Angiogenesis

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [Ga]Ga-AP747 and [Ga]Ga-RGD small animal PET/CT. [Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [Ga]Ga-RGD. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [Ga]Ga-AP747 PET signal was more than twice higher than that of [Ga]Ga-RGD on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [Ga]Ga-RGD.France Life Imagin

Control of liver regeneration and atrophy by modulation of hepatic portal venous flow in porcine modele : application of major hepatectomy preconditioning

Le principal frein au développement de la transplantation hépatique à donneur vivant est le risque de complication et de décès encourus par le donneur. Nous proposons une préparation du donneur par la réalisation d'un rétrécissement (sténose) de 20% de la veine d'un coté de son foie afin de faire grossir ce dernier sans altérer la viabilité du futur greffon. Pour cela, sur 32 porcs, nous avons recherché la plus petite sténose capable de déclencher le maintien du débit portal et étudié les déclenchements de la prolifération cellulaire et de l'atrophie. Des scanners associés à des scintigraphies hépatobiliaires à la mebrofénine ont été réalisés afin d'étudier les changements morphologiques et fonctionnels du foie. Nous démontrons que la sténose de 20% d'un coté du foie déclenche la régénération hépatique de l'autre coté et permet le gain d'une masse hépatique fonctionnelle. Conclusion : Notre pré-conditionnement est capable de préparer le foie d'un patient à l'hépatectomie majeure.The main hindrance in promoting living donor liver transplantation remains the morbidity and mortality risk for the donor. We propose the realization of a 20% stenosis of the left portal vein (LPV) in order to induce an increase of the functional liver mass without altering the viability of the future graft.Materials and Methods: Thirty-two pigs were included in this program. The hemodynamic study identified the smallest stenosis capable of triggering mechanisms of maintenance of the hepatic blood flow. Cell proliferation and atrophy were studied. Scanners associated with Mebrofenin hepatobiliary scintigraphy were performed to study the morphological and functional changes of the liver.Results: A 20% LPV stenosis trigger liver regeneration in the contralateral lobe inducing a gain in hepatic functional hepatic mass.Conclusion: A 20% LPV stenosis is the effective preconditioning in order to get the remnant liver of living donor ready to take on graft harvesting

Conformable, Stretchable Sensor To Record Bladder Wall Stretch

A soft, conformable, biocompatible strain sensor based on ultra-thin stretchable electronics is reported. The sensor comprises gold thin films patterned on a 50 μm thick polyurethane substrate to produce resistive-based strain sensors for monitoring bladder stretch. The sensor responds linearly as a function of strain from 0 to 50%, with an increasing sensitivity as a function of sensor length. The sensor displays good stability with very little hysteresis when it is subjected to cycling between 0 and a maximum strain of 50%, with the largest deviation between 0 and 50% strain of ∼19% after 100 cycles attributed to the sensor with the longest length (6 mm) because it physically stretches by a greater distance than sensors with a shorter length. “Breaking” tests on the sensor reveal that shorter sensors can withstand higher maximum strains than longer sensors. A biocompatible hydrogel adhesive is used to attach sensors in vitro to the outside wall of a pig’s bladder, and sensor performance is studied with respect to repeated bladder filling and emptying to investigate stretch changes. By monitoring bladder stretch and thus volume noninvasively, the sensor provides a route for developing new treatment options for various urological conditions

Design and validation of a 68Ga-radiolabelled PET imaging agent for in vivo evaluation of angiomotin expression

International audienc

Design and validation of a 68Ga-radiolabelled PET imaging agent for in vivo evaluation of angiomotin expression

International audienc

Cognitive impairment was associated with brain-blood barrier permeability in two models of chronic kidney disease in rats

International audienc

Evaluation of Multiple Embolic Agents for Embolization of the Superior Rectal Artery in an Animal Model

International audienceObjective To prospectively compare the safety of transcatheter embolization of superior rectal arteries in healthy pigs with multiple agents such as coils, spheres and liquids. Materials and Methods Nine adult domestic pigs (three males, mean weight: 60 kg [50-70]) were randomly assigned to the embolization group: copolymer of ethylene vinyl alcohol (EVOH)-OnyxÒ (group 1, n = 3), microspheres 500 l (group 2, n = 3), 2-mm micro-coils (group 3, n = 3). After a selective angiogram has been acquired, the embolic agent was infused at the distal part of rectal arteries. An angio-CT was performed before and after each embolization. After one week, angiography was repeated prior to euthanasia. At necropsy, the anorectal juncture was removed for histopathologic examination. Results At necropsy, 100% of animals embolized with Onyx developed a significant necrosis zone of the distal part of the rectum. Histological examination revealed a mural infarction. For the micro-coil and microsphere groups, gross examination of the intestines did not reveal any evidence of ischaemia. The coils were found in the distal arterial vasculature of the meso-rectum, allowing a downstream revascularization by collaterals. The microspheres and onyx in the rectal wall, more distally. Conclusion Microspheres appear to induce fewer histologic complications than the liquid embolic agent and provide a more distal occlusion than micro-coils. These results suggest that, for superior rectal artery embolization, a super-selective embolization using spheres in human clinical conditions should be more effective and as safe as coil embolization. EVOH might be an unsafe embolization agent for haemorrhoids

