Brigitte Guérin - Academia.edu (original) (raw)

Uploads

Papers by Brigitte Guérin

Expert Review of Neurotherapeutics, 2008

Frontiers in Nuclear Medicine

PurposeAssessment of the radiation dose delivered to a tumor and different organs is a major issu... more PurposeAssessment of the radiation dose delivered to a tumor and different organs is a major issue when using radiolabelled compounds for diagnostic imaging or endoradiotherapy. The present article reports on a study to correlate the mean 18F-fluorodeoxyglucose (18F-FDG) activity in different tissues measured in a mouse model by positron emission tomography (PET) imaging, with the dose assessed in vitro by Fricke dosimetry.MethodsThe dose-response relationship of the Fricke dosimeter and PET data was determined at different times after adding 18F-FDG (0–80 MBq) to a Fricke solution (1 mM ferrous ammonium sulfate in 0.4 M sulfuric acid). The total dose was assessed at 24 h (~13 half-lives of 18F-FDG). The number of coincident events produced in 3 mL of Fricke solution or 3 mL of deionized water that contained 60 MBq of 18F-FDG was measured using the Triumph/LabPET8TM preclinical PET/CT scanner. The total activity concentration measured by PET was correlated with the calculated dose f...

American Journal of Physiology-endocrinology and Metabolism, Jun 1, 2021

Bioorganic & Medicinal Chemistry Letters, Feb 1, 2017

Bioconjugate Chemistry, Aug 26, 2013

In this paper, we describe the synthesis and characterization of a series of new bimodal probes c... more In this paper, we describe the synthesis and characterization of a series of new bimodal probes combining water-soluble sulfonated zinc phthalocyanine (ZnPc) as a fluorescence imaging unit and either (68)Ga/1,4,7,10-tetraazocyclododecane-N,N'N″,N'″-tetraacetic acid (DOTA) or (64)Cu/1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for PET imaging. The two moieties were linked through aliphatic chains of different lengths to modulate amphiphilicity. Labeling of DOTA- or NOTA-ZnPc conjugates with (68)Ga (t1/2 = 68 min) and (64)Cu (t1/2 = 12.7 h) was performed at 100 °C for 15 min with >90% efficiency for all conjugates. In vitro plasma stability assays demonstrated high stability of the (64)Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the (68)Ga/DOTA-ZnPc conjugate, which released up to 7% of free (68)Ga over a 3 h period. Based on in vitro plasma stability results, we performed biodistribution studies on two (64)Cu-labeled derivatives, which allowed us to select a single candidate for preliminary in vivo experiments. Fluorescence and PET imaging confirmed the potential of these novel conjugates to act as bimodal probes.

Journal of Cancer Science & Therapy, Jul 23, 2015

medRxiv (Cold Spring Harbor Laboratory), Mar 28, 2023

Frontiers in Oncology, Jan 18, 2023

Journal of Nuclear Medicine

The Journal of Nuclear Medicine, May 1, 2020

SummaryDiets rich in added sugars, especially high in fructose, are associated with metabolic dis... more SummaryDiets rich in added sugars, especially high in fructose, are associated with metabolic diseases such as insulin resistance, and non-alcoholic fatty liver disease. Studies have shown a link between these pathologies and changes in the microbiome and its metabolites. Given the reported associations in animal models between the microbiome and brown or beige adipose tissue (BAT) function, and the alterations in the microbiome induced by high glucose or high fructose diets, we investigated the potential causal link between high glucose or fructose diets and BAT dysfunction in humans. We show that BAT glucose uptake, but not thermogenesis, is impaired by a high fructose but not high glucose diet, in the absence of changes in body mass, the gastrointestinal microbiome, and faecal short-chain fatty acids. We conclude that BAT metabolic dysfunction occurs independently from changes in gut microbiome composition, and earlier than other pathophysiological abnormalities associated with i...

The Journal of Nuclear Medicine, 2015

The Journal of Nuclear Medicine, 2020

411 Objectives: Quantitative SPECT (QSPECT)/CT is increasingly used in 177Lu theranostics. Beside... more 411 Objectives: Quantitative SPECT (QSPECT)/CT is increasingly used in 177Lu theranostics. Beside dosimetry, QSPECT/CT enables real-time therapeutic response assessment that is potentially predictive of longer-term response, such as molecular imaging response assessed with 68Ga-PET/CT, for which we previously proposed the Theranostic Response Criteria In Solid Tumors (THERCIST) based on molecular tumor volume (MTV). Our aim was to assess if an early decrease in total lesion fraction (TLF: total lesion activity divided by body weight, expressed in percentage of injected activity) on QSPECT during peptide receptor radionuclide therapy (PRRT) predicted an objective response on post-treatment 68Ga-PET/CT. Methods: 32 consecutive patients with neuroendocrine tumor who underwent 68Ga-octreotate-PET/CTs within 4 months prior to and after a personalized, dosimetry-based 177Lu-octreotate PRRT induction course were included. A threshold of 25% of the SUVpeak was used for tumor segmentation. T...

