Detection of Immune-Mediated Tumour Cell Death in Vivo Using Zirconium-89-Labeled APOMAB

Research from the Center for Cancer Biology at the University of South Australia has demonstrated the potential of Zirconium-89-labeled APOMAB to detect immune-mediated tumour cell death in vivo. The study, published in the Journal of Translational Medicine, found that APOMAB-immunoPET showed increased tumour uptake of 89Zirconium-labelled APOMAB after CAR-T cell therapy, immune checkpoint inhibitor (ICI) therapy with and without chemotherapy, and via endogenous T-cell mediated tumour clearance. This breakthrough has significant implications for the early detection and monitoring of treatment responses in patients with cancer.

Key Takeaways:

• APOMAB-targeting of dead tumour cells allows for non-invasive detection of treatment responses earlier than conventional medical imaging methods allow.
• The study demonstrated specific and dose-dependent binding of APOMAB to dead target cells after immune-mediated cell death.
• APOMAB-immunoPET showed increased tumour uptake of 89Zirconium-labelled APOMAB after CAR-T cell therapy, ICI therapy with and without chemotherapy, and via endogenous T-cell mediated tumour clearance.
• The study concluded that APOMAB-immunoPET provides a direct measure of the extent of immune-mediated tumour cell death in vivo.
• The heterogeneous nature of tumour responses to T-cell based therapies was revealed for the first time using radiolabelled APOMAB.
• The study was funded by the Royal Adelaide Hospital Clinical Project Grant, Aushealth Pty Ltd, Ray And Shirl Norman Cancer Research Trust, and Health Services Charitable Gifts Board, Adelaide.
• The research was conducted by a team of researchers from the Translational Oncology Laboratory, Center for Cancer Biology, SA Pathology and University of South Australia.

Statistics:

• 89Zirconium-labelled APOMAB was used in the study, which showed increased tumour uptake after CAR-T cell therapy, ICI therapy with and without chemotherapy, and via endogenous T-cell mediated tumour clearance.
• The study found that APOMAB-immunoPET demonstrated increased tumour uptake of 89Zirconium-labelled APOMAB within days of treatment.
• The study used four distinct preclinical tumour models and a cancer patient to investigate APOMAB-immunoPET as a technique to detect immune-mediated tumour cell death.
• The study revealed a previously FDG-avid pulmonary tumour reduced in size as tumour 89Zr-APOMAB uptake increased over the 12-day scanning period.

Sources:

• Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB. Journal of Translational Medicine, 2025,23(1):1-18.
• Vasilios Liapis, Translational Oncology Laboratory, Center for Cancer Biology, SA Pathology and University of South Australia.
• Nicole L. Wittwer, William Tieu, Tessa Gargett, Michael P. Brown, Alexander H. Staudacher.