Ce projet a eu pour objectif d’étudier la biodistribution in vivo de nanoparticules liposomales c... more Ce projet a eu pour objectif d’étudier la biodistribution in vivo de nanoparticules liposomales ciblant CD44, et en particulier d’évaluer l’effet de l’agent de ciblage (aptamère anti-CD44 greffé en surface des liposomes) sur leur accumulation tumorale. Des liposomes anti-CD44 fluorescents et radiomarqués pour l’imagerie en Tomographie par Emission de Positons ont été conçus. La méthode que nous avons développée a l’avantage d’être applicable à tout type de nanoparticule liposomale, quel que soit l’agent de ciblage. Les résultats de biodistribution obtenus chez des souris porteuses de xénogreffes de cancer du sein surexprimant CD44 ont montré que les liposomes ciblant CD44 ont une accumulation tumorale supérieure à celle des liposomes sans antigène cible, et que cette différence est liée à l’interaction spécifique Aptamère-CD44. Ceci confirme l’intérêt des liposomes fonctionnalisés avec l’aptamère anti-CD44 à visée thérapeutique (après chargement en drogues) dans les types tumoraux surexprimant CD44. Enfin les nanoparticules que nous avons développées constituent de bons agents d’ « imagerie compagnon », permettant de vérifier en imagerie isotopique l’accumulation tumorale de leurs équivalents thérapeutiques avant administration chez les patients.This project aimed to study the in vivo biodistribution of liposomal nanoparticles targeting CD44, and particularly to evaluate the effect of the targeting agent (anti-CD44 aptamer grafted on the surface of liposomes) on their tumor accumulation. Fluorescent and radiolabeled anti-CD44 liposomes for Positron Emission Tomography imaging were designed. The method we developed has the advantage of being applicable to any type of liposomal nanoparticle, regardless of the targeting agent. The biodistribution results obtained in mice bearing CD44 overexpressing breast cancer xenografts showed that CD44-targeting liposomes had greater tumor accumulation than liposomes without a target antigen, and that this difference was related to the specific Aptamer-CD44 interaction. This confirms the interest of liposomes functionalized with the anti-CD44 aptamer as therapeutic agents (after loading in drugs) in tumor types overexpressing CD44. Finally, the nanoparticles that we have developed are good "companion imaging" agents, making it possible to verify by isotopic imaging the tumor accumulation of the therapeutic counterparts before their administration in patients
American journal of nuclear medicine and molecular imaging, 2018
Bioluminescence imaging (BLI) is widely used for in-vivo monitoring of anti-cancer therapy in mic... more Bioluminescence imaging (BLI) is widely used for in-vivo monitoring of anti-cancer therapy in mice. [18F]MEL050 is a Positron Emission Tomography (PET) radiotracer which specifically targets melanin. We evaluated planar BLI and [18F]MEL050-PET/CT for therapy (pro-apoptotic peptide LZDP) monitoring in a mouse model of metastatic pigmented melanoma. Twelve B6-albino mice were intravenously injected with B16-F10-luc2 cells on day 0 (D0). The mice received daily from D2 to D17 either an inactive peptide (G1, n=6), or LZDP (G2, n=6). They underwent both BLI and [18F]MEL050-PET/CT imaging on D2, D8 and D17. The number of visible tumors was determined on BLI and PET/CT. [18F]MEL050 uptake in tumor sites was quantified on PET/CT. After sacrifice (D17), the number of black tumors was counted ex-vivo. On D2, BLI and PET/CT images were visually negative. On D8, BLI detected 8 tumor sites in 4/6 mice of G1 vs 5 in 3/6 mice of G2 (NS); PET/CT was visually negative. On D17, BLI detected 17 tumor ...
Ce projet a eu pour objectif d’étudier la biodistribution in vivo de nanoparticules liposomales c... more Ce projet a eu pour objectif d’étudier la biodistribution in vivo de nanoparticules liposomales ciblant CD44, et en particulier d’évaluer l’effet de l’agent de ciblage (aptamère anti-CD44 greffé en surface des liposomes) sur leur accumulation tumorale. Des liposomes anti-CD44 fluorescents et radiomarqués pour l’imagerie en Tomographie par Emission de Positons ont été conçus. La méthode que nous avons développée a l’avantage d’être applicable à tout type de nanoparticule liposomale, quel que soit l’agent de ciblage. Les résultats de biodistribution obtenus chez des souris porteuses de xénogreffes de cancer du sein surexprimant CD44 ont montré que les liposomes ciblant CD44 ont une accumulation tumorale supérieure à celle des liposomes sans antigène cible, et que cette différence est liée à l’interaction spécifique Aptamère-CD44. Ceci confirme l’intérêt des liposomes fonctionnalisés avec l’aptamère anti-CD44 à visée thérapeutique (après chargement en drogues) dans les types tumoraux surexprimant CD44. Enfin les nanoparticules que nous avons développées constituent de bons agents d’ « imagerie compagnon », permettant de vérifier en imagerie isotopique l’accumulation tumorale de leurs équivalents thérapeutiques avant administration chez les patients.This project aimed to study the in vivo biodistribution of liposomal nanoparticles targeting CD44, and particularly to evaluate the effect of the targeting agent (anti-CD44 aptamer grafted on the surface of liposomes) on their tumor accumulation. Fluorescent and radiolabeled anti-CD44 liposomes for Positron Emission Tomography imaging were designed. The method we developed has the advantage of being applicable to any type of liposomal nanoparticle, regardless of the targeting agent. The biodistribution results obtained in mice bearing CD44 overexpressing breast cancer xenografts showed that CD44-targeting liposomes had greater tumor accumulation than liposomes without a target antigen, and that this difference was related to the specific Aptamer-CD44 interaction. This confirms the interest of liposomes functionalized with the anti-CD44 aptamer as therapeutic agents (after loading in drugs) in tumor types overexpressing CD44. Finally, the nanoparticles that we have developed are good "companion imaging" agents, making it possible to verify by isotopic imaging the tumor accumulation of the therapeutic counterparts before their administration in patients
American journal of nuclear medicine and molecular imaging, 2018
Bioluminescence imaging (BLI) is widely used for in-vivo monitoring of anti-cancer therapy in mic... more Bioluminescence imaging (BLI) is widely used for in-vivo monitoring of anti-cancer therapy in mice. [18F]MEL050 is a Positron Emission Tomography (PET) radiotracer which specifically targets melanin. We evaluated planar BLI and [18F]MEL050-PET/CT for therapy (pro-apoptotic peptide LZDP) monitoring in a mouse model of metastatic pigmented melanoma. Twelve B6-albino mice were intravenously injected with B16-F10-luc2 cells on day 0 (D0). The mice received daily from D2 to D17 either an inactive peptide (G1, n=6), or LZDP (G2, n=6). They underwent both BLI and [18F]MEL050-PET/CT imaging on D2, D8 and D17. The number of visible tumors was determined on BLI and PET/CT. [18F]MEL050 uptake in tumor sites was quantified on PET/CT. After sacrifice (D17), the number of black tumors was counted ex-vivo. On D2, BLI and PET/CT images were visually negative. On D8, BLI detected 8 tumor sites in 4/6 mice of G1 vs 5 in 3/6 mice of G2 (NS); PET/CT was visually negative. On D17, BLI detected 17 tumor ...
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Papers by Florent Antoni