The Journal of Nuclear Medicine, 2016

Molecular Imaging and Biology, 2020

Diabetes, 2020

Excessive exposure of lean tissues to fatty acids leads to insulin resistance. Proper dietary fat... more Excessive exposure of lean tissues to fatty acids leads to insulin resistance. Proper dietary fatty acids (DFA) storage in white adipose tissue (WAT) is thought to prevent lean tissue lipotoxicity. We showed that WAT storage of DFA was impaired in IGT (impaired glucose tolerance) and was associated with greater cardiac DFA uptake and subclinical left-ventricular dysfunction. Whether WAT DFA storage directly impacts cardiac DFA uptake in IGT subjects is not known. We aimed at investigating how inhibition of intracellular lipolysis affected WAT DFA storage, spillover, and cardiac DFA uptake. We recruited 23 participants: 12 IGT, 5 women/7 men, aged (mean ± sem) 64±2.5, BMI= 34.9±3.1 kg/m2 and 11 NGT, 7 women/4 men, aged 62±2, BMI= 30.4±1.6 kg/m2. Cardiac DFA uptake and whole-body organ-specific DFA partitioning were assessed using PET/CT method with oral administration of 18FTHA. NEFA appearance and WAT DFA spillover were measured using stable isotope tracer methods. Nicotinic acid (NA) was used to inhibit WAT DFA spillover. In both groups, NA decreased AUC DFA spillover rate (-31%±19, p=0.014) and AUC NEFA appearance rate (-28%±10, p=0.0002). In NGT group, NA decreased muscle and liver DFA distribution by 30%±8 (p=0.007) and 25%±8 (p=0.024), respectively, and increased WAT DFA distribution by 48%±8 (p=0.001). The same trend was observed in IGT group, but with blunted differences in WAT DFA storage vs. NGT (p=0.73). NA-induced increase in visceral WAT DFA distribution was correlated negatively with change in AUC. Nonesterified fatty acids (NEFA) appearance rate (ρ=-0.58, p=0.004). In both groups, NA did not significantly affect cardiac DFA distribution. In both groups, we estimated that DFA spillover may account for 31%±23 of DFA reaching lean organs over a 6-hour period after meals. Inhibition of WAT DFA spillover enhances DFA WAT storage and reduces liver and skeletal muscle, but not cardiac DFA partitioning. Disclosure E. Montastier: None. C. Noll: None. R. Ye: None. M. Amrani: None. F. Frisch: None. M. Fortin: None. L. Bouffard: None. O. Sarrhini: None. S. Phoenix: None. B. Guerin: None. E.E. Turcotte: None. A.C. Carpentier: Advisory Panel; Self; HLS Therapeutics, Inc.

American Journal of Physiology-Endocrinology and Metabolism, 2019

Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV... more Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14( R,S)-[18F]fluoro-6-thia-heptadecanoic acid and [11C]acetate positron emission tomography methods at the end of both interventions. HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCA...

Scientific Reports, 2019

The proprotein convertase PACE4 has been validated as a potential target to develop new therapeut... more The proprotein convertase PACE4 has been validated as a potential target to develop new therapeutic interventions in prostate cancer (PCa). So far, the most effective compound blocking the activity of this enzyme has been designed based on the structure of a small peptide Ac-LLLLRVKR-NH2 known as the Multi-Leu (ML) peptide. Optimization of this scaffold led to the synthesis of compound C23 (Ac-[DLeu]LLLRVK-amidinobenzylamide) with a potent in vivo inhibitory effect on the tumor growth. However, further developments of PACE4 inhibitors may require additional improvements to counter their rapid renal clearance and to increase their tumor targeting efficiency. Herein, we explored the transformation of the ML-peptide into an albumin-binding prodrug containing a tumor specific release mechanism based on the prostate-specific antigen. Our data confirms that intravenous treatment using the ML-peptide alone has little effect on tumor growth, whereas by using the ML-prodrug in LNCaP xenograf...

