{"id":{"repo_id":"sherbrooke","oai_identifier":"oai:usherbrooke.scholaris.ca:11143/21973"},"canonical_url":"https://search.dev.ndltd.org/etd/sherbrooke/oai:usherbrooke.scholaris.ca:11143/21973","repository":{"repo_id":"sherbrooke","name":"Université de Sherbrooke","base_url":"https://usherbrooke.scholaris.ca/server/oai/request"},"display":{"title":"Développement d’une méthode d’immuno-imagerie permettant d’évaluer le statut immunitaire des tumeurs","abstract":"Tumor immunogenicity is an important indicator of treatment response, including radiotherapy (RT) and immunotherapy (IT). Immune checkpoint inhibitors have so far yielded only a 15% response rate in unselected patients with squamous cell carcinoma of the head and neck. Imaging the immune microenvironment of the tumor could help guide the selection of patients who might benefit most from IT. Additionally, identifying patients with poorly immunogenic tumors can guide the investigation of additional therapies, including RT, which can increase tumor immunogenicity and improve IT efficacy. The overall objective of this thesis is to develop an immuno-imaging method through the development and validation of a new radiotracer, 89Zr-4HMSA-anti-CD3. The method will be used to track tumor-infiltrating lymphocytes and thus assess the immunogenicity of the tumor. Our data show that the synthesis steps were efficiently carried out and that the product demonstrated stability at >95% ex vivo and in vivo. Cell assays showed that the radiotracer is well absorbed by T cells, with a percentage reaching of 38.36 ± 3.1 %IA/106 cells after 3 days. Furthermore, the competition test with non-radioactive CD3 confirmed the specific binding of 89Zr4HMSA-anti-CD3 to the CD3 marker on T lymphocytes. Additionally, in vivo studies conducted on mouse models with head and neck cancer or colon cancer showed that the developed radiotracer enabled visualization of CD3+ T lymphocyte infiltration into the tumor as observed in preliminary PET images. This result was confirmed by biodistribution data. Moreover, we noted that RT treatment was able to increase lymphocyte infiltration, especially in head and neck cancer (6.08 ± 0.34 %IA/g in the irradiated group vs. 3.05 ± 0.450 %IA/g in the non-irradiated group). Similarly, the co-injection of non-radioactive antiCD3 with the radiotracer showed that, although there was no blocking effect on tumor uptake, a decrease in the uptake of 89Zr-4HMSA-anti-CD3 in the spleen was observed, suggesting a need to review the amount of blocking CD3 used to reinforce the specificity results.","abstract_html":"Tumor immunogenicity is an important indicator of treatment response, including radiotherapy (RT) and immunotherapy (IT). Immune checkpoint inhibitors have so far yielded only a 15% response rate in unselected patients with squamous cell carcinoma of the head and neck. Imaging the immune microenvironment of the tumor could help guide the selection of patients who might benefit most from IT. Additionally, identifying patients with poorly immunogenic tumors can guide the investigation of additional therapies, including RT, which can increase tumor immunogenicity and improve IT efficacy. The overall objective of this thesis is to develop an immuno-imaging method through the development and validation of a new radiotracer, 89Zr-4HMSA-anti-CD3. The method will be used to track tumor-infiltrating lymphocytes and thus assess the immunogenicity of the tumor. Our data show that the synthesis steps were efficiently carried out and that the product demonstrated stability at >95% ex vivo and in vivo. Cell assays showed that the radiotracer is well absorbed by T cells, with a percentage reaching of 38.36 ± 3.1 %IA/106 cells after 3 days. Furthermore, the competition test with non-radioactive CD3 confirmed the specific binding of 89Zr4HMSA-anti-CD3 to the CD3 marker on T lymphocytes. Additionally, in vivo studies conducted on mouse models with head and neck cancer or colon cancer showed that the developed radiotracer enabled visualization of CD3+ T lymphocyte infiltration into the