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Targeted Alpha Therapy: Development Of A New Treatment For Metastatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$394,400.00
Summary
Breast cancer is the most commonly diagnosed, malignant cancer in women and prostate cancer is the most common non-life style related cancer in men. In spite of the most aggressive therapy, a significant percentage of men and women die of secondary disease (metastases) which usually spreads in the early stages. Currently, therapy is limited to chemotherapy and hormone therapy, both of which show clinical improvement but long term survival is uncertain. Targeted alpha therapy (TAT) is a new cance ....Breast cancer is the most commonly diagnosed, malignant cancer in women and prostate cancer is the most common non-life style related cancer in men. In spite of the most aggressive therapy, a significant percentage of men and women die of secondary disease (metastases) which usually spreads in the early stages. Currently, therapy is limited to chemotherapy and hormone therapy, both of which show clinical improvement but long term survival is uncertain. Targeted alpha therapy (TAT) is a new cancer treatment that we are developing in mouse models of human breast and prostate cancer. With TAT we are exploiting the fact that aggressive breast and prostate cancer cells, but not normal cells, express a particular tissue-barrier degrading protein system (uPA) which is specifically recognised by a natural inhibitor protein (PAI2). This protein inhibitor is labeled with a highly effective cell killing agent, a radioisotope that emits high energy alpha particles with a short range of only a few cell diameters . The alpha-labeled PAI2 selectively kills cancer cells at their most malignant stage by targeting the uPA system on these cells. Another benefit of TAT is that little radiation damage occurs to nearby or distant normal cells. Thus side-effects would be minimised. The outcome of our research to date has been to show the potential of our unique TAT approach as a possible new therapy for breast and prostate cancer. This therapy may well prove beneficial for other cancers. Further safety evaluations studies in mice will be followed by a dose tolerance clinical trial in humans. We expect to be able to show that our TAT will regress breast and prostate cancer tumours without complications in mice. The human trials will show the tolerance limits to TAT. If successful, TAT could provide the basis for a major change in prognosis and quality of life of breast and prostate cancer patients.Read moreRead less
New Copper and Rhenium Radiopharmaceuticals. The aims of this project are to provide new metal-based radiopharmaceuticals for the treatment of cancer, and the imaging of cancer and other conditions through the design and engineering of new coordination complexes of rhenium and copper. Various strategies will be used to selectively and specifically target these metal complexes to the desired areas in vivo for non-invasive imaging and therapeutic applications. The most promising candidates will be ....New Copper and Rhenium Radiopharmaceuticals. The aims of this project are to provide new metal-based radiopharmaceuticals for the treatment of cancer, and the imaging of cancer and other conditions through the design and engineering of new coordination complexes of rhenium and copper. Various strategies will be used to selectively and specifically target these metal complexes to the desired areas in vivo for non-invasive imaging and therapeutic applications. The most promising candidates will be tested in the appropriate cells.Read moreRead less
Novel Nanoparticle Composites For Molecular Probes In Diagnostic Imaging
Funder
National Health and Medical Research Council
Funding Amount
$170,716.00
Summary
Isotope labelled protein probes, eg. antibodies, are a valuable imaging tool in investigating patient disease. Their biological specificity is their great strength, however, detection sensitivity often limits their use. A novel nanoparticle developed at ANU can increase this signal by a million-fold in comparison with conventional methods of labelling. This approach suits a range of probes and will accommodate many of the isotopes already used in patient diagnostics and therapy.
RadioGenes2: Modelling complex biomolecular interactions in radiated tumours: Towards understanding the genesis of therapeutic radioresistance. About 45% of bladder cancer patients require radiotherapy or surgery. Radiotherapy has a failure rate of ~50%. Surgery (bladder removal) diminishes quality of life considerably. Modelling complex gene interactions in radiated cancer cells will provide crucial knowledge on the molecular genesis of radiotherapy-resistance of tumours. Our findings will prov ....RadioGenes2: Modelling complex biomolecular interactions in radiated tumours: Towards understanding the genesis of therapeutic radioresistance. About 45% of bladder cancer patients require radiotherapy or surgery. Radiotherapy has a failure rate of ~50%. Surgery (bladder removal) diminishes quality of life considerably. Modelling complex gene interactions in radiated cancer cells will provide crucial knowledge on the molecular genesis of radiotherapy-resistance of tumours. Our findings will provide: (i) an accurate mathematical/computational model for diagnosing radiosensitivity; (ii) further insights to be applied in the pharmaceutical sector such as the discovery of novel molecular targets that have the potential to increase radiotherapy success ratios; (iii) a holistic modelling technique applicable to a larger diversity of tumours.Read moreRead less
