify synthesis and purification procedures, are extremely needed. Over the last decade, microfluidics and lab-on-a-chip (LOC technology have boomed as powerful tools in the field of organic chemistry, which potentially provide significant help to the PET chemistry. In this minireview, microfluidic radiolabeling technology is described and its application for synthesis of peptide-based PET tracers is summarized and discussed.

  8. Research Progress of PET Traces for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    TANG Cai-hua1,2;HU Kong-zhen1;TANG Gang-hua1

    2014-02-01

    Full Text Available Alzheimer’s disease (AD is unknown cause progressive degenerative diseases of central nervous system. It is a serious threat to the health of the elderly people. The diagnosis is mainly based on pathological examination after death. With the wide application of positron emission tomography (PET imaging in clinic, in vivo noninvasive imaging diagnosis of AD at the early stage become possible. PET imaging mainly depends on the positron-labeled imaging agents. The PET imaging agents can be used in the early diagnosis and differential diagnosis on AD include several kinds: PET traces for glucose metabolic, PET traces combined with amyloid proteinplaques,tau protein, neurotransmitter and receptor, activation of microglia and PET traces for cell apoptosis.The research progress of various PET tracers were reviewed that can be used in the early diagnosis and differential diagnosis on AD in recent years.

  9. Metabotropic Glutamate Receptor Type 5 (mGluR5) Cortical Abnormalities in Focal Cortical Dysplasia Identified In Vivo With [11C]ABP688 Positron-Emission Tomography (PET) Imaging

    Science.gov (United States)

    DuBois, Jonathan M.; Rousset, Olivier G.; Guiot, Marie-Christine; Hall, Jeffery A.; Reader, Andrew J.; Soucy, Jean-Paul; Rosa-Neto, Pedro; Kobayashi, Eliane

    2016-01-01

    Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses. PMID:27578494

  10. Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.

    Science.gov (United States)

    Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H

    2016-10-01

    To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation.

  11. A PET [18F]altanserin study of 5-HT2A receptor binding in the human brain and responses to painful heat stimulation

    DEFF Research Database (Denmark)

    Kupers, Ronny Clement Florent; Frokjaer, Vibe G; Naert, Arne

    2009-01-01

    -lasting phasic and long-lasting (7-minute) tonic painful stimulation. Significant positive correlations were found between tonic pain ratings and [(18)F]altanserin binding in orbitofrontal (r=0.66; p=0.005), medial inferior frontal (r=0.60; p=0.014), primary sensory-motor (r=0.61; p=0.012) and posterior......There is a large body of evidence that serotonin [5-hydroxytryptamine (5-HT)] plays an important role in the transmission and regulation of pain. Here we used positron emission tomography (PET) to study the relationship between baseline 5-HT(2A) binding in the brain and responses to noxious heat...... stimulation in a group of young healthy volunteers. Twenty-one healthy subjects underwent PET scanning with the 5-HT(2A) antagonist, [(18)F]altanserin. In addition, participants underwent a battery of pain tests using noxious heat stimulation to assess pain threshold, pain tolerance and response to short...

  12. Pre-operative ⁶⁸Ga-DOTANOC somatostatin receptor PET/CT imaging demonstrating multiple synchronous lesions in a patient with head and neck paraganglioma.

    Science.gov (United States)

    Naswa, N; Karunanithi, S; Sharma, P; Soundararajan, R; Bal, C; Kumar, R

    2014-01-01

    Paragangliomas, or glomus tumors, are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by over-production of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a preoperative ⁶⁸Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide (⁶⁸Ga-DOTANOC) positron emission tomography/computed tomography (PET/CT) imaging for staging. This is a unique case in which multiple paraganglioma and pheochromocytoma were demonstrated in a single patient using ⁶⁸Ga-DOTANOC PET/CT. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  13. Development of a new radioligand, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoroethyl-5-methoxybenzyl)acetamide, for pet imaging of peripheral benzodiazepine receptor in primate brain.

    Science.gov (United States)

    Zhang, Ming-Rong; Maeda, Jun; Ogawa, Masanao; Noguchi, Junko; Ito, Takehito; Yoshida, Yuichiro; Okauchi, Takashi; Obayashi, Shigeru; Suhara, Tetsuya; Suzuki, Kazutoshi

    2004-04-22

    To develop a positron emission tomography (PET) ligand for imaging the 'peripheral benzodiazepine receptor' (PBR) in brain and elucidating the relationship between PBR and brain diseases, four analogues (4-7) of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (2) were synthesized and evaluated as ligands for PBR. Of these compounds, fluoromethyl (4) and fluoroethyl (5) analogues had similar or higher affinities for PBR than the parent compound 2 (K(i) = 0.16 nM for PBR in rat brain sections). Iodomethyl analogue 6 displayed a moderate affinity, whereas tosyloxyethyl analogue 7 had weak affinity. Radiolabeling was performed for the fluoroalkyl analogues 4 and 5 using fluorine-18 ((18)F, beta(+); 96.7%, T(1/2) = 109.8 min). Ligands [(18)F]4 and [(18)F]5 were respectively synthesized by the alkylation of desmethyl precursor 3 with [(18)F]fluoromethyl iodide ([(18)F]8) and 2-[(18)F]fluoroethyl bromide ([(18)F]9). The distribution patterns of [(18)F]4 and [(18)F]5 in mice were consistent with the known distribution of PBR. However, compared with [(18)F]5, [(18)F]4 displayed a high uptake in the bone of mice. The PET image of [(18)F]4 for monkey brain also showed significant radioactivity in the bone, suggesting that this ligand was unstable for in vivo defluorination and was not a useful PET ligand. Ligand [(18)F]5 displayed a high uptake in monkey brain especially in the occipital cortex, a region with richer PBR than the other regions in the brain. The radioactivity level of [(18)F]5 in monkey brain was 1.5 times higher than that of [(11)C]2, and 6 times higher than that of (R)-(1-(2-chlorophenyl)-N-[(11)C]methyl,N-(1-methylpropyl)isoquinoline ([(11)C]1). Moreover, the in vivo binding of [(18)F]5 was significantly inhibited by PBR-selective 2 or 1, indicating that the binding of [(18)F]5 in the monkey brain was mainly due to PBR. Metabolite analysis revealed that [(18)F]4 was rapidly metabolized by defluorination to [(18)F]F(-) in the plasma and brain of

  14. Synthesis and in vivo Evaluation of Fluorine-18 and Iodine-123 Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives as PET and SPECT Radiotracers for Mapping A2A Receptors.

    Science.gov (United States)

    Vala, Christine; Morley, Thomas J; Zhang, Xuechun; Papin, Caroline; Tavares, Adriana Alexandre S; Lee, H Sharon; Constantinescu, Cristian; Barret, Olivier; Carroll, Vincent M; Baldwin, Ronald M; Tamagnan, Gilles D; Alagille, David

    2016-09-06

    Imaging agents that target adenosine type 2A (A2A ) receptors play an important role in evaluating new pharmaceuticals targeting these receptors, such as those currently being developed for the treatment of movement disorders like Parkinson's disease. They are also useful for monitoring progression and treatment efficacy by providing a noninvasive tool to map changes in A2A receptor density and function in neurodegenerative diseases. We previously described the successful evaluation of two A2A -specific radiotracers in both nonhuman primates and in subsequent human clinical trials: [(123) I]MNI-420 and [(18) F]MNI-444. Herein we describe the development of both of these radiotracers by selection from a series of A2A ligands, based on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine core of preladenant. Each of this series of 16 ligands was found to bind to recombinant human A2A receptor in the low nanomolar range, and of these 16, six were radiolabeled with either fluorine-18 or iodine-123 and evaluated in nonhuman primates. These initial in vivo results resulted in the identification of 7-(2-(4-(4-(2-[(18) F]fluoroethoxy)phenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine ([(18) F]MNI-444) and 7-(2-(4-(2-fluoro-4-[(123) I]iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-amine ([(123) I]MNI-420) as PET and SPECT radiopharmaceuticals for mapping A2A receptors in brain.

  15. Pets and the immunocompromised person

    Science.gov (United States)

    AIDS patients and pets; Bone marrow transplant patients and pets; Chemotherapy patients and pets ... systems may be advised to give up their pets to avoid getting diseases from the animals. People ...

  16. Trends in PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Moses, William W.

    2000-11-01

    Positron Emission Tomography (PET) imaging is a well established method for obtaining information on the status of certain organs within the human body or in animals. This paper presents an overview of recent trends PET instrumentation. Significant effort is being expended to develop new PET detector modules, especially those capable of measuring depth of interaction. This is aided by recent advances in scintillator and pixellated photodetector technology. The other significant area of effort is development of special purpose PET cameras (such as for imaging breast cancer or small animals) or cameras that have the ability to image in more than one modality (such as PET / SPECT or PET / X-Ray CT).

  17. Strategy for improved [{sup 11}C]DAA1106 radiosynthesis and in vivo peripheral benzodiazepine receptor imaging using microPET, evaluation of [{sup 11}C]DAA1106

    Energy Technology Data Exchange (ETDEWEB)

    Probst, Katrin C. [Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom)]|[BHF Carotid Imaging Group, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom)]. E-mail: kp296@wbic.cam.ac.uk; Izquierdo, David [Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom)]|[BHF Carotid Imaging Group, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom); Bird, Joseph L.E. [BHF Carotid Imaging Group, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom)]|[Department of Medicine, Cardiovascular Medicine Division, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom); Brichard, Laurent; Franck, Dominic; Fryer, Tim D.; Clark, John C. [Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom); Davies, John R. [Cardiovascular Medicine Division, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom); Richards, Hugh K. [Neurology Unit, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom); Davenport, Anthony P. [Clinical Pharmacology Unit, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom); Weissberg, Peter L. [Cardiovascular Medicine Division, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom); Warburton, Elizabeth A. [BHF Carotid Imaging Group, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom)]|[Department of Clinical Neurosciences, University of Cambridge, Addenbrooke' s Hospital, CB2 2QQ Cambridge (United Kingdom)

    2007-05-15

    Introduction: The peripheral benzodiazepine receptor (PBR) has shown considerable potential as a clinical marker of neuroinflammation and tumour progression. [{sup 11}C]DAA1106 ([{sup 11}C]N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)-acetamide) is a promising positron emission tomography (PET) radioligand for imaging PBRs. Methods: A four-step synthetic route was devised to prepare DAA1123, the precursor for [{sup 11}C]DAA1106. Two robust, high yielding methods for radiosynthesis based on [{sup 11}C]-O-methylation of DAA1123 were developed and implemented on a nuclear interface methylation module, producing [{sup 11}C]DAA1106 with up to 25% radiochemical yields at end-of-synthesis based on [{sup 11}C]CH{sub 3}I trapped. Evaluation of [{sup 11}C]DAA1106 for in vivo imaging was performed in a rabbit model with microPET, and the presence of PBR receptor in the target organ was further corroborated by immunohistochemistry. Results: The standard solution method produced 2.6-5.2 GBq (n=19) of [{sup 11}C]DAA1106, whilst the captive solvent method produced 1.6-6.3 GBq (n=10) of [{sup 11}C]DAA1106. Radiochemical purities obtained were 99% and specific radioactivity at end-of-synthesis was up to 200 GBq/{mu}mol for both methods. Based on radiochemical product, shorter preparation times and simplicity of synthesis, the captive solvent method was chosen for routine productions of [{sup 11}C]DAA1106. In vivo microPET [{sup 11}C]DAA1106 scans of rabbit kidney demonstrated high levels of binding in the cortex. The subsequent introduction of nonradioactive DAA1106 (0.2 {mu}mol) produced considerable displacement of the radioactive signal in this region. The presence of PBR in kidney cortex was further corroborated by immunohistochemistry. Conclusions: A robust, high yielding captive solvent method of [{sup 11}C]DAA1106 production was developed which enabled efficacious in vivo imaging of PBR expressing tissues in an animal model.

  18. ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: comparison of easy-to-label recombinant proteins for [{sup 68}Ga]PET imaging of VEGF receptors in angiogenic vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Eder, Matthias [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)], E-mail: m.eder@dkfz.de; Krivoshein, Arcadius V.; Backer, Marina; Backer, Joseph M. [SibTech, Inc., Brookfield, CT 06804 (United States); Haberkorn, Uwe [Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany); Eisenhut, Michael [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)

    2010-05-15

    Introduction: VEGF receptors play a key role in angiogenesis and are important targets for several approved and many experimental drugs. Imaging of VEGF receptor expression in malignant tumors would provide important information, which can influence patient management. The aim of this study was the development of an easy-to-label positron-emitting tracer for imaging VEGF receptors. The tracer is based on engineered single-chain VEGF (scVEGF), expressed with cysteine-containing fusion tag (Cys-tag) for site-specific conjugation of PEGylated bifunctional chelating agents, HBED-CC or NOTA, suitable for labeling with {sup 68}Ga at ambient temperature. Methods: scVEGF-PEG-HBED-CC was synthesized by activating a single carboxyl group of the [Fe(HBED-CC)]{sup -} complex with N-hydroxysuccinimide. Reaction of the activated complex with NH{sub 2}-PEG-maleimide was followed by site-specific conjugation of PEGylated chelator to a thiol group in Cys-tag of scVEGF. The scVEGF-PEG-NOTA conjugate was synthesized using NHS-PEG-maleimide and p-NH{sub 2}-Bn-NOTA. {sup 68}Ga complexation was performed in HEPES buffer (pH 4.2) at room temperature. The functional activity after labeling was tested by radioligand cell binding assays. Biodistribution and PET studies in tumor-bearing mice were performed after 1, 2, 3 and 4 h postinjection. Results: The radiolabeling of scVEGF-PEG-HBED-CC proved more efficient than scVEGF-PEG-NOTA allowing to stop the reaction after 4 min (>97% radiochemical yield). Radioligand cell binding assays performed on HEK-293 cells overexpressing VEGFR-2 revealed no change in the binding properties of {sup 68}Ga-radiolabeled scVEGF relative to other scVEGF-based tracers. Both tracers showed comparable results in biodistribution, such as tumor accumulation and low liver uptake. The tracers were stable in 50% human serum for at least 72 h. Conclusions: The conjugates scVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA revealed comparable in vivo characteristics and allowed easy

  19. Leptospirosis and Pets

    Science.gov (United States)

    ... Bacterial Special Pathogens Branch (BSPB) BSPB Laboratory Submissions Pets Recommend on Facebook Tweet Share Compartir Leptospirosis is ... that can affect human and animals, including your pets. All animals can potentially become infected with Leptospirosis. ...

  20. Heart PET scan

    Science.gov (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  1. (S,S)- and (S,R)-1'-[{sup 18}F]fluorocarazolol, ligands for the visualization of pulmonary {beta}-adrenergic receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Elsinga, Philip H.; Vos, Marten G.; Waarde, Aren van; Braker, Anton H.; Groot, Tjibbe J. de; Anthonio, Rutger L.; Weemaes, Anne-Miek A.; Brodde, Otto-Erich; Visser, Gerben M.; Vaalburg, Willem

    1996-02-01

    The {beta}-adrenoceptor antagonist carazolol has been labelled with fluorine-18 in the isopropyl group via a reductive alkylation by [{sup 18}F]-fluoroacetone of the corresponding (S)-desisopropyl compound according to a known procedure. The introduction of fluorine in the isopropyl group creates a new stereogenic centre resulting in the formation of (S,S)- and (S,R)-1'-[{sup 18}F]fluorocarazolol, which were separated by HPLC. Tissue distribution studies were performed in male Wistar rats. Both the (S,S)- and (S,R)-diastereomers (S.A. 500-2000 Ci/mmol; 18.5-74 TBq/mmol) showed high uptake in lung and heart, which could be blocked by pretreatment of the animals with ({+-})-propranolol. No significant differences were observed between the biodistribution of the two diastereomers. Metabolite analysis showed a rapid appearance of polar metabolites in plasma, while at 60 min postinjection 92% and 82% of the total radioactivity in lung and heart was unmetabolized 1'-[{sup 18}F]fluorocarazolol. In a PET-study with male Wistar rats, the lungs were clearly visualized and the pulmonary uptake was decreased after pretreatment of the animals with ({+-})-propranolol. The heart could not be visualized. Similar results were obtained in PET-studies with lambs.

  2. Dynamic neurotransmitter interactions measured with PET

    Energy Technology Data Exchange (ETDEWEB)

    Schiffer, W.K.; Dewey, S.L.

    2001-04-02

    Positron emission tomography (PET) has become a valuable interdisciplinary tool for understanding physiological, biochemical and pharmacological functions at a molecular level in living humans, whether in a healthy or diseased state. The utility of tracing chemical activity through the body transcends the fields of cardiology, oncology, neurology and psychiatry. In this, PET techniques span radiochemistry and radiopharmaceutical development to instrumentation, image analysis, anatomy and modeling. PET has made substantial contributions in each of these fields by providing a,venue for mapping dynamic functions of healthy and unhealthy human anatomy. As diverse as the disciplines it bridges, PET has provided insight into an equally significant variety of psychiatric disorders. Using the unique quantitative ability of PET, researchers are now better able to non-invasively characterize normally occurring neurotransmitter interactions in the brain. With the knowledge that these interactions provide the fundamental basis for brain response, many investigators have recently focused their efforts on an examination of the communication between these chemicals in both healthy volunteers and individuals suffering from diseases classically defined as neurotransmitter specific in nature. In addition, PET can measure the biochemical dynamics of acute and sustained drug abuse. Thus, PET studies of neurotransmitter interactions enable investigators to describe a multitude of specific functional interactions in the human brain. This information can then be applied to understanding side effects that occur in response to acute and chronic drug therapy, and to designing new drugs that target multiple systems as opposed to single receptor types. Knowledge derived from PET studies can be applied to drug discovery, research and development (for review, see (Fowler et al., 1999) and (Burns et al., 1999)). Here, we will cover the most substantial contributions of PET to understanding

  3. Imaging of receptors in clinical neurosciences

    NARCIS (Netherlands)

    Korf, J

    This article deals with the question why should one determine receptors in the brain with positron and single photon emission tomography (PET and SPECT, respectively). Radiopharmaceuticals for a wide variety of receptors are available now. Receptors studies with PET and SPECT have thus far focused

  4. SPECT and PET in Eating Disorders

    NARCIS (Netherlands)

    van Waarde, Aren; Audenaert, Kurt; Busatto, Geraldo F.; Buchpiguel, Carlos; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; de Vries, Erik FJ; van Waarde, Aren; den Boer, Johan A

    2014-01-01

    Medical imaging techniques like PET and SPECT have been applied for investigation of brain function in anorexia and bulimia nervosa. Regional abnormalities have been detected in cerebral blood flow, glucose metabolism, the availability of several neurotransmitter receptors (serotonin 1A and 2A, dopa

  5. SPECT and PET in Eating Disorders

    NARCIS (Netherlands)

    van Waarde, Aren; Audenaert, Kurt; Busatto, Geraldo F.; Buchpiguel, Carlos; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; de Vries, Erik FJ; van Waarde, Aren; den Boer, Johan A

    2014-01-01

    Medical imaging techniques like PET and SPECT have been applied for investigation of brain function in anorexia and bulimia nervosa. Regional abnormalities have been detected in cerebral blood flow, glucose metabolism, the availability of several neurotransmitter receptors (serotonin 1A and 2A,

  6. Development of N-substituted quinolinimides, as potential PET tracers for the visualisation of {delta}-opioid receptors; Developpement de quinoleinimides N-substitues, traceurs potentiels des recepteurs opiaces de type {delta} pour l'imagerie medicale par TEP

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, Th.

    2005-12-15

    In order to develop radiotracers for in vivo studies of {delta}-opioid receptors by Positron Emission Tomography (PET) or Single Photon Emission computed Tomography (SPECT), we undertook the synthesis of halogenated analogues (chlorinated and brominated) of compound 12. These analogues were prepared by a convergent synthesis and from these novel structures a halogen exchange reaction has been performed to complete this series. These molecules were tested to determine their in vitro affinity and selectivity toward {delta} opioid receptors. The compounds 12 and 15 were labelled with carbon-11. The radiosynthesis of compound 12, in weak radioactivity chemistry, was performed first by the Stille reaction and second by a new methodology based on the transfer reaction of [{sup 11}C]-methyl group. This new methodology used a mono-organotin compound prepared by addition of [{sup 11}C]-iodomethane onto Lappert's stannylene. The compound [{sup 11}C]-12 was obtained with 60 and 10% radiochemical yield respectively. In order to produce higher radioactivity quantities, the Stille reaction was automated. The compounds [{sup 11}C]-12 and [{sup 11}C]-15 were obtained in 40 minutes with a specific radioactivity ranging from 322 to 747 mCi/{mu}mol. (author)

  7. PET imaging of α{sub 7} nicotinic acetylcholine receptors: a comparative study of [{sup 18}F]ASEM and [{sup 18}F]DBT-10 in nonhuman primates, and further evaluation of [{sup 18}F]ASEM in humans

    Energy Technology Data Exchange (ETDEWEB)

    Hillmer, Ansel T.; Li, Songye; Zheng, Ming-Qiang; Lin, Shu-fei; Nabulsi, Nabeel; Holden, Daniel; Pracitto, Richard; Labaree, David; Ropchan, Jim; Esterlis, Irina; Cosgrove, Kelly P.; Carson, Richard E.; Huang, Yiyun [Yale University, PET Center, New Haven, CT (United States); Scheunemann, Matthias; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig (Germany)

    2017-06-15

    The α{sub 7} nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α{sub 7} nAChRs PET radioligands, [{sup 18}F]ASEM 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([{sup 18}F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [{sup 18}F]DBT-10 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([{sup 18}F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [{sup 18}F]ASEM in humans. PET scans with high specific activity [{sup 18}F]ASEM or [{sup 18}F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [{sup 18}F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [{sup 18}F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [{sup 18}F]ASEM distribution volume (V{sub T}). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V{sub T} was assessed. In the rhesus monkey brain [{sup 18}F]ASEM and [{sup 18}F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [{sup 18}F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [{sup 18}F]ASEM V{sub T}. [{sup 18}F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [{sup 18}F]ASEM V{sub T} in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V{sub T} values ranging from 19.6 ± 2

  8. PET application in psychiatry and psychopharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-07-01

    accumulation was observed in the thalamus and striatum. The thalamus to cerebellum ratio was about 2 at 90 min after the injection of the tracer. Pretreatment with 50 mg of clomipramine resulted in 40-50% occupancy of the serotonin transporter in the thalamus. Another important potential regarding the use of PET in the psychiatric field is the investigation of the pathophysiology of brain disease and normal brain functions from in vivo neurochemistry. Brain dopamine system plays an important role in several neuropsychiatric disorders especially schizophrenia. Dopamine receptors are classified in five different classes; currently D{sub 1} and D{sub 2} receptors can be visualized with PET. Postmortem investigations have demonstrated that in the cortical region, the density of dopamine D{sub 1} receptors is approximately 10-fold that of D{sub 2} receptors. The hypothesis has been proposed that schizophrenic patients have reduced cortical dopamine activity together with increased subcortical dopamine activity. To examine both the cortical and subcortical dopamine D{sub 1} receptors in schizophrenic patients, [{sup 11}C] SCH23390 was employed in a PET study. Eighteen healthy male subjects (27.7{+-}5.6 years) and 17 male schizophrenic patients (27.4{+-}5.9 years) were included. Ten patients were neuroleptic naive and seven patients were drug free. The binding potential was obtained in the several brain regions using the cerebellum as the reference. In the striatum, there were no significant differences between the patients and normal controls. But the binding potentials in the prefrontal cortex were significantly lower in the schizophrenic patients. The binding potentials in the prefrontal cortex were negatively correlated with the BPRS negative symptom subscore. PET has many advantages over other non-invasive techniques, and PET can show us different phenomena which we can not observe with in vitro techniques. Progress in PET study will provide a whole new viewpoint for psychiatric

  9. PET and SPECT imaging in veterinary medicine.

    Science.gov (United States)

    LeBlanc, Amy K; Peremans, Kathelijne

    2014-01-01

    Veterinarians have gained increasing access to positron emission tomography (PET and PET/CT) imaging facilities, allowing them to use this powerful molecular imaging technique for clinical and research applications. SPECT is currently being used more in Europe than in the United States and has been shown to be useful in veterinary oncology and in the evaluation of orthopedic diseases. SPECT brain perfusion and receptor imaging is used to investigate behavioral disorders in animals that have interesting similarities to human psychiatric disorders. This article provides an overview of the potential applications of PET and SPECT. The use of commercially available and investigational PET radiopharmaceuticals in the management of veterinary disease has been discussed. To date, most of the work in this field has utilized the commercially available PET tracer, (18)F-fluorodeoxyglucose for oncologic imaging. Normal biodistribution studies in several companion animal species (cats, dogs, and birds) have been published to assist in lesion detection and interpretation for veterinary radiologists and clinicians. Studies evaluating other (18)F-labeled tracers for research applications are underway at several institutions and companion animal models of human diseases are being increasingly recognized for their value in biomarker and therapy development. Although PET and SPECT technologies are in their infancy for clinical veterinary medicine, increasing access to and interest in these applications and other molecular imaging techniques has led to a greater knowledge and collective body of expertise for veterinarians worldwide. Initiation and fostering of physician-veterinarian collaborations are key components to the forward movement of this field.

