Imaging visceral adhesion to polymeric mesh using pneumoperitoneal-MRI in an experimental rat model

International audienceBackground: Intraperitoneal mesh implantation is often associated with formation of adhesion to the mesh. This experimental study examines the potential of minimally invasive pneumoperitoneal-MRI to assess these adhesions in a preclinical context. Methods: Uncoated polyethylene terephthalate meshes were placed intraperitoneally in rats, in regard to the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Examinations were performed 2-weeks post mesh implantation using a rodent dedicated high field MRI. Respiratory-triggered T2 weighted images were acquired prior to and after intraperitoneal injection of ~8-10mL gas to induce a mechanical stress on the abdominal wall. Results Adhesions are occasionally seen in sham operated rats as opposed to rats receiving polyethylene terephthalate meshes. On high-resolution images, meshes can be detected due to their characteristic net-shape. Angers.. However, evidence of adherence is only found if intraperitoneal gas injection is performed, when a ~1-cm elevation of the abdominal wall is observed. When adherence occurs between the mesh and the caecum, the latter remains in contact with the wall. Looser adherences between visceral tissue and meshes are also observed. Conclusions T2-weighted pneumoperitoneal-MR imaging is a powerful tool for assessing adherence after intraperitoneal mesh implantation. According to the mini-invasive procedure adopted here, this approach may allow a temporal follow-up of adherence fate

Effective Targeting Of Endometrial Tissue By 16α-[18f]Fluoro-17β-Œstradiol ([18f]-Fes): Preliminary Results In The Diagnosis Of Endometriosis

International audienc

Effective Targeting Of Endometrial Tissue By 16α-[18f]Fluoro-17β-Œstradiol ([18f]-Fes): Preliminary Results In The Diagnosis Of Endometriosis

International audienc

18F-FES and 18F-FDG micro-PET/CT imaging for the evaluation of nanovectorized radiotherapy with 188Re in a murine model of endometrial cancer

International audienceAim: To evaluate changes in tumour glycolysis measured by positron emission tomography (PET) with [18F]fluoro-desoxyglucose ([18F]-FDG) and in steroid hormone receptor expression measured by PET with 16α-[18F]fluoro-17β-oestradiol ([18F]-FES) following internal radiotherapy with nanoparticles loaded with rhenium-188 (LNC-188Re-SSS) in a preclinical murine model of human endometrial cancer. Materials and methods: Ishikawa endometrial carcinoma cell lines were implanted subcutaneously in nude mice (n=10). D28 after inoculation, mice (n=5) were treated with an intra-tumor injection of LNC-188Re-SSS. Treatment efficiency in the LNC-188Re-SSS group was compared to control group (n=5) in term of tumour growth assessed by clinical palpation and micro-PET/CT imaging. For each mouse, two [18F]-FDG and two [18F]-FES micro-PET/CT were performed on separate imaging days, at baseline before therapy, and two weeks later.Results: Fourteen days after treatment with LNC-188Re-SSS, tumour progression was significantly inhibited compared to the control group (p&lt;0.006). [18F]-FDG uptake remained stable in the treated group (p=0.9) and was significantly lower than in control group (p=0.03), in which [18F]-FDG tumour uptake increased significantly (p=0.003). An excellent correlation was observed between [18F]-FDG tumour uptake and tumour volume (r=0.88, p=0.0016). At baseline focal [18F]-FES uptake corresponding to the known subcutaneous tumour were observed in both group of mice, and after treatment no significant [18F]-FES uptake difference was observed between the treated and untreated groups (p=0.75). The [18F]-FES tumor uptake was not correlated with the tumour volume (r=0.1613, p=0.68). A significant correlation was found between tumour ERα-score, measured by immunohistochemistry, and [18F]-FES uptake (r=0.6821, p=0.043).Conclusion: Because after treatment, significant changes in tumour uptake was observed only with [18F]FDG and not with [18F]-FES, [18F]-FES does not appear to be able to monitor the therapeutic effect of internal radiation with LNC-188Re-SSS.</p

Ciblage des tissus endométriaux par la 16α-[18F]fluoro-17β-œstradiol (PET-[18F]FES) : résultats préliminaires dans le diagnostic de l’endométriose

