Time filter

Source Type

Allen B.J.,Center for Experimental Radiation Oncology | Bezak E.,Royal Adelaide Hospital | Bezak E.,University of Adelaide | Marcu L.G.,Royal Adelaide Hospital | And 2 more authors.
BioMed Research International | Year: 2013

Purpose. Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival. Methods. The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted. Results. Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease. Conclusion. The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology. © 2013 Barry J. Allen et al.


Sgouros G.,Johns Hopkins University | Roeske J.C.,Loyola University | McDevitt M.R.,Sloan Kettering Cancer Center | Palm S.,International Atomic Energy Agency | And 6 more authors.
Journal of Nuclear Medicine | Year: 2010

The potential of α-particle emitters to treat cancer has been recognized since the early 1900s. Advances in the targeted delivery of radionuclides and radionuclide conjugation chemistry, and the increased availability of α-emitters appropriate for clinical use, have recently led to patient trials of radiopharmaceuticals labeled with α-particle emitters. Although α-emitters have been studied for many decades, their current use in humans for targeted therapy is an important milestone. The objective of this work is to review those aspects of the field that are pertinent to targeted α-particle emitter therapy and to provide guidance and recommendations for human α-particle emitter dosimetry. Copyright © 2010 by the Society of Nuclear Medicine, Inc.


Allen B.J.,Center for Experimental Radiation Oncology | Abbas Rizvi S.M.,Center for Experimental Radiation Oncology | Qu C.F.,Center for Experimental Radiation Oncology | Smith R.C.,University of Sydney
Cancers | Year: 2011

Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (~100 μm diameter), causing apoptosis in some 70-90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro-metastatic pancreatic cancer with over-expression of MUC1 and uPA receptors in post-surgical patients with minimal residual disease. The observation of tumor regression in a Phase I clinical trial of targeted alpha therapy for metastatic melanoma indicates that alpha therapy can regress tumors by a process called tumor anti-vascular alpha therapy (TAVAT). As a consequence, this therapy could be indicated for the management of non-surgical pancreatic cancer tumors. © 2011 by the authors; licensee MDPI, Basel, Switzerland.


Melville G.,Center for Experimental Radiation Oncology | Melville P.,Center for Experimental Radiation Oncology
Applied Radiation and Isotopes | Year: 2013

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation by bombarding Ra-226 with high-energy neutrons from a neutron source to produce Ra-225 and hence Ac-225, which can be used as a generator to produce Bi-213 for use in 'Targeted Alpha Therapy' for cancer.This paper examines the possibility of producing Ac-225 by neutron capture using a theoretical model in which neutron energy is convoluted with the corresponding neutron cross sections of Ra-226. The total integrated yield can then be obtained.This study shows that an intense beam of high-energy neutrons could initiate neutron capture on Ra-226 to produce Ra-225 and hence practical amounts of Ac-225 and a useful reduction of Ra-226. © 2012 Elsevier Ltd.


Allen B.J.,Center for Experimental Radiation Oncology
Current Radiopharmaceuticals | Year: 2011

The objectives in the application of targeted alpha therapy (TAT) for cancer therapy are reviewed. These relate to elimination of isolated cancer cells, cell clusters and tumors. Requirements for isolated cancer cells are good cellular targeting, high specific activity, and very short range. The regression of cell clusters in the peri-vascular space requires high capillary permeability and short range cross fire whereas for developed tumors, good bioavailabilty and anti- capillary activity are essential. Current sources of alpha radiation are reviewed and the prospects for commercial sources for clinical application are discussed. The Ac:Bi generator is the most practical alpha source, bringing therapy to Nuclear Medicine with the same practicality as the Mo:Tc generator has for imaging. The status quo of TAT is briefly reviewed with respect to dose normalization, real time microdosimetry and biological dosimetry for deterministic and stochastic effects and toxicity. The role of Monte Carlo calculations is emphasized. The strengths and weaknesses of TAT are examined and the way forward for clinical acceptance is discussed. © 2011 Bentham Science Publishers Ltd.


PubMed | Center for Experimental Radiation Oncology
Type: Journal Article | Journal: Cancers | Year: 2013

Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213Bi using the chelators cDTPA and CHX-A to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (~100 m diameter), causing apoptosis in some 70-90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro-metastatic pancreatic cancer with over-expression of MUC1 and uPA receptors in post-surgical patients with minimal residual disease. The observation of tumor regression in a Phase I clinical trial of targeted alpha therapy for metastatic melanoma indicates that alpha therapy can regress tumors by a process called tumor anti-vascular alpha therapy (TAVAT). As a consequence, this therapy could be indicated for the management of non-surgical pancreatic cancer tumors.


PubMed | Center for Experimental Radiation Oncology
Type: Journal Article | Journal: Current radiopharmaceuticals | Year: 2011

The objectives in the application of targeted alpha therapy (TAT) for cancer therapy are reviewed. These relate to elimination of isolated cancer cells, cell clusters and tumors. Requirements for isolated cancer cells are good cellular targeting, high specific activity, and very short range. The regression of cell clusters in the peri-vascular space requires high capillary permeability and short range cross fire whereas for developed tumors, good bioavailabilty and anti- capillary activity are essential. Current sources of alpha radiation are reviewed and the prospects for commercial sources for clinical application are discussed. The Ac:Bi generator is the most practical alpha source, bringing therapy to Nuclear Medicine with the same practicality as the Mo:Tc generator has for imaging. The status quo of TAT is briefly reviewed with respect to dose normalization, real time microdosimetry and biological dosimetry for deterministic and stochastic effects and toxicity. The role of Monte Carlo calculations is emphasized. The strengths and weaknesses of TAT are examined and the way forward for clinical acceptance is discussed.

Loading Center for Experimental Radiation Oncology collaborators
Loading Center for Experimental Radiation Oncology collaborators