Search PubMed⌕ Search

Biomedical subjects

Xavier Montet

Publications and source records attributed to Xavier Montet.

At least 19 recordsLinked to original sources
PubMed2006

Multivalent effects of RGD peptides obtained by nanoparticle display.

The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE=IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V)beta(3) function on endothelial cells in vivo.

Animals↗
PubMed2006

Interaction of functionalized superparamagnetic iron oxide nanoparticles with brain structures.

Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) combined with magnetic resonance imaging (MRI) are under clinical evaluation to enhance detection of neurodegenerative diseases. A major improvement would be to link therapeutic drugs to the SPIONs to achieve targeted drug delivery, either at the cell surface or intracellularly, together with active disease detection, without inducing cell reaction. Our objectives were to define the characteristics of SPIONS able to achieve cell-specific interaction with brain-derived structures. Our system consisted in an iron oxide core (9-10 nm diameter) coated either with dextran (Sinerem and Endorem) or various functionalized polyvinyl alcohols (PVAs) (PVA-SPIONs). We investigated the cellular uptake, cytotoxicity, and interaction of these various nanoparticles with brain-derived endothelial cells, microglial cells, and differentiating three-dimensional aggregates. None of the nanoparticles coated with dextran or the various PVAs was cytotoxic or induced the production of the inflammatory mediator NO used as a reporter for cell activation. AminoPVA-SPIONs were taken up by isolated brain-derived endothelial and microglial cells at a much higher level than the other SPIONs, and no inflammatory activation of these cells was observed. AminoPVA-SPIONs did not invade brain cells aggregates lower than the first cell layer and did not induce inflammatory reaction in the aggregates. Fluorescent aminoPVA-SPIONs derivatized with a fluorescent reporter molecule and confocal microscopy demonstrated intracellular uptake by microglial cells. Fluorescent aminoPVA-SPIONs were well tolerated by mice. Therefore, functionalized aminoPVA-SPIONs represent biocompatible potential vector systems for drug delivery to the brain that may be combined with MRI detection of active lesions in neurodegenerative diseases.

Animals↗
PubMed2006

Simultaneous fluorescence imaging of protease expression and vascularity during murine colonoscopy for colonic lesion characterization.

BACKGROUND: Molecularly targeted fluorescent probes are currently being developed to improve the endoscopic detection of intestinal pathologic conditions. OBJECTIVE: We report on the development and testing of a novel multichannel microendoscope capable of quantitatively reporting such probes simultaneously at different wavelengths in real time. We assessed the feasibility of detecting and quantifying beacons that can be activated by protease and correlating imaging with disease state. DESIGN: The microendoscope consisted of a 20-gauge fiberoptic catheter and dichroic beam splitters that simultaneously display visible light, 700 nm and 800 nm near infrared (NIR) fluorescent light. NIR interchannel separation was tested on in vitro phantoms. Two mouse models were used (Apcmin(+/-) mice for colonic adenomas and CT26 murine colon cancer). A perfusion probe and one activated by protease at a separate wavelength were injected before endoscopic evaluation. RESULTS: The microendoscope fluorochrome detection limit was approximately 10 fmol; ratio imaging in the NIR was accurate (+/-8% of true probe concentration between 0.3 to 100 microg/ml of a protease sensor). Both colonic adenomas and adenocarcinomas were clearly visible in the NIR channel on protease probe administration in live mice. Ratio imaging of protease activity/perfusion increased from healthy colon to adenomas to adenocarcinomas. LIMITATIONS: Evaluation across additional spontaneous tumor models may provide more data on the translation of these findings. CONCLUSIONS: Our data show the feasibility of multichannel microendoscopic imaging of molecular targets in vivo and that ratio imaging may provide a novel means for characterizing colonic lesions. When scaled up clinically, this could aid in increasing lesion detection and quantitative assessment of distinct molecular markers.

Adenocarcinoma↗
PubMed2006

Enzyme-based visualization of receptor-ligand binding in tissues.

New methods of elucidating the ligand-binding activity of receptors could improve our understanding of receptor function, key events they control, and their presence in normal and pathological states. We describe a method for visualizing receptor-ligand binding in cells and tissues that substitutes fluorescein for radioactive labels, and detects receptor bound, fluoresceinated ligand with an antifluorescein/horseradish peroxidase amplification system. Receptor-bound ligand is then visualized by light microscopy against a standard hemotoxylin-stained background of cell structure. Quantitative versions of the assay provide an apparent dissociation constant and number of receptors per cell at saturation in cell or tissue specimens. Receptors examined include the folate receptor, bombesin peptide-binding receptors, the epidermal growth factor receptor, the neuropeptide Y receptor, the asialoglycoprotein receptor, and RGD peptide-binding integrins. Using fluoresceinated versions of molecules, we show the method can visualize and quantitate receptor-bound ligands in cell culture monolayers and animal tissue specimens. Ligand binding to receptors present in tissues was visualized in normal and pathological samples of human tissue microarrays. The enzyme-amplified detection of receptor-bound fluoresceinated ligand is a simple and nonradioactive-based method that provides information on the receptor activity in tissue specimens.