  10. FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

    Science.gov (United States)

    2016-06-02

    Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  11. Age and sex effects on 5-HT(4) receptors in the human brain: a [(11)C]SB207145 PET study

    DEFF Research Database (Denmark)

    Madsen, Karine; Haahr, Mette T; Marner, Lisbeth;

    2011-01-01

    Experimental studies indicate that the 5-HT(4) receptor activation influence cognitive function, affective symptoms, and the development of Alzheimer's disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men....... This study aimed to investigate sex and age effects on 5-HT(4) receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [(11)C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14...... men and 16 women). The output parameter, BP(ND), was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller-Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT(4) receptor binding...

  12. PET imaging to measure therapy-related occupancy and disease-induced changes of expression of adenosine A1 receptors in the rodent brain

    NARCIS (Netherlands)

    Paul, Souman

    2014-01-01

    Rol van adenosine A1 receptor in de vroege fase van encefalitis Adenosine A1 receptoren (A1R) spelen een belangrijke rol bij de bescherming van hersencellen tijdens de vroege fase van hersenontsteking (encefalitis) bij ratten en mogelijk ook bij mensen. Dat concludeert Souman Paul in zijn proefschri

  13. Design, synthesis, radiolabeling and in vivo evaluation of potential positron emission tomography (PET) radioligands for brain imaging of the 5-HT7 receptor

    DEFF Research Database (Denmark)

    Lacivita, Enza; Niso, Mauro; Hansen, Hanne D.

    2014-01-01

    Here we describe the design, synthesis, and pharmacological evaluation of a set of compounds structurally related to the high affinity serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (6, LP-211). Specific structural modifications were performed in or...

  14. Adenosine A(1) Receptors in the Central Nervous System : Their Functions in Health and Disease, and Possible Elucidation by PET Imaging

    NARCIS (Netherlands)

    Paul, S.; Elsinga, P. H.; Ishiwata, K.; Dierckx, R. A. J. O.; van Waarde, A.

    2011-01-01

    Adenosine is a neuromodulator with several functions in the central nervous system (CNS), such as inhibition of neuronal activity in many signaling pathways. Most of the sedating, anxiolytic, seizure-inhibiting and protective actions of adenosine are mediated by adenosine A(1) receptors (A(1)R) on t

  15. Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with (11)C-SA4503 and microPET

    NARCIS (Netherlands)

    Kuzhuppilly Ramakrishnan, Nisha; Visser, Anniek K. D.; Schepers, Marianne; Luurtsema, Gert; Nyakas, Csaba J.; Elsinga, Philip H.; Ishiwata, Kiichi; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2014-01-01

    RATIONALE: Sigma-1 receptor agonists are under investigation as potential disease-modifying agents for several CNS disorders. Donepezil, an acetylcholinesterase inhibitor used for the symptomatic treatment of Alzheimer's disease, is also a high-affinity sigma-1 agonist. OBJECTIVES: The objectives of

  16. Direct comparison of [18F]MH.MZ and [18F]altanserin for 5-HT2A receptor imaging with PET

    DEFF Research Database (Denmark)

    Hansen, Hanne Demant; Ettrup, Anders; Herth, Matthias Manfred

    2013-01-01

    and the favourable radiophysical properties of fluorine-18. Here, we present a direct comparison of [(18) F]altanserin and [(18) F]MH.MZ. 5-HT(2A) receptor binding in pig cortex and cerebellum was investigated by autoradiography with [(3) H]MDL 100907, [(18) F]MH.MZ, and [(18) F]altanserin. [(18) F]MH.MZ and [(18) F...

  17. Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with (11)C-SA4503 and microPET

    NARCIS (Netherlands)

    Kuzhuppilly Ramakrishnan, Nisha; Visser, Anniek K. D.; Schepers, Marianne; Luurtsema, Gert; Nyakas, Csaba J.; Elsinga, Philip H.; Ishiwata, Kiichi; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2014-01-01

    RATIONALE: Sigma-1 receptor agonists are under investigation as potential disease-modifying agents for several CNS disorders. Donepezil, an acetylcholinesterase inhibitor used for the symptomatic treatment of Alzheimer's disease, is also a high-affinity sigma-1 agonist. OBJECTIVES: The objectives of

  18. Age and sex effects on 5-HT(4) receptors in the human brain: a [(11)C]SB207145 PET study

    DEFF Research Database (Denmark)

    Madsen, Karine; Haahr, Mette T; Marner, Lisbeth;

    2011-01-01

    . This study aimed to investigate sex and age effects on 5-HT(4) receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [(11)C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14...

  19. Disaster Preparedness for Your Pet

    Science.gov (United States)

    ... and prepare a disaster kit for your pet. Leaving pets out of evacuation plans can put pets, ... during an evacuation Contact your local emergency management office and ask if they offer accommodations for owners ...

  20. Sensory analysis of pet foods.

    Science.gov (United States)

    Koppel, Kadri

    2014-08-01

    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities.

  1. Clinical PET application

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Moo; Hong, Song W.; Choi, Chang W.; Yang, Seong Dae [Korea Cancer Center Hospital, Seoul (Korea)

    1997-12-01

    PET gives various methabolic images, and is very important, new diagnostic modality in clinical oncology. In Korea Cancer Center Hospital, PET is installed as a research tool of long-mid-term atomic research project. For the efficient use of PET for clinical and research projects, income from the patients should be managed to get the raw material, equipment, manpower, and also for the clinical PET research. 1. Support the clinical application of PET in oncology. 2. Budgetary management of income, costs for raw material, equipment, manpower, and the clinical PET research project. In this year, 250 cases of PET images were obtained, which resulted total income of 180,000,000 won. 50,000,000 won was deposited for the 1998 PET clinical research. Second year PET clinical research should be managed under unified project. Increased demand for {sup 18}FDG in and outside KCCH need more than 2 times production of {sup 18}FDG in a day purchase of HPLC pump and {sup 68}Ga pin source which was delayed due to economic crisis, should be done early in 1998. (author). 2 figs., 3 tabs.

  2. In vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States) and Department of Radiology, Columbia University, New York, NY 10032 (United States) and Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: rnw7@columbia.edu; Chang, Raymond C. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Zhao, Jun [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Carambot, Patty E. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-02-15

    Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K {sub D}=0.5{+-}0.2 nM, log P=2.9) sigma-1 receptor radiotracer [{sup 18}F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [{sup 18}F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [{sup 18}F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [{sup 18}F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([{sup 18}F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([{sup 18}F]SFE) (K {sub D}=5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [{sup 18}F]SFE was synthesized (n=4) as previously described in good yield (54{+-}6% EOB), high specific activity (2.1{+-}0.6 Ci/{mu}mol EOS) and radiochemical purity (98{+-}1%) and evaluated in awake adult male rats. Results: Similar to [{sup 18}F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [{sup 18}F]SFE were highest in occipital cortex (1.86{+-}0.06 %ID/g) and frontal cortex (1.76{+-}0.38 %ID/g), and lowest in the hippocampus (1.01{+-}0.02%ID/g). Unlike [{sup 18}F]FPS, [{sup 18}F]SFE cleared from the brain with {approx}40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [{sup 18}F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [{sup 18}F]SFE in discrete brain regions. Conclusions

  3. In vivo biodistribution of an androgen receptor avid PET imaging agent 7-{alpha}-fluoro-17 {alpha}-methyl-5-{alpha}-dihydrotestosterone ([{sup 18}F]FMDHT) in rats pretreated with cetrorelix, a GnRH antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Garg, Sudha; Doke, Aniruddha; Black, Kimberly W.; Garg, Pradeep K. [Wake Forest University Health Sciences, PET Center, Department of Radiological Sciences, Winston Salem, NC (United States)

    2008-02-15

    For this study, we have assessed the in vivo distribution and androgen receptor (AR) seeking properties of an F-18-labeled androgen [{sup 18}F]FMDHT in rats castrated with a GnRH antagonist. The radiochemical synthesis of [{sup 18}F]FMDHT was performed using a previously published method. The radiochemical synthesis provided the desired product in good radiochemical yields and radiochemical purity. In vivo biodistribution studies were performed in chemically castrated rats. The animals were castrated using cetrorelix, a GnRH antagonist. To assess the specificity of [{sup 18}F]FMDHT towards ARs, a separate group of animals was pretreated with a large dose of androgen before the [{sup 18}F]FMDHT injection. The in vivo biodistribution results show selective uptake of [{sup 18}F]FMDHT in the prostate that ranged from 0.46 + 0.10 %ID/g at 1 h to 0.59 + 0.16 %ID/g at 3 h with prostate to muscle ratio ranging from 8.06 + 2.46 at 1 h to 18.81 + 4.90 at 3 h. These in vivo distribution studies document a high selectivity and specificity of [{sup 18}F]FMDHT towards AR rich tissues and suggests that [{sup 18}F]FMDHT may be a useful in vivo PET imaging ligand. (orig.)

  4. [PET/CT in breast cancer: an update].

    Science.gov (United States)

    Groheux, D; Moretti, J-L; Giacchetti, S; Hindié, E; Teyton, P; Cuvier, C; Bousquet, G; Misset, J-L; Boin, C; Espié, M

    2009-11-01

    The authors discuss the various roles of 18F-FDG PET/CT in the management of breast cancer. Roles of new tracers such as F-18 fluoro-L-thymidine (a marker of cell proliferation), 18-fluoro-17-B-estradiol (marker of estrogen receptor) and sodium fluoride (marker of bone matrix) are also mentioned. There is little justification for the use of FDG-PET/CT in patient with clinically T1 (occult distant metastases, notably, early osteomedullary infiltration. Thus, for these tumors, initial PET/CT can enable better intramodality treatment planning or a change in treatment. PET/CT as a whole-body examination is also very efficient in case of suspicion of recurrence. On the other hand, many studies show that this functional imaging could be used to assess early response to neoadjuvant chemotherapy or to chemotherapy of metastatic disease. 18FDG-PET/CT could thus become an unavoidable modality to answer various clinical situations.

  5. Development of F-18 Labeled Radiotracers for PET Imaging of Brain Alpha-1 Noradrenergic Receptors: Potential PTSD Vulnerability and Diagnostic Biomarkers

    Science.gov (United States)

    2012-09-01

    by the NIMH Psychoactive Drug Screening Pro-gram (PDSP). The HEAT analog exhibing the best profile of α1NAR vs. off-target neurotransmitter receptor... drug that blocks excessive stimulation of CNS α1NARs (13)] robustly reduces combat-related nightmares and sleep disturbance and improves overall CSS...to this question, we developed a chiral -HPLC method for the separation of the optical isomers of 2-Fluoro-HEAT [#2], as illustrated in Figure 3. In

  6. Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing tumors

    Energy Technology Data Exchange (ETDEWEB)

    Abourbeh, Galith [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904 (Israel); Dissoki, Samar [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Jacobson, Orit [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Litchi, Amir [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Daniel, Revital Ben [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Laki, Desirediu [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel); Levitzki, Alexander [Unit of Cellular Signaling, Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904 (Israel); Mishani, Eyal [Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Jerusalem 91120 (Israel)]. E-mail: mishani@md.huji.ac.il

    2007-01-15

    Overexpression of epidermal growth factor receptor (EGFR) has been implicated in tumor development and malignancy. Evaluating the degree of EGFR expression in tumors could aid in identifying patients for EGFR-targeted therapies and in monitoring treatment. Nevertheless, no currently available assay can reliably quantify receptor content in tumors. Radiolabeled inhibitors of EGFR-TK could be developed as bioprobes for positron emission tomography imaging. Such imaging agents would not only provide a noninvasive quantitative measurement of EGFR content in tumors but also serve as radionuclide carriers for targeted radiotherapy. The potency, reversibility, selectivity and specific binding characteristics of ML04, an alleged irreversible inhibitor of EGFR, were established in vitro. The distribution of the F-18-labeled compound and the extent of EGFR-specific tumor uptake were evaluated in tumor-bearing mice. ML04 demonstrated potent, irreversible and selective inhibition of EGFR, combined with specific binding to the receptor in intact cells. In vivo distribution of the radiolabeled compound revealed tumor/blood and tumor/muscle activity uptake ratios of about 7 and 5, respectively, 3 h following administration of a radiotracer. Nevertheless, only minor EGFR-specific uptake of the compound was detected in these studies, using either EGFR-negative tumors or blocking studies as controls. To improve the in vivo performance of ML04, administration via prolonged intravenous infusion is proposed. Detailed pharmacokinetic characterization of this bioprobe could assist in the development of a kinetic model that would afford accurate measurement of EGFR content in tumors.

  7. In vivo evaluation of [{sup 11}C]N-(2-chloro-5-thiomethylphenyl)-N'- (3-methoxy-phenyl)-N'-methylguanidine ([{sup 11}C]GMOM) as a potential PET radiotracer for the PCP/NMDA receptor

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. E-mail: rnw7@columbia.edu; Slifstein, Mark; Dumont, Filip; Zhao Jun; Chang, Raymond C.; Sudo, Yasuhiko; Sultana, Abida; Balter, Andrew; Laruelle, Marc

    2004-10-01

    The development of imaging methods to measure changes in NMDA ion channel activation would provide a powerful means to probe the mechanisms of drugs and device based treatments (e.g., ECT) thought to alter glutamate neurotransmission. To provide a potential NMDA/PCP receptor PET tracer, we synthesized the radioligand [{sup 11}C]GMOM (K{sub i} = 5.2 {+-}0.3 nM; log P = 2.34) and evaluated this ligand in vivo in awake male rats and isoflurane anesthetized baboons. In rats, the regional brain uptake of [{sup 11}C]GMOM ranged from 0.75{+-}0.13% ID/g in the medulla and pons to 1.15{+-}0.17% ID/g in the occipital cortex. MK801 (1 mg/kg i.v.) significantly reduced (24-28%) [{sup 11}C]GMOM uptake in all regions. D-serine (10 mg/kg i.v.) increased [{sup 11}C]GMOM %ID/g values in all regions (10-24%) reaching significance in the frontal cortex and cerebellum only. The NR2B ligand RO 25-6981 (10 mg/kg i.v.) reduced [{sup 11}C]GMOM uptake significantly (24-38%) in all regions except for the cerebellum and striatum. Blood activity was 0.11{+-}0.03 %ID/g in the controls group and did not vary significantly across groups. PET imaging in isoflurane-anesthetized baboons with high specific activity [{sup 11}C]GMOM provided fairly uniform regional brain distribution volume (V{sub T}) values (12.8-17.1 ml g{sup -1}). MK801 (0.5 mg/kg, i.v., n = 1, and 1.0 mg/kg, i.v., n = 1) did not significantly alter regional V{sub T} values, indicating a lack of saturable binding. However, the potential confounding effects associated with ketamine induction of anesthesia along with isoflurane maintenance must be considered because both agents are known to reduce NMDA ion channel activation. Future and carefully designed studies, presumably utilizing an optimized NMDA/PCP site tracer, will be carried out to further explore these hypotheses. We conclude that, even though [{sup 11}C]GMOM is not an optimized PCP site radiotracer, its binding is altered in vivo in awake rats as expected by modulation of

  8. Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

    2008-02-15

    {sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  9. My Pet Rock

    Science.gov (United States)

    Lark, Adam; Kramp, Robyne; Nurnberger-Haag, Julie

    2008-01-01

    Many teachers and students have experienced the classic pet rock experiment in conjunction with a geology unit. A teacher has students bring in a "pet" rock found outside of school, and the students run geologic tests on the rock. The tests include determining relative hardness using Mohs scale, checking for magnetization, and assessing luster.…

  10. My Pet Rock

    Science.gov (United States)

    Lark, Adam; Kramp, Robyne; Nurnberger-Haag, Julie

    2008-01-01

    Many teachers and students have experienced the classic pet rock experiment in conjunction with a geology unit. A teacher has students bring in a "pet" rock found outside of school, and the students run geologic tests on the rock. The tests include determining relative hardness using Mohs scale, checking for magnetization, and assessing luster.…

  11. Mobile PET Center Project

    Science.gov (United States)

    Ryzhikova, O.; Naumov, N.; Sergienko, V.; Kostylev, V.

    2017-01-01

    Positron emission tomography is the most promising technology to monitor cancer and heart disease treatment. Stationary PET center requires substantial financial resources and time for construction and equipping. The developed mobile solution will allow introducing PET technology quickly without major investments.

  12. Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Jammaz, I. Al, E-mail: jammaz@kfshrc.edu.sa; Al-Otaibi, B.; Amer, S.; Okarvi, S.M.

    2011-10-15

    In an attempt to visualize folate receptors that overexpress on many cancers, [{sup 18}F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([{sup 18}F]-1, [{sup 18}F]-2-folates and [{sup 18}F]-8, [{sup 18}F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [{sup 18}F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [{sup 18}F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [{sup 18}F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [{sup 18}F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response

  13. Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET.

    Science.gov (United States)

    Jones, Anthony K P; Watabe, Hiroshi; Cunningham, Vin J; Jones, Terry

    2004-10-01

    Central neuropathic pain (CNP) is pain resulting from damage to the central nervous system. Up till now, it has not been possible to identify a common lesion or pharmacological deficit in these patients. This preliminary study in a group of patients with CNP with predominantly post-stroke pain, demonstrates that there is significantly less opioid receptor binding in a number of cortical and sub-cortical structures that are mostly, but not exclusively, within the medial pain system in patients compared to age-matched pain-free controls. The reductions in opioid receptor binding within the medial system were observed mainly in the dorsolateral (Brodman area 10) and anterior cingulate (Brodman area 24 with some extension into area 23) and insula cortices and the thalamus. There were also reductions in the lateral pain system within the inferior parietal cortex (Brodman area 40). These changes in binding could not be accounted for by the cerebral lesions shown by CT or MRI, which were outside the areas of reduced binding and the human pain system. To our knowledge this is the first systematic demonstration of a reduction in opioid receptor-binding capacity in neurones within the human nociceptive system in patients with CNP. This may be a key common factor resulting in undamped nociceptor activity within some of the structures that are predominantly within the medial nociceptive system. If confirmed, these findings may explain why certain patients with CNP require high doses of synthetic opiates to achieve optimum analgesia. The findings also raise the possibility of new pharmacological approaches to treatment.

  14. Usage of Recycled Pet

    Directory of Open Access Journals (Sweden)

    A. Ebru Tayyar

    2010-01-01

    Full Text Available The increasing industrialization, urbanization and the technological development have caused to increase depletion of the natural resources and environmental pollution's problem. Especially, for the countries which have not enough space recycling of the waste eliminating waste on regular basis or decreasing the amount and volume of waste have provided the important advantages. There are lots of studies and projects to develop both protect resources and prevent environmental pollution. PET bottles are commonly used in beverage industry and can be reused after physical and chemical recycling processes. Usage areas of recycled PET have been developed rapidly. Although recycled PET is used in plastic industry, composite industry also provides usage alternatives of recycled PET. Textile is a suitable sector for recycling of some plastics made of polymers too. In this study, the recycling technologies and applications of waste PET bottles have been investigated and scientific works in this area have been summarized.

  15. Test-retest reproducibility of dopamine D{sub 2/3} receptor binding in human brain measured by PET with [{sup 11}C]MNPA and [{sup 11}C]raclopride

    Energy Technology Data Exchange (ETDEWEB)

    Kodaka, Fumitoshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Ito, Hiroshi [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); National Institute of Radiological Sciences, Biophysics Program, Molecular Imaging Center, Chiba (Japan); Kimura, Yasuyuki; Fujie, Saori; Takano, Harumasa; Fujiwara, Hironobu; Sasaki, Takeshi; Suhara, Tetsuya [National Institute of Radiological Sciences, Molecular Neuroimaging Program, Molecular Imaging Center, Chiba (Japan); Nakayama, Kazuhiko [Jikei University School of Medicine, Department of Psychiatry, Tokyo (Japan); Halldin, Christer; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden)

    2013-04-15

    Dopamine D{sub 2/3} receptors (D{sub 2/3}Rs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D{sub 2/3} {sup HIGH}), which has a high affinity for endogenous dopamine, and low-affinity state (D{sub 2/3} {sup LOW}). The density of D{sub 2/3} {sup HIGH} can be measured with (R)-2-{sup 11}CH{sub 3}O-N-n-propylnorapomorphine ([{sup 11}C]MNPA), while total density of D{sub 2/3} {sup HIGH} and D{sub 2/3} {sup LOW} (D{sub 2/3}Rs) can be measured with [{sup 11}C]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential (BP) of [{sup 11}C]MNPA to that of [{sup 11}C]raclopride ([{sup 11}C]MNPA/[{sup 11}C]raclopride) may reflect the proportion of the density of D{sub 2/3} {sup HIGH} to that of D{sub 2/3}Rs. In the caudate and putamen, [{sup 11}C]MNPA/[{sup 11}C]raclopride reflects the proportion of the density of D{sub 2} {sup HIGH} to that of D{sub 2}Rs. To evaluate the reliability of the PET paradigm with [{sup 11}C]MNPA and [{sup 11}C]raclopride, we investigated the test-retest reproducibility of non-displaceable BP (BP{sub ND}) measured with [{sup 11}C]MNPA and of [{sup 11}C]MNPA/[{sup 11}C]raclopride in healthy humans. Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [{sup 11}C]MNPA and [{sup 11}C]raclopride scans. BP{sub ND} values in the caudate and putamen were calculated. Test-retest reproducibility of BP{sub ND} of [{sup 11}C]MNPA and [{sup 11}C]MNPA/[{sup 11}C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). The absolute variability of [{sup 11}C]MNPA BP{sub ND} was 5.30 {+-} 3.96 % and 12.3 {+-} 7.95 % and the ICC values of [{sup 11}C]MNPA BP{sub ND} were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [{sup 11}C]MNPA/[{sup 11}C]raclopride was 6.11 {+-} 3.68 % and 11.60 {+-} 5.70 % and the ICC values of [{sup

  16. Dopamine D2/3 Receptor Availability in the Striatum of Antipsychotic-Free Older Patients with Schizophrenia - A [11C]-raclopride PET Study

    Science.gov (United States)

    Nakajima, Shinichiro; Caravaggio, Fernando; Mamo, David C.; Mulsant, Benoit H.; Chung, Jun Ku; Plitman, Eric; Iwata, Yusuke; Gerretsen, Philip; Uchida, Hiroyuki; Suzuki, Takefumi; Mar, Wanna; Wilson, Alan A.; Houle, Sylvain; Graff-Guerrero, Ariel

    2015-01-01

    Background No study has examined dopamine D2/3 receptor (D2/3R) availability in antipsychotic-free older patients with schizophrenia. Methods We included patients with schizophrenia 50 years or older who were antipsychotic-free for at least 3 months. We compared non-displaceable binding potential (BPND) of [11C]-raclopride in the caudate, putamen, ventral striatum, and globus pallidus between patients and age- and sex-matched healthy controls. Results Ten patients participated (antipsychotic-naïve=4). No differences in BPND were found between patients and controls in any ROIs (F(1, 72)=.42, p=.52). Conclusion The preliminary results suggest no differences in D2/3R availability between antipsychotic-free older patients with schizophrenia and controls. PMID:25757713

  17. Automated cGMP-compliant radiosynthesis of [(18) F]-(E)-PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5.

    Science.gov (United States)

    Park, Jun Young; Son, Jeongmin; Yun, Mijin; Ametamey, Simon M; Chun, Joong-Hyun

    2017-09-25

    (E)-3-(Pyridin-2-yl ethynyl)cyclohex-2-enone O-(3-(2-[(18) F]-fluoroethoxy)propyl) oxime ([(18) F]-(E)-PSS232, [(18) F]2a) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu5 ) in vivo. The mGlu5 has become an attractive therapeutic and diagnostic target owing to its role in many neuropsychiatric disorders. Several carbon-11- and fluorine-18-labelled radiotracers have been developed to measure mGlu5 receptor occupancy in the human brain. The radiotracer [(18) F]2a, which is used as an analogue for [(11) C]ABP688 ([(11) C]1) and has a longer physical half-life, is a selective radiotracer that exhibits high binding affinity for mGlu5 . Herein, we report the fully automated radiosynthesis of [(18) F]2a using a commercial GE TRACERlab(TM) FX-FN synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron-produced [(18) F]fluoride ion at 100 °C in dimethyl sulfoxide (DMSO), followed by high-performance liquid chromatography (HPLC) purification and formulation, readily provided [(18) F]2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [(18) F]-(E)-conformer was greater than 95%. Molar activity was determined to be 63.6 ± 9.6 GBq/μmol (n = 5), and the overall synthesis time was 70 min. This article is protected by copyright. All rights reserved.

