Papers by Sébastien Tremblay
The Journal of Nuclear Medicine, 2015
Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, Jan 2, 2017
We automated radiochemical synthesis of 1-[(11)C]acetoacetate in a commercially available radioch... more We automated radiochemical synthesis of 1-[(11)C]acetoacetate in a commercially available radiochemistry module, TRASIS AllInOne by [(11)C]carboxylation of the corresponding enolate anion generated in situ from isopropenylacetate and MeLi, and purified by ion-exchange column resins.1-[(11)C]acetoacetate was synthesized with high radiochemical purity (95%) and specific activity (~ 66.6GBq/µmol, n = 30) with 35% radiochemical yield, decay corrected to end of synthesis. The total synthesis required ~ 16min. PET imaging studies were conducted with 1-[(11)C]acetoacetate in vervet monkeys to validate the radiochemical synthesis. Tissue uptake distribution was similar to that reported in humans.
Journal of Alzheimer's disease : JAD, 2017
Aerobic training has some benefits for delaying the onset or progression of Alzheimer's disea... more Aerobic training has some benefits for delaying the onset or progression of Alzheimer's disease (AD). Little is known about the implication of the brain's two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits. To determine whether aerobic exercise training modifies brain energy metabolism in mild AD. In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program. Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 μmol/100...
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2011
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2007
Journal of Labelled Compounds and Radiopharmaceuticals, 2008
Journal of Nuclear Medicine
2006 IEEE Nuclear Science Symposium Conference Record, 2006
ABSTRACT Normally the brain almost exclusively uses glucose as a fuel but during fasting it can r... more ABSTRACT Normally the brain almost exclusively uses glucose as a fuel but during fasting it can rely on the increased supply of ketones (beta-hydroxybutyrate, acetoacetate and acetone) produced in liver mitochondria from fatty acid beta-oxidation. Raised blood ketones produced on a very high fat ketogenic diet can significantly reduce seizures in children. Ketones also have other 'protective' effects on the brain but their metabolism by the brain is still poorly understood. The aim of the present work was to assess the brain uptake of 11C-acetoacetate using positron emission tomography (PET) imaging. In order to vary plasma ketones, we used rats (3 groups of 4 rats) under three dietary conditions - control diet (high carbohydrate; low plasma ketones), fat-rich ketogenic diet (moderate plasma ketones), and 48 h fasting (moderate plasma ketones). Tissue perfusion of the tracer and oxygen consumption were measured in heart and brain. In brain but not heart, the ketogenic diet enhanced tracer perfusion and oxygen consumption relative to the two other diets. Our data show that the brain's ability to utilize increased availability of blood ketones may relate in some way to concurrent glucose availability.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2010
From the Newsline editor: Strategies to counter increasingly challenging and unpredictable medica... more From the Newsline editor: Strategies to counter increasingly challenging and unpredictable medical isotope supply shortages have ranged from proposals to build new networks of nuclear reactors to requirements for higher levels of coordination and cooperative planning among existing international producers. Here, a group of Canadian academic and industry researchers propose a different solution with potential for near-term implementation. D irect production of 99m Tc from isotopically enriched 100 Mo via proton bombardment has received little attention, despite the fact that measured production yields indicate that up to 1.4 TBq of 99m Tc can be produced in 6 h using a high-current, medium-energy medical cyclotron. If produced with suitable radioisotopic and chemical purity, such an amount of 99m Tc would suffice to fulfill the requirements of a large metropolitan area. We compared the chemical, radiochemical, and biologic properties of cyclotron-and generatorderived 99m Tc for common nuclear imaging procedures. Our results, presented here for Newsline readers, suggest that a medical cyclotron can produce U.S. Pharmacopeia (USP)compliant, Good Manufacturing Practice (GMP)-grade 99m Tc radiopharmaceuticals that can be used as a substitute for generator-derived 99m Tc radiopharmaceuticals for nuclear imaging procedures. Direct production of 99m Tc using cyclotrons can be considered as a potential means to alleviate the current (and recurrent) challenges in isotope supply. Implementing networks of medium-energy, high-current medical cyclotrons would reduce reliance on nuclear reactors and attenuate the negative consequences associated with the use of fission technology.
Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2011
Cerebral metabolic rate of glucose (CMRg) is lower in individuals affected by cognitive decline a... more Cerebral metabolic rate of glucose (CMRg) is lower in individuals affected by cognitive decline and dementia, especially in Alzheimer's disease. However, as yet there is no consensus as to whether CMRg decreases during healthy aging. Epidemiological studies show that weekly consumption of fish abundant in o3 fatty acids has a protective effect on cognition during aging. Thus, the primary objective of this human study was to use positron emission tomography analysis with 18 F-fluorodeoxyglucose to evaluate whether supplementation with a fish oil rich in o3 fatty acids increases cerebral glucose metabolism in young or elderly adults. Healthy young (23 7 5 y old; n ¼5) and elderly (76 73 y old; n ¼6) women and men were included in the study. Semi-quantitative expression of the data as 'standardized uptake values' showed that elderly participants had significantly lower cerebral glucose metabolism compared with the young group. However, when expressed quantitatively a CMRg, there was no effect of age or o3 supplementation on glucose metabolism in any of the brains regions studied. Higher plasma triglyceride levels and higher plasma insulin levels were associated with lower CMRg in several regions, suggesting that a trend towards the metabolic syndrome may be associated with cerebral hypometabolism. We conclude that under these experimental conditions, o3 supplementation did not affect brain glucose metabolism in the healthy elderly. Future studies in this area should address whether glucose intolerance or other conditions linked to the metabolic syndrome impact negatively on brain glucose metabolism and cognition.