Expert Review of Neurotherapeutics, 2008

Frontiers in Nuclear Medicine

PurposeAssessment of the radiation dose delivered to a tumor and different organs is a major issu... more PurposeAssessment of the radiation dose delivered to a tumor and different organs is a major issue when using radiolabelled compounds for diagnostic imaging or endoradiotherapy. The present article reports on a study to correlate the mean 18F-fluorodeoxyglucose (18F-FDG) activity in different tissues measured in a mouse model by positron emission tomography (PET) imaging, with the dose assessed in vitro by Fricke dosimetry.MethodsThe dose-response relationship of the Fricke dosimeter and PET data was determined at different times after adding 18F-FDG (0–80 MBq) to a Fricke solution (1 mM ferrous ammonium sulfate in 0.4 M sulfuric acid). The total dose was assessed at 24 h (~13 half-lives of 18F-FDG). The number of coincident events produced in 3 mL of Fricke solution or 3 mL of deionized water that contained 60 MBq of 18F-FDG was measured using the Triumph/LabPET8TM preclinical PET/CT scanner. The total activity concentration measured by PET was correlated with the calculated dose f...

American Journal of Physiology-endocrinology and Metabolism, Jun 1, 2021

Bioorganic & Medicinal Chemistry Letters, Feb 1, 2017

Bioconjugate Chemistry, Aug 26, 2013

In this paper, we describe the synthesis and characterization of a series of new bimodal probes c... more In this paper, we describe the synthesis and characterization of a series of new bimodal probes combining water-soluble sulfonated zinc phthalocyanine (ZnPc) as a fluorescence imaging unit and either (68)Ga/1,4,7,10-tetraazocyclododecane-N,N'N″,N'″-tetraacetic acid (DOTA) or (64)Cu/1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for PET imaging. The two moieties were linked through aliphatic chains of different lengths to modulate amphiphilicity. Labeling of DOTA- or NOTA-ZnPc conjugates with (68)Ga (t1/2 = 68 min) and (64)Cu (t1/2 = 12.7 h) was performed at 100 °C for 15 min with >90% efficiency for all conjugates. In vitro plasma stability assays demonstrated high stability of the (64)Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the (68)Ga/DOTA-ZnPc conjugate, which released up to 7% of free (68)Ga over a 3 h period. Based on in vitro plasma stability results, we performed biodistribution studies on two (64)Cu-labeled derivatives, which allowed us to select a single candidate for preliminary in vivo experiments. Fluorescence and PET imaging confirmed the potential of these novel conjugates to act as bimodal probes.

Journal of Cancer Science & Therapy, Jul 23, 2015

medRxiv (Cold Spring Harbor Laboratory), Mar 28, 2023

Frontiers in Oncology, Jan 18, 2023

Journal of Nuclear Medicine

The Journal of Nuclear Medicine, May 1, 2020

SummaryDiets rich in added sugars, especially high in fructose, are associated with metabolic dis... more SummaryDiets rich in added sugars, especially high in fructose, are associated with metabolic diseases such as insulin resistance, and non-alcoholic fatty liver disease. Studies have shown a link between these pathologies and changes in the microbiome and its metabolites. Given the reported associations in animal models between the microbiome and brown or beige adipose tissue (BAT) function, and the alterations in the microbiome induced by high glucose or high fructose diets, we investigated the potential causal link between high glucose or fructose diets and BAT dysfunction in humans. We show that BAT glucose uptake, but not thermogenesis, is impaired by a high fructose but not high glucose diet, in the absence of changes in body mass, the gastrointestinal microbiome, and faecal short-chain fatty acids. We conclude that BAT metabolic dysfunction occurs independently from changes in gut microbiome composition, and earlier than other pathophysiological abnormalities associated with i...

The Journal of Nuclear Medicine, 2015

The Journal of Nuclear Medicine, 2020

411 Objectives: Quantitative SPECT (QSPECT)/CT is increasingly used in 177Lu theranostics. Beside... more 411 Objectives: Quantitative SPECT (QSPECT)/CT is increasingly used in 177Lu theranostics. Beside dosimetry, QSPECT/CT enables real-time therapeutic response assessment that is potentially predictive of longer-term response, such as molecular imaging response assessed with 68Ga-PET/CT, for which we previously proposed the Theranostic Response Criteria In Solid Tumors (THERCIST) based on molecular tumor volume (MTV). Our aim was to assess if an early decrease in total lesion fraction (TLF: total lesion activity divided by body weight, expressed in percentage of injected activity) on QSPECT during peptide receptor radionuclide therapy (PRRT) predicted an objective response on post-treatment 68Ga-PET/CT. Methods: 32 consecutive patients with neuroendocrine tumor who underwent 68Ga-octreotate-PET/CTs within 4 months prior to and after a personalized, dosimetry-based 177Lu-octreotate PRRT induction course were included. A threshold of 25% of the SUVpeak was used for tumor segmentation. T...

