ImmunoPET imaging–based pharmacokinetic profiles of an antibody and its Fab targeting endothelin A receptors on glioblastoma stem cells in a preclinical orthotopic model - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Nuclear Medicine and Molecular Imaging Année : 2023

ImmunoPET imaging–based pharmacokinetic profiles of an antibody and its Fab targeting endothelin A receptors on glioblastoma stem cells in a preclinical orthotopic model

Jean Philippe Hugnot

Résumé

Background: The resistance of glioblastoma stem cells (GSCs) to treatment is one of the causes of glioblastoma (GBM) recurrence. Endothelin A receptor (ETA) overexpression in GSCs constitutes an attractive biomarker for targeting this cell subpopulation, as illustrated by several clinical trials evaluating the therapeutic efficacy of endothelin receptor antagonists against GBM. In this context, we have designed an immunoPET radioligand combining the chimeric antibody targeting ETA, chimeric-Rendomab A63 (xiRA63), with 89Zr isotope and evaluated the abilities of xiRA63 and its Fab (ThioFab-xiRA63) to detect ETA+ tumors in a mouse model xenografted orthotopically with patient-derived Gli7 GSCs. Results: Radioligands were intravenously injected and imaged over time by µPET-CT imaging. Tissue biodistribution and pharmacokinetic parameters were analyzed, highlighting the ability of [89Zr]Zr-xiRA63 to pass across the brain tumor barrier and achieve better tumor uptake than [89Zr]Zr-ThioFab-xiRA63. Conclusions: This study shows the high potential of [89Zr]Zr-xiRA63 in specifically targeting ETA+ tumors, thus raising the possibility of detecting and treating ETA+ GSCs, which could improve the management of GBM patients.

Dates et versions

hal-04122041 , version 1 (08-06-2023)

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Marie Hautiere, Delphine Vivier, Donovan Pineau, Caroline Denis, Dimitri Kereselidze, et al.. ImmunoPET imaging–based pharmacokinetic profiles of an antibody and its Fab targeting endothelin A receptors on glioblastoma stem cells in a preclinical orthotopic model. European Journal of Nuclear Medicine and Molecular Imaging, 2023, 50 (11), pp.3192-3201. ⟨10.1007/s00259-023-06268-3⟩. ⟨hal-04122041⟩
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