Amino Acid Sequence↗
PubMed2006

Nanoparticle imaging of integrins on tumor cells.

Nanoparticles 10 to 100 nm in size can deliver large payloads to molecular targets, but undergo slow diffusion and/or slow transport through delivery barriers. To examine the feasibility of nanoparticles targeting a marker expressed in tumor cells, we used the binding of cyclic arginine-glycine-aspartic acid (RGD) nanoparticle targeting integrins on BT-20 tumor as a model system. The goals of this study were: 1) to use nanoparticles to image alpha(V)beta3 integrins expressed in BT-20 tumor cells by fluorescence-based imaging and magnetic resonance imaging, and, 2) to identify factors associated with the ability of nanoparticles to target tumor cell integrins. Three factors were identified: 1) tumor cell integrin expression (the alpha(V)beta3 integrin was expressed in BT-20 cells, but not in 9L cells); 2) nanoparticle pharmacokinetics (the cyclic RGD peptide cross-linked iron oxide had a blood half-life of 180 minutes and was able to escape from the vasculature over its long circulation time); and 3) tumor vascularization (the tumor had a dense capillary bed, with distances of <100 microm between capillaries). These results suggest that nanoparticles could be targeted to the cell surface markers expressed in tumor cells, at least in the case wherein the nanoparticles and the tumor model have characteristics similar to those of the BT-20 tumor employed here.

Animals↗
PubMed2005

Assessment of intra-articular volume of the wrist: a comparative study between CT-arthrography and dissection.

The aim of this study was to compare the intra-articular volumes of the wrist's joint measured by CT-arthrography and by dissection on ten cadavers. A good correlation was found between CT-arthrography and dissection in the assessment of the intra-articular volume of both wrist joints. A volume of 1.34 (+/-0.46) milliliter and 0.97 (+/-0.32) milliliter were found by Ct-arthrography for the radiocarpal and midcarpal joints, respectively. Dissection of the same wrists gives a volume of 1.24 (+/-0.33) and 0.90 (+/-0.21) for the radiocarpal and midcarpal joints, respectively. The knowledge of normal wrist-joint volume is a major prerequisite to evaluate carpal instability without ligaments' tears. We believe that CT-arthrography could be helpful in evaluating patients with suspected carpal instability.

Arthrography↗
PubMed2005

Tomographic fluorescence mapping of tumor targets.

Methods that allow robust imaging of specific molecular targets and biological processes in vivo should have widespread applications in biology and clinical medicine. Here we use a quantitative, three-dimensional fluorescence-mediated tomographic technique (FMT) that enables rapid measurements of fluorochrome-based affinity tags in live xenograft models. We validate the method by showing its sensitivity in quantitating tumor angiogenesis and therapeutic modulation using an anti-vascular endothelial growth factor antibody. Furthermore, we show the feasibility of simultaneous multichannel measurements of distinct biological phenomena such as receptor tyrosine kinase expression and angiogenesis. FMT measurements can be done serially, with short imaging times and within the same live animal. The described method should be valuable for rapidly profiling biological phenomena in vivo.

Animals↗
PubMed2005

Magnetic resonance imaging with hepatospecific contrast agents in cirrhotic rat livers.

OBJECTIVE: During biliary cirrhosis in rats, organic anion-transporting peptides (Oatps) and ATP-dependent multidrug resistance-associated protein 2 (Mrp2) that are likely to transport the contrast agent Gd-BOPTA through hepatocytes are down-regulated. However, the consequences of such down-regulation on the signal intensity (SI) enhancement are unknown. Consequently, the aim of our study was to measure the hepatic SI enhancement during Gd-BOPTA perfusion as well as the Oatp and Mrp2 expression in normal and cirrhotic livers. MATERIALS AND METHODS: The hepatic SI enhancement during Gd-BOPTA perfusion was measured in livers isolated from normal rats and rats that had a bile duct ligation (BDL) 15, 30, and 60 days before the perfusion. Hepatic injury and transporter expression were measured in control and cirrhotic rats. RESULTS: BDL induced a severe hepatic injury that increased over time with a down-regulation of the transporter expression. The extracellular space (assessed by Gd-DTPA perfusion) increased with the severity of the disease. Gd-BOPTA-induced SI enhancement remained similar in BDL-15 and BDL-30 rats than in control rats but significantly decreased in severe cirrhosis (BDL-60 rats). In comparison, the Mn-DPDP-induced SI enhancement decreases proportionally to the severity of the disease. CONCLUSION: During biliary cirrhosis, Gd-BOPTA-induced SI enhancement could not be related to the hepatic expression of transporters.

