Integrins, an important superfamily of cell adhesion receptors, play an essential role in cancer progression, metastasis, and angiogenesis, establishing them as prime targets for both diagnostic and therapeutic applications. Despite their significant potential, integrin-targeted therapies have faced substantial challenges in clinical trials, including variable efficacy and unmet high expectations. Nevertheless, the consistent expression of integrins on tumor and stromal cells underscores their ongoing relevance and potential.
View Article and Find Full Text PDFCardiovascular diseases, including fatal myocardial infarctions from atheromatous plaques, are the primary global mortality cause. Detecting stenotic atheromatous plaques is possible through coronary angiography, but vulnerable plaques with eccentric remodeling are undetectable with current diagnostic methods. Addressing this challenge, our group developed a radiopharmaceutical drug targeting vascular cell adhesion molecule 1 (VCAM-1), radiolabeled with technetium-99m.
View Article and Find Full Text PDFBackground: Soluble oligomeric forms of Tau protein have emerged as crucial players in the propagation of Tau pathology in Alzheimer's disease (AD). Our objective is to introduce a single-domain antibody (sdAb) named 2C5 as a novel radiotracer for the efficient detection and longitudinal monitoring of oligomeric Tau species in the human brain.
Methods: The development and production of 2C5 involved llama immunization with the largest human Tau isoform oligomers of different maturation states.
Background: Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit.
View Article and Find Full Text PDFIn this study, the total phenolic and flavonoid contents (TPC and TFC), secondary metabolite composition (LC-HRMS/MS analyses) and antioxidant potential (DPPH, ABTS, GOR, CUPRAC, and phenanthroline assays) of L. (LT) extracts were determined. Our results showed for the first time that the extracts (PE, CHCl, AcOEt, and -BuOH) of LT exert antioxidant activity.
View Article and Find Full Text PDFTo date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) could be used as an alternative non-invasive tool to detect liver inflammation in the setting of chronic liver disease. To do so, we radiolabeled anti-VCAM-1 nanobody (Tc-cAbVCAM1-5) and used single-photon emission computed tomography (SPECT) to quantify liver uptake in preclinical models of non-alcoholic fatty liver disease (NAFLD) with various degree of liver inflammation: wild-type mice fed a normal or high-fat diet (HFD), FOZ fed a HFD and C57BL6/J fed a choline-deficient or -supplemented HFD.
View Article and Find Full Text PDFObjectives: To assess the diagnostic performances of CZT myocardial perfusion reserve (MPR) for the detection of territories with simultaneous impaired coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients without obstructive coronary artery disease.
Methods: Patients were prospectively included before being referred for coronary angiography. All patients underwent CZT MPR before invasive coronary angiography (ICA) and coronary physiology assessment.
In this study, six vacuum liquid chromatography (VLC) fractions (F1-F6) of the -BuOH extract of Murb. (BELN) were examined for their anticancer capacity. The composition of secondary metabolites was analyzed by LC-HRMS/MS.
View Article and Find Full Text PDFContext: is the largest genus of the Linaceae family; the species of this genus are known to have anticancer activity.
Objective: In this study, ethyl acetate extracts of Murb. (EAELN) and L.
Coronary physiological assessment is now widely used to assess epicardial coronary lesions in cath lab. Based on clinical evidence, fractional flow reserve (FFR) is the gold standard method to select whether epicardial coronary lesions need revascularization. While additional epicardial indexes, such as instantaneous wave-free ratio (iFR), are also used for revascularization decision-making, several indexes are now also available to explore the coronary microcirculation.
View Article and Find Full Text PDFExtracellular vesicles (EVs) have been exploited as bio-inspired drug delivery systems (DDS) in the biomedical field. EVs have more advantages than synthetic nanoparticles: they are naturally equipped to cross extra- and intra-cellular barriers. Furthermore, they can deliver functional biomolecules from one cell to another even far away in the body.
View Article and Find Full Text PDFFront Cardiovasc Med
February 2022
Atherosclerotic plaque rupture or erosion remain the primary mechanism responsible for myocardial infarction and the major challenge of cardiovascular researchers is to develop non-invasive methods of accurate risk prediction to identify vulnerable plaques before the event occurs. Multimodal imaging, by CT-TEP or CT-SPECT, provides both morphological and activity information about the plaque and cumulates the advantages of anatomic and molecular imaging to identify vulnerability features among coronary plaques. However, the rate of acute coronary syndromes remains low and the mechanisms leading to adverse events are clearly more complex than initially assumed.
