32 research outputs found
Scintigraphie isotopique couplĂ©e au scanner : intĂ©rĂȘt dans le diagnostic de dysfonctionnement de pompe Ă baclofĂšne
Biodistribution et toxicité des nanocapsules chargées en 188Re aprÚs injection intratumorale par convection enhanced delivery chez la souris
Objectifs
DĂ©terminer la faisabilitĂ©, lâintĂ©rĂȘt et la toxicitĂ© hĂ©matologique de lâadministration intratumorale par convection enhanced delivery (CED) de nanocapsules chargĂ©es en 188Re (NCL-188Re).
Matériels et méthodes
LâĂ©tude de biodistribution des NCL-188Re vs perrhĂ©nate (188ReO4â) a Ă©tĂ© rĂ©alisĂ©e sur des souris nude (n = 30). Les animaux ont Ă©tĂ© sĂ©parĂ©s en 2 groupes : injection intratumorale de 188ReO4â pour le premier groupe (n = 15, 3 MBq) et de NCL-188Re pour le second groupe (n = 15, 3 MBq). Les animaux ont Ă©tĂ© sacrifiĂ©s Ă 1 h (n = 10), 24 h (n = 10) et 72 h (n = 10) aprĂšs lâinjection, les organes prĂ©levĂ©s et comptĂ©s. La toxicitĂ© hĂ©matologique des NCL-188Re a Ă©tĂ© Ă©valuĂ©e par prises de sang de 50 ΌL (sinus rĂ©tro-orbitaire) rĂ©alisĂ©es Ă j2, j7, j14 et j21 aprĂšs traitement par NaCl (n = 4), NCL-188Re (3 MBq, n = 4), NCL-188Re (6 MBq, n = 4) et NCL-188Re (12 MBq, n = 4).
RĂ©sultats
La vectorisation par NCL a permis de limiter lâĂ©limination urinaire du 188Re puisque dĂšs 24 h post-IV 0,1 ± 0,1 % de la dose injectĂ©e (%D.I.) vs 81,9 ± 7,5 % D.I. sont retrouvĂ©s dans les urines pour les formes NCL188Re-SSS et 188ReO4-, respectivement, (p = 0,016). Celle-ci permet Ă©galement de retrouver une activitĂ© significativement supĂ©rieure dans la tumeur Ă tous les temps de lâĂ©tude. Lâadministration unique de NCL-188Re a induit une toxicitĂ© modĂ©rĂ©e pour les activitĂ©s injectĂ©es les plus Ă©levĂ©es (12 MBq) se manifestant principalement par une thrombopĂ©nie transitoire de nadir j14âj18. Il nâa pas Ă©tĂ© observĂ© de toxicitĂ© au niveau des autres lignĂ©es cellulaires pour les activitĂ©s administrĂ©es de 3 et 6 MBq.
Conclusions
Les rĂ©sultats obtenus montrent la faisabilitĂ© de lâinjection intratumorale par CED et lâintĂ©rĂȘt de la vectorisation du 188Re par les NCL. Les premiers signes de toxicitĂ© hĂ©matologiques sont en faveur du fractionnement des doses administrĂ©es et dâun meilleur ciblage par fonctionnalisation des NCL aux oestrogĂšnes pour permettre une meilleure rĂ©tention tumorale
16α-[18F]-fluoro-17Ă-oestradiol ([18F]FES): A biomarker for imaging oestrogen receptor expression with positron emission tomography (PET)
Oestrogens play a major role in the development of gynaecological oestrogen-dependent diseases that overexpress oestrogen receptors (ER+). The ER status is assessed using immunohistochemistry analysis of tissues samples. It is believed that a non-invasive method such as positron emission tomography (PET) that would accurately evaluate and quantify in vivo the presence of ER could play an important role in managing such diseases. PET using fluorinated oestrogen analogues may be helpful in selecting patients who will benefit from endocrine therapy or could be used to identify high-grade cancer with poorer prognosis. Among more than 20 fluorinated oestrogens analogues that have been proposed as PET tracer candidates, 16a-[18F]fluoro-17b-oestradiol ([18F]FES) has been the most actively investigated in preclinical and clinical studies
Lipid Nanocapsules Loaded with Rhenium-188 Reduce Tumor Progression in a Rat Hepatocellular Carcinoma Model
International audienceBACKGROUND: Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC(188)Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model. METHODOLOGY/PRINCIPAL FINDINGS: Animals were treated with an injection of LNC(188)Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, nâ=â12; 120 MBq, nâ=â11) were compared with sham (nâ=â12), blank LNC (nâ=â7) and (188)Re-perrhenate (nâ=â4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC(188)Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC(188)Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. CONCLUSIONS/SIGNIFICANCE: Overall, these results demonstrate that internal radiation with LNC(188)Re-SSS is a promising new strategy for hepatocellular carcinoma treatment
Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity
<p>Abstract</p> <p>Background</p> <p>PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor<sup>Âź </sup>EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.</p> <p>Methods</p> <p>In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.</p> <p>Results</p> <p>NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.</p> <p>Conclusion</p> <p>These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.</p
Escalade de dose et efficacité des nanocapsules chargées en 188Re dans un modÚle d'adénocarcinome de l'endomÚtre chez la souris
Objectifs
Ăvaluation de lâefficacitĂ© de lâadministration intratumorale par convection enhanced delivery (CED) de nanocapsules chargĂ©es en 188Re (NCL-188Re) sur un modĂšle hĂ©tĂ©rotopique dâadĂ©nocarcinome de lâendomĂštre (Ishikawa) selon un schĂ©ma dâescalade de dose.
