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Theranostics 2023; 13(15):5584-5596. doi:10.7150/thno.87168 This issue Cite

Research Paper

Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction

Céline Chevaleyre1, Anthony Novell1, Nicolas Tournier1, Ambre Dauba1, Steven Dubois2, Dimitri Kereselidze1, Erwan Selingue3, Benoit Jego1, Bernard Maillère2, Benoit Larrat3, Hervé Nozach2, Charles Truillet1,✉

1. Paris-Saclay University, CEA, CNRS, Inserm, BioMaps, Service Hospitalier Frédéric Joliot, Orsay France.
2. Paris-Saclay University, CEA, INRAE, Medicines and Healthcare Technologies Department, SIMoS, Gif-sur-Yvette, France.
3. Paris-Saclay University, CEA, CNRS, NeuroSpin/BAOBAB, Centre d'études de Saclay, Bâtiment 145, 91191 Gif sur Yvette, France.

✉ Corresponding author: Charles Truillet, charles.truilletfr.

Citation:
Chevaleyre C, Novell A, Tournier N, Dauba A, Dubois S, Kereselidze D, Selingue E, Jego B, Maillère B, Larrat B, Nozach H, Truillet C. Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction. Theranostics 2023; 13(15):5584-5596. doi:10.7150/thno.87168. https://www.thno.org/v13p5584.htm
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Abstract

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Rationale: The passage of antibodies through the blood-brain barrier (BBB) and the blood-tumoral barrier (BTB) is determinant not only to increase the immune checkpoint inhibitors efficacy but also to monitor prognostic and predictive biomarkers such as the programmed death ligand 1 (PD-L1) via immunoPET. Although the involvement of neonatal Fc receptor (FcRn) in antibody distribution has been demonstrated, its function at the BBB remains controversial, while it is unknown at the BTB. In this context, we assessed FcRn's role by pharmacokinetic immunoPET imaging combined with focused ultrasounds (FUS) using unmodified and FcRn low-affinity IgGs targeting PD-L1 in a preclinical orthotopic glioblastoma model.

Methods: Transcranial FUS were applied over the whole brain in mice shortly before injecting the anti-PD-L1 IgG 89Zr-DFO-C4 or its FcRn low-affinity mutant 89Zr-DFO-C4Fc-MUT in a syngeneic glioblastoma murine model (GL261-GFP). Brain uptake was measured from PET scans acquired up to 7 days post-injection. Kinetic modeling was performed to compare the brain kinetics of both C4 formats.

Results: FUS efficiently enhanced the delivery of both C4 radioligands in the brain with high reproducibility. 89Zr-DFO-C4Fc-MUT mean concentrations in the brain reached a significant uptake of 3.75±0.41%ID/cc with FUS against 1.92±0.45%ID/cc without, at 1h post-injection. A substantial and similar entry of both C4 radioligands was observed at a rate of 0.163±0.071 mL/h/g of tissue during 10.4±4.6min. The impaired interaction with FcRn of 89Zr-DFO-C4Fc-MUT significantly decreased the efflux constant from the healthy brain tissue to plasma compared with non-mutated IgG. Abolishing FcRn interaction allows determining the target engagement related to the specific binding as soon as 12h post-injection.

Conclusion: Abolishing Fc-FcRn interaction confers improved kinetic properties to 89Zr-DFO-C4Fc-MUT for immunoPET imaging. FUS-aided BBB/BTB disruption enables quantitative imaging of PD-L1 expression by glioblastoma tumors within the brain.

Keywords: ImmunoPET, therapeutic ultrasound, Fc receptor, neonatal, PD-L1, Immune Checkpoint Inhibitors, Glioblastoma

Citation styles

APA
Chevaleyre, C., Novell, A., Tournier, N., Dauba, A., Dubois, S., Kereselidze, D., Selingue, E., Jego, B., Maillère, B., Larrat, B., Nozach, H., Truillet, C. (2023). Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction. Theranostics, 13(15), 5584-5596. https://doi.org/10.7150/thno.87168.

ACS
Chevaleyre, C.; Novell, A.; Tournier, N.; Dauba, A.; Dubois, S.; Kereselidze, D.; Selingue, E.; Jego, B.; Maillère, B.; Larrat, B.; Nozach, H.; Truillet, C. Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction. Theranostics 2023, 13 (15), 5584-5596. DOI: 10.7150/thno.87168.

NLM
Chevaleyre C, Novell A, Tournier N, Dauba A, Dubois S, Kereselidze D, Selingue E, Jego B, Maillère B, Larrat B, Nozach H, Truillet C. Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction. Theranostics 2023; 13(15):5584-5596. doi:10.7150/thno.87168. https://www.thno.org/v13p5584.htm

CSE
Chevaleyre C, Novell A, Tournier N, Dauba A, Dubois S, Kereselidze D, Selingue E, Jego B, Maillère B, Larrat B, Nozach H, Truillet C. 2023. Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction. Theranostics. 13(15):5584-5596.

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