ATP-Binding Cassette Transporters↗
PubMed2005

Nanoparticles for the optical imaging of tumor E-selectin.

We designed a fluorescent peptide-magnetic nanoparticle conjugate that images E-selectin expression in mouse xenograft models of Lewis lung carcinoma (LLC) by fluorescence reflectance imaging. It was synthesized by attaching the E-selectin-binding peptide (ESBP; CDSDSDITWDQLWDLMK) to a CLIO(Cy5.5) nanoparticle to yield ESBP-CLIO(Cy5.5). Internalization by activated human umbilical vein endothelial cells (HUVECs) was rapid and mediated by E-selectin, indicated by the lack of uptake of nanoparticles bearing similar numbers of a scrambled peptide (Scram). To demonstrate the specificity of E-selectin targeting to ESBP-CLIO(Cy5.5) in vivo, we coinjected ESBP-CLIO(Cy5.5) and Scram-CLIO(Cy3.5) and demonstrated a high Cy5.5/Cy3.5 fluorescence ratio using the LLC. Histology showed that ESBP-CLIO was associated with tumor cells as well as endothelial cells, but fluorescence-activated cell sorter analysis showed a far less expression of E-selectin on LLC than on HUVECs. Using immunohistochemistry, we demonstrated E-selectin expression in both endothelial cells and cancer cells in human prostate cancer specimens. We conclude that ESBP-CLIO(Cy5.5) is a useful probe for imaging E-selectin associated with the LLC tumor, and that E-selectin is expressed not only on endothelial cells but also on LLC cells and human prostate cancer specimens.

Animals↗
PubMed2003

Ultrasound diagnosis of anterior iliopsoas impingement in total hip replacement.

Iliopsoas impingement syndrome, an infrequent complication of total hip replacement, has been rarely reported in the radiological literature. It follows chronic friction of the posterior aspect of the iliopsoas muscle and tendon against the acetabular cup, a piece of cement, or cup fixation screws. Clinical findings are non-specific and an imaging modality is required to diagnose the condition. Computed tomography (CT) is considered the gold standard imaging modality in evaluating iliopsoas impingement. We report a case of a patient in which the diagnosis was made by ultrasound and later confirmed by CT.

Aged↗
PubMed2003

Kinetics of gadobenate dimeglumine in isolated perfused rat liver: MR imaging evaluation.

PURPOSE: To compare in the entire liver, the hepatic kinetics of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine (Gd-DTPA) and to evaluate the hepatic transport of Gd-BOPTA. MATERIALS AND METHODS: The authors studied both contrast agents in isolated perfused rat livers by measuring the magnetic resonance (MR) signal intensity (SI) in 12 rats, as well as the gadolinium concentrations in hepatic tissues in 42 rats. The intrahepatic transport of Gd-BOPTA was investigated with pharmacologic antagonism by using bromosulfophthalein. MR imaging was performed at 1.5 T with a fast gradient-echo T1-weighted MR sequence. RESULTS: The hepatic kinetics based on the MR SI measured over time showed a rapid steady state during Gd-DTPA perfusion, while the SI continuously increased during the 30-minute Gd-BOPTA perfusion period. The pharmacokinetic modeling indicated that the half-lives of Gd-DTPA entry and exit were identical (mean, 1.3 minutes +/- 0.9 [standard error of mean]) and shorter than those observed with Gd-BOPTA (P <.001). The uptake of Gd-BOPTA was faster (mean half-life, 4.8 minutes +/- 0.3) than the washout (mean half-life, 17.5 minutes +/- 2.8) (P =.001). The combined perfusion of bromosulfophthalein and Gd-BOPTA decreased the SI enhancement in comparison with the perfusion of Gd-BOPTA alone (mean, 0.56 +/- 0.03 vs 2.54 +/- 0.39, P <.001). The entry and exit kinetic parameters obtained during the perfusion of Gd-BOPTA plus bromosulfophthalein were identical and comparable to those obtained during Gd-DTPA perfusion (P =.95). Acute bile duct ligation did not interfere with the uptake of Gd-BOPTA in hepatocytes, but it slowed down the excretion by approximately 50%. Measurements of gadolinium concentrations in hepatic tissues confirmed these findings. CONCLUSION: In the liver, the hepatospecific contrast agent Gd-BOPTA enters into hepatocytes likely through the organic anion transporting peptide 1.

