Assessment of a one-week ketogenic diet on brain glycolytic metabolism and on the status epilepticus stage of a lithium-pilocarpine rat model.

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [F]-FDG PET.

Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study.

Background: This translational study explores multi-tracer PET imaging for the non-invasive detection of the IDH1 mutation which is a positive prognostic factor in glioma.

Methods: U87 human high-grade glioma (HGG) isogenic cell lines with or without the IDH1 mutation (CRISP/Cas9 method) were stereotactically grafted into rat brains, and examined, in vitro, in vivo and ex vivo. PET imaging sessions, with radiotracers specific for glycolytic metabolism ([F]FDG), amino acid metabolism ([F]FDopa), and inflammation ([F]DPA-714), were performed sequentially during 3-4 days.

Programming by Methyl Donor Deficiency during Pregnancy and Lactation Produces Cardiomyopathy in Adult Rats Subjected to High Fat Diet.

Scope: Vitamin B12 and folate (methyl donors) deficiency is frequent during pregnancy. Experimental rat models with methyl donor deficit during pregnancy and lactation (Initial methyl donor deficit (iMDD)) produce impaired myocardium fatty acid oxidation and mitochondrial energy metabolism at weaning.

Methods And Results: The consequences of iMDD on heart of rat pups under normal diet after weaning and high fat diet (HF) between day (D) 50 and D185 are investigated.

Implementation of iMiDEV™, a new fully automated microfluidic platform for radiopharmaceutical production.

iMiDEV™ microfluidic system is a new automated tool for a small-scale production of radiopharmaceuticals. This new radiochemistry module utilizes microfluidic cassettes capable of producing diversified radiopharmaceuticals in liquid phase reactions in an automated synthesizer. The user interface is intuitive and designed to give the operator all the information required and to allow driving the synthesis either manually or fully automatically.

Synthesis of a DOTA--glyco bifunctional chelating agent and preliminary and study of [Ga]Ga-DOTA--glyco-RGD.

The design of bifunctional chelating agents (BFCA) allowing straightforward radiometal labelling of biomolecules is a current challenge. We report herein the development of a bifunctional chelating agent based on a DOTA chelator linked to a -glycosyl compound, taking advantage of the robustness and hydrophilicity of this type of carbohydrate derivative. This new BFCA was coupled with success by CuAAC with c(RGDfK) for αβ integrin targeting.

A 1-week extension of a ketogenic diet provides a further decrease in myocardial F-FDG uptake and a high detectability of myocarditis with FDG-PET.

Background: Short periods of fasting and/or low-carbohydrate diet have been proven beneficial for decreasing the myocardial uptake of F-fluorodeoxyglucose (F-FDG) and enhancing the detection of inflammatory heart diseases by F-FDG positron emission tomography (PET). This study aimed at determining whether this benefit is increased when a low-carbohydrate ketogenic diet is prolonged up to 7 days.

Methods: Wistar rats underwent serial F-FDG-PET imaging after an 18-hour fasting period and after 2, 4 and 7 days of a ketogenic diet (3% carbohydrate) and they were compared to rats submitted to the same protocol but with normal diet (44% carbohydrate).

PET imaging of Ga-NODAGA-RGD, as compared with F-fluorodeoxyglucose, in experimental rodent models of engrafted glioblastoma.

Background: Tracers triggering αvβ3 integrins, such as certain RGD-containing peptides, were found promising in previous pilot studies characterizing high-grade gliomas. However, only limited comparisons have been performed with current PET tracers. This study aimed at comparing the biodistribution of F-fluorodeoxyglucose (F-FDG) with that of Ga-NODAGA-RGD, an easily synthesized monomeric RGD compound with rapid kinetics, in two different rodent models of engrafted human glioblastoma.

Synthesis and preliminary in vivo evaluation of new [F]fluoro-inositols as Positron Emission Tomography radiotracers.

This study describes the synthesis and radiosynthesis of eight new [F]fluoro-inositol-based radiotracers in myo- and scyllo-inositol configuration. These radiotracers are equipped with a propyl linker bearing fluorine-18. This fluorinated arm is either on a hydroxyl group, i.

Quantitative SPM Analysis Involving an Adaptive Template May Be Easily Applied to [F]FDG PET Images of the Rat Brain.

