Pilot Feasibility Study: 18 F-DPA-714 PET/CT Macrophage Imaging in Triple-Negative Breast Cancers (EITHICS).

Abstract: Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism.

Potential of TSPO radioligands: Bridging brain tumor diagnostics to the peripheries.

Translocator protein (TSPO) is involved in several cellular mechanisms such as steroidogenesis, immunomodulation, cell proliferation and differentiation. Overexpressed in several neurodegenerative diseases and brain cancer, TSPO radioligands have been developed over the last 20 years in positron emission tomography (PET) imaging. Recently, TSPO radioligands have extended beyond their initial application due to their specific binding to activated macrophages, making them a compelling biomarker for deciphering the intricacies of the tumor microenvironment (TME).

Cerebral Metabolic Signature of Chronic Benzodiazepine Use in Nondemented Older Adults: An FDG-PET Study in the MEMENTO Cohort.

Objective: We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline.

Methods: Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE ε 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use.

Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks.

The metabotropic glutamate receptor subtype 5 (mGluR5) is a class C G-protein-coupled receptor (GPCR) that has been implicated in various neuronal processes and, consequently, in several neuropsychiatric or neurodevelopmental disorders. Over the past few decades, mGluR5 has become a major focus for pharmaceutical companies, as an attractive target for drug development, particularly through the therapeutic potential of its modulators. In particular, allosteric binding sites have been targeted for better specificity and efficacy.

Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study.

Nitrous oxide (NO) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a major depressive episode resistant to at least one antidepressant and 10 healthy controls-HC, aged 25-50, only females) were exposed to a 1-h single session of EMONO and followed for 1 week.

Glutamatergic synapse in autism: a complex story for a complex disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD.

Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update.

Neuroinflammation is a significant contributor to Alzheimer's disease (AD). Until now, PET imaging of the translocator protein (TSPO) has been widely used to depict the neuroimmune endophenotype of AD. The aim of this review was to provide an update to the results from 2018 and to advance the characterization of the biological basis of TSPO imaging in AD by re-examining TSPO function and expression and the methodological aspects of interest.

Benzodiazepine use and neuroimaging markers of Alzheimer's disease in nondemented older individuals: an MRI and 18F Florbetapir PET study in the MEMENTO cohort.

Recent evidence suggests an association between benzodiazepines (BZDs) use and lower brain amyloid load, a hallmark of AD pathophysiology. Other AD-related markers include hippocampal atrophy, but the effect of BZDs on hippocampal volume remains unclear. We aimed at 1) replicating findings on BZDs use and brain amyloid load and 2) investigating associations between BZDs use and hippocampal volume, in the MEMENTO clinical cohort of nondemented older adults with isolated memory complaint or light cognitive impairment at baseline.

Development of PET Radioligands Targeting COX-2 for Colorectal Cancer Staging, a Review of and Preclinical Imaging Studies.

Colorectal cancer (CRC) is the second most common cause of cancer death, making early diagnosis a major public health challenge. The role of inflammation in tumorigenesis has been extensively explored, and among the identified markers of inflammation, cyclooxygenase-2 (COX-2) expression seems to be linked to lesions with a poor prognosis. Until now, COX-2 expression could only be accessed by invasive methods, mainly by biopsy.

Study of influence of the glutamatergic concentration of [F]FPEB binding to metabotropic glutamate receptor subtype 5 with N-acetylcysteine challenge in rats and SRM/PET study in human healthy volunteers.

Altered glutamate signaling is thought to be involved in a myriad of psychiatric disorders. Positron emission tomography (PET) imaging with [F]FPEB allows assessing dynamic changes in metabotropic glutamate receptor 5 (mGluR5) availability underlying neuropathological conditions. The influence of endogenous glutamatergic levels into receptor binding has not been well established yet.

Fully automated radiosynthesis of [F]LBT999 on TRACERlab FX and AllinOne modules, a PET radiopharmaceutical for imaging the dopamine transporter in human brain.

Background: Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester ([F]LBT999) is a selective radioligand for the in vivo neuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET).

Usefulness of PET With [F]LBT-999 for the Evaluation of Presynaptic Dopaminergic Neuronal Loss in a Clinical Environment.

