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The Australian Translational Medicinal Chemistry Facility (ATMCF), Therapeutic Innovation Australia (TIA) Pipeline Accelerator 2019-20 project award:

Posted on: 26 October 2020Uncategorized

Development of radioligands as a diagnostic tool in cancer treatment

Partner – Cyclotek (Aust) Pty Ltd

The important research collaboration between Cyclotek and the ATMCF aims to develop radioligands, namely 18F PET radiotracers, as diagnostic tools that have the potential to significantly shift the current treatment paradigm of certain types of cancers. The radiopharmaceutical capability is being led by Dr Rob Ware and the Cyclotek team, while the ATMCF, through Director Professor Jonathan Baell, are driving the small molecule development aspect of this partnership.

Cancers are diseases where cells develop a number of critical mutations leading to disordered metabolism and escape from mechanisms that regulate normal bodily function. The basic mechanisms of cancer development involve a large variety of genetic mutations and, combined with the characteristic genetic instability of malignant cells, results in diversity of cancer behaviour and a varied response to treatment between individuals.

Fortunately, the disrupted cellular processes of cancers offer points of vulnerability for the tumours themselves, providing opportunities for targeted therapies. To achieve effective treatment with minimal side-effects, precise and accurate diagnosis of the abnormal metabolic and genetic characteristics of disease is required for individual patients. Thus, the inability to diagnose disease status and monitor progression remains one of the greatest challenges for treatment and for development of new drugs.

An appropriately optimised small molecule, labelled with a fluorine radioisotope, can be monitored in patients using PET and serve as a precise tool to dissect disease status. PET imaging has a unique capacity to non-invasively visualise, qualify and quantify biochemical and/or physiological function of cancers enabling guidance for selection and, monitoring of treatment progress as well as informing prognosis. When allied with related molecular entities, incorporating therapeutic radionuclides, highly tumour-specific cell death can be achieved.

Cyclotek is a compound manufacturer of Radiopharmaceuticals that was established in 2001 to provide efficient and reliable supply of quality Positron Emission Tomography (PET) radiopharmaceuticals (tracers) for the Australian and New Zealand market. Cyclotek are also a major player in the advancement of personalized medicine, with numerous collaborations across both industry and academia, enabling progression of clinical and non-clinical research.

The ATMCF is a national drug discovery capability that applies medicinal chemistry expertise to translate biomedical research towards clinical relevance. Facilitated by TIA, through funding from the National Collaborative Research Infrastructure Strategy (NCRIS), and based at The Monash Institute of Pharmaceutical Sciences (MIPS), Parkville, the ATMCF enables collaboration between researchers and industry to identify, synthesize and optimise bioactive compounds (small molecules) with a specific potency, selectivity and pharmacokinetic profile.