View Article and Find Full Text PDFFront Cell Dev Biol
October 2021
AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis under conditions of energy stress. Though heart is one of the most energy requiring organs and depends on a perfect match of energy supply with high and fluctuating energy demand to maintain its contractile performance, the role of AMPK in this organ is still not entirely clear, in particular in a non-pathological setting. In this work, we characterized cardiomyocyte-specific, inducible AMPKα1 and α2 knockout mice (KO), where KO was induced at the age of 8 weeks, and assessed their phenotype under physiological conditions.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
February 2022
Purpose: Coronary microvascular dysfunction (CMVD) plays a major role in the occurrence of cardiovascular events (CVE). We recently suggested the clinical potential of myocardial perfusion entropy (MPE) quantification from SPECT myocardial perfusion images (MPI) for the prognosis of CVE occurrence. We hypothesized that the quantification of MPE from SPECT MPI would allow the assessment of CMVD-related MPE variations in a preclinical model of type 2 diabetes (T2D) including treatment with the anti-diabetic incretin liraglutide (LIR).
View Article and Find Full Text PDFBackground: Atherosclerosis is associated with a worse prognosis in many diseases such as ischemic cardiomyopathy, but its impact in non-ischemic dilated cardiomyopathy (dCMP) is lesser known. Our aim was to study the prognostic impact of coronary atherosclerotic burden (CAB) in patients with dCMP.
Methods: Consecutive patients with dCMP and left ventricular (LV) dysfunction diagnosed by concomitant analysis of invasive coronary angiography (ICA) and CMR imaging were identified from registry-database.
Aims: The objective of this study was to determine the accuracy of right ventricular function (RVF) assessed by Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography (CZT-ERNA).
Methods And Results: Twenty-one consecutive patients with cardiomyopathy (aged 54 ± 19 years; 62% male) were included. RV ejection fraction (EF) and volumes were analyzed by CZT-ERNA and compared with values obtained by cardiac magnetic resonance imaging (CMR).
NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein-coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice bearing GIST-882 tumors were employed.
View Article and Find Full Text PDFBackground: Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using I-6-deoxy-6-iodo-D-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging.
Methods: The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling.
Purpose: Risk stratification of patients with type 2 diabetes mellitus (T2D) remains suboptimal. We hypothesized that myocardial perfusion entropy (MPE) quantified from SPECT myocardial perfusion images may provide incremental prognostic value in T2D patients independently from myocardial ischemia.
Methods: T2D patients with very high and high cardiovascular risk were prospectively included (n = 166, 65 ± 12 years).
Unlabelled: Mesothelin is a membrane-associated protein overexpressed in pancreatic ductal adenocarcinoma (PDAC). Some mesothelin-targeted therapies are in clinical development but the identification of patients eligible for such therapies is still challenging. The objective of this study was to perform the imaging of mesothelin in mice models of PDAC with a technetium-labeled anti-mesothelin single-domain antibody (Tc-A1).
View Article and Find Full Text PDFObjective: In Genetic Absence Epilepsy Rats From Strasbourg (GAERSs), epileptogenesis takes place during brain maturation and correlates with increased mRNA expression of D3 dopamine receptors (D3R). Whether these alterations are the consequence of seizure repetition or contribute to the development of epilepsy remains to be clarified. Here, we addressed the involvement of the dopaminergic system in epilepsy onset in GAERSs.
View Article and Find Full Text PDFRecent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
September 2019
Purpose: To determine whether the assessment of regional wall thickening (WT) in addition to myocardial perfusion from stress supine acquisitions could compensate for the lack of prone acquisition and the corresponding decrease in the diagnostic performance of SPECT myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease (CAD).
Methods: The study group comprised 41 patients (123 vessels) with known or suspected CAD prospectively recruited for systematic prone and supine Tl stress SPECT MPI. The diagnostic performance of SPECT MPI was determined for various image sets including nongated supine images (supine NG), nongated combined prone and supine images (prone and supine NG) and gated supine images, allowing WT evaluation from NG images in addition to perfusion (supine NG + WT) using invasive coronary angiography and fractional flow reserve as the gold standards.
Purpose: Insulin resistance is a key feature of the metabolic syndrome and type 2 diabetes, in which noninvasive assessment is not currently allowed by any methodology. We previously validated an iodinated tracer of glucose transport (6DIG) and a new methodology for the in vivo quantification of cardiac insulin resistance in rodents. The aim of this study was to investigate the safety, biodistribution, and radiation dosimetry of this method using I-6DIG in 5 healthy and 6 diabetic volunteers.
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