The density of the neuronal dopamine transporter (DAT) is directly correlated with the presynaptic dopaminergic system injury. In a first study, we evaluated the brain distribution and kinetics of [F]LBT-999, a DAT PET radioligand, in a group of eight healthy subjects. Taking into account the results obtained in healthy volunteers, we wanted to evaluate whether the loss of presynaptic striatal dopaminergic fibers could be estimated, under routine clinical conditions, using [F]LBT-999 and a short PET acquisition.

Innovative Molecular Imaging for Clinical Research, Therapeutic Stratification, and Nosography in Neuroscience.

Over the past few decades, several radiotracers have been developed for neuroimaging applications, especially in PET. Because of their low steric hindrance, PET radionuclides can be used to label molecules that are small enough to cross the blood brain barrier, without modifying their biological properties. As the use of 11C is limited by its short physical half-life (20 min), there has been an increasing focus on developing tracers labeled with 18F for clinical use.

Benzodiazepine use and brain amyloid load in nondemented older individuals: a florbetapir PET study in the Multidomain Alzheimer Preventive Trial cohort.

It remains unclear whether benzodiazepines (BZDs) constitute a risk factor for Alzheimer's disease (AD). In this study, we investigated associations between chronic use of BZDs and brain amyloid load, a hallmark of AD, in 268 nondemented older individuals. F-florbetapir positron emission tomography scans were performed to assess amyloid load as measured by standardized uptake value ratios, which were compared between chronic BZD users and nonusers using adjusted multiple linear regressions.

Clinical Results in Medullary Thyroid Carcinoma Suggest High Potential of Pretargeted Immuno-PET for Tumor Imaging and Theranostic Approaches.

Monoclonal antibody (mAb)-based therapies have experienced considerable growth in cancer management. When labeled with radionuclides, mAbs also represent promising probes for imaging or theranostic approaches. Initially, mAbs have been radiolabeled with single-photon emitters, such as I, Tc, or In, for diagnostic purposes or to improve radioimmunotherapy (RIT) using dosimetry estimations.

The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use.

The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim, the majority of them being derived from the chemical structure of cocaine. The development of such a tracer, from its conception to its use, is a long process, the expected result being to obtain the best radiopharmaceutical adapted for clinical protocols.

Interest of FDG-PET in the Management of Mantle Cell Lymphoma.

FDG-PET changed response assessment and therapy strategy in diffuse large B-cell lymphoma and Hodgkin disease lymphoma. The value of FDG-PET evaluation in MCL has not been extensively studied and a recent expert consensus highlighted the need for more studies addressing this question. Data of the literature show the value of FDG-PET at baseline in patients with MCL, underlining the good sensitivity of this examination for the initial staging of this pathology, but also the potential impact of semi-quantitative analysis in this indication.

Design of selective COX-2 inhibitors in the (aza)indazole series. Chemistry, in vitro studies, radiochemistry and evaluations in rats of a [F] PET tracer.

A series of novel derivatives exhibiting high affinity and selectivity towards the COX-2 enzyme in the (aza) indazole series was developed. A short synthetic route involving a bromination/arylation sequence under microwave irradiation and direct C-H activation were established in the indazole and azaindazole series respectively. In vitro assays were conducted and structural modifications were carried out on these scaffolds to furnish compound 16 which exhibited effective COX-2 inhibitory activity, with IC values of 0.

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study).

Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4-20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD.

The Place of PET to Assess New Therapeutic Effectiveness in Neurodegenerative Diseases.

In vivo exploration of neurodegenerative diseases by positron emission tomography (PET) imaging has matured over the last 20 years, using dedicated radiopharmaceuticals targeting cellular metabolism, neurotransmission, neuroinflammation, or abnormal protein aggregates (beta-amyloid and intracellular microtubule inclusions containing hyperphosphorylated tau). The ability of PET to characterize biological processes at the cellular and molecular levels enables early detection and identification of molecular mechanisms associated with disease progression, by providing accurate, reliable, and longitudinally reproducible quantitative biomarkers. Thus, PET imaging has become a relevant imaging method for monitoring response to therapy, approved as an outcome measure in bioclinical trials.

TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

Peripheral sterile inflammatory diseases (PSIDs) are a heterogeneous group of disorders that gathers several chronic insults involving the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system and wherein inflammation is the cornerstone of the pathophysiology. In PSID, timely characterization and localization of inflammatory are crucial for an adequate care for patients. In brain diseases, positron emission tomography (PET) exploration of inflammation has matured over the last 20 years, through the development of radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO) as molecular biomarkers of activated microglia.