Friday, 16 August 2024 11:00am – 12:00pm

This seminar will be delivered in Lecture Theatre 3

Speaker: Professor Paul Donnelly

Host: Prof. Tony Masters

Title: Theranostics with Metallic Radionuclides: Targeting Metalloenzymes and Receptors Over-expressed in Cancer

Abstract: The use of the same molecule for both diagnosis and therapy is called ‘theranostics’. One approach to theranostics is to use one radionuclide for diagnostic imaging and another radionuclide to deliver therapeutic radiation. Selectivity for cancer tissue is possible by incorporating metallic radionuclides into chelates that are attached to molecules that selectively bind to enzymes or receptors that are over-expressed in tumours.

Copper-64 is a positron emitting radionuclide that can be used for diagnostic positron imaging tomography (PET) imaging whilst beta emitting copper-67 can be used for targeted radiotherapy. Our work into designing copper complexes that target prostate specific membrane antigen (PSMA), a zinc enzyme that is overexpressed in prostate cancer, will be presented. The design and synthesis of bivalent sarcophagine ligands that bind to PSMA and form very stable complexes with copper-64 and copper-67 will be presented. The pre-clinical evaluation in animal models and first-in-human studies will also be presented.

The monoclonal antibody girentuximab binds to carbonic anhydrase IX, a zinc enzyme that is overexpressed on the surface of several cancers. We have radiolabelled girentuximab with positron emitting zirconium-89 for diagnostic PET imaging as well as alpha particle emitting actinium-225 for alpha-particle targeted therapy. The synthetic chemistry as well as pre-clinical evaluation in tumour models will be presented.

Figure 1. a) Radiolabelled antibodies can be used for imaging and therapy. b) PET imaging with a ⁸⁹Zr-DFOSq-girentuximab in CAIX positive mouse model.

Bio: Professor Paul Donnelly is a graduate of the University of Western Australia where his PhD was supervised by A/Prof Jack Harrowfield. He then pursued a Postdoctoral Fellowship and Junior Research Fellowship at the University of Oxford under the supervision of Prof Jonathan Dilworth. Paul returned to Australia supported by an Australian Research Council Australian Postdoctoral Fellowship and was then appointed as a Lecturer at the University of Melbourne. He has also been awarded an Australian Research Council Future Fellowship (2013-2017) and was promoted to Professor in 2018.

His research interests lie in fundamental inorganic chemistry and its application to medicine and biology. He has a particular interest in the design and synthesis of new metal-based imaging and therapeutic agents. Paul has co-authored over 200 research publications and is listed as inventor on over 18 patents, many of which have been licensed to companies. His research into metal-based compounds for imaging and therapy has stimulated several clinical trials that span cancer targeting copper and zirconium radiopharmaceuticals to potential therapeutics for Motor Neuron Disease, and Parkinson’s disease. He has supervised 15 PhD students and 29 Hons/MSc students.

Donnelly is the founding scientist of two start-up companies, Clarity Pharmaceuticals and Procypra Therapeutics (sold Collaborative to Medicinal Development). Both companies aim to translate basic research to the clinic. Professor Donnelly has received several awards in recognition of his research including: the Burrows Award, the Rennie Medal, the Biota Award for Medicinal Chemistry and the Alan Sargeson Lectureship all from the Royal Australian Chemical Institute – as well as the David Syme Prize (best original research work in biology, physics, chemistry or geology in Australia), Grimwade Prize for Industrial Chemistry and the Dean’s Award for Research Excellence.