Neurobiology of Aging, 2014
The extent to which the age-related decline in regional brain glucose uptake also applies to othe... more The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 AE 6% (mean AE SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p ¼ 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p ¼ 0.11). Rate constants (min À1) of glucose (Kg) and acetoacetate (Ka) were significantly lower (À11 AE 6%; [p ¼ 0.005], and À19 AE 5%; [p ¼ 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p ¼ 0.030) and post-central gyrus (p ¼ 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging.
![Research paper thumbnail of Novel Radiolabeled Peptides for Breast and Prostate Tumor PET Imaging: 64Cu/and 68Ga/NOTA-PEG-[d-Tyr6,βAla11,Thi13,Nle14]BBN(6–14)](https://attachments.academia-assets.com/105792767/thumbnails/1.jpg)
Bioconjugate Chemistry, 2012
Bombesin (BBN)-based radiolabeled peptides exhibit promising properties for targeted imaging of g... more Bombesin (BBN)-based radiolabeled peptides exhibit promising properties for targeted imaging of gastrin-releasing peptide receptors (GRPR)-positive tumors. The aim of this study was to evaluate with positron emission tomography (PET) the pharmacokinetic and imaging properties of two novel BBN-based radiolabeled peptides, 64 Cu/ and 68 Ga/NOTA-PEG-BBN(6-14), for diagnosis of breast and prostate cancers using small animal models. Competitive binding assays on T47D breast and PC3 prostate cancer cells showed that the affinity for GRPR depends on the complexed metal and can vary up to a factor of about 3; 64 Cu/NOTA-PEG-BBN(6-14) was found to have the lowest inhibition constant (1.60 ± 0.59 nM). 64 Cu/ and 68 Ga/NOTA-PEG-BBN(6-14) presented similar cell uptake on T47D and PC3 cells and were stable in vivo. Biodistribution studies of radiolabeled peptides carried out in Balb/c and tumor-bearing Balb/c nude mice showed that 64 Cu/NOTA-PEG-BBN(6-14) presented higher GRPR-mediated uptake in pancreas and adrenal glands, but comparable PC3 tumor uptake as 68 Ga/NOTA-PEG-BBN(6-14). Finally, receptor-dependent responses were observed during blocking studies with unlabeled peptide in both biodistribution and small-animal PET imaging studies. Our results confirmed the dependence of the affinity and pharmacokinetics of BBN-based radiopeptides on the complexed radiometal. Interspecies differences between mouse and human GRPR binding properties were also noted in these preclinical studies. Considering their good imaging characteristics, both 64 Cu/NOTA-PEG-BBN(6-14) and 68 Ga/NOTA-PEG-BBN(6-14) are promising candidates for GRPR-targeted PET imaging of breast and prostate cancers.
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010
Journal of the American Chemical Society, 2004
Experimental section 5-Hydroxy-2'-deoxyuridine (5-oh-dUrd) was synthesized by bromination of 2'-d... more Experimental section 5-Hydroxy-2'-deoxyuridine (5-oh-dUrd) was synthesized by bromination of 2'-deoxyuridine in water followed by treatment with collidine, according to a reported procedure (
Journal of Labelled Compounds and Radiopharmaceuticals, 2008
ABSTRACT 1-[11C]-β-hydroxybutyrate was produced by conversion from 1-[11C]-acetoacetate using (D)... more ABSTRACT 1-[11C]-β-hydroxybutyrate was produced by conversion from 1-[11C]-acetoacetate using (D)-β-hydroxybutyrate dehydrogenase in the presence of nicotinamide adenine dinucleotide with purification by ion exchange column chromatography. Radiochemical yield at the end of the synthesis was 10% for a total synthesis time of 36 min. High-performance liquid chromatography analysis showed ≤4% impurities, principally unconverted acetoacetate. Residual tetrahydrofuran (34±11 ppm) and ethanol (77±30 ppm) were well under the tolerable limits for human studies. Copyright © 2008 John Wiley & Sons, Ltd.
AJP: Endocrinology and Metabolism, 2009
Normally, the brain's fuel is glucose, but during fasting it increasingly relies on ketones (... more Normally, the brain's fuel is glucose, but during fasting it increasingly relies on ketones (β-hydroxybutyrate, acetoacetate, and acetone) produced in liver mitochondria from fatty acid β-oxidation. Although moderately raised blood ketones produced on a very high fat ketogenic diet have important clinical effects on the brain, including reducing seizures, ketone metabolism by the brain is still poorly understood. The aim of the present work was to assess brain uptake of carbon-11-labeled acetoacetate (11C-acetoacetate) by positron emission tomography (PET) imaging in the intact, living rat. To vary plasma ketones, we used three dietary conditions: high carbohydrate control diet (low plasma ketones), fat-rich ketogenic diet (raised plasma ketones), and 48-h fasting (raised plasma ketones). 11C-acetoacetate metabolism was measured in the brain, heart, and tissue in the mouth area. Using 11C-acetoacetate and small animal PET imaging, we have noninvasively quantified an approximatel...
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Papers by Sébastien Tremblay