Characterisation and improvement of radiation beams used for radiotherapy of small lesions. This project aims to characterise the radiation dose from a medical linear accelerator after the beam has been shaped by a mini-multileaf collimator. The characterisation will be achieved through a combination of computer simulations and experimental investigation of the beam using the technique of three-dimensional gel dosimetry. When the dosage characteristics are known, techniques will be developed to ....Characterisation and improvement of radiation beams used for radiotherapy of small lesions. This project aims to characterise the radiation dose from a medical linear accelerator after the beam has been shaped by a mini-multileaf collimator. The characterisation will be achieved through a combination of computer simulations and experimental investigation of the beam using the technique of three-dimensional gel dosimetry. When the dosage characteristics are known, techniques will be developed to improve radiotherapy treatments in patients with small lesions with sizes of up to a few centimetres. This will lead to an improved outcome for some cancer patients.Read moreRead less
Automated 3-Dimensional Biomedical Registration for Whole-body Images from Combined PET/CT Scanners. This project will aid rapid assimilation of very large medical imaging datasets from different imaging devices, and will have clinical applications in diagnosis and treatment and improve patient care. The research, when extended to protein registration, will facilitate analysis of DNA and advance research in bioinformatics and biotechnology. The research could also be used for target recognition, ....Automated 3-Dimensional Biomedical Registration for Whole-body Images from Combined PET/CT Scanners. This project will aid rapid assimilation of very large medical imaging datasets from different imaging devices, and will have clinical applications in diagnosis and treatment and improve patient care. The research, when extended to protein registration, will facilitate analysis of DNA and advance research in bioinformatics and biotechnology. The research could also be used for target recognition, mosaic construction, content-based retrieval, in remote sensing and multimedia. Benefits to Australia include the provision of a readily adaptable image registration program for patient care (e.g., early detection of cancers, dementia), cutting-edge research, high-quality training for students, and encouraging international research collaboration.Read moreRead less
Correction of the Effects of Gradient Field Nonlinearity in Magnetic Resonance Imaging - A Complete 3-Dimensional Approach. The outcomes of this research will have direct benefits to various areas of diagnostic and interventional medicine especially in neurological diseases such as Alzheimer's disease, stroke, multiple sclerosis or brain tumors. The techniques developed in this project will in general enable MRI to provide a higher quality service to the community.
Functionalised MMP Inhibitors as Radiodiagnostic, Radiotherapeutic, and Radiation-Sensitising Agents for Metastatic Cancer. Identifying and treating malignant cancers is one of the major challenges facing the scientific and medical communities. In order to minimise side effects that accompany most treatments of cancer it is necessary to find ways of targeting the therapy to tumours and away from healthy organs. A difference between tumours and healthy tissues is the amount of the proteins (calle ....Functionalised MMP Inhibitors as Radiodiagnostic, Radiotherapeutic, and Radiation-Sensitising Agents for Metastatic Cancer. Identifying and treating malignant cancers is one of the major challenges facing the scientific and medical communities. In order to minimise side effects that accompany most treatments of cancer it is necessary to find ways of targeting the therapy to tumours and away from healthy organs. A difference between tumours and healthy tissues is the amount of the proteins (called MMPs) that tumours use to break out of their surroundings, to break into and out of the blood system, and to establish new colonies of cancer cells or metastases. This difference also distinguishes the most aggressive cancers. The purpose of this project is to develop means of identifying and targeting cancers using molecules that bind to these MMP proteins.Read moreRead less
New methods to improve regional isotope therapy of liver tumours in cancer patients. The most common cause of death in cancer patients is secondary tumours in vital organs. Successful treatment of liver tumours with regional isotope therapy now offers improved survival rates. This project will research novel radiolabelled nanoparticles and advanced computer imaging algorithms to improve regional isotope therapy of liver tumours. It will provide better methods of objective assessment and manageme ....New methods to improve regional isotope therapy of liver tumours in cancer patients. The most common cause of death in cancer patients is secondary tumours in vital organs. Successful treatment of liver tumours with regional isotope therapy now offers improved survival rates. This project will research novel radiolabelled nanoparticles and advanced computer imaging algorithms to improve regional isotope therapy of liver tumours. It will provide better methods of objective assessment and management that can reduce risk and improve patient survival.Read moreRead less
Fibre Optic Dosimeters for Medical and Environmental Applications. We will develop fibre optic dosimeters for environmental monitoring and radiation therapy. A novel approach using refractive index gradients will be used to capture scintillator light while rejecting noise. New knowledge will be gained of the mechanisms of radiation damage in scintillators and glasses. The small, flexible, accurate fibre optic dosimeters will be equivalent in absorbing characteristics to human tissue, making them ....Fibre Optic Dosimeters for Medical and Environmental Applications. We will develop fibre optic dosimeters for environmental monitoring and radiation therapy. A novel approach using refractive index gradients will be used to capture scintillator light while rejecting noise. New knowledge will be gained of the mechanisms of radiation damage in scintillators and glasses. The small, flexible, accurate fibre optic dosimeters will be equivalent in absorbing characteristics to human tissue, making them superior to all currently available dosimeters. Fibre optic dosimeters will enable new adaptive radiotherapy techniques and provide quality assurance of dose delivery in radiotherapy. Their multiplexing capability will lead to applications in monitoring of workplaces and aerospace environments.Read moreRead less