Animals↗
PubMed2003

Inflow effect correction in fast gradient-echo perfusion imaging.

The purposes of this study were to assess the extent of the inflow effect on signal intensity (SI) for fast gradient-recalled-echo (GRE) sequences used to observe first-pass perfusion, and to develop and validate a correction method for this effect. A phantom experiment with a flow apparatus was performed to determine SI as a function of Gd-DTPA concentration for various velocities. Subsequently a flow-sensitive calibration method was developed, and validated on bolus injections into an open-circuit flow apparatus and in vivo. It is shown that calibration methods based on static phantoms are not appropriate for accurate signal-to-concentration conversion in images affected by high flow. The flow-corrected calibration method presented here can be used to improve the accuracy and robustness of the arterial input function (AIF) determination for tissue perfusion quantification using MRI and contrast media.

Blood Flow Velocity↗
PubMed2003

Imaging of fractures of the lateral process of the talus, a frequently missed diagnosis.

Although if fractures of the lateral process of the talus (LPT) have been considered rare the widespread diffusion in snowboard practice has resulted in a dramatic increase in their frequency. If unrecognized they can result in secondary osteoarthritis of the ankle and/or talo-calcaneal joints and chronic pain and stiffness. Due to the complex anatomy of the region, these fractures are difficult to detect by standard radiographs. A high degree of suspicion is then necessary to diagnose them. Once suspected on the basis of physical examination and/or non concluding radiographs, computed tomography (CT) is the best modality to confirm the diagnosis and accurately appreciate the number of the fragments and their position which have therapeutic consequences (medical vs. surgical treatment). A better knowledge of these lesions seems necessary to the general radiologist to allow an early diagnosis in order to avoid chronic sequel. The purpose of this article is to report three additional cases of LPT fractures and discuss their pathogenesis, diagnosis and treatment.

Adult↗
PubMed2003

Noninvasive measurement of absolute renal perfusion by contrast medium-enhanced magnetic resonance imaging.

OBJECTIVE: The aim of this study was to validate the quantification of absolute renal perfusion (RP) determined by dynamic magnetic resonance imaging (MRI) and contrast media using an experimental model in the rabbit and a transit-timed ultrasound flow probe around the left renal artery as comparison. MATERIAL AND METHODS: An MR-compatible ultrasonic time-of-flight flow-probe was placed around the left renal artery in 9 New Zealand white rabbits. Absolute RP in basal state, after mechanical renal artery stenosis, intravenous dopamine, angiotensin II, or colloid infusion was measured using dynamic MRI and intravenous injection of gadoteridol. The results were correlated to the renal artery flow measured inside the magnet with the transit-timed flow-probe. For the signal intensity concentration conversion, we applied different calibrations according to various velocities measured in the aorta by a phase contrast sequence to correct for inflow effect. MRI-derived RP (in mL/min) was calculated by the maximum upslope method, where RP/volume was defined as the ratio of the cortex contrast enhancement slope over the maximum of the arterial input function determined in the aorta. RESULTS: Reproducible arterial and renal transit curve with excellent contrast to noise ratio were obtained. The MRI derived perfusion was systematically underestimated by comparison to the ultrasonic transit-timed flow-probe but was linearly correlated with these measures (r = 0.80, P < 0.001). CONCLUSIONS: Using a flow-sensitive calibration, an accurate arterial input function can be measured from the blood MR signal and used in a realistic model to assess the RP. There was a good correlation between the MR-derived RP and the renal artery blood flow measured by the flow-meter. This experimental study validates absolute RP quantification by MRI and contrast media injection and justifies further clinical studies.

Animals↗
PubMed2002

Sonographic and MRI appearance of tensor fasciae suralis muscle, an uncommon cause of popliteal swelling.

A 20-year-old white man presented with a localized unilateral swelling in the popliteal fossa. Ultrasound (US) showed the presence of an accessory muscle, the tensor fasciae suralis. The muscle was located in the proximal portion of the popliteal fossa, superficial to the medial head of the gastrocnemius. Its long tendon extended inferiorly to join the Achilles tendon. Magnetic resonance images correlated well with the US findings, confirming the diagnosis. Tensor fasciae suralis muscle is a rare cause of popliteal swelling and must be differentiated from other masses. Both US and magnetic resonance imaging can diagnose it but we suggest US as the first-line technique in its evaluation.

Adult↗