  18. Synthesis and in vivo evaluation of [O-methyl-{sup 11}C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT{sub 2A} receptor PET ligand

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, J.S. Dileep [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: dk2038@columbia.edu; Prabhakaran, Jaya [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Erlandsson, Kjell [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Majo, Vattoly J. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Simpson, Norman R. [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Pratap, Mali [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Heertum, Ronald L. van [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Mann, J. John [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Parsey, Ramin V. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-05-15

    The serotonin{sub 2A} (5-HT{sub 2A}) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT{sub 2A} antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K {sub i}=0.79 nM) 5HT{sub 2A} antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [{sup 11}C]methyltriflate in order to determine the suitability of [{sup 11}C]MPM to quantify 5-HT{sub 2A} in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40{+-}5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [{sup 11}C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT{sub 2A} receptors. The time-activity curves for the high-binding regions peaked at {approx}45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT{sub 2A} receptors but also 38% blocking in cerebellum, which has a low 5-HT{sub 2A} receptor concentration. Although [{sup 11}C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT{sub 2A} receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT{sub 2A} receptors with PET.

  19. Radiosynthesis and in vivo evaluation of N-[{sup 11}C]methylated imidazopyridineacetamides as PET tracers for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sekimata, Katsuhiko [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Hatano, Kentaro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)], E-mail: hatanok@nils.go.jp; Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Abe, Junichiro [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192 Japan (Japan); Biggio, Giovanni; Serra, Mariangela [Department of Experimental Biology, University of Cagliari, Cagliari 09100 (Italy); Laquintana, Valentino; Denora, Nunzio; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano [Pharmaco-Chemistry Department, University of Bari, Bari 70125 (Italy); Ito, Kengo [Department of Brain Sciences and Molecular Imaging, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522 (Japan)

    2008-04-15

    Imidazopyridineacetoamide 5-8, a series of novel and potentially selective peripheral benzodiazepine receptor (PBR) ligands with affinities comparable to those of known PBR ligands, was investigated. Radiosyntheses of [{sup 11}C]5, 6, 7 or 8 was accomplished by N-methylation of the corresponding desmethyl precursors with [{sup 11}C]methyl iodide in the presence of NaH in dimethylformamide (DMF), resulting in 25% to 77% radiochemical yield and specific activitiy of 20 to 150 MBq/nmol. Each of the labeled compounds was injected in ddY mice, and the radioactivity and weight of dissected peripheral organs and brain regions were measured. Organ distribution of [{sup 11}C]7 was consistent with the known PBR distribution. Moreover, [{sup 11}C]7 showed the best combination of brain uptake and PBR binding, leading to its high retention in the olfactory bulb and cerebellum, areas where PBR density is high in mouse brain. Coinjection of PK11195 or unlabeled 7 significantly reduced the brain uptake of [{sup 11}C]7. These results suggest that [{sup 11}C]7 could be a useful radioligand for positron emission tomography imaging of PBRs.

  20. Preparation and first evaluation of [{sup 18}F]FE-SUPPY: a new PET tracer for the adenosine A{sub 3} receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wadsak, Wolfgang [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Mien, Leonhard-Key [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Shanab, Karem [Dept. of Drug and Natural Product Synthesis, Faculty of Life Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Ettlinger, Dagmar E. [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Haeusler, Daniela [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Sindelar, Karoline [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Lanzenberger, Rupert R. [Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Spreitzer, Helmut [Dept. of Drug and Natural Product Synthesis, Faculty of Life Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Viernstein, Helmut [Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Keppler, Bernhard K. [Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Dudczak, Robert; Kletter, Kurt [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Mitterhauser, Markus [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria)]|[Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria)]|[Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhouser@meduniwien.ac.at

    2008-01-15

    Introduction: Changes of the adenosine A{sub 3} receptor subtype (A3AR) expression have been shown in a variety of pathologies, especially neurological and affective disorders, cardiac diseases and oncological and inflammation processes. Recently, 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE-SUPPY) was presented as a high-affinity ligand for the A3AR with good selectivity. Our aims were the development of a suitable labeling precursor, the establishment of a reliable radiosynthesis for the fluorine-18-labeled analogue [{sup 18}F]FE-SUPPY and a first evaluation of [{sup 18}F]FE-SUPPY in rats. Methods: [{sup 18}F]FE-SUPPY was prepared in a feasible and reliable manner by radiofluorination of the corresponding tosylated precursor. Biodistribution was carried out in rats, and organs were removed and counted. Autoradiography was performed on rat brain slices in the presence or absence of 2-Cl-IB-MECA. Results: Overall yields and radiochemical purity were sufficient for further preclinical and clinical applications. The uptake pattern of [{sup 18}F]FE-SUPPY found in rats mainly followed the described mRNA distribution pattern of the A3AR. Specific uptake in brain was demonstrated by blocking with a selective A3AR agonist. Conclusion: We conclude that [{sup 18}F]FE-SUPPY has the potential to serve as the first positron emission tomography tracer for the A3AR.

  1. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  2. Clinical application of PET

    Energy Technology Data Exchange (ETDEWEB)

    Lomena, Francisco [Hospital Clinico Villarroel, Barcelona (Spain). Nuclear Medicine]. E-mail: flomena@clinic.ub.es; Soler, Marina [CETIR Grup Medic. Esplkugues de Llobregat, Barcelona (Spain). PET Unit

    2005-10-15

    Positron emission tomography (PET) is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI), which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluorodeoxyglucose-F 18 (FDG) PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.(author)

  3. Combined PET/MRI

    DEFF Research Database (Denmark)

    Bailey, D. L.; Pichler, B. J.; Gückel, B.

    2015-01-01

    This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from...... February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology......, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both...

  4. PET/CT Artifacts

    OpenAIRE

    Blodgett, Todd M.; Mehta, Ajeet S.; Mehta, Amar S.; Laymon, Charles M; Carney, Jonathan; Townsend, David W.

    2011-01-01

    There are several artifacts encountered in PET/CT imaging, including attenuation correction (AC) artifacts associated with using CT for attenuation correction. Several artifacts can mimic a 2-deoxy-2-[18F] fluoro-D-glucose (FDG) avid malignant lesions and therefore recognition of these artifacts is clinically relevant. Our goal was to identify and characterize these artifacts and also discuss some protocol variables that may affect image quality in PET/CT.

  5. PET and PET/CT in endocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Dudczak, Robert [Department of Nuclear Medicine, Medical University of Vienna (Austria)], E-mail: robert.dudczak@meduniwien.ac.at; Traub-Weidinger, Tatjana [Department of Nuclear Medicine, Medical University of Vienna (Austria)

    2010-03-15

    Functional information provided by PET tracers together with the superior image quality and the better data quantification by PET technology had a changing effect on the significance of nuclear medicine in medical issues. Recently introduced hybrid PET/CT systems together with the introduction of novel PET radiopharmaceuticals have contributed to the fact that nuclear medicine has become a growing diagnostic impact on endocrinology. In this review imaging strategies, different radiopharmaceuticals including the basic mechanism of their cell uptake, and the diagnostic value of PET and PET/CT in endocrine tumours except differentiated thyroid carcinomas will be discussed.

  6. First-in-human uPAR PET

    DEFF Research Database (Denmark)

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene

    2015-01-01

    A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive...... of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu...... for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment...

  7. {sup 68}Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUV{sub max}

    Energy Technology Data Exchange (ETDEWEB)

    Boy, Christian; Poeppel, Thorsten D.; Jentzen, Walter; Brandau, Wolfgang; Bockisch, Andreas [University Hospital Essen, University of Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); Heusner, Till A.; Antoch, Gerald [University Hospital Essen, University of Duisburg-Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Redmann-Bischofs, Anja; Unger, Nicole; Mann, Klaus; Petersenn, Stephan [University of Duisburg-Essen, Department of Endocrinology and Division of Laboratory Research, Essen (Germany)

    2011-07-15

    By targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUV{sub max}) and sst mRNA. A total of 120 patients were subjected to diagnostic {sup 68}Ga-DOTATOC positron emission tomography (PET)/CT (age range 19-83 years). SUV{sub max} values were measured in physiologically normal tissues defined by normal morphology, absence of surgical intervention and absence of metastatic spread during clinical follow-up. Expression of sst subtypes (sst1-sst5) was measured independently in pooled adult normal human tissue by real-time reverse transcriptase polymerase chain reaction (RT-PCR). SUV{sub max} revealed a region-specific pattern (e.g., mean {+-} SD, spleen 31.1 {+-} 10.9, kidney 16.9 {+-} 5.3, liver 12.8 {+-} 3.6, stomach 7.0 {+-} 3.1, head of pancreas 6.2 {+-} 2.3, small bowel 4.8 {+-} 1.8, thyroid 4.7 {+-} 2.2, bone 3.9 {+-} 1.3, large bowel 2.9 {+-} 0.8, muscle 2.1 {+-} 0.5, parotid gland 1.9 {+-} 0.6, axillary lymph node 0.8 {+-} 0.3 and lung 0.7 {+-} 0.3). SUV{sub max} was age independent. Gender differences were evident within the thyroid (female/male: 3.7 {+-} 1.6/5.5 {+-} 2.4, p < 0.001; Mann-Whitney U test) and the pancreatic head (5.5 {+-} 1.9/6.9 {+-} 2.2, p < 0.001). The sst mRNA was widely expressed and heterogeneous, showing sst1 to be most abundant. SUV{sub max} values exclusively correlated with sst2 expression (r = 0.846, p < 0.001; Spearman rank correlation analysis), whereas there was no correlation of SUV{sub max} with the expression of the other four subtypes. In normal human tissues {sup 68}Ga-DOTATOC imaging has been related to the expression of sst2 at the level of mRNA. The novel normative database may improve diagnostics, monitoring and therapy of sst-expressing tumours or inflammation on a molecular basis. (orig.)

  8. [{sup 18}F]D.P.A.-714: a novel fluorine-18-labelled pyrazolo[1,5-a]pyrimidine acetamide for imaging the peripheral benzodiazepine receptors with PET - radiosynthesis on a zymate-xp robotic system

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Damont, A.; Hinnen, F.; Kuhnast, B.; Chauveau, F.; Van camp, N.; Hantraye, P.; Tavitian, B. [Servvice Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); James, M.; Creelman, A.; Fulton, R.; Kassiou, M. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Vercouillie, J.; Guilloteau, D. [Universite Francois Rabelais de Tours, 37 (France); Vercouillie, J.; Guilloteau, D. [Centre Hospitalier Regional Universitaire, 37 - Tours (France); Selleri, S.; Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia)

    2008-02-15

    {sup 11}C D.P.A.-713 (N,N-diethyl-2-[2-(4-[{sup 11}C]methoxy-phenyl)-5,7-dimethyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) is a recently developed carbon-11-labelled (half life: 20.4 min)pyrazolo[1,5-a]pyrimidine acetamide for the in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.)). Preliminary results obtained in a rodent-model demonstrates that {sup 11}C D.P.A.-713 showed a high potential to in vivo image neuro-inflammation and additionally, this radioligand allowed a higher contrast between the lesioned area and the corresponding area in the intact contralateral hemisphere when compared to the radioligand of reference. D.P.A-714 (N,N-diethyl-2-[2-[4-(2-fluoro-ethoxy)phenyl] -5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]acetamide), a chemically closely related derivative of D.P.A.-713, had been designed with a fluorine atom in its structure, allowing ultimate labelling with fluorine-18, a longer-lived positron-emitter (half life:109.8 min) and today one of the most attractive PET isotopes for radiopharmaceutical chemistry. D.P.A.-714 as well as its corresponding tosylated derivative have been re-synthesized in 2 chemicals steps from D.P.A.-713. D.P.A.-714 has then been labelled at its aromatic fluoro-ethoxy group from the corresponding tosyl-derivative using the K{sup 18}FF-kryptofix{sub 222} (in CH{sub 3}CN (3 mL) at 85 degrees C for 5 min or D.M.S.O. (600 {mu}L) at 130 degrees C for 5 min). {sup 18}FD.P.A.-714 was then purified using semi preparative X terra reverse phase H.P.L.C., adequately formulated for i.v. injection and was found to be > 95% chemically and radiochemically pure. The total synthesis time was less than 90 min and the specific radioactivities at the end of the radiosynthesis ranged from 1 to 3 Ci/micro-mole. (N.C.)

  9. Medical application of PET technology

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Moo; Choi, C. W.; An, S. H.; Woo, K. S.; Chung, W. S.; Yang, S. D.; Jun, G. S. and others

    1999-04-01

    We performed following studies using PET technology: 1. Clinical usefulness of [{sup 18}F]FDG whole body PET in malignant disease 2. Clinical usefulness of quantitative evaluation of F-18-FDG 3. Pilot study of C-11 methionine PET in brain tumor 4. PET study in patients with Parkinson's disease 5. A study on the clinical myocardial PET image. PET gives various metabolic information for the living human body, and is very important, new diagnostic modality. The PET study will give us the information of cancer patients such as early detection of cancer, staging, recurrence detection and characterization of cancer. The quantitative analysis using PET could be applied to evaluate the pathophysiology of various diseases and develop new drugs and develop new radiopharmaceuticals.

  10. PET applications in pediatrics

    Energy Technology Data Exchange (ETDEWEB)

    Shulkin, B. L. [Ann Arbor, Univ. of Michigan Medical Center (United States). Pediatric Nuclear Medicine Section

    1997-12-01

    This article summarizes the major PET studies which have been performed in pediatric patients to elucidate and characterize diseases and normal development. Issues special for the application of the technique in children, such as dosimetry, patient preparation, and image acquisition are discussed. Studies of central nervous system (CNS) development and pathology, including epilepsy, intraventricular hemorrhage, neonatal asphyxia, tumors, and effects on the CNS from treatment of other tumors are reviewed. These have contributed information fundamental to their understanding of CNS development and pathology. PET investigations into the pathophysiology of congenital heart disease have begun and hold great promise to aid their understanding of these conditions. The second major area in which PET has been applied is the study of non CNS neoplasms. Neuroblastoma has been investigated with tracers which explore basic biochemical features which characterize this tumor, as well as with tracers which explore biochemical events relatively specific for this malignancy. Other common and uncommon tumors of childhood are discussed. The PET technique has been shown useful for answering questions of clinical relevance for the management of these uncommon neoplasms. PET is likely to continue to aid their understanding of many pediatric diseases and may gain more widespread clinical acceptance as the technology continues to disseminate rapidly.

  11. Characterization of the radioactive metabolites of the 5-HT{sub 1A} receptor radioligand, [O-methyl-{sup 11}C]WAY-100635, in monkey and human plasma by HPLC: Comparison of the behaviour of an identified radioactive metabolite with parent radioligand in monkey using PET

    Energy Technology Data Exchange (ETDEWEB)

    Osman, Safiye; Lundkvist, Camilla; Pike, Victor W.; Halldin, Christer; McCarron, Julie A.; Swahn, Carl-Gunnar; Ginovart, Natalie; Luthra, Sajinder K.; Bench, Christopher J.; Grasby, Paul M.; Wikstroem, Haakan; Barf, Tjeerd; Cliffe, Ian A.; Fletcher, Allan; Farde, Lars

    1996-07-01

    N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N- (2-pyridyl)cyclohexanecarboxamide (WAY-100635), labelled in the O-methyl group with carbon-11 (t{sub (1(2))} = 20.4 min), is a promising radioligand for application with positron emission tomography (PET) to the study of 5-HT{sub 1A} receptors in living human brain. An understanding of the metabolism of this new radioligand is crucial to the development of a biomathematical model for the interpretation of the kinetics of radioactivity uptake in brain in terms of receptor-binding parameters. After intravenous injection of [O-methyl-{sup 11}C]WAY-100635 into humans, radioactivity was found to clear rapidly from blood and plasma. By using established methods for the analysis of radioactivity in plasma, it was found that intravenously injected [O-methyl-{sup 11}C]WAY-100635 is rapidly metabolised to more polar radioactive compounds in a cynomolgus monkey and in humans. Thus, at 60 min postinjection, parent radioligand represented 40% and 5% of the radioactivity in monkey and human plasma, respectively. In monkey and human, one of the radioactive metabolites was identified as the descyclohexanecarbonyl analogue of the parent radioligand, namely [O-methyl-{sup 11}C]WAY-100634. This compound is known to have high affinity for 5-HT{sub 1A} receptors and {alpha}{sub 1}-adrenoceptors. In a PET experiment it was demonstrated that, after IV injection of [O-methyl-{sup 11}C]WAY-100634 into a cynomolgus monkey, radioactivity was avidly taken up by brain. Uptake of radioactivity was higher in 5-HT{sub 1A} receptor-rich frontal cortex than in cerebellum, which is devoid of 5-HT{sub 1A} receptors. Polar radioactive metabolites appeared in plasma. The results suggest that the use of WAY-100635 labelled with carbon-11 in its cyclohexanecarbonyl moiety may provide enhanced signal contrast in PET studies and a possibility to develop a simple biomathematical model for regional brain radioactivity uptake.

  12. PET imaging in multiple sclerosis

    NARCIS (Netherlands)

    Faria, Daniele de Paula; Copray, Sjef; Buchpiguel, Carlos; Dierckx, Rudi; de Vries, Erik

    2014-01-01

    Positron emission tomography (PET) is a non-invasive technique for quantitative imaging of biochemical and physiological processes in animals and humans. PET uses probes labeled with a radioactive isotope, called PET tracers, which can bind to or be converted by a specific biological target and thus

  13. Cognitive dysfunction in senior pets.

    Science.gov (United States)

    Crowell-Davis, Sharon L

    2008-02-01

    Aging pets can experience declines in memory, learning, perception, and awareness. These pets may be disoriented, forget previously learned behaviors, develop new fears and anxiety, or change their interactions with people. When these changes are due to cognitive dysfunction, behavioral and environmental adjustments along with medical therapy can slow the progression and keep pets active longer.

  14. Reliability of (18)F-FDG PET Metabolic Parameters Derived Using Simultaneous PET/MRI and Correlation With Prognostic Factors of Invasive Ductal Carcinoma: A Feasibility Study.

    Science.gov (United States)

    Jena, Amarnath; Taneja, Sangeeta; Singh, Aru; Negi, Pradeep; Sarin, Ramesh; Das, Pratap K; Singhal, Manish

    2017-09-01

    The objective of our study was to correlate semiquantitative PET parameters-standardized uptake value (SUV) and total lesion glycolysis (TLG)-derived in simultaneous PET/MRI using MRI-based attenuation correction with clinical and histopathologic prognostic factors in patients with breast cancer. Eighty-two invasive ductal carcinomas in 69 women were included in the study. All the subjects underwent whole-body (WB) PET/MRI (supine WB mode) and dedicated PET/MRI of the breast (prone breast imaging mode) for staging on a simultaneous PET/MRI system. The SUV and TLG values were calculated from (18)F-FDG PET data using MRI-based attenuation correction (2-point Dixon sequence for tissue segmentation). Relationships between SUV and TLG values and clinical and histopathologic parameters (i.e., tumor size, tumor grade, Ki-67 status, and hormonal receptor expression status) were evaluated using Spearman correlation coefficient analysis. A significant correlation was observed between mean SUV (SUVmean) and maximum SUV (SUVmax) values derived with WB PET and regional PET of the breasts performed simultaneously with MRI (r = 0.88 and 0.89, respectively). A significant difference (p PET/MRI are reliable and correlate with clinicopathologic features such as grade as well as subtype and thus could be used in the prognostication of breast cancer.

  15. PET-CT; PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Schober, O. [Univeritaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Heindel, W. [Univeritaetsklinikum Muenster (Germany). Inst. fuer Klinische Radiologie

    2008-07-01

    Positron emission tomography - computerized tomography (PET-CT) is the fusion of two modern imaging techniques. The book includes the following chapters: 1. fundamentals: radiation protection aspects, radionuclide production, contrast agents, patient preparation, image interpretation; 2. diagnostics of carcinomas: carcinomas in brain, head-throat, thyroid, lungs, intestinal tract, gynecological carcinomas, urinary tract and bladder carcinomas, prostate carcinomas, malignant lymphomas, malignant malinomas, carcinomas in the skeletal system; 3. infections; 4. diagnostics of cardiovascular diseases; 5. diagnostics of neurodegenerative diseases; 6. developments and perspectives, 7. attachments: internet links, glossary, abbreviations.

  16. Clinical application of pet

    Directory of Open Access Journals (Sweden)

    Francisco Lomeña

    2005-10-01

    Full Text Available Positron emission tomography (PET is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT and magnetic resonance imaging (MRI, which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluordeoxyglucose-F18 (FDG PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.A tomografia por emissão de pósitrons (PET é uma técnica de diagnóstico por imagem que fornece informação sobre o metabolismo e funcionamento dos tecidos, diferente de outras técnicas de imagens como tomografia computadorizada (TC e ressonância magnética (RM, as quais fornecem informações estruturais ou anatômicas. O PET alcançou seu desenvolvimento em investigação biomédica devido à sua capacidade de usar traçadores análogos a muitas substâncias endógenas e de medir in vivo e de forma não invasiva seu consumo em diferentes órgãos e tecidos dos mamíferos 18Fluordesoxiglicose (FDG PET tem provado ser uma exploração de uso clínico com excelente relação custo benefício em oncologia e em muitas doenças neurológicas. Os atuais tomógrafos por PET-CT podem chegar a ser a melhor ferramenta de diagnóstico nos pacientes que sofrem de câncer.

  17. PET/MR in oncology

    DEFF Research Database (Denmark)

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin

    2012-01-01

    of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number...... be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new...

  18. PET/MR in oncology

    DEFF Research Database (Denmark)

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin

    2012-01-01

    of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number...... be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new...

  19. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  20. Fusion of PET and MRI for Hybrid Imaging

    Science.gov (United States)

    Cho, Zang-Hee; Son, Young-Don; Kim, Young-Bo; Yoo, Seung-Schik

    Recently, the development of the fusion PET-MRI system has been actively studied to meet the increasing demand for integrated molecular and anatomical imaging. MRI can provide detailed anatomical information on the brain, such as the locations of gray and white matter, blood vessels, axonal tracts with high resolution, while PET can measure molecular and genetic information, such as glucose metabolism, neurotransmitter-neuroreceptor binding and affinity, protein-protein interactions, and gene trafficking among biological tissues. State-of-the-art MRI systems, such as the 7.0 T whole-body MRI, now can visualize super-fine structures including neuronal bundles in the pons, fine blood vessels (such as lenticulostriate arteries) without invasive contrast agents, in vivo hippocampal substructures, and substantia nigra with excellent image contrast. High-resolution PET, known as High-Resolution Research Tomograph (HRRT), is a brain-dedicated system capable of imaging minute changes of chemicals, such as neurotransmitters and -receptors, with high spatial resolution and sensitivity. The synergistic power of the two, i.e., ultra high-resolution anatomical information offered by a 7.0 T MRI system combined with the high-sensitivity molecular information offered by HRRT-PET, will significantly elevate the level of our current understanding of the human brain, one of the most delicate, complex, and mysterious biological organs. This chapter introduces MRI, PET, and PET-MRI fusion system, and its algorithms are discussed in detail.

  1. Choosing a Pet

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    THE capital boasts countless markets of all kinds,but some of its insect,bird and pet markets immortalize Beijing culture and folkloric traditions.Don’t miss it! The Huasheng Tianqiao Market,south of the famous Panjiayuan Antique Market, was moved a few years ago and rebuilt in the

  2. I Love Petting Zoos!

    Centers for Disease Control (CDC) Podcasts

    2010-03-23

    This Kidtastics podcast helps children learn about how to stay safe and healthy when visiting petting zoos and other animal exhibits.  Created: 3/23/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/23/2010.

  3. Cold Weather Pet Safety

    Science.gov (United States)

    ... they can be knocked over, potentially starting a fire. Check your furnace before the cold weather sets in to make ... avoided because of the risk of burns or fire. Heated pet mats should also be used ... to burrow, get them back inside quickly because they are showing signs of ...

  4. PET's indsats under lup

    DEFF Research Database (Denmark)

    Hansen, Peer Henrik

    2006-01-01

    En undersøgelseskommission nedsat i 1999. Fem medlemmer skal undersøge PET's efterretningsvirksomhed i forhold til politiske partier, faglige konflikter og politisk ideologiske bevægelser i Danmark under den kolde krig. Kommissionens rapport forventes færdig næste år. Udgivelsesdato: 2. juli 2006...

  5. Pets and Parasites

    Science.gov (United States)

    ... to Be SafeTo avoid dog bites, teach your child how to behave around dogs.December 2010September 2000familydoctor.org editorial staffAvoiding SnakebitesRead Article >>Pets and AnimalsAvoiding SnakebitesLearn how to identify, treat, and ...