Matériels et méthodes
Les souris (n = 40) ont Ă©tĂ© traitĂ©es lorsque le grand axe tumoral a atteint 8 mm. Les animaux ont Ă©tĂ© sĂ©parĂ©s en 2 groupes tĂ©moins : injection intratumorale par CED de NaCl (groupe 1 ; n = 8) et de NCL blanches (groupe 2 ; n = 8), et 3 groupes traitĂ©s par injection intratumorale en CED de NCL-188Re (groupe 3 ; 3 MBq ; n = 8/groupe 4 ; 6 MBq ; n = 8 et groupe 5 ; 12 MBq ; n = 8). La rĂ©ponse thĂ©rapeutique a Ă©tĂ© Ă©valuĂ©e en mesurant cliniquement et par ÎŒIRM (BioSpec 70/20 USR 7 Tesla Bruker) lâĂ©volution du volume tumoral (VT). Le point limite choisi a Ă©tĂ© le doublement du VT ou un VT > 2150 ΌL.
RĂ©sultats
La radiothĂ©rapie vectorisĂ©e par NCL-188Re a significativement augmentĂ© la mĂ©diane de survie des animaux traitĂ©s des groupes 3, 4 et 5, de 290 %, 290 % et 570 %, respectivement, par rapport au groupe 1 (p = 0,021 ; p = 0,031 ; p < 0,001, respectivement). Le VT moyen du groupe 5 a Ă©tĂ© significativement rĂ©duit par rapport au groupe 1 de j16 (159,6 ± 134,1 ΌL vs 449,7 ± 169,9 ΌL ; p = 0,014) Ă j33 (158,3 ± 197,2 ΌL vs 803,9 ± 499,4 ΌL ; p = 0,006). Pour le groupe 4 seule la valeur Ă j16 a Ă©tĂ© significative (185,1 ± 149,8 ΌL vs 449,7 ± 169,9 ΌL ; p = 0,026). De plus, nous avons observĂ© une diffĂ©rence significative entre le groupe 5 et le groupe 3 de j23 (97,9 ± 115,3 ΌL vs 568,5 ± 641,9 ΌL ; p = 0,049) Ă j33 (158,3 ± 197,2 ΌL vs 636,2 ± 618,8 ΌL ; p = 0,041).
Conclusions
Lâinjection intratumorale unique par CED de NCL-188Re sur modĂšle hĂ©tĂ©rotopique murin de cancer de lâendomĂštre hormono-dĂ©pendant a permis dâobtenir un rĂ©gression tumorale spectaculaire pour les animaux traitĂ©s avec une activitĂ© de 12 MBq. Ces bons rĂ©sultats seront Ă confirmer lors dâĂ©tudes dosimĂ©triques et de fractionnement de dose
Correlation between baseline 18F-FDG PET/CT features and pathological complete response after neoadjuvant chemotherapy in early triple negative breast cancer
International audienceAim of the studyTo evaluate correlation between metabolic and textural parameters on baseline 18F-FDG PET/CT and pathological response after neoadjuvant chemotherapy in non-metastatic triple negative breast cancer (TNBC).MethodsAll consecutive non-metastatic TNBC women treated by neoadjuvant chemotherapy followed by breast surgery who underwent 18F-FDG PET/CT examination at diagnosis between 2012 and 2018 were retrospectively included. Metabolic parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) of the primary tumour and lymph nodes, and textural features (entropy, homogeneity, SRE, LRE, LGZE, HGZE) of the primary tumour were collected. Pathological response was defined according to Sataloff classification.ResultsSeventy-four patients were enrolled. In univariate analysis, metabolic and textural features of the primary breast lesion or metabolic parameters of regional lymph nodes were not predictive of pathological complete response after neoadjuvant chemotherapy.ConclusionMetabolic and textural features of baseline PET/CT do not seem to predict pathological response after neoadjuvant chemotherapy in non-metastatic triple negative breast cancer