Radiolabeled F(ab′)2-cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models

Autor: Claire Bernhard, Alexandra Oudot, Bertrand Collin, Pierre-Simon Bellaye, Mathieu Moreau, D. Vandroux, A. Cochet, L. Dumont, Franck Denat, O. Raguin, J.M. Vrigneaud, F. Brunotte
Přispěvatelé: Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire de Physique Théorique des Liquides ( LPTL ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), OncoDesign, Plateforme d'imagerie préclinique [Centre Georges-François Leclerc] ( CGFL ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Gamétogenèse et Qualité des Gamètes ( GQG ), Université de Lille-Université de Lille, Droit et Santé-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Oncodesign [Dijon], NVH Medicinal (NVH), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Cancer Research
Immunoconjugates
Skin Neoplasms
Theranostic Nanomedicine
Colorectal cancer
medicine.medical_treatment
Cetuximab
030218 nuclear medicine & medical imaging
Hsp90 inhibitor
Mice
0302 clinical medicine
Tissue Distribution
ComputingMilieux_MISCELLANEOUS
Mice
Inbred BALB C
Indium Radioisotopes
General Medicine
3. Good health
Oncology
Cetuximab fragments
030220 oncology & carcinogenesis
Radioimmunotherapy
Colorectal Neoplasms
medicine.drug
Research Article
Biodistribution
EGFR
Mice
Nude
03 medical and health sciences
Immunoglobulin Fab Fragments
In vivo
Spect imaging
[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology
medicine
HSP90
Animals
Humans
neoplasms
Tomography
Emission-Computed
Single-Photon
business.industry
medicine.disease
Xenograft Model Antitumor Assays
digestive system diseases
Radioimmunodetection
Cancer research
Radiopharmaceuticals
business
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Clinical and Translational Oncology
Clinical and Translational Oncology, 2018, 〈10.1007/s12094-018-1886-4〉
Clinical & Translational Oncology
Clinical and Translational Oncology, Springer, 2018, 20 (12), pp.1557-1570. ⟨10.1007/s12094-018-1886-4⟩
ISSN: 1699-048X
DOI: 10.1007/s12094-018-1886-4〉
Popis: Purpose This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111In and 177Lu, respectively. Methods We designed F(ab′)2-fragments of cetuximab radiolabeled with 111In and 177Lu. 111In-F(ab′)2-cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111In-F(ab′)2-cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177Lu-F(ab′)2-cetuximab was evaluated in SWISS nude mice bearing A431 tumors. Results Radiolabeling procedure did not change F(ab′)2-cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111In-DOTAGA-F(ab′)2-cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab′)2-cetuximab. SPECT imaging of 111In-DOTAGA-F(ab′)2-cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, 177Lu-DOTAGA-F(ab′)2-cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses. Conclusions 111In-DOTAGA-F(ab′)2-cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. 177Lu-DOTAGA-F(ab′)2-cetuximab is an interesting theranostic tool allowing therapy and imaging. Electronic supplementary material The online version of this article (10.1007/s12094-018-1886-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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