Immuno-PET Imaging of PD-L1 Expression in Cancer

Immuno-positron emission tomography (Immuno-PET) of programmed death ligand-1 (PD-L1) enables non-invasive, whole-body visualisation and quantification of this key immune checkpoint. By radiolabelling antibodies or antibody fragments that selectively bind PD-L1, clinicians and researchers can map spatial heterogeneity of PD-L1 expression across primary and metastatic lesions, monitor dynamic changes in response to therapy, and guide patient selection for immune checkpoint therapies. This approach overcomes limitations of tissue biopsy, which may fail to capture intra- and inter-tumour variability. Advances in tracer design—ranging from full-length monoclonal antibodies to camelid single-domain antibodies (nanobodies)—have improved pharmacokinetics, signal-to-noise ratios and optimal imaging windows. Immuno-PET has been applied in various tumour types, including non-small-cell lung cancer, melanoma and renal cell carcinoma, demonstrating correlations between tracer uptake and immunohistochemical PD-L1 scores as well as clinical outcomes. Preclinical models have further highlighted the capacity of Immuno-PET to track therapy-induced modulation of PD-L1, for instance following radiotherapy or interferon exposure. Collectively, these developments position Immuno-PET of PD-L1 as a powerful tool for personalised management of patients receiving checkpoint blockade.

Research from Nature Portfolio

Whole-body PET-CT studies in patients with non-small-cell lung cancer have established that radiolabelled PD-1 and PD-L1 tracers can quantify tumour uptake heterogeneity both between patients and across individual lesions, revealing discordance between biopsy-based PD-L1 scoring and in vivo distribution. In preclinical models, camelid single-domain antibodies specific for PD-L1 have been used to demonstrate consistent tracer uptake in brown adipose tissue independent of metabolic activation, validating a high-affinity VHH tracer and illustrating the potential to visualise immune-relevant tissues in vivo. These foundational efforts have informed subsequent clinical translation and tracer optimisation.

Immuno-PET Imaging of PD-L1 Expression in Cancer publication trend

The graph below shows the total number of articles in immuno-pet imaging of pd-l1 expression in cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Immuno-PET: PET imaging technique using radiolabelled antibodies to visualise specific molecular targets.

PD-L1: Programmed death ligand-1, an immune checkpoint protein that downregulates T-cell activity.

Radiotracer: A radioactive compound that binds selectively to a biological target for imaging.

Zirconium-89 (89Zr): A PET radioisotope with a half-life suitable for imaging slow-clearing antibodies.

Nanobody: A single-domain antibody derived from camelid heavy-chain antibodies, offering rapid tissue penetration and clearance.

References

1. Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nature Communications (2018).
2. PD-L1 is an activation-independent marker of brown adipocytes. Nature Communications (2017).
3. Quantitative PET imaging of PD-L1 expression in xenograft and syngeneic tumour models using a site-specifically labelled PD-L1 antibody. European Journal of Nuclear Medicine and Molecular Imaging (2019).
4. 89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer. Annals of Oncology (2021).
5. Anti-Human PD-L1 Nanobody for Immuno-PET Imaging: Validation of a Conjugation Strategy for Clinical Translation. Biomolecules (2020).