Purpose: The Statistical Parametric Mapping (SPM) software is frequently used for the quantitative analysis of patients' brain images obtained from 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography ([F]FDG PET). However, its adaptation to small animals is difficult, particularly for the initial step of spatial normalization which requires a specific brain anatomical template. This study was aimed at determining whether SPM analysis can be applied to rat, and more specifically to the lithium-pilocarpine model of epilepsy, by using an adaptive template.

Development of 6-[(18) F]fluoro-carbohydrate-based prosthetic groups and their conjugation to peptides via click chemistry.

This work describes the development of new 6-[(18) F]fluoro-carbohydrate-based prosthetic groups equipped with an azido arm that are able to participate in copper(I)-catalyzed cycloadditions for (18) F labeling of biomolecules under mild conditions. The radiolabeling in high radiochemical yields (up to 68 ± 6%) of these different prosthetic groups is presented. The flexibility of the azido arm introduced on the carbohydrate moieties allows efficient click reactions with different alkyne functionalized peptides such as gluthation or Arg-Gly-Asp derivatives in order to prepare glycopeptides.

TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction.

Rationale: Optimal outcome after myocardial infarction (MI) depends on a coordinated healing response in which both debris removal and repair of the myocardial extracellular matrix play a major role. However, adverse remodeling and excessive inflammation can promote heart failure, positioning leucocytes as central protagonists and potential therapeutic targets in tissue repair and wound healing after MI.

Objective: In this study, we examined the role of triggering receptor expressed on myeloid cells-1(TREM-1) in orchestrating the inflammatory response that follows MI.

Identification of candidate long non-coding RNAs in response to myocardial infarction.

Background: Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs. LncRNAs regulate gene expression, thus having the possibility to modulate disease progression. In this study, we investigated the changes of lncRNAs expression in the heart after myocardial infarction (MI).

Assessment of the early stage of cardiac remodeling of spontaneously hypertensive heart failure rats using the quantitative 3-dimensional analysis provided by acipimox-enhanced FDG-PET.

Spontaneously hypertensive heart failure rats (SHHF) appear to constitute an original model for analyzing the evolution of the metabolic syndrome towards heart failure. This study aimed to characterize early cardiac dysfunction and remodeling in SHHF rats: (1) as compared with spontaneously hypertensive rats (SHR) and with a control group of Kyoto rats (WKY), and (2) by using the 3-dimensional quantitative analysis provided by acipimox-enhanced positron emission tomography (PET) with (18)F-fluorodesoxyglucose (FDG). Left ventricular (LV) ejection fraction (EF) and volume were quantified by automatic software on the FDG-PET images recorded in SHR (n = 20), SHHF (n = 18) and WKY-rats (n = 19) at ages 3 or 10 months old.

Cardioprotective effects of adenosine within the border and remote areas of myocardial infarction.

Background: Adenosine may have beneficial effects on left ventricular function after myocardial infarction (MI), but the magnitude of this effect on remote and MI areas is controversial. We assessed the long-term effects of adenosine after MI using electrocardiogram-triggered 18 F-fluorodeoxyglucose positron emission tomography.

Methods: Wistar rats were subjected to coronary ligation and randomized into three groups treated daily for 2 months by NaCl (control; n = 7), 2-chloroadenosine (CADO; n = 8) or CADO with 8-sulfophenyltheophilline, an antagonist of adenosine receptors (8-SPT; n = 8).

Sustained therapeutic perfusion outside transplanted sites in chronic myocardial infarction after stem cell transplantation.

This study aimed at comparing long-term variations in the perfusion of chronic myocardial infarction (MI) areas after local injections of autologous bone marrow stem cells (BMSCs). 14 coronary ligated rats with transmural chronic MI (4 months) were used: a control group (n = 7) versus a treated group (n = 7) in which (111)In labeled-BMSCs were directly engrafted on MI areas. By using (111)In/(99m)Tc SPECT and Sestamibi gated-SPECT,.

Adenosine stimulates the migration of human endothelial progenitor cells. Role of CXCR4 and microRNA-150.