The Journal of Nuclear Medicine, 2016

Molecular Imaging and Biology, 2020

Diabetes, 2020

Excessive exposure of lean tissues to fatty acids leads to insulin resistance. Proper dietary fat... more Excessive exposure of lean tissues to fatty acids leads to insulin resistance. Proper dietary fatty acids (DFA) storage in white adipose tissue (WAT) is thought to prevent lean tissue lipotoxicity. We showed that WAT storage of DFA was impaired in IGT (impaired glucose tolerance) and was associated with greater cardiac DFA uptake and subclinical left-ventricular dysfunction. Whether WAT DFA storage directly impacts cardiac DFA uptake in IGT subjects is not known. We aimed at investigating how inhibition of intracellular lipolysis affected WAT DFA storage, spillover, and cardiac DFA uptake. We recruited 23 participants: 12 IGT, 5 women/7 men, aged (mean ± sem) 64±2.5, BMI= 34.9±3.1 kg/m2 and 11 NGT, 7 women/4 men, aged 62±2, BMI= 30.4±1.6 kg/m2. Cardiac DFA uptake and whole-body organ-specific DFA partitioning were assessed using PET/CT method with oral administration of 18FTHA. NEFA appearance and WAT DFA spillover were measured using stable isotope tracer methods. Nicotinic acid (NA) was used to inhibit WAT DFA spillover. In both groups, NA decreased AUC DFA spillover rate (-31%±19, p=0.014) and AUC NEFA appearance rate (-28%±10, p=0.0002). In NGT group, NA decreased muscle and liver DFA distribution by 30%±8 (p=0.007) and 25%±8 (p=0.024), respectively, and increased WAT DFA distribution by 48%±8 (p=0.001). The same trend was observed in IGT group, but with blunted differences in WAT DFA storage vs. NGT (p=0.73). NA-induced increase in visceral WAT DFA distribution was correlated negatively with change in AUC. Nonesterified fatty acids (NEFA) appearance rate (ρ=-0.58, p=0.004). In both groups, NA did not significantly affect cardiac DFA distribution. In both groups, we estimated that DFA spillover may account for 31%±23 of DFA reaching lean organs over a 6-hour period after meals. Inhibition of WAT DFA spillover enhances DFA WAT storage and reduces liver and skeletal muscle, but not cardiac DFA partitioning. Disclosure E. Montastier: None. C. Noll: None. R. Ye: None. M. Amrani: None. F. Frisch: None. M. Fortin: None. L. Bouffard: None. O. Sarrhini: None. S. Phoenix: None. B. Guerin: None. E.E. Turcotte: None. A.C. Carpentier: Advisory Panel; Self; HLS Therapeutics, Inc.

American Journal of Physiology-Endocrinology and Metabolism, 2019

Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV... more Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14( R,S)-[18F]fluoro-6-thia-heptadecanoic acid and [11C]acetate positron emission tomography methods at the end of both interventions. HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCA...

Scientific Reports, 2019

The proprotein convertase PACE4 has been validated as a potential target to develop new therapeut... more The proprotein convertase PACE4 has been validated as a potential target to develop new therapeutic interventions in prostate cancer (PCa). So far, the most effective compound blocking the activity of this enzyme has been designed based on the structure of a small peptide Ac-LLLLRVKR-NH2 known as the Multi-Leu (ML) peptide. Optimization of this scaffold led to the synthesis of compound C23 (Ac-[DLeu]LLLRVK-amidinobenzylamide) with a potent in vivo inhibitory effect on the tumor growth. However, further developments of PACE4 inhibitors may require additional improvements to counter their rapid renal clearance and to increase their tumor targeting efficiency. Herein, we explored the transformation of the ML-peptide into an albumin-binding prodrug containing a tumor specific release mechanism based on the prostate-specific antigen. Our data confirms that intravenous treatment using the ML-peptide alone has little effect on tumor growth, whereas by using the ML-prodrug in LNCaP xenograf...