tumor as observed in preliminary PET images. This result was confirmed by biodistribution data. Moreover, we noted that RT treatment was able to increase lymphocyte infiltration, especially in head and neck cancer (6.08 ± 0.34 %IA/g in the irradiated group vs. 3.05 ± 0.450 %IA/g in the non-irradiated group). Similarly, the co-injection of non-radioactive antiCD3 with the radiotracer showed that, although there was no blocking effect on tumor uptake, a decrease in the uptake of 89Zr-4HMSA-anti-CD3 in the spleen was observed, suggesting a need to review the amount of blocking CD3 used to reinforce the specificity results.","abstract_has_math":false,"creators":["Saidi, Nour Elhouda"],"institution":"Université de Sherbrooke","degree_name":"M. Sc.","degree_level":"Maîtrise","degree_discipline":"Sciences des radiations et imagerie biomédicale","degree_department":null,"school":null,"contributors":[],"advisors":["Oweida, Ayman","Guérin, Brigitte"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024","date_published":"2024","updated_at":"2026-07-27T21:07:32Z","subjects":["Cancer","CD3","Lymphocyte T","Imagerie TEP","Immunothérapie","Radiothérapie","T lymphocyte","PET imaging","Immunotherapy","Radiotherapy"],"languages":["fr"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11143/21973","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Oweida, Ayman","Guérin, Brigitte"]},{"key":"dc:creator","label":"Author","values":["Saidi, Nour Elhouda"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-09-13T15:51:35Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-09-13T15:51:35Z"]},{"key":"dc:date.issued","label":"Date","values":["2024"]},{"key":"dc:publisher","label":"Institution","values":["Université de Sherbrooke"]},{"key":"dc:type","label":"Dc Type","values":["Mémoire de maîtrise"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Sciences des radiations et imagerie biomédicale"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Maîtrise"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M. 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Immune checkpoint inhibitors have so far yielded only a 15% response rate in unselected patients with squamous cell carcinoma of the head and neck. Imaging the immune microenvironment of the tumor could help guide the selection of patients who might benefit most from IT. Additionally, identifying patients with poorly immunogenic tumors can guide the investigation of additional therapies, including RT, which can increase tumor immunogenicity and improve IT efficacy. The overall objective of this thesis is to develop an immuno-imaging method through the development and validation of a new radiotracer, 89Zr-4HMSA-anti-CD3. The method will be used to track tumor-infiltrating lymphocytes and thus assess the immunogenicity of the tumor. Our data show that the synthesis steps were efficiently carried out and that the product demonstrated stability at >95% ex vivo and in vivo. Cell assays showed that the radiotracer is well absorbed by T cells, with a percentage reaching of 38.36 ± 3.1 %IA/106 cells after 3 days. Furthermore, the competition test with non-radioactive CD3 confirmed the specific binding of 89Zr4HMSA-anti-CD3 to the CD3 marker on T lymphocytes. Additionally, in vivo studies conducted on mouse models with head and neck cancer or colon cancer showed that the developed radiotracer enabled visualization of CD3+ T lymphocyte infiltration into the tumor as observed in preliminary PET images. This result was confirmed by biodistribution data. Moreover, we noted that RT treatment was able to increase lymphocyte infiltration, especially in head and neck cancer (6.08 ± 0.34 %IA/g in the irradiated group vs. 3.05 ± 0.450 %IA/g in the non-irradiated group). Similarly, the co-injection of non-radioactive antiCD3 with the radiotracer showed that, although there was no blocking effect on tumor uptake, a decrease in the uptake of 89Zr-4HMSA-anti-CD3 in the spleen was observed, suggesting a need to review the amount of blocking CD3 used to reinforce the specificity results.","L'immunogénicité