Pharmacokinetic modelling of radiolabelled antibodies to understand resistance mechanisms in immunotherapy.

Dr Mélanie White-Koning

Using Position Emission Tomography (PET) imaging, we want to study the evolution of PDL1 (Programmed Death ligand-1) and TIM3 (T-cell immunoglobulin and mucin containing protein-3) during immunotherapy treatment by labelling an anti-PDL1 antibody with zirconium 89 (89Zr).  The study of in vivo pharmacokinetics in murine models of non-small cell lung cancer will make it possible to determine the distribution, metabolisation and elimination of radiotracers after intravenous injection as well as their tumour distribution (sensitivity, specificity). For this purpose, blood and organ samples will be taken to model the distribution of the radiotracer and validate its application in vivo. The treatments used in this study will be immune checkpoint inhibitors such as nivolumab or pembrolizumab according to the current administration schemes in humans.  Once validated, these radiotracers will be used to visualise the evolution of biomarkers during the course of the disease and to characterise patients potentially responsive to immune checkpoint inhibitors. This will allow a better understanding of the resistance mechanisms to these treatments and the role of the tumour microenvironment.

Financing :

• CIFRE (Zionexa-GE)
• FEDER (Europe –Région)

Collaboration

• TONIC (Inserm UMR 1214),
• ex-Zionexa (now GE),
• projet PiR²

 Illustration :

Imagerie préclinique de [89Zr]DFO-anti-PDL1 dans des souris saines (A) et des souris avec tumeur pulmonaire (B) / Preclinical imaging of [89Zr]DFO-anti-PDL1 in healthy (A) and lung cancer grafted mice (B).

partnership