  6. PET and PET/CT in malignant melanoma; PET y PET/CT en melanoma maligno

    Energy Technology Data Exchange (ETDEWEB)

    Garcia O, J.R. [Nuclear Medicine and Molecular Imaging PET/CT, Centro Medico ABC, Mexico D.F. (Mexico)

    2007-07-01

    The advantages that it has the PET/CT are: 1. It diminishes mainly positive false lesions. It identifies physiologic accumulate places. 2. It diminishes in smaller grade false negative. Small injuries. Injuries with low grade concentration. Injure on intense activity areas. 3. Precise anatomical localization of accumulate places. 4. Reduction of the acquisition time. (Author)

  7. Birds Kept as Pets

    Science.gov (United States)

    ... Bird Importation website . Choosing a bird Match a bird's attitude, temperament, size, and activity level with your family, ... 2009;135:68-77 Compendium of Measures To Control Chlamydophila psittaci ... Pet Birds (Avian Chlamydiosis), 2010 [PDF – 17 pages] National Association ...

  8. Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[{sup 18}F]fluoromethyl-5-methyl-adamantane ({sup 18}F-MEM): a potential radioligand for mapping the NMDA-receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Samnick, Samuel; Ametamey, Simon; Leenders, Klaus L.; Vontobel, Peter; Quack, Guenter; Parsons, Chris G.; Neu, Henrik; Schubiger, Pius A

    1998-05-01

    The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane ({sup 19}F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that {sup 19}F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the {sup 18}F-labelled analog {sup 18}F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl-5- methyl-adamantane and the subsequent cleavage of the BOC-protecting group using aqueous HCl. The {sup 18}F-MEM was obtained in 22{+-}7% radiochemical yield (decay-corrected to EOB) in a total synthesis time including HPLC purification of 90 min. A biodistribution study after IV injection of {sup 18}F-MEM in mice showed a fast clearance of radioactivity from blood and relatively high initial uptake in the kidney and in the lung, which gradually decreased with time. The brain uptake was high (up to 3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10, 6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation of the radioactivity in the mouse brain was consistent with the known distribution of the PCP recognition site. Preliminary PET evaluation of the radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich regions (frontal cortex, striata, and temporal cortex). Delineation of the hippocampus, a region known to contain a high density of NMDA receptors, was not possible owing to the resolution of the PET tomograph. The regional brain uptake of {sup 18}F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801, indicating competition for the same binding sites. In a preliminary experiment, haloperidol, a dopamine D2 and sigma receptor

  9. Fundamentals of PET and PET/CT imaging.

    Science.gov (United States)

    Basu, Sandip; Kwee, Thomas C; Surti, Suleman; Akin, Esma A; Yoo, Don; Alavi, Abass

    2011-06-01

    In this review, the fundamental principles of fluorodeoxyglucose (FDG) positron emission tomography (PET) and FDG PET/computed tomography (CT) imaging have been described. The basic physics of PET instrumentation, radiotracer chemistry, and the artifacts, as well as normal physiological or benign pathological variants, have been described and presented to the readers in a lucid manner to enable them an easy grasp of the fundamentals of the subject. Finally, we have outlined the current developments in quantitative PET imaging, including dual time point and delayed PET imaging, time-of-flight technology in PET imaging and partial volume correction, and global disease assessment with their potential of being incorporated into the assessment of benign and malignant disorders.

  10. 64Cu-DOTATATE PET/MRI for detection of activated macrophages in carotid atherosclerotic plaques

    DEFF Research Database (Denmark)

    Pedersen, Sune Folke; Sandholt, Benjamin Vikjær; Keller, Sune Høgild

    2015-01-01

    positron emission tomography (PET) and the novel PET ligand [(64)Cu] [1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid]-d-Phe1,Tyr3-octreotate (64Cu-DOTATATE) to specifically target macrophages via the somatostatin receptor subtype-2 in vivo. APPROACH AND RESULTS: Ten patients underwent...

  11. 'Reverse discordance' between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan: the plausible explanations and its implications for high-dose therapy with radiolabeled somatostatin receptor analogs.

    Science.gov (United States)

    Basu, Sandip; Abhyankar, Amit; Kand, Purushottam; Kumar, Rakesh; Asopa, Ramesh; Rajan, Mysore Govinda Ramakrishna; Nayak, Uday; Shimpi, Hemant; Das, Tapas; Venkatesh, Meera; Chakrabarty, Sudipta; Banerjee, Sharmila

    2011-07-01

    In this technical note, an unusual discordance between diagnostic and posttherapeutic scan resulting from the use of different somatostatin receptor ligands in two settings is described. Such observation, we believe, is multifactorial, but most importantly arises due to different receptor affinity profile of the ligands and different somatostatin receptor subtype expression in different tumors. It is important for the treating physician to be aware of this phenomenon that would aid in improving our understanding of complex ligand-receptor interactions in various somatostatin receptor-positive tumors with its possible implications for therapeutic decision making with radiolabeled somatostatin receptor analogues.

  12. Are Pets Good For Us?

    Institute of Scientific and Technical Information of China (English)

    邢连香

    2006-01-01

    A pet animal keeps us feel happy.Pets can staywith us when we are left by ourselves,and pets in-vite us to love and be loved.Often a cat or dog cankeep us easy at time when human words don’t help.Pets also keep us get close to the more natural animalworld.Learning to care for a pet helps a child to growup into a loving man or woman who feels responsible(有责任的) towards those dependent (依靠) on him.A pet dog can make us believe in others for we cansee faithfulness (忠诚) in the dog.In fact,we keeppets not only fo...

  13. Ingredients: where pet food starts.

    Science.gov (United States)

    Thompson, Angele

    2008-08-01

    Every clinician is asked "What should I feed my pet?" Understanding the ingredients in pet food is an important part of making the best recommendation. Pet food can be as simple as one ingredient or as complicated as containing more than 60 ingredients. Pet food and its ingredients are regulated by the Food and Drug Administration and state feed officials. Part of that regulation is the review and definition of ingredients. Existing ingredients change and new ingredients become available so the need for ingredient definitions grows. Ingredients for product formulations are chosen based on their nutrient content, digestibility, palatability, functionality, availability, and cost. As an example, a typical, nutritionally complete dry dog food with 42 ingredients is examined and the ingredients are discussed here. Safe, healthy pet food starts with safe ingredients sourced from well-monitored suppliers. The ultimate goal of both veterinarians and pet food manufacturers is the same--long healthy lives for dogs and cats.

  14. Infections That Pets Carry (For Parents)

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Infections That Pets Carry KidsHealth > For Parents > Infections That Pets Carry ... how to protect your family from infections. How Pets Spread Infections Like people, all animals carry germs . ...

  15. Pet overpopulation: An economic analysis

    OpenAIRE

    Coate, Stephen; Knight, Brian

    2009-01-01

    This paper considers the problem of pet overpopulation. It develops a tractable dynamic model whose positive predictions square well with key features of the current U.S. market for pets. The model is used to understand, from a welfare economic perspective, the sense in which there is \\overpopulation" of pets and the underlying causes of the problem. The paper also employs the model to consider what policies might be implemented to deal with the problem. A calibrated example is developed to i...

  16. PET and Recycling

    Directory of Open Access Journals (Sweden)

    Funda Sevencan

    2007-08-01

    Full Text Available This review aims to clarify the need of decreasing the environmental effects caused by human and draw attention to the increasing environmental effects of plastics wastes. Plastics consist of organic molecules with high density molecules or polymers. Main resources of plastics are the residue of oil rafineries. Several advantages of plastics, have increased the usage continuously. Polyethylene Terephthalate (PET is the most commonly used plastics. PET is used to protect food, drinking water, fruit juice, alcoholic beverage, and food packing films. By the increasing interest on the environmental effects of plastic wastes, concerns on the recyclable packing materials also grew up. Also the daily use of recyclable containers consisting PET have increased. There are five steps for recycling of plastics. These steps are; using large amounts of plastics, collecting them in a big center, classifying and sorting the plastics, reproducing the polymers and obtaining new products with melted plastics. Providing a healthy recycling of plastics, the consumers should have knowledge and responsibility. The consumer should know what he/she has to do before putting the plastics in the recycling containers. Recycling containers and bags should be placed near the sources of plastic wastes. Consequently, the plastic wastes and environmental problems they cause will be on the agenda in future. [TAF Prev Med Bull. 2007; 6(4: 307-312

  17. PET imaging in ectopic Cushing syndrome: a systematic review.

    Science.gov (United States)

    Santhanam, Prasanna; Taieb, David; Giovanella, Luca; Treglia, Giorgio

    2015-11-01

    Cushing syndrome due to endogenous hypercortisolism may cause significant morbidity and mortality. The source of excess cortisol may be adrenal, pituitary, or ectopic. Ectopic Cushing syndrome is sometimes difficult to localize on conventional imaging like CT and MRI. After performing a multilevel thoracoabdominal imaging with CT, the evidence regarding the use of radiotracers for PET imaging is unclear due to significant molecular and etiological heterogeneity of potential causes of ectopic Cushing's syndrome. In our systematic review of literature, it appears that GalLium-based (Ga68) somatostatin receptor analogs have better sensitivity in diagnosis of bronchial carcinoids causing Cushing syndrome and FDG PET appears superior for small-cell lung cancers and other aggressive tumors. Further large-scale studies are needed to identify the best PET tracer for this condition.

  18. Extended suicide with a pet.

    Science.gov (United States)

    Cooke, Brian K

    2013-01-01

    The combination of the killing of a pet and a suicide is a perplexing scenario that is largely unexplored in the literature. Many forensic psychiatrists and psychologists may be unaccustomed to considering the significance of the killing of a pet. The subject is important, however, because many people regard their pets as members of their family. A case is presented of a woman who killed her pet dog and herself by carbon monoxide poisoning. The purpose of this article is to provide an initial exploration of the topic of extended suicide with a pet. Forensic mental health evaluations may have a role in understanding the etiology of this event and in opining as to the culpability of individuals who attempt to or successfully kill a pet and then commit suicide. Because the scientific literature is lacking, there is a need to understand this act from a variety of perspectives. First, a social and anthropological perspective will be presented that summarizes the history of the practice of killing of one's pet, with a focus on the ancient Egyptians. A clinical context will examine what relationship animals have to mental illness. A vast body of existing scientific data showing the relevance of human attachment to pets suggests that conclusions from the phenomena of homicide-suicide and filicide-suicide are applicable to extended suicide with a pet. Finally, recommendations will be proposed for both clinical and forensic psychiatrists faced with similar cases.

  19. Respiratory gating in cardiac PET

    DEFF Research Database (Denmark)

    Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E

    2017-01-01

    BACKGROUND: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim...... stress (82)RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4.......7) min(-1), P PET...

  20. Targeted microbubbles for imaging tumor angiogenesis: assessment of whole-body biodistribution with dynamic micro-PET in mice

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Cheng, Zhen; Davis, Corrine;

    2008-01-01

    To evaluate in vivo whole-body biodistribution of microbubbles (MBs) targeted to tumor angiogenesis-related vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by using dynamic micro-positron emission tomography (PET) in living mice....

  1. Modification of Fluorescent Photoinduced Electron Transfer (PET) Sensors/Switches To Produce Molecular Photo-Ionic Triode Action**

    Science.gov (United States)

    Huxley, Allen J M; Schroeder, Marc; Nimal Gunaratne, H Q; Prasanna de Silva, A

    2014-01-01

    The fluorophore-spacer1-receptor1-spacer2-receptor2 system (where receptor2 alone is photoredox-inactive) shows ionically tunable proton-induced fluorescence off-on switching, which is reminiscent of thermionic triode behavior. This also represents a new extension to modular switch systems based on photoinduced electron transfer (PET) towards the emulation of analogue electronic devices. PMID:24574178

  2. Synthesis, in vitro and in vivo pharmacology of a C-11 labeled analog of CP-101,606, ({+-})threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[{sup 11}C]methoxyphenyl) peridino]-1-propanol, as a PET tracer for NR2B subunit-containing NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Haradahira, Terushi E-mail: terushi@nirs.go.jp; Maeda, Jun; Okauchi, Takashi; Zhang, Ming-Rong; Hojo, Junko; Kida, Takayo; Arai, Takuya; Yamamoto, Fumihiko; Sasaki, Shigeki; Maeda, Minoru; Suzuki, Kazutoshi; Suhara, Tetsuya

    2002-07-01

    A carbon-11 labeled methoxyl analog of CP-101,606, ({+-})threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[{sup 11}C]methoxyphenyl) piperidino]-1-propanol [({+-})[{sup 11}C]1], was synthesized as a new subtype-selective PET radioligand for NMDA receptors. The in vitro binding studies using rat brain slices demonstrated that ({+-})[{sup 11}C]1 shows an extremely high-specific binding to the NR2B subunit of NMDA receptors. In contrast to the in vitro binding, the in vivo binding to mouse and monkey brains showed no apparent specific localization of the radioactivity in any of the brain regions. Metabolism and physicochemical properties such as the lipophilicity of ({+-})[{sup 11}C]1 seemed unlikely to affect the in vivo ({+-})[{sup 11}C]1 binding. Among the various endogenous ligands acting at the NMDA receptors, polyamines (spermine and spermidine) and divalent cations (Mg{sup 2+,} Zn{sup 2+,} and Ca{sup 2+}) strongly inhibited the in vitro ({+-})[{sup 11}C]1 binding. Thus, the present studies point to the possibility that the polyamines and cations behave as endogenous inhibitors for ({+-})[{sup 11}C]1 binding, leading to the loss of the specific binding in vivo.

  3. Cost-effectiveness of PET and PET/Computed Tomography

    DEFF Research Database (Denmark)

    Gerke, Oke; Hermansson, Ronnie; Hess, Søren

    2015-01-01

    measure by means of incremental cost-effectiveness ratios when considering the replacement of the standard regimen by a new diagnostic procedure. This article discusses economic assessments of PET and PET/computed tomography reported until mid-July 2014. Forty-seven studies on cancer and noncancer...

  4. 10 "Poison Pills" for Pets

    Science.gov (United States)

    ... by Animal/Species Browse by Topic Browse by Discipline Resources Tools for K-12 Educators You are here: Home | Public Resources | Pet ... of all phone calls to the ASPCA Animal Poison Control Center (APCC) are about human medications. Your pet can easily ingest dropped pills ...

  5. Small Molecule PET-Radiopharmaceuticals

    NARCIS (Netherlands)

    Elsinga, Philip H.; Dierckx, Rudi A. J. O.

    2014-01-01

    This review describes several aspects required for the development of small molecule PET-tracers. Design and selection criteria are important to consider before starting to develop novel PET-tracers. Principles and latest trends in C-11 and F-18-radiochemistry are summarized. In addition an update o

  6. Welfare assessment in pet rabbits

    NARCIS (Netherlands)

    Schepers, F.; Koene, P.; Beerda, B.

    2009-01-01

    One million pet rabbits are kept in The Netherlands, but there are no data available on their behaviour and welfare. This study seeks to assess the welfare of pet rabbits in Dutch households and is a first step in the development of a welfare assessment system. In an internet survey, housing

  7. Prospective evaluation of {sup 68}Ga-DOTANOC PET-CT in differentiated thyroid cancer patients with raised thyroglobulin and negative {sup 131}I-whole body scan: comparison with {sup 18}F-FDG PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Parveen; Lata, Sneh; Sharma, Punit; Singh, Harmandeep; Malhotra, Arun; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India)

    2014-07-15

    The purpose of the study was to evaluate the role of {sup 68}Ga-DOTANOC PET-CT in differentiated thyroid cancer (DTC) patients with negative {sup 131}I-whole body scan (WBS) along with serially increasing serum thyroglobulin (Tg), and compare the same with {sup 18}F-FDG PET-CT. Sixty two DTC patients with serially rising Tg levels and negative {sup 131}I-WBS were prospectively enrolled. All patients underwent {sup 68}Ga-DOTANOC PET-CT and {sup 18}F-FDG PET-CT within an interval of two weeks. PET-CT analysis was done on a per-patient basis, location wise and lesion wise. All PET-CT lesions were divided into four categories-local, nodal, pulmonary and skeletal. Histopathology and/or serial serum Tg level, clinical and imaging follow up (minimum-1 year) were used as a reference standard. Ga-DOTANOC PET-CT demonstrated disease in 40/62 (65 %) patients and {sup 18}F-FDG PET-CT in 45/62 (72 %) patients, with no significant difference on McNemar analysis (p = 0.226). Per-patient sensitivity and specificity of {sup 68}Ga-DOTANOC PET-CT was 78.4 %, 100 %, and for {sup 18}F-FDG PET-CT was 86.3 %, 90.9 %, respectively. Out of 186 lesions detected by both PET-CTs, 121/186 (65 %) lesions were seen on {sup 68}Ga-DOTANOC PET-CT and 168/186 (90.3 %) lesions on {sup 18}F-FDG PET-CT (p < 0.0001). There were 103/186 (55 %) lesions concordant on both. Excellent agreement was noted between {sup 68}Ga-DOTANOC PET-CT and {sup 18}F-FDG PET-CT for detection of local disease (k = 0.92), while moderate agreement was noted for nodal and pulmonary disease (k = 0.67). {sup 68}Ga-DOTANOC PET-CT changed management in 21/62 (34 %) patients and {sup 18}F-FDG PET-CT in 17/62 (27 %) patients. Ga-DOTANOC PET-CT is inferior to {sup 18}F-FDG PET-CT on lesion based but not on patient based analysis for detection of recurrent/residual disease in DTC patients with negative WBS scan and elevated serum Tg levels. It can also help in selection of potential candidates for peptide receptor radionuclide therapy

  8. Supplements for exotic pets.

    Science.gov (United States)

    Mejia-Fava, Johanna; Colitz, Carmen M H

    2014-09-01

    The use of supplements has become commonplace in an effort to complement traditional therapy and as part of long-term preventive health plans. This article discusses historical and present uses of antioxidants, vitamins, and herbs. By complementing traditional medicine with holistic and alternative nutrition and supplements, the overall health and wellness of exotic pets can be enhanced and balanced. Further research is needed for understanding the strengths and uses of supplements in exotic species. Going back to the animals' origin and roots bring clinicians closer to nature and its healing powers.

  9. PET and PET/CT - relevance in breast cancer patients; PET und PET/CT - Stellenwert beim Mammakarzinom

    Energy Technology Data Exchange (ETDEWEB)

    Palmedo, H. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Bonn (Germany)

    2004-12-01

    Breast cancer is the most frequent malignant tumor of women in Germany. In spite of an increasing incidence mortality has slightly declined most likely due to improvements in diagnosis and therapy of the disease. FDG-PET has a high diagnostic accuracy for the detection of lymph node and distant metastases. However, PET is no alternative to axillary dissection or sentinel node biopsy because sensitivity for small lymph node metastases is limited. For N-staging, FDG-PET delivers valuable information if mammaria-interna or mediastinal lymph node disease has to be proven (1b-indication). Individually, PET can add important diagnostic information in patients with suspected distant metastases but unsuspicious or equivocal conventional imaging (2-indication). FDG-PET shows unique and favourable properties for early therapy monitoring during preoperative chemotherapy. Larger studies have to confirm these results. (orig.)

  10. PET imaging reveals brain functional changes in internet gaming disorder

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Mei; Zhang, Ying; Du, Fenglei; Hou, Haifeng; Chao, Fangfang; Zhang, Hong [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Chen, Qiaozhen [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Psychiatry, Hangzhou (China)

    2014-07-15

    Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D{sub 2} (D{sub 2})/Serotonin 2A (5-HT{sub 2A}) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D{sub 2} receptor and glucose metabolism. Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and {sup 11}C-N-methylspiperone ({sup 11}C-NMSP) to assess the availability of D{sub 2}/5-HT{sub 2A} receptors and with {sup 18}F-fluoro-D-glucose ({sup 18}F-FDG) to assess regional brain glucose metabolism, a marker of brain function. {sup 11}C-NMSP and {sup 18}F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D{sub 2} receptors was observed in the striatum, and was correlated to years of overuse. A low level of D{sub 2} receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. For the first time, we report the evidence that D{sub 2} receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D{sub 2}/5-HT{sub 2A} receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects. (orig.)

  11. Diagnostic and prognostic correlates of preoperative FDG PET for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Vinh-Hung, Vincent [University of Geneva, Department of Imaging and Medical Information Sciences, University Hospitals of Geneva, Geneva (Switzerland); University of Geneva, Radiation Oncology, University Hospitals of Geneva, Geneva (Switzerland); Everaert, Hendrik [Vrije Universiteit Brussel, Department of Nuclear Medicine, UZ Brussel, Brussels (Belgium); Lamote, Jan; Vanhoeij, Marian; Verfaillie, Guy [Vrije Universiteit Brussel, Department of Surgery, UZ Brussel, Brussels (Belgium); Voordeckers, Mia; Parijs, Hilde van; Ridder, Mark de [Vrije Universiteit Brussel, Department of Radiotherapy, UZ Brussel, Brussels (Belgium); Fontaine, Christel [Vrije Universiteit Brussel, Department of Medical Oncology UZ Brussel, Brussels (Belgium); Vees, Hansjoerg; Ratib, Osman [University of Geneva, Department of Imaging and Medical Information Sciences, University Hospitals of Geneva, Geneva (Switzerland); Vlastos, Georges [University of Geneva, Department of Surgical Senology, University Hospitals of Geneva, Geneva (Switzerland)

    2012-10-15

    To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients. (orig.)

  12. {sup 68}Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Sathekge, Mike; Lengana, Thabo; Modiselle, Moshe; Vorster, Mariza; Zeevaart, JanRijn; Ebenhan, Thomas [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine, Pretoria (South Africa); Maes, Alex [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine, Pretoria (South Africa); AZ Groeninge, Department of Nuclear Medicine, Kortrijk (Belgium); Wiele, Christophe van de [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine, Pretoria (South Africa); University Ghent, Department of Radiology and Nuclear Medicine, Ghent (Belgium)

    2017-04-15

    To report on imaging findings using {sup 68}Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients. {sup 68}Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status. Out of 81 tumor lesions identified, 84% were identified on {sup 68}Ga-PSMA-HBED-CC PET. {sup 68}Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p = 0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p = 0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and {sup 68}Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r = 0.407, p = 0.015). {sup 68}Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry. (orig.)

  13. FDG PET imaging dementia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medical School and Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2007-04-15

    Dementia is a major burden for many countries including South Korea, where life expectancy is continuously growing and the proportion of aged people is rapidly growing. Neurodegenerative disorders, such as, Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia. Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, can cause dementia, and cerebrovascular disease also can cause dementia. Depression or hypothyroidism also can cause cognitive deficits, but they are reversible by management of underlying cause unlike the forementioned dementias. Therefore these are called pseudodementia. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new drugs postpone progression of dementias or target specific proteins that cause dementia. Efficient pharmacologic treatment of dementia needs not only to distinguish underlying causes of dementia but also to be installed as soon as possible. Therefore, differential diagnosis and early diagnosis of dementia are utmost importance. F-18 FDG PET is useful for clarifying dementing diseases and is also useful for early detection of the disease. Purpose of this article is to review the current value of FDG PET for dementing diseases including differential diagnosis of dementia and prediction of evolving dementia.

  14. 36 CFR 2.15 - Pets.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 2.15 Section 2.15 Parks... USE AND RECREATION § 2.15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public... area closed to the possession of pets by the superintendent. This subparagraph shall not apply to...

  15. 36 CFR 1002.15 - Pets.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Pets. 1002.15 Section 1002.15....15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public building, public... possession of pets by the Board. This paragraph shall not apply to guide dogs accompanying visually...

  16. 7 CFR 502.11 - Pets.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 502.11 Section 502.11 Agriculture Regulations of... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.11 Pets. Pets... vaccinations. Pets that are the property of employees residing on BARC must be up to date on their...

  17. Pet food recalls and pet food contaminants in small animals.

    Science.gov (United States)

    Bischoff, Karyn; Rumbeiha, Wilson K

    2012-03-01

    Most pet foods are safe, but incidents of chemical contamination occur and lead to illness and recalls. There were 11 major pet food recalls in the United States between 1996 and 2010 that were due to chemical contaminants or misformulations: 3 aflatoxin, 3 excess vitamin D3, 1 excess methionine, 3 inadequate thiamine, and 1 adulteration with melamine and related compounds and an additional 2 warnings concerning a Fanconilike renal syndrome in dogs after ingesting large amounts of chicken jerky treat products. This article describes clinical findings and treatment of animals exposed to the most common pet food contaminants.