des tumeurs est un indicateur important de la réponse au traitement, y compris la radiothérapie (RT) et l'immunothérapie (IT). Les essais cliniques de l’IT avec les inhibiteurs de point de contrôle n'ont jusqu'à présent donné qu'un taux de réponse de 15% chez les patients atteints de cancer épidermoïde de la tête et du cou non sélectionnés. L'imagerie du microenvironnement immunitaire de la tumeur pourrait aider à guider la sélection des patients pouvant bénéficier le plus de l'IT. De plus, l'identification des patients atteints de tumeurs faiblement immunogènes peut guider l'investigation de thérapies supplémentaires, y compris la RT qui peut augmenter l'immunogénicité de la tumeur et améliorer l'efficacité de l'IT. L’objectif général de ce mémoire est le développement d’une méthode d’immuno-imagerie via le développement et la validation d’un nouveau radiotraceur le 89Zr-4HMSA-anti-CD3 pour suivre les lymphocytes infiltrant la tumeur et ainsi évaluer le statut immunitaire et l’immunogénicité de la tumeur. Le développement du radiotraceur a montré que les étapes de synthèse ont été réalisées efficacement et que le produit est démontré stable >95% ex vivo et in vivo. Les essais cellulaires ont montré que le radiotraceur est bien capté par les cellules EL4 avec un pourcentage qui atteint 38,36 ± 3,1 %AI/106 cellules après 3 jours. De plus, le test de la compétition avec le CD3 non radioactif a confirmé la spécificité de la liaison du 89Zr-4HMSA-anti-CD3 au marqueur CD3 de lymphocyte T. Par ailleurs, les études in vivo réalisées sur des modèles de souris porteuses de cancer de tête et du cou ou du cancer du côlon, ont montré que le radiotraceur développé a permis de visualiser l’infiltration des lymphocytes T CD3+ dans la tumeur tel qu’observé sur les images TEP préliminaires. Ce résultat a été confirmé par les données de la biodistribution. De plus, nous avons noté que le traitement par RT était capable d’augmenter l’infiltration lymphocytaire surtout dans le cancer de tête et du cou (6,08 ± 0,34 %AI/g chez le groupe irradié vs 3,05 ± 0,450 %AI/g chez le groupe non irradié). De même, la co-injection d’anti-CD3 non radioactif avec le radiotraceur a montré que, bien qu’il n’y ait pas d’effet de blocage sur la captation tumorale, une diminution de la captation du 89Zr-4HMSA-anti-CD3 au niveau de la rate a été observé ce qui incite à revoir la quantité du CD3 bloquant utilisé pour renforcer les résultats relatifs à la spécificité."]},{"key":"dc:title","label":"Title","values":["Développement d’une méthode d’immuno-imagerie permettant d’évaluer le statut immunitaire des tumeurs"]}]}],"canonical_facts":{"dc:contributor.advisor":["Oweida, Ayman","Guérin, Brigitte"],"dc:creator":["Saidi, Nour Elhouda"],"dc:date.accessioned":["2024-09-13T15:51:35Z"],"dc:date.available":["2024-09-13T15:51:35Z"],"dc:date.issued":["2024"],"dc:description.abstract":["Tumor immunogenicity is an important indicator of treatment response, including radiotherapy (RT) and immunotherapy (IT). Immune checkpoint inhibitors have so far yielded only a 15% response rate in unselected patients with squamous cell carcinoma of the head and neck. Imaging the immune microenvironment of the tumor could help guide the selection of patients who might benefit most from IT. Additionally, identifying patients with poorly immunogenic tumors can guide the investigation of additional therapies, including RT, which can increase tumor immunogenicity and improve IT efficacy. The overall objective of this thesis is to develop an immuno-imaging method through the development and validation of a new radiotracer, 89Zr-4HMSA-anti-CD3. The method will be used to track tumor-infiltrating lymphocytes and thus assess the immunogenicity of the tumor. Our data show that the synthesis steps were efficiently carried out and that the product demonstrated stability at >95% ex vivo and in vivo. Cell assays showed that the radiotracer is well absorbed by T cells, with a percentage reaching of 38.36 ± 3.1 %IA/106 cells after 3 days. Furthermore, the competition test with non-radioactive CD3 