Immuno-PET Imaging for Cancer Therapy Monitoring

Immuno‐PET imaging harnesses the specificity of immune‐targeting agents with the sensitivity of positron emission tomography to visualise and quantify immune cell behaviour within tumours. By labelling antibodies, antibody fragments or small peptides with positron‐emitting isotopes, this approach enables non‐invasive mapping of key immune populations—such as CD8+ T cells, tumour-associated macrophages and activated effector cells—in real time. Monitoring changes in tracer uptake offers an early indication of therapeutic efficacy, long before alterations in tumour size become apparent. This technology addresses unmet needs in precision oncology by revealing heterogeneity of immune infiltration across lesions, guiding patient selection for immune checkpoint inhibitors and informing adaptive treatment strategies. Recent advances have improved tracer design for enhanced pharmacokinetics and reduced off-target binding, while clinical translation is now demonstrating safety, reproducibility and prognostic value. As immunotherapies evolve, immuno-PET stands poised to become an indispensable tool for therapy monitoring, biomarker discovery and personalised treatment planning.

Research from Nature Portfolio

In a first-in-human trial, a zirconium-89-labelled, CD8-specific one-armed antibody tracer was administered to patients before and during immune checkpoint therapy. Imaging revealed heterogeneous and patient‐specific distribution of CD8+ T cells in lymphoid organs and metastatic lesions. Higher tumour uptake correlated with mismatch repair deficiency and improved survival, while distinct changes at the lesion level highlighted variable pharmacodynamics. Re-imaging indicated stable average uptake but underlined the diverse dynamics of T cell infiltration across individual tumours, underscoring the potential of this immuno-PET tracer to inform therapeutic decision-making and prognostication.

Immuno-PET Imaging for Cancer Therapy Monitoring publication trend

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

Technical terms

Immuno-PET imaging: A molecular imaging technique combining immune-specific binding agents with positron emission tomography to visualise immune cells in vivo.

Radiotracer: A molecule labelled with a positron-emitting isotope that binds selectively to a biological target for PET detection.

Tumour-infiltrating lymphocytes (TILs): Immune cells, primarily T cells, that have migrated into the tumour microenvironment and mediate anti-tumour immunity.

Standardised Uptake Value (SUV): A semi-quantitative PET metric that normalises tissue tracer concentration to injected dose and patient body weight.

Nanobody: A small single-domain antibody fragment derived from camelids, offering rapid tissue penetration, high specificity and fast blood clearance.

Granzyme B: A serine protease released by activated cytotoxic T cells and natural killer cells that induces apoptosis in target cells, serving as a functional biomarker of immune activation.

References

1. Immuno-PET imaging of tumor-infiltrating lymphocytes using zirconium-89 radiolabeled anti-CD3 antibody in immune-competent mice bearing syngeneic tumors. PLOS ONE (2018).
2. ImmunoPET imaging of human CD8+ T cells with novel 68Ga-labeled nanobody companion diagnostic agents. Journal of Nanobiotechnology (2021).
3. In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET. ACS Central Science (2021).
4. Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial. Nature Medicine (2022).