  18. PET-Based Thoracic Radiation Oncology.

    Science.gov (United States)

    Simone, Charles B; Houshmand, Sina; Kalbasi, Anusha; Salavati, Ali; Alavi, Abass

    2016-07-01

    Fluorodeoxyglucose-PET is increasingly being integrated into multiple aspects of oncology. PET/computed tomography (PET/CT) has become especially important in radiation oncology. With the increasing use of advanced techniques like intensity-modulated radiation therapy and proton therapy, PET/CT scans have played critical roles in the target delineation of tumors for radiation oncologists delivering conformal treatment techniques. Use of PET/CT is well established in lung cancer and several other thoracic malignancies. This article details the current uses of PET/CT in thoracic radiation oncology with a focus on lung cancer and describes expected future roles of PET/CT for thoracic tumors.

  19. Small Molecule PET Tracers for Transporter Imaging.

    Science.gov (United States)

    Kilbourn, Michael R

    2017-09-01

    As the field of PET has expanded and an ever-increasing number and variety of compounds have been radiolabeled as potential in vivo tracers of biochemistry, transporters have become important primary targets or facilitators of radiotracer uptake and distribution. A transporter can be the primary target through the development of a specific high-affinity radioligand: examples are the multiple high-affinity radioligands for the neuronal membrane neurotransmitter or vesicular transporters, used to image nerve terminals in the brain. The goal of a radiotracer might be to study the function of a transporter through the use of a radiolabeled substrate, such as the application of 3-O-[(11)C]methyl]glucose to measure rates of glucose transport through the blood-brain barrier. In many cases, transporters are required for radiotracer distributions, but the targeted biochemistries might be unrelated: an example is the use of 2-deoxy-2-[(18)F]FDG for imaging glucose metabolism, where initial passage of the radiotracer through cell membranes requires the action of specific glucose transporters. Finally, there are transporters such as p-glycoprotein that function to extrude small molecules from tissues, and can effectively work against successful uptake of radiotracers. The diversity of structures and functions of transporters, their importance in human health and disease, and their role in therapeutic drug disposition suggest that in vivo imaging of transporter location and function will continue to be a point of emphasis in PET radiopharmaceutical development. In this review, the variety of transporters and their importance for in vivo PET radiotracer development and application are discussed. Transporters have thus joined the other major protein targets such as G-protein coupled receptors, ligand-gated ion channels, enzymes, and aggregated proteins as of high interest for understanding human health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Carbon-11 and iodine-123 labelled iomazenil: a direct PET-SPET comparison

    Energy Technology Data Exchange (ETDEWEB)

    Westera, G. [Div. of Nuclear Medicine, Dept. of Radiology, Univ. Hospital Zurich (Switzerland); Buck, A. [Div. of Nuclear Medicine, Dept. of Radiology, Univ. Hospital Zurich (Switzerland); Burger, C. [Div. of Nuclear Medicine, Dept. of Radiology, Univ. Hospital Zurich (Switzerland); Leenders, K.L. [Paul Scherrer Inst., Villigen (Switzerland); Schulthess, G.K. von [Div. of Nuclear Medicine, Dept. of Radiology, Univ. Hospital Zurich (Switzerland); Schubiger, A.P. [Paul Scherrer Inst., Villigen (Switzerland)

    1996-01-01

    The benzodiazepine receptor ligand iomazenil was labelled with carbon-11 to allow a direct positron emission tomography/single-photon emission tomography (PET/SPET) comparison with the well-known iodine-123 labelled compound. Imaging showed the same regional distribution for both modalities. Blood sample activity was corrected for metabolites by extraction with chloroform and high-performance liquid chromatographic analysis. Metabolism is very fast: 5 Min after application more than 85% of the plasma activity is present as hydrophilic metabolites. Kinetic methods were used to obtain regional estimates of transport rate constants and receptor concentrations. A three-compartment model was employed which gave transport rate constants for brain uptake (K{sub 1}) and the distribution volume for the specifically receptor bound compartment (DV{sub S}). K{sub 1} varied from 0.32 to 0.50 ml/min per gram for the cortical regions, cerebellum, thalamus and striatum for PET and SPET. The coefficient of variation of the SPET parameters was quite comparable to that of the PET parameters, especially after 180 min (PET 90 min) study duration. Thus quantitative benzodiazepine receptor information can be obtained from dynamic SPET imaging in the same way as with PET. (orig./MG)

  1. Current status of PET imaging in Huntington's disease.

    Science.gov (United States)

    Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

    2016-06-01

    To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading "Huntington Disease" combined with text and key words "Huntington Disease", "Neuroimaging" and "PET". Only peer-reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([(18)F]FDG and [(15)O]H2O), presynaptic ([(18)F]fluorodopa, [(11)C]β-CIT and [(11)C]DTBZ) and postsynaptic ([(11)C]SCH22390, [(11)C]FLB457 and [(11)C]raclopride) dopaminergic function, phosphodiesterases ([(18)F]JNJ42259152, [(18)F]MNI-659 and [(11)C]IMA107), and adenosine ([(18)F]CPFPX), cannabinoid ([(18)F]MK-9470), opioid ([(11)C]diprenorphine) and GABA ([(11)C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed for monitoring potential neuroprotective and preventive treatment in HD.

  2. PET/TAC in Oncology; PET/TAC en Oncologia

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez V, A.M. [Especialista en Medicina Nuclear, Profa. Depto. Radiologia de la Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain)

    2007-07-01

    From this presentation of PET-TAC in oncology the following advantages on the conventional PET are obtained: 1. More short study and stadium in one session. 2. It adds the information of both techniques. 3. Better localization of leisure: affected organ, stadium change (neck, mediastinum, abdomen). 4. Reduction of false positive (muscle, brown fat, atelectasis, pneumonias, intestine, urinary vials, etc.). 5. Reduction of negative false. 6. Reduction of not conclusive. 7. More understandable for other specialists. 8. Biopsies guide. 9. Planning radiotherapy.

  3. Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D2/3 receptors and sub-cortical volumes in the human basal ganglia: A PET study with (18)F-MNI-659 and (11)C-raclopride with correction for partial volume effect.

    Science.gov (United States)

    Fazio, Patrik; Schain, Martin; Mrzljak, Ladislav; Amini, Nahid; Nag, Sangram; Al-Tawil, Nabil; Fitzer-Attas, Cheryl J; Bronzova, Juliana; Landwehrmeyer, Bernhard; Sampaio, Cristina; Halldin, Christer; Varrone, Andrea

    2017-05-15

    Phosphodiesterase 10A enzyme (PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington´s disease (HD). PDE10A is expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D2/3 receptors (D2/3 R). The aim of this study was to examine the availability of PDE10A enzyme in relation with age and gender and to compare those changes with those related to D2/3 R and volumes in different regions of the basal ganglia. As a secondary objective we examined the relative distribution of D2/3 R and PDE10A enzyme in the striatum and globus pallidus. Forty control subjects (20F/20M; age: 44±11y, age range 27-69) from an ongoing positron emission tomography (PET) study in HD gene expansion carriers were included. Subjects were examined with PET using the high-resolution research tomograph (HRRT) and with 3T magnetic resonance imaging (MRI). The PDE10A radioligand (18)F-MNI-659 and D2/3 R radioligand (11)C-raclopride were used. The outcome measure was the binding potential (BPND) estimated with the two-tissue compartment model ((18)F-MNI-659) and the simplified reference tissue model ((11)C-raclopride) using the cerebellum as reference region. The PET data were corrected for partial volume effects. In the striatum, PDE10A availability showed a significant age-related decline that was larger compared to the age-related decline of D2/3 R availability and to the age-related decline of volumes measured with MRI. In the globus pallidus, a less pronounced decline of PDE10A availability was observed, whereas D2/3 R availability and volumes seemed to be rather stable with aging. The distribution of the PDE10A enzyme was different from the distribution of D2/3 R, with higher availability in the globus pallidus. These results indicate that aging is associated with a considerable physiological reduction of the availability of PDE10A enzyme in the

  4. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis.

    Science.gov (United States)

    Gormsen, Lars C; Haraldsen, Ate; Kramer, Stine; Dias, Andre H; Kim, Won Yong; Borghammer, Per

    2016-12-01

    Cardiac sarcoidosis (CS) is a potentially fatal condition lacking a single test with acceptable diagnostic accuracy. (18)F-FDG PET/CT has emerged as a promising imaging modality, but is challenged by physiological myocardial glucose uptake. An alternative tracer, (68)Ga-DOTANOC, binds to somatostatin receptors on inflammatory cells in sarcoid granulomas. We therefore aimed to conduct a proof-of-concept study using (68)Ga-DOTANOC to diagnose CS. In addition, we compared diagnostic accuracy and inter-observer variability of (68)Ga-DOTANOC vs. (18)F-FDG PET/CT. Nineteen patients (seven female) with suspected CS were prospectively recruited and dual tracer scanned within 7 days. PET images were reviewed by four expert readers for signs of CS and compared to the reference standard (Japanese ministry of Health and Welfare CS criteria). CS was diagnosed in 3/19 patients. By consensus, 11/19 (18)F-FDG scans and 0/19 (68)Ga-DOTANOC scans were rated as inconclusive. The sensitivity of (18)F-FDG PET for diagnosing CS was 33 %, specificity was 88 %, PPV was 33 %, NPV was 88 %, and diagnostic accuracy was 79 %. For (68)Ga-DOTANOC, accuracy was 100 %. Inter-observer agreement was poor for (18)F-FDG PET (Fleiss' combined kappa 0.27, NS) and significantly better for (68)Ga-DOTANOC (Fleiss' combined kappa 0.46, p = 0.001). Despite prolonged pre-scan fasting, a large proportion of (18)F-FDG PET/CT images were rated as inconclusive, resulting in low agreement among reviewers and correspondingly poor diagnostic accuracy. By contrast, (68)Ga-DOTANOC PET/CT had excellent diagnostic accuracy with the caveat that inter-observer variability was still significant. Nevertheless, (68)Ga-DOTANOC PET/CT looks very promising as an alternative CS PET tracer. Current Controlled Trials NCT01729169 .

  5. Veterinarians' role for pet owners facing pet loss.

    Science.gov (United States)

    Fernandez-Mehler, P; Gloor, P; Sager, E; Lewis, F I; Glaus, T M

    2013-05-25

    Owners' satisfaction with, and expectations from, their veterinarians around euthanasia, including questions on disposal of pet remains subject to animal species, clients' gender, age, family conditions, area of living and type of veterinary clinic visited were evaluated by questionnaire. Questionnaires were to be filled out by clients consecutively visiting the individual practices and hospitals for any kind of consultations. Of 2350 questionnaires distributed, 2008 were returned and available for analysis. Owner satisfaction concerning the procedure of euthanasia was high (92 per cent, 1173/1272). After the event of euthanasia, 14 per cent (170/1250) had changed their veterinarian, even though 75 per cent of these 170 had been satisfied with the procedure. Most owners (88 per cent) expected veterinarians to talk about their pet's final destination, and 38 per cent expected this to happen early in the pet's life. For 81 per cent clients, the veterinarian was the primary informant about the possibilities concerning the disposal of pet remains, and 33 per cent indicated their veterinarian as the contact person to talk about pet loss. Area of living, or veterinary specialisation, only marginally influenced the answers. Veterinarians play an important role to inform their clients concerning questions around euthanasia and the care of pet remains, and to support them during the process of mourning.

  6. PET kinetic analysis --pitfalls and a solution for the Logan plot.

    Science.gov (United States)

    Kimura, Yuichi; Naganawa, Mika; Shidahara, Miho; Ikoma, Yoko; Watabe, Hiroshi

    2007-01-01

    The Logan plot is a widely used algorithm for the quantitative analysis of neuroreceptors using PET because it is easy to use and simple to implement. The Logan plot is also suitable for receptor imaging because its algorithm is fast. However, use of the Logan plot, and interpretation of the formed receptor images should be regarded with caution, because noise in PET data causes bias in the Logan plot estimates. In this paper, we describe the basic concept of the Logan plot in detail and introduce three algorithms for the Logan plot. By comparing these algorithms, we demonstrate the pitfalls of the Logan plot and discuss the solution.

  7. Take Care with Pet Reptiles

    Science.gov (United States)

    ... Past Emails CDC Features Take Care with Pet Reptiles and Amphibians Language: English Español (Spanish) Recommend on ... messages, and helpful resources. Safe Handling Tips for Reptiles and Amphibians Always wash your hands thoroughly after ...

  8. PET and PET/CT in tumour of undetermined origin; PET y PET/CT en tumor de origen indeterminado

    Energy Technology Data Exchange (ETDEWEB)

    Garcia O, J.R. [Nuclear Medicine and Molecular Imaging, PET/CT, Centro Medico ABC, Mexico D.F. (Mexico)

    2007-07-01

    In this presentation the following conclusions were obtained regarding the use of PET and PET/CT in patient with cancer of unknown primary: 1. Detection of the primary one in 1/3 at 1/2 of patient. 2. It detects metastases in other places in 50%. 3. It changes the initial therapy planned in 1/3 at 1/2 of patient. 4. Useful in initial phases of protocol study to limit the other procedures. After standard evaluation. Before advanced protocol. 5. PET/CT study increases the % of primary detection, although in a non significant way vs. PET. 6. They are required more studies to value their utility to a more objective manner. (Author)

  9. Do carotid MR surface coils affect PET quantification in PET/MR imaging?

    Energy Technology Data Exchange (ETDEWEB)

    Willemink, Martin J; Eldib, Mootaz [Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Leiner, Tim [Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Fayad, Zahi A; Mani, Venkatesh [Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (United States)

    2015-05-18

    To evaluate the effect of surface coils for carotid MR imaging on PET quantification in a clinical simultaneous whole-body PET/MR scanner. A cylindrical phantom was filled with a homogeneous 2L water-FDG mixture at a starting dose of 301.2MBq. Clinical PET/MR and PET/CT systems were used to acquire PET-data without a coil (reference standard) and with two carotid MRI coils (Siemens Special Purpose 8-Channel and Machnet 4-Channel Phased Array). PET-signal attenuation was evaluated with Osirix using 51 (PET/MR) and 37 (PET/CT) circular ROIs. Mean and maximum standardized uptake values (SUVs) were quantified for each ROI. Furthermore, SUVs of PET/MR and PET/CT were compared. For validation, a patient was scanned with an injected dose of 407.7MBq on both a PET/CT and a PET/MR system without a coil and with both coils. PET/MR underestimations were -2.2% (Siemens) and -7.8% (Machnet) for SUVmean, and -1.2% (Siemens) and -3.3% (Machnet) for SUVmax, respectively. For PET/CT, underestimations were -1.3% (Siemens) and -1.4% (Machnet) for SUVmean and -0.5% (both Siemens and Machnet) for SUVmax, respectively using no coil data as reference. Except for PET/CT SUVmax values all differences were significant. SUVs differed significantly between PET/MR and PET/CT with SUVmean values of 0.51-0.55 for PET/MR and 0.68-0.69 for PET/CT, respectively. The patient examination showed that median SUVmean values measured in the carotid arteries decreased from 0.97 without a coil to 0.96 (Siemens) and 0.88 (Machnet). Carotid surface coils do affect attenuation correction in both PET/MR and PET/CT imaging. Furthermore, SUVs differed significantly between PET/MR and PET/CT.

  10. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian

    2013-01-01

    described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...... Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases...... that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations....

  11. Are Pets in the Bedroom a Problem?

    Science.gov (United States)

    Krahn, Lois E; Tovar, M Diane; Miller, Bernie

    2015-12-01

    The presence of pets in the bedroom can alter the sleep environment in ways that could affect sleep. Data were collected by questionnaire and interview from 150 consecutive patients seen at the Center for Sleep Medicine, Mayo Clinic in Arizona. Seventy-four people (49%) reported having pets, with 31 (41% of pet owners) having multiple pets. More than half of pet owners (56%) allowed their pets to sleep in the bedroom. Fifteen pet owners (20%) described their pets as disruptive, whereas 31 (41%) perceived their pets as unobtrusive or even beneficial to sleep. Health care professionals working with patients with sleep concerns should inquire about the presence of companion animals in the sleep environment to help them find solutions and optimize their sleep.

  12. Advances in Clinical PET/MRI Instrumentation.

    Science.gov (United States)

    Herzog, Hans; Lerche, Christoph

    2016-04-01

    In 2010, the first whole-body PET/MRI scanners installed for clinical use were the sequential Philips PET/MRI with PMT-based, TOF-capable technology and the integrated simultaneous Siemens PET/MRI. Avalanche photodiodes as non-magneto-sensitive readout electronics allowed PET integrated within the MRI. The experiences with these scanners showed that improvements of software aspects, such as attenuation correction, were necessary and that efficient protocols combining optimally PET and MRI must be still developed. In 2014, General Electric issued an integrated PET/MRI with SiPM-based PET detectors, allowing TOF-PET. Looking at the MRI components of current PET/MR imaging systems, primary improvements come from sequences and new coils.

  13. Nutritional sustainability of pet foods.

    Science.gov (United States)

    Swanson, Kelly S; Carter, Rebecca A; Yount, Tracy P; Aretz, Jan; Buff, Preston R

    2013-03-01

    Sustainable practices meet the needs of the present without compromising the ability of future generations to meet their needs. Applying these concepts to food and feed production, nutritional sustainability is the ability of a food system to provide sufficient energy and essential nutrients required to maintain good health in a population without compromising the ability of future generations to meet their nutritional needs. Ecological, social, and economic aspects must be balanced to support the sustainability of the overall food system. The nutritional sustainability of a food system can be influenced by several factors, including the ingredient selection, nutrient composition, digestibility, and consumption rates of a diet. Carbon and water footprints vary greatly among plant- and animal-based ingredients, production strategy, and geographical location. Because the pet food industry is based largely on by-products and is tightly interlinked with livestock production and the human food system, however, it is quite unique with regard to sustainability. Often based on consumer demand rather than nutritional requirements, many commercial pet foods are formulated to provide nutrients in excess of current minimum recommendations, use ingredients that compete directly with the human food system, or are overconsumed by pets, resulting in food wastage and obesity. Pet food professionals have the opportunity to address these challenges and influence the sustainability of pet ownership through product design, manufacturing processes, public education, and policy change. A coordinated effort across the industry that includes ingredient buyers, formulators, and nutritionists may result in a more sustainable pet food system.

  14. Game Design to Introduce Pets

    Directory of Open Access Journals (Sweden)

    Wahyu Febriyanto

    2017-02-01

    Full Text Available Introduction of animals from an early age can make children to love animals, especially pets. Children are the easiest group to receive stimulation, such as for example the stimulation of introducing children to the pet. Various media are used by parents to introduce pet. For examplle, by the media of books, multimedia, etc. One of the interesting media to introduce pet is with game. Of these problems then need to know how to make concept and design game to introduced pets for children age 3-6 years. In this paper, author formulate how to make pet game design include game genre, user interface design, image model selection, game characters, and game engine. The expected design of this game can be formulation of learning through proper game as a learning tool children. Game design derived from this writing by using model 2-dimensional images are funny and interesting coloring. And combines several game genres into one, or use the mini games that children do not get bored quickly. Design of GUI (Graphical User Interface is made as simple as possible so that children easily understand in playing this game, but also must use an interesting image

  15. PET scanning of macrophages in patients with scleroderma fibrosing alveolitis

    Energy Technology Data Exchange (ETDEWEB)

    Branley, Howard M. [Imperial College London, Hammersmith Campus, London (United Kingdom)], E-mail: Howard.Branley@whittington.nhs.uk; Bois, Roland M. du; Wells, Athol U. [Royal Brompton Hospital, London (United Kingdom); Jones, Hazel A. [Imperial College London, Hammersmith Campus, London (United Kingdom)

    2008-11-15

    Rationale: Assessment of disease activity in fibrosing alveolitis due to systemic sclerosis (FASSc) is difficult without using invasive investigation. A repeatable noninvasive method of assessing disease at a cellular level such as with positron emission tomography (PET) could be of great value in evaluating high-resolution changes in the pathological process. Objectives: To investigate whether the level of inflammatory cell traffic and lung density in FASSc, imaged in vivo by PET, is different to controls and whether they are associated with changes in pulmonary function indices. Methods: We used PET to measure lung density and tissue uptake of {sup 11}C-[R]-PK11195, a ligand that binds to receptors found in abundance in macrophages. Fifteen patients with FASSc were compared to seven controls. Results: A trend of reduced uptake of {sup 11}C-[R]-PK11195 was observed in FASSc patients (P=.09) and correlated inversely with lung density (r=-.62; P<.05), which was significantly elevated in FASSc [0.35{+-}0.02 vs. 0.23{+-}0.02 g/cc (mean{+-}S.E.M.); P<.005]. Conclusion: These results demonstrate that inflammatory cell traffic and lung density can be imaged in vivo in FASSc using PET, and that this approach might be of potential value in understanding, in situ, components of pathogenesis that may have value for prognosis.

  16. FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC

    Institute of Scientific and Technical Information of China (English)

    Matthijs; H; van; Gool; Tjeerd; S; Aukema; Koen; J; Hartemink; Renato; A; Valdés; Olmos; Houke; M; Klomp; Harm; van; Tinteren

    2014-01-01

    Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung cancer(NSCLC).The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC,treated with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKI).All published articles from 1November 2003 to 1 November 2013 reporting on 18FFDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected.In total 7studies,including data of 210 patients were eligible for analyses.Our report shows that FDG-PET/CT responseduring EGFR-TKI therapy has potential in targeted treatment for NSCLC.FDG-PET/CT response is associated with clinical and radiologic response and with survival.Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment.Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment.If metabolic response does not occur within the first weeks of EGFR-TKI treatment,patients may be spared(further)unnecessary toxicity of ineffective treatment.Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

  17. Acetaminophen Metabolite N-Acylphenolamine Induces Analgesia via Transient Receptor Potential Vanilloid 1 Receptors Expressed on the Primary Afferent Terminals of C-fibers in the Spinal Dorsal Horn.

    Science.gov (United States)

    Ohashi, Nobuko; Uta, Daisuke; Sasaki, Mika; Ohashi, Masayuki; Kamiya, Yoshinori; Kohno, Tatsuro

    2017-08-01

    The widely used analgesic acetaminophen is metabolized to N-acylphenolamine, which induces analgesia by acting directly on transient receptor potential vanilloid 1 or cannabinoid 1 receptors in the brain. Although these receptors are also abundant in the spinal cord, no previous studies have reported analgesic effects of acetaminophen or N-acylphenolamine mediated by the spinal cord dorsal horn. We hypothesized that clinical doses of acetaminophen induce analgesia via these spinal mechanisms. We assessed our hypothesis in a rat model using behavioral measures. We also used in vivo and in vitro whole cell patch-clamp recordings of dorsal horn neurons to assess excitatory synaptic transmission. Intravenous acetaminophen decreased peripheral pinch-induced excitatory responses in the dorsal horn (53.1 ± 20.7% of control; n = 10; P N-acylphenolamine decreased the amplitudes of monosynaptic excitatory postsynaptic currents evoked by C-fiber stimulation (control, 462.5 ± 197.5 pA; N-acylphenolamine, 272.5 ± 134.5 pA; n = 10; P = 0.022) but not those evoked by stimulation of Aδ-fibers. These phenomena were mediated by transient receptor potential vanilloid 1 receptors, but not cannabinoid 1 receptors. The analgesic effects of acetaminophen and N-acylphenolamine were stronger in rats experiencing an inflammatory pain model compared to naïve rats. Our results suggest that the acetaminophen metabolite N-acylphenolamine induces analgesia directly via transient receptor potential vanilloid 1 receptors expressed on central terminals of C-fibers in the spinal dorsal horn and leads to conduction block, shunt currents, and desensitization of these fibers.

