Molecular imaging of tumor-associated angiogenesis using a novel magnetic resonance imaging contrast agent targeting αvβ3 integrin

The recent introduction of biological anticancer therapy has renewed the interest in functional imaging of tumor-associated angiogenesis (TAA) as a tool to monitor early therapy response. The present study evaluated imaging of TAA using P1227, a novel, small molecular magnetic resonance imaging (MRI) probe targeting alpha(v)beta(3) integrin. HT29 human colorectal cancers were grown in athymic mice. Dynamic MRI was performed using a three-dimensional VIBE sequence up to 110 min after injection of P1227 or gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA). Specificity was assessed by using P1227 1 h after intravenous administration of the alpha(v)beta(3) inhibitor cilengitide. Regions of interest were drawn encompassing the tumor rim and normal muscle. Imaging data were compared with microvessel density and alpha(v)beta(3) expression. Using P1227, specific enhancement of the angiogenic tumor rim, but not of normal muscle, was observed, whereas Gd-DOTA enhanced tumor and normal muscle. After administering cilengitide, enhancement with P1227, but not with DOTA, was significantly suppressed during the first 20 min. When using P1227, a significant correlation was observed between normalized enhancement of the tumor rim and immunohistochemical alpha(v)beta(3) integrin expression. Molecular MRI using a small monogadolinated tracer targeting alpha(v)beta(3) integrin and moderate magnetic field strength holds promise in assessing colorectal TAA

Toxoplasmosis: Overview from a One Health perspective

Toxoplasmosis is paradigmatic of the One Health approach, as the causative parasite Toxoplasma gondii infects virtually all warm-blooded animals, including humans. This makes T. gondii one of the most successful parasites on earth, infecting up to a third of the global human population. Moreover, the T. gondii disease burden has been ranked among the highest of all parasitic diseases. To reduce the disease burden of toxoplasmosis in humans, interventions are needed in the animal reservoirs, necessitating close collaboration between both the human and veterinary medical sectors. In the present special issue of FAWPAR, several of the most pertinent topics related to the impact and control of toxoplasmosis are addressed by leading experts in the field. This collection of papers highlights state-of-the-art knowledge, gaps in knowledge and future perspectives, as well as the benefits of current and proposed future activities to tackle toxoplasmosis within the One Health context

Modélisation de la perfusion quantitative en imagerie par résonance magnétique (IRM) cardiaque in-vivo

L\u27analyse paramétrique de la distribution d\u27un agent de contraste est proposée pour l\u27interprétation clinique des études de premier passage et la quantification de la perfusion myocardique en IRM. Notre premier objectif concerne la correction de variations spatiales d\u27intensité des images. Notre second objectif concerne l\u27application d\u27une technique robuste de traitement du signal RMN et de déconvolution adaptée au faible rapport signal sur bruit. Les données analysées proviennent d\u27expériences menées in-vivo proche des conditions cliniques pour différents stress pharmacologiques appliqués sur des cochons présentant une sténose au niveau de l\u27artère coronaire circonflexe gauche. Les mesures d\u27agrément et de précision entre observateurs sont respectivement de 57,1% et 53,1% pour l\u27analyse visuelle et 81,2% et 81,1% pour l\u27analyse des cartes paramétriques. Une relation linéaire des paramètres de perfusion en fonction des mesures de microsphères radioactives est obtenue pour les faibles débits<250 ml/100g/min : i.e. sur la variation de signal DSI y=0,06x+6, r=0,82, la pente ascendante y=0,026x+2, r=0,79 et le débit sanguin régional rMBF y=2,9x+130, r=0,76. Pour les forts débits, les courbes d\u27intensité du signal IRM dans le sang et le myocarde sont atténuées donnant une sous-estimation des mesures de paramètres. L\u27analyse du signal en fonction du taux de relaxation R1 est appliquée en tenant compte des échanges d\u27eau dans le tissu. Nous avons montré sur une série d\u27images au repos et sous stress que la réserve coronaire est de 3,87 pour les débits mesurés en R1 en prenant un temps d\u27échange intermédiaire alors que la réserve coronaire est de 2,83 pour les débits mesurés en intensité du signal IRM. Enfin, nous avons montré sur une série d\u27images au repos et sous stress que le calcul des cartes de paramètres physiologiques en chaque pixel est possible en appliquant une régularisation spatiale pour lisser l\u27image paramétrique avec prise en compte des discontinuités

Molecular imaging in oncology drug development

International audienceTremendous breakthroughs are being made in cancer drug discovery and development. However, such breakthroughs come at a high financial cost. At a time when there is increasing pressure on drug pricing, in part because of increased life expectancy, it is more important than ever to drive new therapeutics towards patients as efficiently as possible. In this review we discuss the applications of molecular imaging in oncology drug development, with a focus on its ability to enable better early decision making, to increase efficiency and thereby to lower costs

Near-Infrared-Emitting BODIPY-trisDOTA 111 In as a Monomolecular Multifunctional Imaging Probe: From Synthesis to In Vivo Investigations

International audienceA new generation of monomolecular imaging probes (MOMIP) based on a distyryl-BODIPY (BODIPY= boron-dipyrromethene) coupled with three DOTA macrocycles has been prepared (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The MOMIP presents good fluorescence properties and is very stable in serum. The bimodal probe was conjugated to trastuzumab, and an optical in vivo study showed high accumulation of the imaging agent at the tumor site. In-111 radiometallation of the bioconjugate was performed in high radiochemical yield, highlighting the potential of this new BODIPY-chelators derivative as a bimodal imaging probe