Poster Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

Investigating the HER2-3 dimer as a theranostic target in brain metastases (#205)

Jodi M Saunus 1 2 , Priyakshi Kalita-de Croft 1 2 , F.T. Lee 3 , Fares Al-Ejeh 2 , Malcolm Lim 1 2 , Kathleen Ensbey 2 , Colleen Niland 1 2 , Rosalind L Jeffree 4 5 , Paul Thomas 6 7 , Bryan W Day 2 , Stephen Rose 1 6 8 , Andrew M Scott 3 9 , Sunil R Lakhani 1 4 10
  1. The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia
  2. QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  3. Olivia Newton-John Cancer Research Institute and La Trobe University, Heidelberg, Victoria, Australia
  4. University of Queensland School of Medicine, The University of Queensland, Herston, Queensland, Australia
  5. Kenneth G. Jamieson Department of Neurosurgery, The Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  6. Herston Imaging Research Facility (HIRF), Royal Brisbane & Women’s Hospital, Herston, Queensland, Australia
  7. Specialised PET Services Queensland, Metro North Hospital and Health Service, Herston, Queensland, Australia
  8. CSIRO, The Australian eHealth Research Centre, Royal Brisbane & Women’s Hospital, Herston, Queensland, Australia
  9. Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia
  10. Pathology Queensland, The Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

The development of brain metastases marks a serious downturn in the course of disease for cancer patients, marked by high morbidity and virtually 100% mortality. Brain metastases are becoming more frequent in line with population ageing and improving treatment of systemic disease, and the incidence now outweighs that of any individual malignancy. The societal burden is further increased by expensive multimodal treatments and hospitalisations. Diagnosis is normally based on magnetic resonance imaging (MRI) of symptomatic patients – that is, once tumours are sufficiently advanced to produce neurological symptoms through localised disruption of brain tissue architecture. Furthermore, obtaining diagnostic information on potential therapeutic targets is difficult, with histopathologic assessment limited to surgical candidates (patients with suitable performance status and operable disease).


We propose that clinical management could be improved by the development of theranostic approaches, providing precise and sensitive diagnostic information on the extent of disease, expression of targetable markers and ancillary parameters impacting on drug uptake (e.g. perfusion dynamics and interstitial pressure). We and others have shown that the HER2-3 dimer is overexpressed and activated in BM from multiple primary cancer types. Here, we present new data demonstrating efficacy of HER2-3 combination therapy (trastuzumab+pertuzumab) in intracranial SKBr3 and MDA-MB-361 breast cancer xenografts. On the imaging side, we have developed a pertuzumab-based PET tracer (Ptz-89Zr) with favourable in vitro stability, HER2-binding affinity, and in vivo biodistribution properties. The next phase is a pilot clinical PET-MRI study in brain metastatic HER2+ breast cancer patients using the Ptz-89Zr tracer, where we aim to delineate relationships between the administered dose, uptake and retention over time, tumour size and perfusion.


We anticipate this work will provide important information about factors affecting the uptake of monoclonal antibody-based therapies in these unique tumours, and on the feasibility of applying theranostics for brain metastasis management in the future.