| Added by | JPPOUGET |
|---|---|
| Group name | EquipeJPP |
| Item Type | Journal Article |
| Title | Preclinical Pharmacokinetics and Dosimetry of an 89Zr Labelled Anti-PDL1 in an Orthotopic Lung Cancer Murine Model |
| Creator | Krache et al. |
| Author | Anis Krache |
| Author | Charlotte Fontan |
| Author | Carine Pestourie |
| Author | Manuel Bardiès |
| Author | Yann Bouvet |
| Author | Pierre Payoux |
| Author | Etienne Chatelut |
| Author | Melanie White-Koning |
| Author | Anne-Sophie Salabert |
| Abstract | Anti-PDL1 is a monoclonal antibody targeting the programmed death-cell ligand (PD-L1) by blocking the programmed death-cell (PD-1)/PD-L1 axis. It restores the immune system response in several tumours, such as non-small cell lung cancer (NSCLC). Anti-PDL1 or anti-PD1 treatments rely on PD-L1 tumoural expression assessed by immunohistochemistry on biopsy tissue. However, depending on the biopsy extraction site, PD-L1 expression can vary greatly. Non-invasive imaging enables whole-body mapping of PD-L1 sites and could improve the assessment of tumoural PD-L1 expression. METHODS: Pharmacokinetics (PK), biodistribution and dosimetry of a murine anti-PDL1 radiolabelled with zirconium-89, were evaluated in both healthy mice and immunocompetent mice with lung cancer. Preclinical PET (?PET) imaging was used to analyse [89Zr]DFO-Anti-PDL1 distribution in both groups of mice. Non-compartmental (NCA) and compartmental (CA) PK analyses were performed in order to describe PK parameters and assess area under the concentration-time curve (AUC) for dosimetry evaluation in humans. RESULTS: Organ distribution was correctly estimated using PK modelling in both healthy mice and mice with lung cancer. Tumoural uptake occurred within 24 h post-injection of [89Zr]DFO-Anti-PDL1, and the best imaging time was at 48 h according to the signal-to-noise ratio (SNR) and image quality. An in vivo blocking study confirmed that [89Zr]DFO-anti-PDL1 specifically targeted PD-L1 in CMT167 lung tumours in mice. AUC in organs was estimated using a 1-compartment PK model and extrapolated to human (using allometric scaling) in order to estimate the radiation exposure in human. Human-estimated effective dose was 131 ?Sv/MBq. CONCLUSION: The predicted dosimetry was similar or lower than other antibodies radiolabelled with zirconium-89 for immunoPET imaging. |
| Publication | Frontiers in Medicine |
| Volume | 8 |
| Pages | 741855 |
| Date | 2021 |
| Journal Abbr | Front Med (Lausanne) |
| Language | eng |
| DOI | 10.3389/fmed.2021.741855 |
| ISSN | 2296-858X |
| Library Catalog | PubMed |
| Extra | PMID: 35174180 PMCID: PMC8841431 |
| Tags | anti-PDL1, original, PET, pharmacokinetics, preclinical, scienitific, zirconium-89 |
| Date Added | 2024/12/07 - 07:32:10 |
| Date Modified | 2024/12/15 - 11:29:05 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
