Successful realisation of nanomedicines in clinical application is limited and can be considerably attributed to the biological heterogeneity between animals used in preclinical testing, and the patients assessed in clinical trials.  In the modern era of a search for personalised treatment nanomedicines provide the perfect architecture to build an individualised treatment plan, but translation of these new constructs requires a robust and flexible treatment methodology that can be validated not only in mice but in animal models more similar to humans. In this project we demonstrated the application of comparative oncology towards the diagnosis and treatment of canine patients with spontaneously occurring cancers with targeted nanomedicines. Each of these canine patients provides an opportunity to give new cutting edge treatments to companion animals, while also developing personalised medicines for canines and humans.

The first canine patient was diagnosed with prostate cancer and the standard clinical tracer targeted towards prostate-specific membrane antigen (PSMA) 68Ga-PSMA was used to confirm this diagnosis using PET-CT.  A nanomedicine prepared for the same target was also injected at a later time.  Neither the 68Ga-PSMA or nanomedicine were able to positively identify the tumour, and after biopsy it was found that the tumour was in fact PSMA negative.  The canine was treated with a nanomedicine loaded with a chemotherapeutic and after analysis of a biopsy of the tumour tissue taken prior to treatment, a more specific target (EGFR) was found to be overexpressed in the cancer.  After imaging a second time with the nanomedicine targeted to this receptor, positive identification of the tumour was made.  MRI also revealed a change in the composition of the tumour tissue, indicating a positive effect by the therapeutic nanomedicine and further validating the application of these constructs for use in future personalised medicine approaches to cancer treatment in humans.

We aim to repeat this process to provide personalised therapies for other canine patients in the future across multiple cancer types.

This project is lead by myself, Professor Kristofer J. Thurecht and Rod Straw from the Brisbane Veterinary Specialist Centre (BVSC) and his team. The team at CAI involves radiochemists, materials chemists and radiographers. People involved in the project are listed below with their roles and affiliations (see affiliations by superscript below).

  • Rod Straw1 – Director of BVSC
  • Nicolas L. Fletcher2,3,4 – Radiochemistry
  • Craig Bell2,3,4 – Nanomaterial preparation
  • Sarah Daniel2,3 – Radioactive dose administration and PET-CT imaging
  • Nicole Atcheson2 – Radiographer
  • Aiman Al-Najjar2 – MRI Specialist
  • Christopher B. Howard2,4,5,6,7 – Bispecific antibody preparation
  • Stephen M. Mahler4,7 – Bispecific antibody preparation
  • Kristofer J. Thurecht2,4,5,6 – Project design and direction

Affiliations

  1. Brisbane Veterinary Specialist Centre, Albany Creek, QLD 4035, Australia
  2. Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia.
  3. Department of Nuclear Medicine and Specialised PET Services, Royal Brisbane and Women’s Hospital
  4. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
  5. ARC Centre of Excellence in Convergent BioNano Science and Technology, The University of Queensland, St Lucia, QLD 4072, Australia
  6. ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St Lucia, QLD 4072, Australia
  7. ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St Lucia, QLD 4072, Australia

Media

Publications & Presentations

Applied comparative oncology of nanomedicines to diagnose and treat canine prostate cancer

Abstract Reviewed Presentations
Zachary H. Houston, Nicholas L. Fletcher, Craig Bell, Sarah Daniel, Nicole Atcheson, Aiman Al-Najar, Christopher B. Howard, Stephen M. Mahler, Rod Straw, Kristofer J. Thurecht
Publication year: 2019