Applied research

• Develop new and advanced imaging techniques and equipment for application in biomedicine,
• Foster the growth of Australian expertise in biomedical imaging and build the nations capacity to serve the needs of researchers, clinicians and industry people working in the field.

Current CRC-BID projects include:

• Preparation and automation of the synthesis of 18F-Ethyl-Tyrosine (FET) for technology transfer to Cyclotek for Glioma clinical trials at Peter MacCallum Cancer Centre. The CRC-BID is investigating the use of FET by Australian hospitals.
• Preparation and automation of the synthesis of 18F-MEL050 for transfer to Cyclotek for phase 0/1 clinical trial. This trial is presently underway.
• Preparation and automation of the synthesis of 18F-FPM for transfer to Cyclotek for phase 0/1 clinical trials.
• Preparation and automation of the synthesis of 18F-Flumazenil to Cyclotek for epilepsy clinical trial. This trial is in collaboration with Royal Melbourne Hospital (provided patients) and Peter MacCallum Cancer Centre (imaging the patients).
• Preparation and automation of the synthesis of 18F-Annexin. This protein will be used as a standard that will be compared with other apoptosis (cell death) indicating radiopharmaceuticals.
• Development of therapeutic vectors for melanoma cancer.  These vectors will be studied in pre-clinical animal models at ANSTO lifesciences and Peter MacCallum Cancer Centre.
• Development of vectors for NPY (Neuro peptide Y) target. These vectors will be studied in pre-clinical animal models at Peter MacCallum Cancer Centre and the Garvan Institute.
• Development of vectors for αvβ3 (angiogenesis) target. These vectors will be studied in pre-clinical animal models at Peter MacCallum Cancer Centre. 
• Preparation and automation of the synthesis of 18F-fluoro-azomycin arabinoside to transfer this technology to Cyclotek for clinical trials at Peter MacCallum Cancer Centre and other institutions as a hypoxia marker.

These projects are decided upon by the members of the CRC-BID, which includes ANSTO Lifesciences and Peter MacCallum Cancer Centre. Cyclotek, a commercial radiopharmacy, provides input for the commercial viability of these projects.

Visit the CRC-BID website for more information.

Project Leader : Ivan Greguric

Despite many targeted studies over the last decade, little is understood about the connection between substance abuse and the onset of psychosis in adolescence.

More information about the brain mechanisms underlying the onset of drug abuse-induced psychosis could lead to the development of treatments to neutralise or reduce any psychosis causing effects of such drug abuse, and shed light on the neuronal functions whose disturbances result in disorganised thinking, attention deficits and the memory and language problems that characterise psychotic disorders such as schizophrenia.

The project uses in vitro techniques such as autoradiography and in situ hybridisation, as well as in vivo molecular imaging such as micro SPECT/PET to investigate the effects of long term substance abuse in the brain of adolescent and adult rats. Initially ANSTO will use the in vitro methodologies to identify a number of cellular elements whose expression/concentration is modified after chronic exposure to drugs of abuse, with focus on cannabinoids. In a follow-up study ANSTO will perform in vivo SPECT/PET micro imaging in order to image and follow the chronic effects of drugs on the cellular elements identified above.

Future studies will investigate the effects of cannabinoids in animal models of psychosis, such as in animals made vulnerable to develop psychotic-like behaviour during adolescence due to genetic or environmental manipulations.

Project Leader: Dr Katerina Zavitsanou

At present, there is no cure or effective long term treatment for these diseases. Most, but not all, of these diseases have an onset that is later in life. ANSTO LifeSciences focuses to provide an imaging technique that can detect the disease for testing the effect of treatments. This priority will become more important in the coming years as the older (> 60 yr) population increases in proportion to the general population.

ANSTO researchers have targeted the Peripheral Benzodiazepine Receptor (PBR). The PBR was targeted to take advantage of the fact that there are few PBRs in a normal brain. The PBR are concentrated mainly in the peripheral tissue (e.g. adrenal glands). However, the PBR are up-regulated in microglial cells in the brain. These cells (similar to macrophages) are increased in response to an inflammatory stimulus that occurs in the brain. All of the diseases cited above have this characteristic. This suggests that PBR-directed compounds could be used in any or all of these diseases.

ANSTO LifeSciences has synthesised a number of small molecules which bind with high affinity to this receptor. These compounds have been labelled with both SPECT (¹²³I) and PET (¹⁸F) isotopes and the intellectual property has been secured.

Project Leaders: Filomena Mattner, Chris Fookes, Andrew Katsifis

The development of imaging compounds to detect and treat a range of cancers is a priority.

There is a higher incidence of Melanoma in Australia than other countries and, in New South Wales, it is the fourth most common cancer. While localised melanoma has a high survival rate, metastatic disease has no effective treatment, and effective treatments are needed. For imaging of melanoma lesions to determine spread, ¹⁸F-FDG has a high sensitivity/specificity. In cases where there is high clinical suspicion of metastatic disease, but the patients images are FDG-negative, compounds which localise by an alternate mechanism could be useful.

Pancreatic cancer is a very difficult cancer to detect and treat. The five-year survival rate in the US is <4% and in NSW, it is 7%. In the US, it is the fourth leading cause of death. Surgery is the only cure, but only 20% of patients are eligible for surgery. Even after surgery, the five-year survival rate is only 20%. Standard diagnostic modalities are not effective for preoperative diagnosis and this impinges on surgical decisions. FDG may provide the answer as a physiological means of diagnosis, primary and metastases. However, effective treatments are needed.

Breast cancer is the second leading cause of cancer death for women in the US. While most women present with localised disease, a significant fraction (20%) present with metastases. Women with localised disease have a high (~80% over five year) survival rate. However, in those with metastatic disease, only 20% survive longer than five years. Again, additional treatments would aid these patients.

Prostate cancer is the fifth leading cause of death in the US. It usually strikes men over 65 yr (220,000 new cases a year). Screening is done using the presence of prostate specific antigen in the blood. Biopsy is used to make the diagnosis. At initial diagnosis, the Gleason score, a histological measure of the cancer aggressiveness, is used for surgical decisions. After prostate removal, the blood prostate specific antigen is used to detect recurrence. Standard diagnostic modalities are ineffective in detecting most prostate cancer lesions. In the US, an ¹¹¹In labelled antibody is used to determine soft tissue metastatic disease but has a modest sensitivity/specificity (65-70%). A prostate cancer specific PET imaging agent could improve initial staging and managing recurrence. Eventually, all prostate cancer patients become refractory to hormone treatment. For these patients, chemotherapy is ineffective and alternative treatments are needed.

A number of small molecule high affinity σ₂-directed vectors have been synthesized. There is good previous experience with animal models of breast and prostate cancer. However, at present experiments with σ₂-directed vectors in prostate cancer animal models have been delayed due to the unavailability of the animal involved.

Project leaders: Tien Pham, Ivan Greguric, Filomena Mattner, Andrew Katsifis