  18. Parasites, pets, and people.

    Science.gov (United States)

    Marx, M B

    1991-03-01

    It is important for the family physician to understand that patients' relationships with their pets play an important role in helping maintain mental and physical health yet provide the potential for causing illness in the patient. Toxocara canis (dog roundworm) and Toxocara cati (cat roundworm) are the ascarids most commonly responsible for VLM and ocular larva migrans in humans. These roundworms live in their adult stage in the small intestine of the dog and cat where their eggs are passed in the feces. The eggs containing the infective larva are very sticky, thus an infant crawling around on the floor can easily pick these up on fingers that almost invariably end up in the mouth. Infections are usually mild and asymptomatic but with a persistent eosinophilia. Ocular larva migrans is the form usually occurring in older children and adults. Some public health veterinarians recommend that a puppy or kitten should not be obtained as a companion for a child who is not old enough to read, thus bypassing the crawling and toddler stages. Hookworm eggs, shed in the feces of infected dogs or cats, develop into the infective second stage within a week. Humans are usually infected when bare areas of skin such as bare feet or the torso come in contact with soil contaminated with the larvae. The second-stage larvae are able to penetrate the intact skin of humans and the foot pads of dogs and cats. In the United States, the common dog hookworm, A. caninum, is a widespread parasite. Human intestinal ancylostomiasis caused by this species is rare, with only six cases recorded in the literature. Infection in humans or animals by the common tapeworm of dogs and cats (Dipylidium caninum) requires ingestion of the intermediate host, the dog or cat flea containing the larva (cysticercoids) of the agent. Many cases in humans are asymptomatic. Dipylidiasis affects mainly infants and young children who may swallow a flea that hops up while the infant is crawling on the floor or fondling

  19. Parasites in pet reptiles

    Science.gov (United States)

    2011-01-01

    Exotic reptiles originating from the wild can be carriers of many different pathogens and some of them can infect humans. Reptiles imported into Slovenia from 2000 to 2005, specimens of native species taken from the wild and captive bred species were investigated. A total of 949 reptiles (55 snakes, 331 lizards and 563 turtles), belonging to 68 different species, were examined for the presence of endoparasites and ectoparasites. Twelve different groups (Nematoda (5), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (4)) of endoparasites were determined in 26 (47.3%) of 55 examined snakes. In snakes two different species of ectoparasites were also found. Among the tested lizards eighteen different groups (Nematoda (8), Cestoda (1), Trematoda (1), Acanthocephala (1), Pentastomida (1) and Protozoa (6)) of endoparasites in 252 (76.1%) of 331 examined animals were found. One Trombiculid ectoparasite was determined. In 563 of examined turtles eight different groups (Nematoda (4), Cestoda (1), Trematoda (1) and Protozoa (2)) of endoparasites were determined in 498 (88.5%) animals. In examined turtles three different species of ectoparasites were seen. The established prevalence of various parasites in reptiles used as pet animals indicates the need for examination on specific pathogens prior to introduction to owners. PMID:21624124

  20. Quantitative PET imaging with the 3T MR-BrainPET

    Energy Technology Data Exchange (ETDEWEB)

    Weirich, C., E-mail: c.weirich@fz-juelich.de [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany); Scheins, J.; Lohmann, P.; Tellmann, L. [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany); Byars, L.; Michel, C. [Siemens Healthcare, Molecular Imaging, Knoxville, TN (United States); Rota Kops, E.; Brenner, D.; Herzog, H.; Shah, N.J. [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany)

    2013-02-21

    The new hybrid imaging technology of MR-PET allows for simultaneous acquisition of versatile MRI contrasts and the quantitative metabolic imaging with PET. In order to achieve the quantification of PET images with minimal residual error the application of several corrections is crucial. In this work we present our results on quantification with the 3T MR BrainPET scanner.

  1. Effect of Attenuation Correction on Regional Quantification Between PET/MR and PET/CT

    DEFF Research Database (Denmark)

    Teuho, Jarmo; Johansson, Jarkko; Linden, Jani

    2016-01-01

    UNLABELLED: A spatial bias in brain PET/MR exists compared with PET/CT, because of MR-based attenuation correction. We performed an evaluation among 4 institutions, 3 PET/MR systems, and 4 PET/CT systems using an anthropomorphic brain phantom, hypothesizing that the spatial bias would be minimize...

  2. PET for Staging of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    A.H.Hoelscher

    2004-01-01

    FDG-PET is of clinical value especially for detection of distant metastases or recurrent esophageal cancer. For the staging of primary tumor or locoregional lymph node metastasis PET is currently not suitable.

  3. Pet Meds Sending Kids to the ER

    Science.gov (United States)

    ... Health and Human Services. More Health News on: Child Safety Pet Health Poisoning Recent Health News Related MedlinePlus Health Topics Child Safety Pet Health Poisoning About MedlinePlus Site Map FAQs Customer ...

  4. Exercises in PET Image Reconstruction

    Science.gov (United States)

    Nix, Oliver

    These exercises are complementary to the theoretical lectures about positron emission tomography (PET) image reconstruction. They aim at providing some hands on experience in PET image reconstruction and focus on demonstrating the different data preprocessing steps and reconstruction algorithms needed to obtain high quality PET images. Normalisation, geometric-, attenuation- and scatter correction are introduced. To explain the necessity of those some basics about PET scanner hardware, data acquisition and organisation are reviewed. During the course the students use a software application based on the STIR (software for tomographic image reconstruction) library 1,2 which allows them to dynamically select or deselect corrections and reconstruction methods as well as to modify their most important parameters. Following the guided tutorial, the students get an impression on the effect the individual data precorrections have on image quality and what happens if they are forgotten. Several data sets in sinogram format are provided, such as line source data, Jaszczak phantom data sets with high and low statistics and NEMA whole body phantom data. The two most frequently used reconstruction algorithms in PET image reconstruction, filtered back projection (FBP) and the iterative OSEM (ordered subset expectation maximation) approach are used to reconstruct images. The exercise should help the students gaining an understanding what the reasons for inferior image quality and artefacts are and how to improve quality by a clever choice of reconstruction parameters.

  5. Magnetic Resonance-based Motion Correction for Quantitative PET in Simultaneous PET-MR Imaging.

    Science.gov (United States)

    Rakvongthai, Yothin; El Fakhri, Georges

    2017-07-01

    Motion degrades image quality and quantitation of PET images, and is an obstacle to quantitative PET imaging. Simultaneous PET-MR offers a tool that can be used for correcting the motion in PET images by using anatomic information from MR imaging acquired concurrently. Motion correction can be performed by transforming a set of reconstructed PET images into the same frame or by incorporating the transformation into the system model and reconstructing the motion-corrected image. Several phantom and patient studies have validated that MR-based motion correction strategies have great promise for quantitative PET imaging in simultaneous PET-MR. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Potential impact of {sup 68}Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Nyuyki, Fonyuy; Plotkin, Michail; Michel, Roger; Steffen, Ingo; Fahdt, Daniel; Brenner, Winfried [Charite-Universitaetsmedizin Berlin, Department for Nuclear Medicine, Berlin (Germany); Graf, Reinhold [Charite-Universitaetsmedizin Berlin, Department for Radiation Therapy, Campus Virchow, Berlin (Germany); Denecke, Timm [Charite-Universitaetsmedizin Berlin, Department for Radiology, Campus Virchow, Berlin (Germany); Geworski, Lilli [Charite-Universitaetsmedizin Berlin, Department for Nuclear Medicine, Berlin (Germany); Medizinische Hochschule Hannover, Department for Radiation Safety and Medical Physics, Hannover (Germany); Wurm, Reinhard [Charite-Universitaetsmedizin Berlin, Department for Radiation Therapy, Campus Virchow, Berlin (Germany); Klinikum Frankfurt (Oder), Department for Radiation Therapy and Radiooncology, Frankfurt (Germany)

    2010-02-15

    Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with {sup 68}Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of {sup 68}Ga-DOTATOC-PET/CT on the definition of the ''gross tumour volume'' (GTV) in meningiomas, in order to assess the potential value of this method. Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and {sup 68}Ga-DOTATOC-PET/CT examinations. History: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV{sub CT/MRI} was 22({+-}19)cm{sup 3}; GTV{sub PET} was 23({+-}20)cm{sup 3}. Additional GTV, obtained as a result of PET was 9({+-}10)cm{sup 3} and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7({+-}11)cm{sup 3}). Common GTV as obtained by both CT/MRI and PET was 15({+-}14)cm{sup 3}. The mean bi-directional difference between the GTV{sub CT/MRI} and GTV{sub PET} accounted to 16({+-}15)cm{sup 3} (93%, p < 0.001). In a subgroup of seven patients with multiple meningiomas, PET showed a total of 19 lesions; nine of them were not recognizable by CT or MRI. {sup 68}Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration

  7. Preclinical PET Neuroimaging of [11C]Bexarotene

    Directory of Open Access Journals (Sweden)

    Benjamin H. Rotstein PhD

    2016-08-01

    Full Text Available Activation of retinoid X receptors (RXRs has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [11C]CO2 fixation and preliminary positron emission tomography (PET neuroimaging that demonstrated brain permeability in nonhuman primate with regional binding distribution consistent with RXRs. In this study, the brain uptake and saturability of [11C]bexarotene were studied in rats and nonhuman primates by PET imaging under baseline and greater target occupancy conditions. [11C]Bexarotene displays a high proportion of nonsaturable uptake in the brain and is unsuitable for RXR occupancy measurements in the central nervous system.

  8. THE CHARACTERISTICS OF EEC PET INSTRUMENTATION

    NARCIS (Netherlands)

    PAANS, AMJ

    1991-01-01

    As a result of a Guide-Questionnaire distributed among all European PET centers an inventory of the European PET instrumentation has become available in a data base. An overview and analysis of the European PET equipment, cyclotrons, scanners and software, together with some global information on th

  9. 36 CFR 13.1106 - Pets.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1106 Section 13.1106 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... Provisions § 13.1106 Pets. Pets are prohibited except— (a) On the Bartlett Cove Public Use Dock; (b) On...

  10. Pets in the family: practical approaches.

    Science.gov (United States)

    Hodgson, Kate; Darling, Marcia

    2011-01-01

    Adapting family life cycle theory to include pets provides veterinarians with a framework for understanding and reinforcing the human-animal bond. The family genogram with pets is a practice tool that identifies all people and pets in the family, enhancing the practice of One Health at the community level.

  11. 7 CFR 503.11 - Pets.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 503.11 Section 503.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.11 Pets. No pets or animals of any kind may be...

  12. 36 CFR 13.978 - Pets.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.978 Section 13.978 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... (fda) § 13.978 Pets. Possessing a pet is prohibited— (a) In the FDA, except in public parking areas,...

  13. 7 CFR 500.10 - Pets.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 500.10 Section 500.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE NATIONAL ARBORETUM Conduct on U.S. National Arboreturm Property § 500.10 Pets. Pets brought upon...

  14. 36 CFR 13.1310 - Pets.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1310 Section 13.1310... SYSTEM UNITS IN ALASKA Special Regulations-Kenai Fjords National Park General Provisions § 13.1310 Pets. (a) Pets are prohibited— (1) In the Exit Glacier Developed Area except in the parking lot, on...

  15. 36 CFR 13.1234 - Pets.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  16. The modification behaviour for Si implanted PET

    Institute of Scientific and Technical Information of China (English)

    吴瑜光; 张通和; 刘安东; 张旭; 周固

    2003-01-01

    Polyethylene terephthalate (PET) has been modified by Si ion implantation with a dose ranging from 1 × 1016 to 2 × 1017 ions /cm2 using a metal vapor vacuum arc(MEVVA)source. The surface morphology was observed by atomic force microscopy (AFM). The change in the microstructure of Si implanted PET was observed with a transmission electron microscope (TEM). It is believed that the change would improve the conductive properties and wear resistance. The electrical properties of PET have been improved via Si ion implantation. The resistivity of implanted PET decreased obviously with an increase in ion dose. When Si ion dose was 2 × 1017 cm?2, the resistivity of PET could be less than 7.9 Ω@m. The surface hardness and modulus increased obviously. The mechanical property of the implanted PET has been modified greatly. The hardness and modulus of Si implanted PET with a dose of 2 × 1017/cm2 are 12.5 and 2.45 times greater than those of pristine PET, respectively. The area of cutting groove for Si implanted PET is narrower and shallower than those of the unimplanted PET. So the wear resistance is greatly raised. In comparison with metal ion implantation, the improvement of mechanical properties is obvious in ion implantation into PET. Si ion beam modification mechanism of PET is discussed.

  17. THE CHARACTERISTICS OF EEC PET INSTRUMENTATION

    NARCIS (Netherlands)

    PAANS, AMJ

    1991-01-01

    As a result of a Guide-Questionnaire distributed among all European PET centers an inventory of the European PET instrumentation has become available in a data base. An overview and analysis of the European PET equipment, cyclotrons, scanners and software, together with some global information on

  18. THE CHARACTERISTICS OF EEC PET INSTRUMENTATION

    NARCIS (Netherlands)

    PAANS, AMJ

    1991-01-01

    As a result of a Guide-Questionnaire distributed among all European PET centers an inventory of the European PET instrumentation has become available in a data base. An overview and analysis of the European PET equipment, cyclotrons, scanners and software, together with some global information on th

  19. Pet therapy: dogs de-stress students.

    Science.gov (United States)

    Young, Judith S

    2012-01-01

    Research supports the efficacy of the human-animal bond and pet therapy in a variety of settings. At nursing students' request at one school, the author began offering pet therapy prior to examinations. Anecdotal evidence of a study with the author's Golden Retriever, Goldilocks, demonstrates that pet therapy can reduce test anxiety and improve nursing student performance.

  20. Understanding advertising in pet nutrition.

    Science.gov (United States)

    Brown, R G

    1994-04-01

    Advertising is part of the effort to attract attention of consumers to products, in this case, pet foods. It is generally benign in its effect, but it can be misleading, although rarely deliberately so. It uses a specialized vocabulary, which must be mastered if one is to understand what is intended. For all of the expense and effort, advertising figures directly in relatively few decisions to purchase. Its main intention is to call our attention to a particular pet food and to give that product an image. If the pet food does not perform in the consumer's hands, then all of the advertising on earth will not be persuasive. On the other hand, if a product performs well, the word-of-mouth will be positive and that mode of advertising is one of the most effective.

  1. PET and SPECT in neurology

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, Rudi A.J.O. [Groningen University Medical Center (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Ghent Univ. (Belgium). Dept. of Radiology and Nuclear Medicine; Vries, Erik F.J. de; Waarde, Aren van [Groningen University Medical Center (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Otte, Andreas (ed.) [Univ. of Applied Sciences Offenburg (Germany). Faculty of Electrical Engineering and Information Technology

    2014-07-01

    PET and SPECT in Neurology highlights the combined expertise of renowned authors whose dedication to the investigation of neurological disorders through nuclear medicine technology has achieved international recognition. Classical neurodegenerative disorders are discussed as well as cerebrovascular disorders, brain tumors, epilepsy, head trauma, coma, sleeping disorders, and inflammatory and infectious diseases of the CNS. The latest results in nuclear brain imaging are detailed. Most chapters are written jointly by a clinical neurologist and a nuclear medicine specialist to ensure a multidisciplinary approach. This state-of-the-art compendium will be valuable to anybody in the field of neuroscience, from the neurologist and the radiologist/nuclear medicine specialist to the interested general practitioner and geriatrician. It is the second volume of a trilogy on PET and SPECT imaging in the neurosciences, the other volumes covering PET and SPECT in psychiatry and in neurobiological systems.

  2. Radiosynthesis and biodistribution of a histamine H{sub 3} receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[{sup 11}C]benzyl]-morpholine: evaluation of a potential PET ligand

    Energy Technology Data Exchange (ETDEWEB)

    Airaksinen, Anu J. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Jablonowski, Jill A. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Mey, Margreet van der [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Barbier, Ann J. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Klok, Rob P. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Verbeek, Joost [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Schuit, Robert [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Herscheid, Jacobus D.M. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Leysen, Josee E. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Carruthers, Nicholas I. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Lammertsma, Adriaan A. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Windhorst, Albert D. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands)]. E-mail: bwindhorst@rnc.vu.nl

    2006-08-15

    The potent histamine H{sub 3} receptor antagonist JNJ-10181457 () was successfully labeled with {sup 11}C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28{+-}8%) and high specific radioactivity (56{+-}26 GBq/{mu}mol). The binding of [{sup 11}C] to H{sub 3} receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [{sup 11}C] in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H{sub 3} antagonists, JNJ-5207852 () and unlabeled Compound (), in a concentration-dependent manner. The biodistribution of [{sup 11}C] in rats was measured at 5, 10, 30 and 60 min. The uptake of [{sup 11}C] in regions rich in H{sub 3} receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [{sup 11}C] in the rat brain could not be blocked by pretreatment with either Compound () (30 min or 24 h pretreatment) or cold Compound () (30-min pretreatment). The biodistribution of [{sup 11}C] in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H{sub 3}(-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [{sup 11}C] could not specifically label H{sub 3} receptors in rodent brain in vivo. Possible causes are discussed.

  3. Challenges in the development of dopamine D2- and D3-selective radiotracers for PET imaging studies.

    Science.gov (United States)

    Mach, Robert H; Luedtke, Robert R

    2017-08-31

    The dopamine D2-like receptors (ie, D2/3 receptors) have been the most extensively studied CNS receptor with Positron Emission Tomography (PET). The 3 different radiotracers that have been used in these studies are [(11) C]raclopride, [(18) F]fallypride, and [(11) C]PHNO. Because these radiotracers have a high affinity for both dopamine D2 and D3 receptors, the density of dopamine receptors in the CNS is reported as the D2/3 binding potential, which reflects a measure of the density of both receptor subtypes. Although the development of D2- and D3-selective PET radiotracers has been an active area of research for many years, this by and large presents an unmet need in the area of translational PET imaging studies. This article discusses some of the challenges that have inhibited progress in this area of research and the current status of the development of subtype selective radiotracers for imaging D3 and D2 dopamine receptors with PET. Copyright © 2017 John Wiley & Sons, Ltd.

  4. N-(4-F-18-Fluorobenzoyl)Interleukin-2 for PET of Human-Activated T Lymphocytes

    NARCIS (Netherlands)

    Di Gialleonardo, Valentina; Signore, Alberto; Glaudemans, Andor W. J. M.; Dierckx, Rudi A. J. O.; De Vries, Erik F. J.

    2012-01-01

    Interleukin-2 (IL2) binds with high affinity to the IL2 receptors overexpressed on activated T lymphocytes in various pathologic conditions. Radiolabeling of IL2 with a positron-emitting isotope could provide a tool for noninvasive PET of activated T cells in immune-mediated diseases. We report the

  5. Competitive advantage of PET/MRI.

    Science.gov (United States)

    Jadvar, Hossein; Colletti, Patrick M

    2014-01-01

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. PET/CT in the thorax: pitfalls.

    Science.gov (United States)

    Truong, Mylene T; Viswanathan, Chitra; Carter, Brett W; Mawlawi, Osama; Marom, Edith M

    2014-01-01

    PET/CT is widely used in the staging and assessment of therapeutic response in patients with malignancies. Accurate interpretation of PET/CT requires knowledge of the normal physiologic distribution of [18F]-fluoro-2-deoxy-d-glucose, artifacts due to the use of CT for attenuation correction of the PET scan and potential pitfalls due to malignancies that are PET negative and benign conditions that are PET positive. Awareness of these artifacts and potential pitfalls is important in preventing misinterpretation that can alter patient management. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Palliative care and compound in household pets.

    Science.gov (United States)

    Gaskins, Jessica L

    2012-01-01

    Palliative care is not a term solely used for humans when discussing health care; the term is also used when discussing veterinary patients. Pets are considered part of the family by pet owners, and they have a special relationship that only another pet owner can fully understand. This article discusses some of the healthcare problems that affect pets (and their owners), statistics on the most commonly used medications for veterinary patients, quality of life, and discussions on the veterinary pharmacist-owner-palliative pet relationship and how compounding pharmacists can prepare patient-specific medications.

  8. Kinetic modeling in PET imaging of hypoxia

    DEFF Research Database (Denmark)

    Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas

    2014-01-01

    Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can...... be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET...... analysis for PET imaging of hypoxia....

  9. Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jin Ho; Choi, Yong, E-mail: ychoi.image@gmail.com; Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun [Department of Electronic Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742 (Korea, Republic of); Oh, Chang Hyun; Park, Hyun-wook [Department of Electrical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Kim, Kyung Min; Kim, Jong Guk [Korea Institute of Radiological and Medical Science, 75 Nowon-ro, Nowon-gu, Seoul 139-709 (Korea, Republic of)

    2015-05-15

    Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was

  10. Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain.

    Science.gov (United States)

    Jung, Jin Ho; Choi, Yong; Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun; Oh, Chang Hyun; Park, Hyun-wook; Kim, Kyung Min; Kim, Jong Guk

    2015-05-01

    The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of

  11. The MiniPET: a didactic PET system

    Science.gov (United States)

    Pedro, R.; Silva, J.; Gurriana, L.; Silva, J. M.; Maio, A.; Soares Augusto, J.

    2013-03-01

    The MiniPET project aims to design and build a small PET system. It consists of two 4 × 4 matrices of 16 LYSO scintillator crystals and two PMTs with 16 channels resulting in a low cost system with the essential functionality of a clinical PET instrument. It is designed to illustrate the physics of the PET technique and to provide a didactic platform for the training of students and nuclear imaging professionals as well as for scientific outreach. The PET modules can be configured to test for the coincidence of 511 keV gamma rays. The model has a flexible mechanical setup [1] and can simulate 14 diferent ring geometries, from a configuration with as few as 18 detectors per ring (ring radius phi=51 mm), up to a geometry with 70 detectors per ring (phi=200 mm). A second version of the electronic system [2] allowed measurement and recording of the energy deposited in 4 detector channels by photons from a 137Cs radioactive source and by photons resulting of the annihilation of positrons from a 22Na radioactive source. These energy spectra are used for detector performance studies, as well as angular dependency studies. In this paper, the mechanical setup, the front-end high-speed analog electronics, the digital acquisition and control electronics implemented in a FPGA, as well as the data-transfer interface between the FPGA board and a host PC are described. Recent preliminary results obtained with the 4 active channels in the prototype are also presented.

  12. Synthetic techniques of radiopharmaceuticals production labeled with C-11 for PET in cardiology

    Science.gov (United States)

    Dyubkov, V. S.; Ekaeva, I. V.; Katunina, T. A.; Rumyantsev, A. S.; Silchenkov, A. V.; Tuflina, T. V.

    2017-01-01

    Positron emission tomography (PET) and PET-Computerised Tomography (CT) are unique, non-invasive diagnostic techniques, in which the local, temporal and quantitative distributions of radioactive labelled substances are measured to investigate physiological processes. It is well known that PET centre of Bakulev Scientific Centre for Cardiovascular Surgery is the oldest one in Moscow. During more than fifteen years a large number of patients have received PET scans. Due to main stream of Scientific Centre, emphasis is placed on examining the heart functioning. For the diagnosis innervation of the heart muscle a number of radiopharmaceuticals are used, including PET radiopharmaceuticals such as 11C-CGP 12177, 11C-meta-hydroxyephedrine as well as its synthetic analogues labelled with other PET radionuclides (18F, 68Ga). 11C-meta-hydroxyephedrine is one of the most perspective radiopharmaceutical for an investigation of cardiac receptors function due to required materials availability for a radio synthesis in Russia. The main advantage of proposed 11C-meta-hydroxyephedrine synthesis technique is the use of a catalyst which allows one decrease reaction time from 5 minutes to 30 seconds. Obtained results allow one decrease reaction time of methylation and increase radiochemical and technological yields.

  13. Principles of PET/MR Imaging.

    Science.gov (United States)

    Disselhorst, Jonathan A; Bezrukov, Ilja; Kolb, Armin; Parl, Christoph; Pichler, Bernd J

    2014-06-01

    Hybrid PET/MR systems have rapidly progressed from the prototype stage to systems that are increasingly being used in the clinics. This review provides an overview of developments in hybrid PET/MR systems and summarizes the current state of the art in PET/MR instrumentation, correction techniques, and data analysis. The strong magnetic field requires considerable changes in the manner by which PET images are acquired and has led, among others, to the development of new PET detectors, such as silicon photomultipliers. During more than a decade of active PET/MR development, several system designs have been described. The technical background of combined PET/MR systems is explained and related challenges are discussed. The necessity for PET attenuation correction required new methods based on MR data. Therefore, an overview of recent developments in this field is provided. Furthermore, MR-based motion correction techniques for PET are discussed, as integrated PET/MR systems provide a platform for measuring motion with high temporal resolution without additional instrumentation. The MR component in PET/MR systems can provide functional information about disease processes or brain function alongside anatomic images. Against this background, we point out new opportunities for data analysis in this new field of multimodal molecular imaging. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. PET/MR Imaging in Gynecologic Oncology.

    Science.gov (United States)

    Ohliger, Michael A; Hope, Thomas A; Chapman, Jocelyn S; Chen, Lee-May; Behr, Spencer C; Poder, Liina

    2017-08-01

    MR imaging and PET using 2-Deoxy-2-[(18)F]fluoroglucose (FDG) are both useful in the evaluation of gynecologic malignancies. MR imaging is superior for local staging of disease whereas fludeoxyglucose FDG PET is superior for detecting distant metastases. Integrated PET/MR imaging scanners have great promise for gynecologic malignancies by combining the advantages of each modality into a single scan. This article reviews the technology behind PET/MR imaging acquisitions and technical challenges relevant to imaging the pelvis. A dedicated PET/MR imaging protocol; the roles of PET and MR imaging in cervical, endometrial, and ovarian cancers; and future directions for PET/MR imaging are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Niccolini, Flavia; Politis, Marios [Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King' s College London, London (United Kingdom)

    2016-11-15

    To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism. MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded. Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABA{sub A} receptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson's disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABA{sub A} receptors were decreased in metabolically affected cortical and subcortical regions in PSP patients. PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments. (orig.)

  16. Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males.

    Science.gov (United States)

    Chiba, Junko; Suzuki, Hiroetsu; Aoyama, Hiroaki; Katayama, Kentaro; Suzuki, Katsushi

    2011-04-01

    The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells.

