Bifunctional Hexadentate Pyclen-Based Chelating Agent for Mild Radiofluorination in Aqueous Solution at Room Temperature with a Ga-F Ternary Complex.

Positron Emission Tomography (PET) is used in oncology for tumor diagnosis, commonly relying on fluorine-18 (F) emission detection. The conventional method of F incorporation on to probes by covalent bonding is harsh for sensitive biomolecules, which are nonetheless compounds of choice for the development of targeted probes. This study explores gallium-F (GaF) coordination, a milder alternative method occurring in aqueous media at the final stage of radiosyntheses.

Imaging quantitative changes in blood-brain barrier permeability using [F]2-fluoro-2-deoxy-sorbitol ([F]FDS) PET in relation to glial cell recruitment in a mouse model of endotoxemia.

The quantitative relationship between the disruption of the blood-brain barrier (BBB) and the recruitment of glial cells was explored in a mouse model of endotoxemia. [F]2-Fluoro-2-deoxy-sorbitol ([F]FDS) PET imaging was used as a paracellular marker for quantitative monitoring of BBB permeability after i.v injection of increasing doses of lipopolysaccharide (LPS) or vehicle (saline, n = 5).

Optimization of a 1,4,7-Triazacyclononane-1,4-diacetic acid (NODA) Derivative Radiofluorination by Al F Complexation Using a Design of Experiments Approach.

Fluorine-18 ( F) is the most favorable positron emitter for radiolabeling Positron Emission Tomography (PET) probes. However, conventional F labeling through covalent C-F bond formation is challenging, involving multiple steps and stringent conditions unsuitable for sensitive biomolecular probes whose integrity may be altered. Over the past decade, an elegant new approach has been developed involving the coordination of an aluminum fluoride {Al F} species in aqueous media at a late-stage of the synthetic process.

A major role for CD4 T cells in driving cytokine release syndrome during CAR T cell therapy.

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy represents a breakthrough for the treatment of B cell malignancies. Yet, it can lead to severe adverse events, including cytokine release syndrome (CRS), which may require urgent clinical management. Whether interpatient variability in CAR T cell subsets contributes to CRS is unclear.

Synthetic Melanin Acts as Efficient Peptide Carrier in Cancer Vaccine Strategy.

We previously reported that a novel peptide vaccine platform, based on synthetic melanin nanoaggregates, triggers strong cytotoxic immune responses and significantly suppresses tumor growth in mice. However, the mechanisms underlying such an efficacy remained poorly described. Herein, we investigated the role of dendritic cells (DCs) in presenting the antigen embedded in the vaccine formulation, as well as the potential stimulatory effect of melanin upon these cells, in vitro by coculture experiments and ELISA/flow cytometry analysis.

Translating Molecules into Imaging-The Development of New PET Tracers for Patients with Melanoma.

Melanoma is a deadly disease that often exhibits relentless progression and can have both early and late metastases. Recent advances in immunotherapy and targeted therapy have dramatically increased patient survival for patients with melanoma. Similar advances in molecular targeted PET imaging can identify molecular pathways that promote disease progression and therefore offer physiological information.

STAT3 inhibition protects against neuroinflammation and BACE1 upregulation induced by systemic inflammation.

Abnormal activation of the transcriptional factor STAT3 (signal transducer and activator of transcription 3) was recently associated with Alzheimer Disease (AD). STAT3 phosphorylation is critical for cytokine secretion linked to neuroinflammation. Moreover, STAT3 may act as a transcriptional regulator of BACE1 (β-APP cleaving enzyme-1), the key enzyme in amyloid β (Aβ) production.

Astroglial Connexin 43 Deficiency Protects against LPS-Induced Neuroinflammation: A TSPO Brain µPET Study with [F]FEPPA.

Astroglial connexin 43 (Cx43) has been recognized as a crucial immunoregulating factor in the brain. Its inactivation leads to a continuous immune recruitment, cytokine expression modification and a specific humoral autoimmune response against the astrocytic extracellular matrix but without brain lesions or cell lysis. To assess the impact of Cx43 deletion on the brain's inflammatory response, TSPO expression was studied by positron emission tomography (PET) imaging with a specific radioligand, [F]FEPPA, in basal conditions or upon Lipopolysaccharides (LPS)-induced inflammatory challenge.

Evaluation of planar bioluminescence imaging and microPET/CT for therapy monitoring in a mouse model of pigmented metastatic melanoma.

Bioluminescence imaging (BLI) is widely used for monitoring of anti-cancer therapy in mice. [F]MEL050 is a Positron Emission Tomography (PET) radiotracer which specifically targets melanin. We evaluated planar BLI and [F]MEL050-PET/CT for therapy (pro-apoptotic peptide LZDP) monitoring in a mouse model of metastatic pigmented melanoma.

[F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model.

[F]FEPPA is a specific ligand for the translocator protein of 18 kDa (TSPO) used as a positron emission tomography (PET) biomarker for glial activation and neuroinflammation. [F]FEPPA radiosynthesis was optimized to assess in a mouse model the cerebral inflammation induced by an intraperitoneal injection of serovar lipopolysaccharides (LPS; 5 mg/kg) 24 h before PET imaging. [F]FEPPA was synthesized by nucleophilic substitution (90 °C, 10 min) with tosylated precursor, followed by improved semi-preparative HPLC purification (retention time 14 min).

Evaluation of TSPO PET imaging, a marker of glial activation, to study the neuroimmune footprints of morphine exposure and withdrawal.

Introduction: A growing area of research suggests that neuroimmunity may impact the pharmacology of opioids. Microglia is a key component of the brain immunity. Preclinical and clinical studies have demonstrated that microglial modulators may improve morphine-induced analgesia and prevent the development of tolerance and dependence.