confirmed the specific binding of 89Zr4HMSA-anti-CD3 to the CD3 marker on T lymphocytes. Additionally, in vivo studies conducted on mouse models with head and neck cancer or colon cancer showed that the developed radiotracer enabled visualization of CD3+ T lymphocyte infiltration into the tumor as observed in preliminary PET images. This result was confirmed by biodistribution data. Moreover, we noted that RT treatment was able to increase lymphocyte infiltration, especially in head and neck cancer (6.08 ± 0.34 %IA/g in the irradiated group vs. 3.05 ± 0.450 %IA/g in the non-irradiated group). Similarly, the co-injection of non-radioactive antiCD3 with the radiotracer showed that, although there was no blocking effect on tumor uptake, a decrease in the uptake of 89Zr-4HMSA-anti-CD3 in the spleen was observed, suggesting a need to review the amount of blocking CD3 used to reinforce the specificity results.","L'immunogénicité des tumeurs est un indicateur important de la réponse au traitement, y compris la radiothérapie (RT) et l'immunothérapie (IT). Les essais cliniques de l’IT avec les inhibiteurs de point de contrôle n'ont jusqu'à présent donné qu'un taux de réponse de 15% chez les patients atteints de cancer épidermoïde de la tête et du cou non sélectionnés. L'imagerie du microenvironnement immunitaire de la tumeur pourrait aider à guider la sélection des patients pouvant bénéficier le plus de l'IT. De plus, l'identification des patients atteints de tumeurs faiblement immunogènes peut guider l'investigation de thérapies supplémentaires, y compris la RT qui peut augmenter l'immunogénicité de la tumeur et améliorer l'efficacité de l'IT. L’objectif général de ce mémoire est le développement d’une méthode d’immuno-imagerie via le développement et la validation d’un nouveau radiotraceur le 89Zr-4HMSA-anti-CD3 pour suivre les lymphocytes infiltrant la tumeur et ainsi évaluer le statut immunitaire et l’immunogénicité de la tumeur. Le développement du radiotraceur a montré que les étapes de synthèse ont été réalisées efficacement et que le produit est démontré stable >95% ex vivo et in vivo. Les essais cellulaires ont montré que le radiotraceur est bien capté par les cellules EL4 avec un pourcentage qui atteint 38,36 ± 3,1 %AI/106 cellules après 3 jours. De plus, le test de la compétition avec le CD3 non radioactif a confirmé la spécificité de la liaison du 89Zr-4HMSA-anti-CD3 au marqueur CD3 de lymphocyte T. Par ailleurs, les études in vivo réalisées sur des modèles de souris porteuses de cancer de tête et du cou ou du cancer du côlon, ont montré que le radiotraceur développé a permis de visualiser l’infiltration des lymphocytes T CD3+ dans la tumeur tel qu’observé sur les images TEP préliminaires. Ce résultat a été confirmé par les données de la biodistribution. De plus, nous avons noté que le traitement par RT était capable d’augmenter l’infiltration lymphocytaire surtout dans le cancer de tête et du cou (6,08 ± 0,34 %AI/g chez le groupe irradié vs 3,05 ± 0,450 %AI/g chez le groupe non irradié). De même, la co-injection d’anti-CD3 non radioactif avec le radiotraceur a montré que, bien qu’il n’y ait pas d’effet de blocage sur la captation tumorale, une diminution de la captation du 89Zr-4HMSA-anti-CD3 au niveau de la rate a été observé ce qui incite à revoir la quantité du CD3 bloquant utilisé pour renforcer les résultats relatifs à la spécificité."],"dc:identifier.uri":["http://hdl.handle.net/11143/21973"],"dc:language.iso":["fr"],"dc:publisher":["Université de Sherbrooke"],"dc:subject":["Cancer","CD3","Lymphocyte T","Imagerie TEP","Immunothérapie","Radiothérapie","T lymphocyte","PET imaging","Immunotherapy","Radiotherapy"],"dc:title":["Développement d’une méthode d’immuno-imagerie permettant d’évaluer le statut immunitaire des tumeurs"],"dc:type":["Mémoire de maîtrise"],"thesis:degree_discipline":["Sciences des radiations et imagerie biomédicale"],"thesis:degree_level":["Maîtrise"],"thesis:degree_name":["M. Sc."],"thesis:institution_name":["Faculté de médecine et des sciences de la santé"]},"updated_at":"2026-07-27T21:07:32Z"}