Background: Administration of endothelial progenitor cells (EPC) represents a promising option to regenerate the heart after myocardial infarction, but is limited because of low recruitment and engraftment in the myocardium. Mobilization and migration of EPC are mainly controlled by stromal cell-derived factor 1α (SDF-1α) and its receptor CXCR4. We hypothesized that adenosine, a cardioprotective molecule, may improve the recruitment of EPC to the heart.

Comparison of equipressor doses of norepinephrine, epinephrine, and phenylephrine on septic myocardial dysfunction.

Background: Myocardial depression is a frequent event during septic shock and may mimic a cardiogenic shock state with decreased cardiac output. Nevertheless, data are scarce regarding the myocardial effects of vasopressors used to treat hypotension. In this study, the authors compared the effects of three commonly used vasopressors acting on different adrenergic receptors on myocardial function in a rodent model of septic shock, as explored with conductance catheter and positron emission tomography.

Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction.

Background: Prediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers.

Methods: Blood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutaneous coronary intervention. Messenger RNA was extracted from whole blood cells.

Acipimox-enhanced ¹⁸F-fluorodeoxyglucose positron emission tomography for characterizing and predicting early remodeling in the rat infarct model.

The rat myocardial infarction (MI) model is widely used to study left ventricular (LV) remodeling. In this study, acipimox-enhanced (18)F-Fluorodeoxyglucose (FDG) gated-positron emission tomography (PET) was assessed for characterizing and predicting early remodeling in the rat infarct model. Nineteen Wistar rats had surgical occlusion of the left anterior descending coronary artery and 7 were sham-operated.

ECG-triggered 18F-fluorodeoxyglucose positron emission tomography imaging of the rat heart is dramatically enhanced by acipimox.

Purpose: 18F-Fluorodeoxyglucose (FDG) imaging, provided by current positron emission tomography (PET) systems dedicated to small animals,might provide a precise functional assessment of the left ventricle (LV) in rats, although conventional metabolic conditioning by hyperinsulinaemic glucose clamping is not well adapted to this setting. This study was aimed at assessing cardiac FDG PET in rats premedicated with acipimox, a potent nicotinic acid derivative yielding comparable image quality to clamping in man.

Methods: Metabolic conditioning was compared in Wistar rats between a conventional oral glucose loading (1.

Intramyocardial Implantation of bone marrow-derived stem cells enhances perfusion in chronic myocardial infarction: dependency on initial perfusion depth and follow-up assessed by gated pinhole SPECT.

Unlabelled: Cell therapy-induced changes in the perfusion of areas of myocardial infarction (MI) remain unclear. This study investigated whether an original pinhole SPECT technique could be applied to a rat MI model to analyze local improvement in myocardial perfusion relating to engraftment sites of bone marrow-derived stem cells (BMSCs).

Methods: Four-month-old MI rats were either untreated (n = 8) or treated (n = 10) by intramyocardial injection of (111)In-labeled BMSCs.

Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium.

Cell therapy with bone marrow mesenchymal stem cells (BMSCs) is a new strategy for treating ischemic heart failure, but data concerning the distribution and retention of transplanted cells remain poor. We investigated the short-term myocardial retention of BMSCs when these cells are directly injected within necrotic or intact myocardium. 111Indium-oxine-labeled autologous BMSCs were injected within either 1-month-old infarction (n = 6) or normal myocardium (n = 6) from rats.

Feasibility of in vivo dual-energy myocardial SPECT for monitoring the distribution of transplanted cells in relation to the infarction site.

Purpose: Cell therapy using bone marrow mesenchymal stem cells (BMSCs) shows promise in the treatment of myocardial infarction (MI) but accurate cell delivery within MI areas remains critical. In the present study, we tested the feasibility of in vivo pinhole SPECT imaging for monitoring the sites of intramyocardial implanted BMSCs in relation to targeted MI areas in rats.

Methods: BMSCs were labelled with (111)In-oxine and injected within the fibrotic areas of 3-month-old MI in ten rats.

Initial infarct size predicts subsequent cardiac remodeling in the rat infarct model: an in vivo serial pinhole gated SPECT study.

Unlabelled: The rat infarct model is widely used to study left ventricular (LV) remodeling, a main cause of heart failure characterized by progressive LV dilatation. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The aim of this study was to assess this new imaging technique for predicting and quantifying variable LV remodeling from the rat infarct model.