International audienceObjectifsLa tomographie par émission de positons (TEP) à la 16α-[18F]fluoro-17β-œstradiol ([18F]FES) permet d’évaluer in vivo la densité tissulaire en récepteurs aux œstrogènes (RE). Cet article rapporte les premiers cas dans le diagnostic de l’endométriose.Patientes et méthodesDans le cadre de la mise en place du PHRC ENDOTEP, quatre patientes présentant des signes cliniques et morphologiques (échographie pelvienne ± IRM) suspects d’endométriose ont bénéficié d’une TEP-[18F]FES avant cœlioscopie (analyse macroscopique et analyse histologique et immunohistochimique de l’expression en RE des lésions prélevées).RésultatsChez les quatre patientes, le diagnostic d’endométriose a été retenu macroscopiquement et après analyse histologique d’au moins une lésion. Aucune captation de [18F]FES par les lésions d’endométriose n’a été observée chez les trois premières patientes sous traitement œstroprogestatif. La quatrième patiente non traitée et en première partie de cycle menstruel lors de la réalisation de la TEP-[18F]FES présentait en revanche une hyperfixation d’une lésion d’endométriose confirmée en cœlioscopie.ConclusionNous rapportons le premier cas de fixation de [18F]FES par une lésion d’endométriose. À travers le projet ENDOTEP, les performances de la TEP-[18F]FES pour le diagnostic d’endométriose seront évaluées chez des patientes ne recevant pas de traitement hormonal.ObjectifsLa tomographie par émission de positons (TEP) à la 16α-[18F]fluoro-17β-œstradiol ([18F]FES) permet d’évaluer in vivo la densité tissulaire en récepteurs aux œstrogènes (RE). Cet article rapporte les premiers cas dans le diagnostic de l’endométriose.Patientes et méthodesDans le cadre de la mise en place du PHRC ENDOTEP, quatre patientes présentant des signes cliniques et morphologiques (échographie pelvienne ± IRM) suspects d’endométriose ont bénéficié d’une TEP-[18F]FES avant cœlioscopie (analyse macroscopique et analyse histologique et immunohistochimique de l’expression en RE des lésions prélevées).RésultatsChez les quatre patientes, le diagnostic d’endométriose a été retenu macroscopiquement et après analyse histologique d’au moins une lésion. Aucune captation de [18F]FES par les lésions d’endométriose n’a été observée chez les trois premières patientes sous traitement œstroprogestatif. La quatrième patiente non traitée et en première partie de cycle menstruel lors de la réalisation de la TEP-[18F]FES présentait en revanche une hyperfixation d’une lésion d’endométriose confirmée en cœlioscopie.ConclusionNous rapportons le premier cas de fixation de [18F]FES par une lésion d’endométriose. À travers le projet ENDOTEP, les performances de la TEP-[18F]FES pour le diagnostic d’endométriose seront évaluées chez des patientes ne recevant pas de traitement hormonal

Nanovectorized radiotherapy by convection-enhanced delivery (CED), a promising strategy that demonstrates high efficacy in a murine model of human endometrial adenocarcinoma

International audienceAim: To evaluate the biodistribution, the toxicity, the dosimetry and the antitumor efficacy of intra-tumoral injection of rhenium-188 loaded nanoparticles (LNC-188Re-SSS) by CED. Materials and methods: Ishikawa endometrial carcinoma cell lines were implanted subcutaneously in nude mice (n=70). For biodistribution and efficacy studies CED procedure was realized at D28 after tumour implantation. CED was performed using an osmotic pump (0.5μL/min for 20 minutes) after immobilisation of anaesthetized mice on a stereotactic frame. For biodistribution studies, animals (n=30) were injected by CED either with 3MBq of 188ReO4- (n=15) or LNC-188Re-SSS (n=15) and sacrificed at 1h (n=10), 24h (n=10) or 72h (n=10). For efficacy studies, control group mice were injected by CED with saline (n=8) or blank LNC (n=8) and treated group mice were injected with escalating dose of LNC-188Re-SSS: 3MBq (n=8), 6 MBq (n=8) or 12 MBq (n=8). Efficacy on tumour growth was assessed by clinical palpation and μMRI. The time for the tumour volume doubling was chosen as endpoint, leading to the euthanasia of the animal. The physical dose deposited in the tumour for each treated animal was estimated by Monte Carlo simulation (Geant4) using measured biodistribution and μMRI tumour volumes,. Haematological toxicity in mice was evaluated using blood sampling of 50μL (retro-orbital sinus) at D2, D7, D14 and D21 after treatment with saline (n=4) and after treatment with LNC-188Re-SSS, 3MBq (n=4), 6 MBq (n=4) or 12 MBq (n=4). Results: Nanovectorization of 188Re combined with CED allowed the confinement of more than 30 % of ID in the tumour limiting therefore urinary excretion of 188Re since 0,1% versus 81,9% of ID were excreted in urine 24h after CED of LNC-188Re-SSS and 188ReO4- respectively (p=0.016). Nanovectorized radiotherapy has drastically increased the median survival time compared with control group. Animals whose tumor received a dose higher than 69 Gy (69-340 Gy) showed an ISTmedian of + 933%, whereas animals whose tumor received a dose lower than 69 Gy (21-67Gy) showed an ISTmedian of + 391%. Complete response with eradication of the tumor was observed in 4/12 (33.3%) animals of the former group. Depletion of platelets was observed following LNC-188Re-SSS injection with a time to nadir between D14-D21 whereas transient lymphocyte depletion was only observed at D7 for the highest administered activities (12MBq).Conclusion: CED of LNC-188Re-SSS demonstrates interesting biodistribution properties and high efficacy in a model of human endometrial carcinoma.</p