  17. Innovations in PET/CT

    DEFF Research Database (Denmark)

    Levin Klausen, T; Høgild Keller, S; Vinter Olesen, O

    2012-01-01

    especially as spatial resolution improves. Software based image fusion remains a complex issue outside the brain. State of the art image quality in a modern PET/CT system includes incorporation of point spread function (PSF) and time-of-flight (TOF) information into the reconstruction leading to the high...

  18. New Scintillation Detectors for PET

    NARCIS (Netherlands)

    Shah, K.S.

    2010-01-01

    The focus of this thesis is on new detection technologies that can be used in advancing nuclear medicine modalities, particularly positron emission tomography (PET). Several detection technologies are covered in this thesis. First, new Ce3+ doped rare earth trihalide scintillators that can be used

  19. PET and SPECT in psychiatry

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, Rudi A.J.O. [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Ghent Univ. (Belgium); Otte, Andreas [Univ. of Applied Sciences Offenburg (Germany). Faculty of Electrical Engineering and Information Technology; Vries, Erik F.J. de; Waarde, Aren van (eds.) [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging

    2014-09-01

    Covers classical psychiatric disorders as well as other subjects such as suicide, sleep, eating disorders, and autism. Emphasis on a multidisciplinary approach. Written by internationally acclaimed experts. PET and SPECT in Psychiatry showcases the combined expertise of renowned authors whose dedication to the investigation of psychiatric disease through nuclear medicine technology has achieved international recognition. The classical psychiatric disorders as well as other subjects - such as suicide, sleep, eating disorders, and autism - are discussed and the latest results in functional neuroimaging are detailed. Most chapters are written jointly by a clinical psychiatrist and a nuclear medicine expert to ensure a multidisciplinary approach. This state of the art compendium will be valuable to all who have an interest in the field of neuroscience, from the psychiatrist and the radiologist/nuclear medicine specialist to the interested general practitioner and cognitive psychologist. It is the first volume of a trilogy on PET and SPECT imaging in the neurosciences; other volumes will focus on PET and SPECT in neurology and PET and SPECT of neurobiological systems.

  20. New Scintillation Detectors for PET

    NARCIS (Netherlands)

    Shah, K.S.

    2010-01-01

    The focus of this thesis is on new detection technologies that can be used in advancing nuclear medicine modalities, particularly positron emission tomography (PET). Several detection technologies are covered in this thesis. First, new Ce3+ doped rare earth trihalide scintillators that can be used i

  1. SPECT og PET i neurobiologien

    DEFF Research Database (Denmark)

    Paulson, O.B.; Lassen, N.A.

    1997-01-01

    PET (positron emission tomography) and SPECT (single photon emission computed tomography) are isotopic methods in which the distribution is registered of radiolabelled tracers given in such small amounts that they are without effect on the organism or the organism's disposal of them. Thus, a series...

  2. SPECT og PET i neurobiologien

    DEFF Research Database (Denmark)

    Paulson, O B; Lassen, N A

    1997-01-01

    PET (positron emission tomography) and SPECT (single photon emission computed tomography) are isotopic methods in which the distribution is registered of radiolabelled tracers given in such small amounts that they are without effect on the organism or the organism's disposal of them. Thus, a series...

  3. Particle Accelerators for PET radionuclides

    DEFF Research Database (Denmark)

    Jensen, Mikael

    2012-01-01

    The requirements set for particle accelerators for production of radioactive isotopes for PET can easily be derived from first principles. The simple general need is for proton beams with energy in the region 10–20 MeV and current 20–100 microAmps. This is most reliably and cost-effectively achie......The requirements set for particle accelerators for production of radioactive isotopes for PET can easily be derived from first principles. The simple general need is for proton beams with energy in the region 10–20 MeV and current 20–100 microAmps. This is most reliably and cost...... different manufacturers will be discussed the light of what is actually needed for a given PET site operation. Alternatives to the conventional cyclotron have been proposed and tested but have at present very limited use. These alternatives will be discussed, as well as the future possibilities of supplying...... point of demand tracer production with very small cyclotrons of energy well below 10 MeV. The authors best advice at present for new PET sites is to negotiate for conventional cyclotron solutions from experienced manufacturers. It is the combined performance of cyclotron and target in terms of available...

  4. Neuronal pathology in deep grey matter structures: a multimodal imaging analysis combining PET and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Bosque-Freeman, L.; Leroy, C.; Galanaud, D.; Sureau, F.; Assouad, R.; Tourbah, A.; Papeix, C.; Comtat, C.; Trebossen, R.; Lubetzki, C.; Delforge, J.; Bottlaender, M.; Stankoff, B. [Serv. Hosp. Frederic Joliot, Orsay (France)

    2009-07-01

    Objective: To assess neuronal damage in deep gray matter structures by positron emission tomography (PET) using [{sup 11}C]-flumazenil (FMZ), a specific central benzodiazepine receptor antagonist, and [{sup 18}F]-fluorodeoxyglucose (FDG), which reflects neuronal metabolism. To compare results obtained by PET and those with multimodal magnetic resonance imaging (MRI). Background: It is now accepted that neuronal injury plays a crucial role in the occurrence and progression of neurological disability in multiple sclerosis (MS). To date, available MRI techniques do not specifically assess neuronal damage, but early abnormalities, such as iron deposition or atrophy, have been described in deep gray matter structures. Whether those MRI modifications correspond to neuronal damage remains to be further investigated. Materials and methods: Nine healthy volunteers were compared to 10 progressive and 9 relapsing remitting (RR) MS patients. Each subject performed two PET examinations with [{sup 11}C]-FMZ and [{sup 18}F]-FDG, on a high resolution research tomograph dedicated to brain imaging (Siemens Medical Solution, spatial resolution of 2.5 mm). Deep gray matter regions were manually segmented on T1-weighted MR images with the mutual information algorithm (www.brainvisa.info), and co-registered with PET images. A multimodal MRI including T1 pre and post gadolinium, T2-proton density sequences, magnetization transfer, diffusion tensor, and protonic spectroscopy was also performed for each subject. Results: On PET with [{sup 11}C]-FMZ, there was a pronounced decrease in receptor density for RR patients in all deep gray matter structures investigated, whereas the density was unchanged or even increased in the same regions for progressive patients. Whether the different patterns between RR and progressive patients reflect distinct pathogenic mechanisms is currently investigated by comparing PET and multimodal MRI results. Conclusion: Combination of PET and multimodal MR imaging

  5. Synthesis and radiolabeling of N-[4-[4-(2-[{sup 11}C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene -2-carboxamide - a potential radiotracer for D{sub 3} receptor imaging with PET

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnast, Bertrand [Service Hospitalier Frederic Joliot, SHFJ/CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Valette, Heric [Service Hospitalier Frederic Joliot, SHFJ/CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Besret, Laurent [CNRS URA2210, CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Demphel, Stephane [Service Hospitalier Frederic Joliot, SHFJ/CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Coulon, Christine [Service Hospitalier Frederic Joliot, SHFJ/CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Ottaviani, Michele [Service Hospitalier Frederic Joliot, SHFJ/CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Guillermier, Martine [CNRS URA2210, CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Bottlaender, Michel [Service Hospitalier Frederic Joliot, SHFJ/CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France); Dolle, Frederic [Service Hospitalier Frederic Joliot, SHFJ/CEA/DSV, 4 place du General Leclerc, 91401 Orsay (France)]. E-mail: frederic.dolle@cea.fr

    2006-08-15

    FAUC346 (N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzo[b]thiophene -2-carboxamide), an in vitro D{sub 3}-selective ligand, and its normethyl derivative have been synthesized from commercially available 1-(2-substituted-phenyl)piperazines. FAUC346 has been labeled using [{sup 11}C]methyl triflate in acetone containing aqueous NaOH (5 Eq) at -10 deg. C for 1 min, purified on semipreparative reverse-phase high-performance liquid chromatography (HPLC) and formulated as an intravenous injectable solution using a Sep-Pak Plus C{sub 18} device. Up to 5.5 GBq of [{sup 11}C]FAUC346 (N-[4-[4-(2-[methyl-{sup 11}C]methoxyphenyl)piperazin-1-yl]butyl]benzo[b] thiophene-2-carboxamide), with a specific radioactivity of 45-75 GBq/{mu}mol, could be obtained in 30-35 min, including HPLC purification and formulation starting from 44.4 GBq of [{sup 11}C]carbon dioxide. Preliminary pharmacological evaluation of [{sup 11}C]FAUC346 in rat brain clearly demonstrated in vivo selectivity for D{sub 3} receptors and the absence of radiolabeled metabolite within the brain. These encouraging results, however, could not be confirmed in nonhuman primates; therefore, this radioligand does not appear to have the required pharmacological profile for a positron emission tomography probe for imaging D{sub 3} receptors.

  6. PET in cerebrovascular disease; PET bei zerebrovaskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Herholz, K. [Neurologische Universitaetsklinik der Univ. Koeln (Germany)]|[Max-Planck-Institut fuer Neurologische Forschung, Koeln (Germany)

    1997-03-01

    Tissue viability is of particular interest in acute cerebral ischemia because it may be preserved if reperfusion can be achieved rapidly, e.g. by acute thrombolysis. Measurements of regional cerebral blood flow (CBF) and oxygen consumption by PET can assess tissue viability, and they have substantially increased our knowledge of th pathophysiology of ischemic stroke and the associated penumbra. Widerspread clinical application in acute stroke, however, is unlikely because of the large logistic and personnel resources required. In chronic cerebrovascular disease, measurement of regional CBF and glucose metabolism, which is usually coupled, provide detailed insights in disturbance of cortical function, e.g. due to deafferentiation, and contribute to differentiation of dementia types. Chronic misery perfusion, i.e. reduced perfusion that does not match the metabolic demand of the tissue, can be demonstrated by PET. It may be found in some patients with high-grade arterial stenoses. Less severe impairment of brain perfusion can be demonstrated by measurement of the cerebrovascular reserve capacity. The most frequent clinical situations can be assessed by less demanding procedures, e.g. by SPECT. In conclusion, PET has its role in cerebrovascular disease primarily within scientific studies, where high resolution and absolute quantitation of physiological variables are essential. (orig.). 65 refs. [Deutsch] Beim akuten ischaemischen Insult ist die Vitalitaet des Gewebes von besonderem Interesse, da sie durch rasche Reperfusion, z.B. durch Thrombolyse, erhalten bleiben kann. Messungen der zerebralen Durchblutung und des Sauerstoffumsatzes mittels PET geben darueber wesentliche Aufschluesse, und sie sind wichtig fuer das Verstaendnis der Pathophysiologie ischaemischer Infarkte und der Penumbra mit kritischer Perfusion beim Menschen. Ihre breitere Anwendung in der klinischen Patientenversorgung kommt allerdings wegen des hohen Aufwandes derzeit kaum in Betracht. Bei

  7. Role of {sup 18}FDG PET/CT in patients treated with {sup 177}Lu-DOTATATE for advanced differentiated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Matteucci, Federica [Cancer Institute of Romagna (IRST), Unit of Radiometabolic Medicine, Meldola, FC (Italy); Nanni, Oriana; Scarpi, Emanuela [Cancer Institute of Romagna (IRST), Unit of Biostatistics and Clinical Trials, Meldola, FC (Italy); Bodei, Lisa; Gilardi, Laura; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Nicoletti, Stefania [Cancer Institute of Romagna (IRST), Unit of Medical Oncology, Meldola, FC (Italy)

    2013-06-15

    The prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after {sup 177}Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade 1/2 NETs. We retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7 GBq divided into five courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index {<=}2 %, 19 patients), and those with grade 2 tumour (Ki-67 index >3 % to <20 %, 33 patients). On the basis of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET-). FDG PET was positive in 57 % of patients with grade 1 NET and in 66 % of patients with grade 2 NET, and the rates of disease control (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95 % and 79 %, respectively (P = 0.232). In PET- and PET+ patients, the DC rates were 100 % and 76 % (P = 0.020) with a PFS of 32 and 20 months, respectively (P = 0.033). Of the PET+ patients with grade 1 NET, 91 % showed disease control, whereas about one in three PET+ patients with grade 2 NET (32 %) progressed after Lu-PRRT (DC rate 68 %). These results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients with grade 1/2 advanced NETs. Notably, none of PET- patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32 % of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT. (orig.)

  8. The Current and Evolving Role of PET in Personalized Management of Lung Cancer.

    Science.gov (United States)

    Mena, Esther; Yanamadala, Anusha; Cheng, Gang; Subramaniam, Rathan M

    2016-07-01

    Using tumor genomic profiling information has revolutionized the landscape of personalized treatment of lung cancer. The management of lung cancer and non-small cell lung cancer particularly is influenced by discoveries of activating mutations in epidermal growth factor receptor and targeted therapies with tyrosine kinase inhibitors, fusion genes involving anaplastic lymphoma kinase, and targeted therapies for Kristen-Rat-Sarcoma and MET protooncogenes. PET imaging plays an important role in assessing the biologic behavior of lung cancer and defining response to therapy. This review summarizes genomic discoveries in lung cancer and their implications for functional PET imaging.

  9. PET/MRI and PET/CT in advanced gynaecological tumours: initial experience and comparison

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Marcelo A.; Schulthess, Gustav von; Veit-Haibach, Patrick [University Hospital Zurich, Department Medical Radiology, Nuclear Medicine, Zurich (Switzerland); University Hospital Zurich, Department Medical Radiology, Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Zurich (Switzerland); Kubik-Huch, Rahel A.; Freiwald-Chilla, Bianka [Kantonsspital Baden AG, Department of Radiology, Baden (Switzerland); Hauser, Nik [Kantonsspital Baden AG, Department of Gynaecology, Baden (Switzerland); Froehlich, Johannes M. [Guerbet AG, Zurich (Switzerland)

    2015-08-15

    To compare the diagnostic accuracy of PET/MRI and PET/CT for staging and re-staging advanced gynaecological cancer patients as well as identify the potential benefits of each method in such a population. Twenty-six patients with suspicious or proven advanced gynaecological cancer (12 ovarian, seven cervical, one vulvar and four endometrial tumours, one uterine metastasis, and one primary peritoneal cancer) underwent whole-body imaging with a sequential trimodality PET/CT/MR system. Images were analysed regarding primary tumour detection and delineation, loco-regional lymph node staging, and abdominal/extra-abdominal distant metastasis detection (last only by PET/CT). Eighteen (69.2 %) patients underwent PET/MRI for primary staging and eight patients (30.8 %) for re-staging their gynaecological malignancies. For primary tumour delineation, PET/MRI accuracy was statistically superior to PET/CT (p < 0.001). Among the different types of cancer, PET/MRI presented better tumour delineation mainly for cervical (6/7) and endometrial (2/3) cancers. PET/MRI for local evaluation as well as PET/CT for extra-abdominal metastases had therapeutic consequences in three and one patients, respectively. PET/CT detected 12 extra-abdominal distant metastases in 26 patients. PET/MRI is superior to PET/CT for primary tumour delineation. No differences were found in detection of regional lymph node involvement and abdominal metastases detection. (orig.)

  10. Childhood Attachment to Pets: Associations between Pet Attachment, Attitudes to Animals, Compassion, and Humane Behaviour

    Directory of Open Access Journals (Sweden)

    Roxanne D. Hawkins

    2017-05-01

    Full Text Available Attachment to pets has an important role in children’s social, emotional, and cognitive development, mental health, well-being, and quality of life. This study examined associations between childhood attachment to pets and caring and friendship behaviour, compassion, and attitudes towards animals. This study also examined socio-demographic differences, particularly pet ownership and pet type. A self-report survey of over one thousand 7 to 12 year-olds in Scotland, UK, revealed that the majority of children are strongly attached to their pets, but attachment scores differ depending on pet type and child gender. Analysis revealed that attachment to pets is facilitated by compassion and caring and pet-directed friendship behaviours and that attachment to pets significantly predicts positive attitudes towards animals. The findings have implications for the promotion of prosocial and humane behaviour. Encouraging children to participate in pet care behaviour may promote attachment between children and their pet, which in turn may have a range of positive outcomes for both children (such as reduced aggression, better well-being, and quality of life and pets (such as humane treatment. This study enhances our understanding of childhood pet attachment and has implications for humane education and promoting secure emotional attachments in childhood.

  11. 5-HT Radioligands for Human Brain Imaging With PET and SPECT

    Science.gov (United States)

    Paterson, Louise M.; Kornum, Birgitte R.; Nutt, David J.; Pike, Victor W.; Knudsen, Gitte M.

    2014-01-01

    The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging. PMID:21674551

  12. PET/CT and Bremsstrahlung Imaging After 90Y DOTANOC Therapy for Rectal Net With Liver Metastases.

    Science.gov (United States)

    Abdülrezzak, Ümmühan; Kula, Mustafa; Tutuş, Ahmet; Buyukkaya, Fikret; Karaca, Halit

    2015-10-01

    Peptide receptor radionuclide therapy with Lu or Y is promising with successful results in somatostatin receptor-positive tumors. In all radiation therapies, knowledge of the radiation dose received by the target, and other organs in the body is essential to evaluate the risks and benefits of any procedure. We report a case of liver metastases from a rectal neuroendocrine tumor, which was treated with Y DOTANOC. Posttreatment whole-body planar images were acquired through Bremsstrahlung radiations of Y on a γ-camera, and thoracolumbar PET/CT images were acquired on PET.

  13. Veterinarians' role for pet owners facing pet loss

    OpenAIRE

    Fernandez-Mehler, P.; Gloor, P.; Sager, E.; Lewis, F.I.; Glaus, T. M

    2013-01-01

    Owners' satisfaction with, and expectations from, their veterinarians around euthanasia, including questions on disposal of pet remains subject to animal species, clients' gender, age, family conditions, area of living and type of veterinary clinic visited were evaluated by questionnaire. Questionnaires were to be filled out by clients consecutively visiting the individual practices and hospitals for any kind of consultations. Of 2350 questionnaires distributed, 2008 were returned and availab...

  14. Development of a Dual Tracer PET Method for Imaging Dopaminergic Neuromodulation

    Science.gov (United States)

    Converse, Alexander K.; Dejesus, Onofre T.; Flores, Leo G.; Holden, James E.; Kelley, Ann E.; Moirano, Jeffrey M.; Nickles, Robert J.; Oakes, Terrence R.; Roberts, Andrew D.; Ruth, Thomas J.; Vandehey, Nicholas T.; Davidson, Richard J.

    2006-04-01

    The modulatory neurotransmittor dopamine (DA) is involved in movement and reward behaviors, and malfunctions in the dopamine system are implicated in a variety of prevalent and debilitating pathologies including Parkinson's disease, attention deficit/hyperactivity disorder, schizophrenia, and addiction. Positron emission tomography (PET) has been used to separately measure changes in DA receptor occupancy and blood flow in response to various interventions. Here we describe a dual tracer PET method to simultaneously measure both responses with the aim of comparing DA release in particular areas of the brain and associated alterations in neural activity throughout the brain. Significant correlations between reductions in DA receptor occupancy and blood flow alterations would be potential signs of dopaminergic modulation, i.e. modifications in signal processing due to increased levels of extracellular DA. Methodological development has begun with rats undergoing an amphetamine challenge while being scanned with the blood flow tracer [17F]fluoromethane and the dopamine D2 receptor tracer [18F]desmethoxyfallypride.

  15. Feasibility of simultaneous PET/MR of the carotid artery: first clinical experience and comparison to PET/CT

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Knudsen, Andreas; Hag, Anne Mette Fisker;

    2013-01-01

    The study aimed at comparing PET/MR to PET/CT for imaging the carotid arteries in patients with known increased risk of atherosclerosis. Six HIV-positive men underwent sequential PET/MR and PET/CT of the carotid arteries after injection of 400 MBq of 18F-FDG. PET/MR was performed a median of 131 ...

  16. PET Image Reconstruction Using Information Theoretic Anatomical Priors

    Science.gov (United States)

    Somayajula, Sangeetha; Panagiotou, Christos; Rangarajan, Anand; Li, Quanzheng; Arridge, Simon R.

    2011-01-01

    We describe a nonparametric framework for incorporating information from co-registered anatomical images into positron emission tomographic (PET) image reconstruction through priors based on information theoretic similarity measures. We compare and evaluate the use of mutual information (MI) and joint entropy (JE) between feature vectors extracted from the anatomical and PET images as priors in PET reconstruction. Scale-space theory provides a framework for the analysis of images at different levels of detail, and we use this approach to define feature vectors that emphasize prominent boundaries in the anatomical and functional images, and attach less importance to detail and noise that is less likely to be correlated in the two images. Through simulations that model the best case scenario of perfect agreement between the anatomical and functional images, and a more realistic situation with a real magnetic resonance image and a PET phantom that has partial volumes and a smooth variation of intensities, we evaluate the performance of MI and JE based priors in comparison to a Gaussian quadratic prior, which does not use any anatomical information. We also apply this method to clinical brain scan data using F18 Fallypride, a tracer that binds to dopamine receptors and therefore localizes mainly in the striatum. We present an efficient method of computing these priors and their derivatives based on fast Fourier transforms that reduce the complexity of their convolution-like expressions. Our results indicate that while sensitive to initialization and choice of hyperparameters, information theoretic priors can reconstruct images with higher contrast and superior quantitation than quadratic priors. PMID:20851790

  17. Comparison between PET/MR and PET/CT in evaluation of oncological patients%PET/MR与PET/CT的对比研究

    Institute of Scientific and Technical Information of China (English)

    徐白萱; 富丽萍; 关志伟; 尹大一; 刘家金; 杨晖; 张锦明; 陈英茂; 安宁豫

    2014-01-01

    Objective To verify the feasibility of the integrated PET/MR for oncological applications by comparing PET/MR with PET/CT in terms of lesion detection and quantitative measurement.Methods A total of 277 patients (165 males,112 females,average age (52.9± 12.6) years) voluntarily participated in this same-day PET/CT and PET/MR comparative study.The time interval between the two studies was 15-35 min.PET/CT images were acquired and reconstructed following standard protocols.PET/MR covered the body trunk with a sequence combination of transverse T1 weighted imaging (WI) 3D-volumetric interpolated breath-hold,T2WI turbo spin echo with fat saturation,diffusion-weighted imaging,and simultaneous PET acquisition.PET images were reconstructed by vender-provided attenuation correction methods.The results of PET/CT and PET/MR were regarded as positive if any modality (CT,PET or MRI) was positive.SUVmax was obtained by the manually drawn ROI.Detection rates were compared with x2 test and SUVmax from the two modalities was analyzed with Spearman correlation analysis.Results A total of 353 lesions were detected in 220 patients.Compared to PET/CT,PET/MR revealed 30 additional true-positive lesions,while missed 6.The detection rates between PET/CT and PET/MR were significantly different (P<0.05).The lesion-based and patient-based consistency was 89.8% (317/353) and 85.9% (189/220),respectively.There were significant correlations of SUVmax between PET/MR and PET/CT for lesions(rs =0.91,P<0.01) and for normal tissues(rs =0.62-0.76,all P<0.01).Conclusions With reference to PET/CT,integrated PET/MR may provide comparable semi-quantitative measurements of pathological lesions as well as normal tissues.Integrated PET/MR may be more effective to detect lesions in abdomen and pelvis.%目的 通过与PET/CT在病灶检测及定量分析方面的比较,论证PET/MR一体机应用于临床的可行性.方法 2012年5月至2013年2月共300例患者同天间隔15 ~ 35 min行PET

  18. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

    DEFF Research Database (Denmark)

    Boellaard, Ronald; O'Doherty, Mike J; Weber, Wolfgang A

    2010-01-01

    The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography......-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information....

  19. Automated radiosynthesis of [{sup 18}F]PBR111 and [{sup 18}F]PBR102 using the Tracerlab FX{sub FN} and Tracerlab MX{sub FDG} module for imaging the peripheral benzodiazepine receptor with PET

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, Thomas, E-mail: thomas@nucmed.rpa.cs.nsw.gov.au [PET and Nuclear Medicine Department, Royal Prince Alfred Hospital, Missenden road, Camperdown NSW 2050, Sydney (Australia); Pham, Tien Q. [LifeSciences, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Sydney (Australia); Henderson, David [PET and Nuclear Medicine Department, Royal Prince Alfred Hospital, Missenden road, Camperdown NSW 2050, Sydney (Australia); Jackson, Timothy [LifeSciences, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Sydney (Australia); Lam, Peter [PET and Nuclear Medicine Department, Royal Prince Alfred Hospital, Missenden road, Camperdown NSW 2050, Sydney (Australia); Izard, Michael; Katsifis, Andrew [LifeSciences, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Sydney (Australia)

    2012-01-15

    [{sup 18}F]PBR111 and [{sup 18}F]PBR102 are selective radioligands for imaging of the Peripheral Benzodiazepine Receptor (PBR). We have developed a fully automated method for the radiosynthesis of [{sup 18}F]PBR111 and [{sup 18}F]PBR102 in the Tracerlab FX{sub FN} (30{+-}2% radiochemical yield non-decay-corrected for both tracers) and Tracerlab MX{sub FDG} (25{+-}2% radiochemical yield non-decay-corrected for both tracers) from the corresponding p-toluenesulfonyl precursors. For all tracers, radiochemical purity was >99% and specific activity was >150 GBq/{mu}mol after less than 60 min of preparation time. - Highlights: Black-Right-Pointing-Pointer Radiosynthesis of novel ligands PBR111 and PBR102 with fluorine-18. Black-Right-Pointing-Pointer Fully automated synthesis undertaken using the GE Tracerlab FX{sub FN} and MX{sub FDG} modules. Black-Right-Pointing-Pointer Reproducible high yields suitable for clinical applications. Black-Right-Pointing-Pointer Radiosynthesis and formulation achieved in less than 60 mins. Black-Right-Pointing-Pointer PBR111 and PBR102 prepared in high radiochemical yield and specific activity.