Combination of Alcohol and EVOH as a New Embolic Agent: Midterm Tissue and Inflammatory Effects in a Swine Model

International audienceObjective. To evaluate the vascular occlusion and midterm tissue toxicity properties of a combination of ethylene-vinyl alcohol (EVOH) (Squid 18 ®) (75%) and alcohol (25%)-Alco-Squid 18-in a swine model. Materials and Methods. Alco-Squid 18 (75% Squid 18 ® mixed with 25% alcohol) (AS18) was compared to embolization with 96% alcohol alone and to embolization with Squid 18 ® (S18 ®) alone. An arteriovenous malformation (AVM) model was created in group 1 (n � 2). Each AVM model was then embolized with AS18 or S18 ® alone with evaluation of a ratio between the volume of embolic agent divided by the volume of the AVM (evaluated by CT). For group 2 (n � 5), each agent was tested on three different kidneys (upper pole kidney artery). Pre-and postinterventional CTs, angiographies, blood alcohol content dosages, and histological studies (3 months postintervention) were performed. Results. AS18 has better distal distribution than S18 ® alone, both in the kidneys (mean capsule-S18 ® distance: 3.9 mm (±0.23) and mean capsule-AS18 distance: 2.3 mm (±0.11) (p � 0.029) and in the AVM model. Histological exploration found a higher rate of tubular necrosis with AS18 compared with S18 ® alone and alcohol alone (3.78 ± 0.44 compared to 2.33 ± 1.22 (p � 0.012) and 1.22 ± 0.67 (p < 0 .0001)). e blood alcohol content was negligible in all cases. Conclusion. AS18 can suggest a better distal sclerotic and embolic character as compared with S18 ® alone without systemic toxicity

Description of morphological evolution of lung tumors treated by percutaneous radiofrequency ablation: long term follow-up of 100 lesions with chest CT

International audiencePurpose: Radiofrequency ablation (RFA) is a safe and effective minimally invasive treatment for pulmonary tumors. Patterns on chest computed tomography (CT) after RFA are classified into five types; however, the follow-up has not been fully described. The objectives of this study were to describe (1) the CT pattern 3 years after RFA and (2) its evolution over 7 years. Materials and methods: Lesions treated with RFA between 2009 and 2017 and with !3 years of follow-up CT data were included. Lesions with local recurrences were excluded from the study. The morphology of the ablation zone was classified as nodular, fibrotic, atelectatic, cavitary, and disappeared. Other initial anatomical parameters were recorded. Kruskal-Wallis or Chi-square tests were used to compare the groups. Results: One hundred lung RFA scars were included, and a retrospective longitudinal study was performed. Three years after RFA, nodular, fibrotic, atelectatic, and cavitary scars, and disappearance were observed in 49%, 36%, 5%, 3%, and 6% of the scars, respectively. Evolution over 7 years showed that the fibrosis, atelectasis, and disappearance remained stable over time, whereas 28% of nodular scars evolved into fibrotic scars. Additionally, 45% of cavitary scars evolved into nodular scars. Pleural contact was associated with disappearance, and the use of a 20-mm needle was associated with atelectasis. Conclusion: Follow-up after RFA showed that fibrosis, disappearance, and atelectasis remained stable over time. Nodular scars could evolve into fibrotic scars, and cavitary scars could evolve into nodular scars

Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study

International audienceSuccinate influences angiogenesis and neovascularization via a hormonelike effect on G-protein-coupled receptor 91 (GPR91). This effect has been demonstrated in the pathophysiology of diabetic retinopathy and rheumatoid arthritis. To evaluate whether succinate can play a role in acute peripheral ischemia, a preclinical study was conducted with ischemic mice treated with succinate or PBS and evaluated by imaging. Acute ischemia was followed by an increased in GPR91 expression in the ischemic muscle. As assessed with LASER-Doppler, succinate treatment resulted in an earlier and more intense reperfusion of the ischemic hindlimb compared to the control group (* p = 0.0189). A microPET study using a radiolabeled integrin ligand ([68Ga]Ga-RGD2) showed an earlier angiogenic activation in the succinate arm compared to control mice (* p = 0.020) with a prolonged effect. Additionally, clinical recovery following ischemia was better in the succinate group. In conclusion, succinate injection promotes earlier angiogenesis after ischemia, resulting in a more effective revascularization and subsequently a better functional recovery