F-FDG labelling of hematopoietic stem cells: Dynamic study of bone marrow homing by PET-CT imaging and impact on cell functionality.

Purpose Of The Study: After transplantation, cord blood (CB) hematopoietic stem and progenitor cells (HSPCs) are able to home to the bone marrow niche and to reconstitute the hematopoietic system. PET-CT imaging may be a useful method to monitor this parameter in different conditions. The aim of our study was to set up an efficient method for HSPC radiolabelling with [F] fluorodeoxyglucose (F-FDG) and to follow early HSPC homing through PET-CT in mice.

[F]MEL050 as a melanin-targeted PET tracer: Fully automated radiosynthesis and comparison to F-FDG for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases.

Introduction: Melanoma is a highly malignant cutaneous tumor of melanin-producing cells. MEL050 is a synthetic benzamide-derived molecule that specifically binds to melanin with high affinity. Our aim was to implement a fully automated radiosynthesis of [F]MEL050, using for the first time, the AllInOne™ synthesis module (Trasis), and to evaluate the potential of [F]MEL050 for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases, and to compare it with that of [F]FDG.

Diphenhydramine as a selective probe to study H-antiporter function at the blood-brain barrier: Application to [C]diphenhydramine positron emission tomography imaging.

Diphenhydramine, a sedative histamine H-receptor (HR) antagonist, was evaluated as a probe to measure drug/H-antiporter function at the blood-brain barrier. In situ brain perfusion experiments in mice and rats showed that diphenhydramine transport at the blood-brain barrier was saturable, following Michaelis-Menten kinetics with a K = 2.99 mM and V = 179.

Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion.

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp.

[¹¹C]befloxatone brain kinetics is not influenced by Bcrp function at the blood-brain barrier: a PET study using Bcrp TGEM knockout rats.

Knockout (KO) animals are useful tools with which to assess the interplay between P-glycoprotein (P-gp; Abcb1) and the breast cancer resistance protein (Bcrp, Abcg2), two major ABC-transporters expressed at the blood-brain barrier (BBB). However, one major drawback of such deficient models is the possible involvement of compensation between transporters. In the present study, P-gp and Bcrp distribution in the brain as well as P-gp expression levels at the BBB were compared between the Bcrp TGEM KO rat model and the wild-type (WT) strain.

[Extravasation of radiopharmaceuticals: preventive measures and management recommended by SoFRa (Société Française de Radiopharmacie)].

Radiopharmaceuticals extravasation is rare but may have serious clinical issues. Because no specific recommendations are being proposed to date, the goals of our working group created within the French Society of Radiopharmacy are to determine preventive measures and to establish a pragmatic management of extravasation of these drugs. Our preventive measures are to recognize the symptoms (erythema, venous discoloration, swelling), to know the risk factors (which are related to radiopharmaceutical, patient, site of injection, injection technique) and severity (from erythema to skin necrosis, depending on the radionuclide) and how to avoid them (training and awareness of staff, choice of injection site, route of drug administration test, use of a catheter for administration of therapeutic radiopharmaceuticals).

[Stable iodine as a prophylaxis therapy following exposure to radioactive iodines: pharmacological and pharmaceutical characteristics].

More or less rapid radio-induction of thyroidian cancers is the main pathological consequence of an accidental exposure to ingested or inhaled radioactive iodines following a nuclear power plant accident. The prophylactic administration of potassium iodine in a single oral dose has to be practiced as soon as possible after the nuclear accident. The efficacy of this therapy depends on pharmacokinetics of radioidines.

An optimised radiolabel procedure to prepare (99m)Tc-colloidal rhenium sulphide to improve radiochemical purity.

Background: More than 25% of 99mTc colloidal rhenium sulphide preparations have been reported to have a radiochemical purity of <95% in 11 radiopharmacies.

Objectives: To identify the key parameters involved in radiochemical purity, different preparation procedures were analysed to develop an optimised preparation method.

Methods: In the first part of this study, various data such as the Nanocis kit batch number, the eluate volume, the time between the two final elutions, the temperature and duration of heating were collected and analysed to determine the critical parameters that significantly decrease radiochemical purity.

Interleukin-2 treatment effect on imatinib pharmacokinetic, P-gp and BCRP expression in mice.

The aim of this study was to investigate the effect that recombinant interleukin-2 (rIL-2) (0.16 MUI/injection) had on the pharmacokinetics of imatinib (IM) in plasma. In this study, IM was given orally to mice at a dose of 150 mg/kg once a day for 11 days (from day 1 to 11) either alone or in combination with intraperitoneal injections of rIL-2 twice a day from day 8 to 11.

Elastic constants measurement of anisotropic Olivier wood plates using air-coupled transducers generated Lamb wave and ultrasonic bulk wave.

A hybrid elastic wave method is applied to determine the anisotropic constants of Olive wood specimen considered as an orthotropic solid. The method is based on the measurements of the Lamb wave velocities as well as the bulk ultrasonic wave velocities. Electrostatic, air-coupled, ultrasonic transducers are used to generate and receive Lamb waves which are sensitive to material properties.

Finite element modeling of the temperature rise due to the propagation of ultrasonic waves in viscoelastic materials and experimental validation.

The ultrasound stimulated thermography method is usually used to detect the temperature rise at a defect position. The temperature rise can be due to the friction between the edges of the defect and/or the plastic deformation around the defect. This paper presents another aspect of the method when the ultrasounds are propagating in a viscoelastic anisotropic material, such as polymers or fiber-reinforced polymers.