  20. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian

    2013-01-01

    Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...... that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations....

  1. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian

    2013-01-01

    Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...... that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations....

  2. Joint PET-MR respiratory motion models for clinical PET motion correction

    Science.gov (United States)

    Manber, Richard; Thielemans, Kris; Hutton, Brian F.; Wan, Simon; McClelland, Jamie; Barnes, Anna; Arridge, Simon; Ourselin, Sébastien; Atkinson, David

    2016-09-01

    Patient motion due to respiration can lead to artefacts and blurring in positron emission tomography (PET) images, in addition to quantification errors. The integration of PET with magnetic resonance (MR) imaging in PET-MR scanners provides complementary clinical information, and allows the use of high spatial resolution and high contrast MR images to monitor and correct motion-corrupted PET data. In this paper we build on previous work to form a methodology for respiratory motion correction of PET data, and show it can improve PET image quality whilst having minimal impact on clinical PET-MR protocols. We introduce a joint PET-MR motion model, using only 1 min per PET bed position of simultaneously acquired PET and MR data to provide a respiratory motion correspondence model that captures inter-cycle and intra-cycle breathing variations. In the model setup, 2D multi-slice MR provides the dynamic imaging component, and PET data, via low spatial resolution framing and principal component analysis, provides the model surrogate. We evaluate different motion models (1D and 2D linear, and 1D and 2D polynomial) by computing model-fit and model-prediction errors on dynamic MR images on a data set of 45 patients. Finally we apply the motion model methodology to 5 clinical PET-MR oncology patient datasets. Qualitative PET reconstruction improvements and artefact reduction are assessed with visual analysis, and quantitative improvements are calculated using standardised uptake value (SUVpeak and SUVmax) changes in avid lesions. We demonstrate the capability of a joint PET-MR motion model to predict respiratory motion by showing significantly improved image quality of PET data acquired before the motion model data. The method can be used to incorporate motion into the reconstruction of any length of PET acquisition, with only 1 min of extra scan time, and with no external hardware required.

  3. Child vs. Pet: The Effect of Abortion Legalization on the Demand for Pets

    OpenAIRE

    Youjin Hahn; Liang Choon Wang; Hee-Seung Yang

    2012-01-01

    This paper examines whether abortion legalization led to increased demand for pets in the United States. We compare women living in early-legalizing states, whose peak childbearing years occurred in the early 1970s, to women in other states and cohorts and estimate their likelihood of pet ownership and time spent on pets after their peak childbearing years were over. We find the probability of owning any pet is approximately 9.6 percentage points higher for women affected by abortion legaliza...

  4. J-PET analysis framework for the prototype TOF-PET detector

    CERN Document Server

    Krzemień, W; Stola, K; Trybek, D; Bednarski, T; Białas, P; Czerwiński, E; Kapłon, Ł; Kochanowski, A; Korcyl, G; Kowal, J; Kowalski, P; Kozik, T; Molenda, M; Moskal, P; Niedźwiecki, Sz; Pałka, M; Pawlik, M; Raczyński, L; Rudy, Z; Salabura, P; Sharma, N G; Słomski, A; Smyrski, J; Strzelecki, A; Wiślicki, W; Zieliński, M; Zoń, N

    2013-01-01

    Novel TOF-PET scanner solutions demand, apart from the state of the art detectors, software for fast processing of the gathered data, monitoring of the whole scanner and reconstruction of the PET image. In this article we present an analysis framework for the novel STRIP-PET scanner developed by the J-PET collaboration in the Institute of Physics of the Jagiellonian University. This software is based on the ROOT package used in many particle physics experiments.

  5. Critical Care of Pet Birds.

    Science.gov (United States)

    Jenkins, Jeffrey Rowe

    2016-05-01

    Successful care of the critical pet bird patient is dependent on preparation and planning and begins with the veterinarian and hospital staff. An understanding of avian physiology and pathophysiology is key. Physical preparation of the hospital or clinic includes proper equipment and understanding of the procedures necessary to provide therapeutic and supportive care to the avian patient. An overview of patient intake and assessment, intensive care environment, and fluid therapy is included.

  6. The Therapeutic Value of Pets

    OpenAIRE

    1986-01-01

    While domestic pets are capable of transmitting disease and inflicting injury, they may also be of benefit to human health. Studies suggest that companion animals, in addition to their well-known role as helpers to the handicapped, may alleviate depression, solace the lonely, facilitate psycho-therapy, socialize criminals, lower blood pressure, increase survivorship from myocardial infarction and ease the social pain of aging in our society.

  7. Pet Ownership and Evacuation Prior to Hurricane Irene

    Directory of Open Access Journals (Sweden)

    Nick Rohrbaugh

    2012-09-01

    Full Text Available Pet ownership has historically been one of the biggest risk factors for evacuation failure prior to natural disasters. The forced abandonment of pets during Hurricane Katrina in 2005 made national headlines and led to the passage of the Pet Evacuation and Transportation Standards Act (PETS, 2006 which mandated local authorities to plan for companion animal evacuation. Hurricane Irene hit the East Coast of the United States in 2011, providing an excellent opportunity to examine the impact of the PETS legislation on frequency and ease of evacuation among pet owners and non-pet owners. Ninety pet owners and 27 non-pet owners who lived in mandatory evacuation zones completed questionnaires assessing their experiences during the hurricane and symptoms of depression, PTSD, dissociative experiences, and acute stress. Pet ownership was not found to be a statistical risk factor for evacuation failure. However, many pet owners who failed to evacuate continue to cite pet related reasons.

  8. If My Child Has Asthma, Can We Keep Our Pet?

    Science.gov (United States)

    ... Have someone other than your child wash and brush your pet every week (this is advisable for cats as well as dogs). Encourage everyone in the family to wash their hands after playing with your pet. Keep your pet ...

  9. PET-based radiation therapy planning.

    Science.gov (United States)

    Speirs, Christina K; Grigsby, Perry W; Huang, Jiayi; Thorstad, Wade L; Parikh, Parag J; Robinson, Clifford G; Bradley, Jeffrey D

    2015-01-01

    In this review, we review the literature on the use of PET in radiation treatment planning, with an emphasis on describing our institutional methodology (where applicable). This discussion is intended to provide other radiation oncologists with methodological details on the use of PET imaging for treatment planning in radiation oncology, or other oncologists with an introduction to the use of PET in planning radiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. PET imaging in endocrine tumours.

    Science.gov (United States)

    Khan, S; Lloyd, C; Szyszko, T; Win, Z; Rubello, D; Al-Nahhas, A

    2008-06-01

    The role of PET in the assessment of endocrine tumours has been, until recently, restricted to the use of (18)F-fluoro-deoxy-D-glucose ((18)F-FDG). Being a marker of metabolically active lesions that show high grading and low differentiation, FDG is not ideal for this purpose since the majority of endocrine tumours are slow growing and highly differentiated. It is however useful when dedifferentiation takes place and provides excellent prognostic information. A number of hormone precursors and amino acids are labelled with (11)C and used successfully in the management of parathyroid, adrenal and pituitary tumours. However, the short half-life of (11)C radiopharmaceuticals restricts their use to centres with access to an on-site cyclotron, while the high cost of production may limit their use to research purposes. A promising new positron-emission tomography (PET) tracer is Gallium-68 obtained by elution from a long shelf-life generator that makes it economic and cyclotron-independent. Its short half-life and flexible labelling ability to a wide range of peptides and antibodies makes it ideal for PET imaging. In addition to imaging GEP-NETs and phaeochromocytoma, it has the potential to be used in a wider range of endocrine tumours.

  11. The AX-PET project Demonstration of a high resolution axial 3D PET

    CERN Document Server

    Bolle, E; Casella, C; Chesi, E; Clinthorne, N; Cochran, E; De Leo, R; Dissertori, G; Djambazov, G; Fanti, V; Honscheid, K; Huh, S; Johnson, I; Joram, C; Kagan, H; Lustermann, W; Meddi, F; Nappi, E; Nessi-Tedaldi, F; Oliver, J F; Pauss, P; Rafecas, M; Renker, D; Rudge, A; Schinzel, D; Schneider, T; Seguinot, J; Smith, S; Solevi, P; Stapnes, S; Weilhammer, P

    2010-01-01

    The AX-PET is a new geometrical concept for a high resolution 3D PET scanner, based on matrices of axially oriented LYSO crystals interleaved by stacks of WLS, both individually read out by G-APDs. A PET demonstrator, based on two detector modules used in coincidence, is currently under construction.

  12. F-18-FLT PET for visualization of laryngeal cancer : Comparison with F-18-FDG PET

    NARCIS (Netherlands)

    Cobben, DCP; van der Laan, BFAM; Maas, B; Vaalburg, W; Suurmeijer, AJH; Hoekstra, HJ; Jager, PL; Elsinga, PH

    The feasibility of F-18-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with F-18-FDG PET. Methods: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary

  13. Double tracer PET/CT:what is it and what does it mean?

    Institute of Scientific and Technical Information of China (English)

    Mattia Pellicciari; Silvia Ortolani; Elisabetta Grego; Giampaolo Tortora; Sara Cingarlini

    2016-01-01

    68Ga-DOTA-peptide PET/CT is a recommended imaging modality in the workup of neuroendocrine neoplasms (NENs), which shows high diagnostic sensitivity and is a strong predictor of successful somatostatin receptor directed treatments. Although not routinely recommended, reliable evidences show that18F-FDG PET/CT can provide complementary information in this setting with the ability to discriminate slow-proliferating tumors from aggressive, rapidly-proliferating tumors. Further, it has been proposed as an independent prognostic factor for the prediction of either overall survival or progression free survival. In this review, we provide insight into the biologic signiifcance of68Ga-DOTA-peptides and18F-FDG uptake, and of the use of double tracer (68Ga-DOTA-peptides plus18F-FDG) PET/CT in the clinical evaluation of patients affected by NENs.

  14. 胰腺癌:PET诊断学%Pancreatic cancer-Diagnostics:PET

    Institute of Scientific and Technical Information of China (English)

    Uwe Haberkorn

    2007-01-01

    Important challenges for imaging of pancreatic cancer are the late presentation of the disease and the fact that therapeutic management is of limited success. Surgery continues to be the only treatment that offers potential cure. Therefore,defining whether the patient has an operable tumor remains the ultimate aim of imaging in pancreatic cancer. PET and PET/CT with fluorodeoxyglucose (FDG) are of value in differential diagnosis between pancreatitis and carcinoma and for the detection of remote metastases, but relatively inefficient in the detection of nodal disease. The detection of recurrent disease is of little clinical consequence. FDG-PET may be considered as a prognostic marker for patient survival or therapy response, but evidence for these applications is lacking. Future applications will broaden the spectrum of tracers applied using molecules for the assessment of proliferation and detection of receptors.

  15. Advances in time-of-flight PET.

    Science.gov (United States)

    Surti, Suleman; Karp, Joel S

    2016-01-01

    This paper provides a review and an update on time-of-flight PET imaging with a focus on PET instrumentation, ranging from hardware design to software algorithms. We first present a short introduction to PET, followed by a description of TOF PET imaging and its history from the early days. Next, we introduce the current state-of-art in TOF PET technology and briefly summarize the benefits of TOF PET imaging. This is followed by a discussion of the various technological advancements in hardware (scintillators, photo-sensors, electronics) and software (image reconstruction) that have led to the current widespread use of TOF PET technology, and future developments that have the potential for further improvements in the TOF imaging performance. We conclude with a discussion of some new research areas that have opened up in PET imaging as a result of having good system timing resolution, ranging from new algorithms for attenuation correction, through efficient system calibration techniques, to potential for new PET system designs.

  16. Radiology for PET/CT reporting

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Cristina; Fanti, Stefano; Zanoni, Lucia [Univ. Hospital Sant Orsola-Malpighi, Bologna (Italy). Dept. of Nuclear Medicine

    2014-07-01

    Offers rapid access to slice by slice CT descriptions of anatomical structures from PET/CT studies. Presents images and descriptions of CT findings that may be detected while reviewing PET/CT scans. Includes principal MRI findings in diseases susceptible to PET/CT evaluation. Reading PET/CT scans is sometimes challenging. Not infrequently, abnormal findings on CT images are functionally silent and therefore difficult for nuclear medicine practitioners to interpret. Furthermore, in general only a low-dose CT scan is produced as part of the combined PET/CT study, and the resulting CT images may prove suboptimal for image interpretation. This atlas is designed to enable nuclear medicine practitioners who routinely read PET/CT scans to recognize the most common CT abnormalities. Slice-by-slice descriptions are provided of anatomical structures as visualized on CT scans obtained in PET/CT studies. The CT findings that may be detected while reviewing PET/CT scans of various body regions and conditions are then illustrated and fully described. The concluding section of the book is devoted to the principal MRI findings in diseases which cannot be evaluated using PETs/CTs.

  17. Advances in time-of-flight PET

    Science.gov (United States)

    Surti, Suleman; Karp, Joel S.

    2016-01-01

    This paper provides a review and an update on time-of-flight PET imaging with a focus on PET instrumentation, ranging from hardware design to software algorithms. We first present a short introduction to PET, followed by a description of TOF PET imaging and its history from the early days. Next, we introduce the current state-of-art in TOF PET technology and briefly summarize the benefits of TOF PET imaging. This is followed by a discussion of the various technological advancements in hardware (scintillators, photo-sensors, electronics) and software (image reconstruction) that have led to the current widespread use of TOF PET technology, and future developments that have the potential for further improvements in the TOF imaging performance. We conclude with a discussion of some new research areas that have opened up in PET imaging as a result of having good system timing resolution, ranging from new algorithms for attenuation correction, through efficient system calibration techniques, to potential for new PET system designs. PMID:26778577

  18. Combined PET/CT in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Keon Wook [National Cancer Center, Goyang (Korea, Republic of)

    2002-02-01

    Presently, PET is widely used in oncology, but suffers from limitations of poor anatomical information. To compensate for this weakness, a combined PET/CT has been developed by Professor Townsend at the University of Pittsburgh Medical Center. The prototype was designed as PET and CT components combined serially in a gantry. The CT images provide not only accurate anatomical location of the lesions but also transmission map for attenuation correction. More than 300 cancer patients have been studied with the prototype of PET/CT since July, 1998. The PET/TC studies affected the managements in about 20{approx}30% of cancer patients. These changes are a consequence of the more accurate localization of functional abnormalities, and the distinction of pathological from normal physiological uptake. Now a variety of combined PET/CT scanners with high-end PET and high-end CT components are commercially available. With the high speed of multi-slice helical CT, throughput of patient's increases compared to conventional PET. Although some problems (such as a discrepancy in breathing state between the two modalities) still remain, the role of PET/CT in oncology is very promising.

  19. PET-Computed Tomography in Veterinary Medicine.

    Science.gov (United States)

    Randall, Elissa K

    2016-05-01

    PET/CT is an advanced imaging modality that is becoming more commonly used in veterinary medicine. It is most commonly used to image patients with cancer, and the most frequently used radiopharmaceutical is F-18 FDG. F-18 FDG is a glucose analog that highlights areas of increased glucose metabolism on the PET images. CT images provide excellent anatomic depiction and aid in interpretation of the PET data. Many types of cancer are hypermetabolic on PET/CT scans, but normal structures and areas of inflammation are also hypermetabolic, so knowledge of normal imaging and cytologic or histopathologic evaluation of lesions is essential.

  20. Pet food safety: the roles of government, manufacturers, and veterinarians.

    Science.gov (United States)

    Eirmann, Laura; Cowell, Christopher; Thompson, Larry

    2012-01-01

    Food safety is of concern for both human and companion animal health. Government agencies, pet food manufacturers, and veterinarians play crucial roles in ensuring the safety of pet food and safeguarding pets and their owners. Recent legislation will increase the governmental role in regulating pet food and will affect many manufacturers. Veterinarians continue to play a vital role by recognizing and reporting pet food safety issues and by educating clients on matters related to pet food safety.

  1. Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers

    DEFF Research Database (Denmark)

    Ettrup, Anders; Hansen, Martin; Santini, Martin A

    2011-01-01

    Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer....... In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig...

  2. Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers

    DEFF Research Database (Denmark)

    Ettrup, Anders; Hansen, Martin; Santini, Martin A;

    2011-01-01

    Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer....... In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig...

  3. Evaluation of unusual neuroendocrine tumours by means of 68Ga-DOTA-NOC PET.

    Science.gov (United States)

    Fanti, Stefano; Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Montini, Giancarlo; Allegri, Vincenzo; Grassetto, Gaia; Rubello, Domenico; Nanni, Cristina; Franchi, Roberto

    2008-12-01

    (18)F-FDG PET value for the assessment of neuroendocrine tumours (NET) is limited. Preliminary studies indicate that somatostatin receptor PET using (68)Ga-DOTA-peptides is more accurate for disease assessment and provide additional data on receptor status, that are crucial for targeted radionuclide therapy. At present, however, few papers investigated the role of (68)Ga-DOTA-NOC PET in NET, especially in unusual situations. The purpose of the present study was to evaluate (68)Ga-DOTA-NOC for the evaluation of NET of uncommon presentation. Patients with biopsy-proven NET were scheduled for (68)Ga-DOTA-NOC PET; we excluded from further evaluation cases with most common NET tumours (gastro-entero-pancreatic and pulmonary localization of primary lesion, MEN syndromes, medullary thyroid carcinoma, pheochromocytomas). PET results were compared with findings of conventional imaging, including CT, ultrasonography, MR and somatostatin receptor scintigraphy; finally PET results were compared with follow-up data with respect to the impact on patient management. Fourteen patients were finally enrolled; primary tumours were located at uterine level (3 cases), prostate (3 cases), ovary (1 case), kidney (1 case), breast (1 case), ear (1 case); also 3 cases of paraganglioma (at neck, abdominal and mediastinum level) and 1 case of lymphoma were included. (68)Ga-DOTA-NOC PET was positive, showing at least 1 lesion, in 6/14 cases while 5 cases turned out negative and 2 inconclusive. On a clinical basis, (68)Ga-DOTA-NOC provided additional information in comparison to conventional imaging procedures in 7/14 cases, and was considered useful in 12/14 patients, with 8 patients in which (68)Ga-DOTA-NOC PET was determinant for patient's management. Although the number of patients studied is limited, our data show that (68)Ga-DOTA-NOC can be usefully applied for the evaluation of NET of uncommon presentation; in particular very promising results were obtained in paraganglioma. On the other

  4. Standardised uptake values from PET/CT images: comparison with conventional attenuation-corrected PET

    Energy Technology Data Exchange (ETDEWEB)

    Souvatzoglou, M.; Ziegler, S.I.; Martinez, M.J.; Dzewas, G.; Schwaiger, M.; Bengel, F. [Nuklearmedizinische Klinik der Technischen Universitaet Muenchen, Munich (Germany); Busch, R. [Institut fuer Epidemiologie und Statistik der Technischen Universitaet Muenchen, Munich (Germany)

    2007-03-15

    In PET/CT, CT-derived attenuation factors may influence standardised uptake values (SUVs) in tumour lesions and organs when compared with stand-alone PET. Therefore, we compared PET/CT-derived SUVs intra-individually in various organs and tumour lesions with stand-alone PET-derived SUVs. Thirty-five patients with known or suspected cancer were prospectively included. Sixteen patients underwent FDG PET using an ECAT HR+scanner, and subsequently a second scan using a Biograph Sensation 16PET/CT scanner. Nineteen patients were scanned in the reverse order. All images were reconstructed with an iterative algorithm (OSEM). Suspected lesions were grouped as paradiaphragmatic versus distant from the diaphragm. Mean and maximum SUVs were also calculated for brain, lung, liver, spleen and vertebral bone. The attenuation coefficients ({mu} values) used for correction of emission data (bone, soft tissue, lung) in the two data sets were determined. A body phantom containing six hot spheres and one cold cylinder was measured using the same protocol as in patients. Forty-six lesions were identified. There was a significant correlation of maximum and mean SUVs derived from PET and PET/CT for 14 paradiaphragmatic lesions (r=0.97 respectively; p<0.001 respectively) and for 32 lesions located distant from the diaphragm (r=0.87 and r=0.89 respectively; p<0.001 respectively). No significant differences were observed in the SUVs calculated with PET and PET/CT in the lesions or in the organs. In the phantom, radioactivity concentration in spheres calculated from PET and from PET/CT correlated significantly (r=0.99; p<0.001). SUVs of cancer lesions and normal organs were comparable between PET and PET/CT, supporting the usefulness of PET/CT-derived SUVs for quantification of tumour metabolism. (orig.)

  5. Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

    Science.gov (United States)

    Bailey, D L; Pichler, B J; Gückel, B; Barthel, H; Beer, A J; Botnar, R; Gillies, R; Goh, V; Gotthardt, M; Hicks, R J; Lanzenberger, R; la Fougere, C; Lentschig, M; Nekolla, S G; Niederdraenk, T; Nikolaou, K; Nuyts, J; Olego, D; Riklund, K Åhlström; Signore, A; Schäfers, M; Sossi, V; Suminski, M; Veit-Haibach, P; Umutlu, L; Wissmeyer, M; Beyer, T

    2016-10-01

    This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

  6. [68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning

    Directory of Open Access Journals (Sweden)

    Bamberg Michael

    2009-11-01

    Full Text Available Abstract Purpose The observation that human meningioma cells strongly express somatostatin receptor (SSTR 2 was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT. Patients and Methods In 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI and planning-computed tomography (CT was complemented with data from [68Ga]-DOTA-D Phe1-Tyr3-Octreotide (DOTATOC-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan®. Initial gross tumor volume (GTV definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package. Results The integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%. There were major changes of the clinical target volume (CTV which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV-MRI/CT was larger than the GTV-PET in 10 patients (38%, smaller in 13 patients (50% and almost the same in 3 patients (12%. Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible. Conclusion DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery.

  7. Head and neck imaging with PET and PET/CT: artefacts from dental metallic implants

    Energy Technology Data Exchange (ETDEWEB)

    Goerres, Gerhard W.; Hany, Thomas F.; Kamel, Ehab; von Schulthess, Gustav K.; Buck, Alfred [Division of Nuclear Medicine, Department of Radiology, University Hospital Zurich (Switzerland)

    2002-03-01

    Germanium-68 based attenuation correction (PET{sub Ge68}) is performed in positron emission tomography (PET) imaging for quantitative measurements. With the recent introduction of combined in-line PET/CT scanners, CT data can be used for attenuation correction. Since dental implants can cause artefacts in CT images, CT-based attenuation correction (PET{sub CT}) may induce artefacts in PET images. The purpose of this study was to evaluate the influence of dental metallic artwork on the quality of PET images by comparing non-corrected images and images attenuation corrected by PET{sub Ge68} and PET{sub CT}. Imaging was performed on a novel in-line PET/CT system using a 40-mAs scan for PET{sub CT} in 41 consecutive patients with high suspicion of malignant or inflammatory disease. In 17 patients, additional PET{sub Ge68} images were acquired in the same imaging session. Visual analysis of fluorine-18 fluorodeoxyglucose (FDG) distribution in several regions of the head and neck was scored on a 4-point scale in comparison with normal grey matter of the brain in the corresponding PET images. In addition, artefacts adjacent to dental metallic artwork were evaluated. A significant difference in image quality scoring was found only for the lips and the tip of the nose, which appeared darker on non-corrected than on corrected PET images. In 33 patients, artefacts were seen on CT, and in 28 of these patients, artefacts were also seen on PET imaging. In eight patients without implants, artefacts were seen neither on CT nor on PET images. Direct comparison of PET{sub Ge68} and PET{sub CT} images showed a different appearance of artefacts in 3 of 17 patients. Malignant lesions were equally well visible using both transmission correction methods. Dental implants, non-removable bridgework etc. can cause artefacts in attenuation-corrected images using either a conventional {sup 68}Ge transmission source or the CT scan obt