ORCID Profile
0000-0002-7161-9367
Current Organisations
University of Sydney
,
Royal North Shore Hospital
,
NSW Environment Protection Authority (EPA)
,
Oncosil Radiopharmaceutical Company
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Publisher: Springer Science and Business Media LLC
Date: 20-11-2020
DOI: 10.1038/S41598-020-76980-9
Abstract: In positron emission tomography (PET), the finite range over which positrons travel before annihilating with an electron places a fundamental physical limit on the spatial resolution of PET images. After annihilation, the photon pair detected by the PET instrumentation is emitted from a location that is different from the positron-emitting source, resulting in image blurring. Here, we report on the localization of positron range, and hence annihilation quanta, by strong nanoscale magnetization of superparamagnetic iron oxide nanoparticles (SPIONs) in PET-MRI. We found that positron annihilations localize within a region of interest by up to 60% more when SPIONs are present (with [Fe] = 3 mM) compared to when they are not. The resulting full width at half maximum of the PET scans showed the spatial resolution improved by up to $$\\approx$$ ≈ 30%. We also found evidence suggesting that the radiolabeled SPIONs produced up to a six-fold increase in ortho-positronium. These results may also have implications for emerging cancer theranostic strategies, where charged particles are used as therapeutic as well as diagnostic agents and improved dose localization within a tumor is a determinant of better treatment outcomes.
Publisher: British Institute of Radiology
Date: 12-2015
DOI: 10.1259/BJR.20150035
Publisher: Elsevier BV
Date: 02-2023
A Chelate-Free Nano-Platform for Incorporation of Diagnostic and Therapeutic Isotopes
Publisher: Informa UK Limited
Date: 2020
DOI: 10.2147/IJN.S227931
Publisher: Springer Science and Business Media LLC
Date: 04-10-2019
DOI: 10.1038/S41598-019-50861-2
Abstract: In cancer radiation therapy, dose enhancement by nanoparticles has to date been investigated only for external beam radiotherapy (EBRT). Here, we report on an in silico study of nanoparticle-enhanced radiation damage in the context of internal radionuclide therapy. We demonstrate the proof-of-principle that clinically relevant radiotherapeutic isotopes (i.e. 213 Bi, 223 Ra, 90 Y, 177 Lu, 67 Cu, 64 Cu and 89 Zr) labeled to clinically relevant superparamagnetic iron oxide nanoparticles results in enhanced radiation damage effects localized to sub-micron scales. We find that radiation dose can be enhanced by up to 20%, vastly outperforming nanoparticle dose enhancement in conventional EBRT. Our results demonstrate that in addition to the favorable spectral characteristics of the isotopes and their proximity to the nanoparticles, clustering of the nanoparticles results in a nonlinear collective effect that lifies nanoscale radiation damage effects by electron-mediated inter-nanoparticle interactions. In this way, optimal radio-enhancement is achieved when the inter-nanoparticle distance is less than the mean range of the secondary electrons. For the radioisotopes studied here, this corresponds to inter-nanoparticle distances nm, with the strongest effects within 20 nm. The results of this study suggest that radiolabeled nanoparticles offer a novel and potentially highly effective platform for developing next-generation theranostic strategies for cancer medicine.
Publisher: OAE Publishing Inc.
Date: 26-12-2018
Publisher: IOP Publishing
Date: 21-03-2017
Abstract: The addition of gold nanoparticles within target tissue (i.e. a tumour) to enhance the delivered radiation dose is a well studied radiotherapy treatment strategy, despite not yet having been translated into standard clinical practice. While several studies have used Monte Carlo simulations to investigate radiation dose enhancement by Auger electrons emitted from irradiated gold nanoparticles, none have yet considered the effects due to escaping fluorescence photons. Geant4 was used to simulate a water phantom containing 10 mg ml
Publisher: Informa UK Limited
Date: 02-2020
DOI: 10.2147/IJN.S241971
Publisher: IOP Publishing
Date: 24-03-2014
Publisher: IOP Publishing
Date: 28-07-2015
DOI: 10.1088/0031-9155/60/15/6087
Abstract: Radium-223 dichloride ((223)Ra) is an alpha particle emitter and a natural bone-seeking radionuclide that is currently used for treating osteoblastic bone metastases associated with prostate cancer. The stochastic nature of alpha emission, hits and energy deposition poses some challenges for estimating radiation damage. In this paper we investigate the distribution of hits to cells by multiple alpha particles corresponding to a typical clinically delivered dose using a Monte Carlo model to simulate the stochastic effects. The number of hits and dose deposition were recorded in the cytoplasm and nucleus of each cell. Alpha particle tracks were also visualized. We found that the stochastic variation in dose deposited in cell nuclei ([Formula: see text]40%) can be attributed in part to the variation in LET with pathlength. We also found that [Formula: see text]18% of cell nuclei receive less than one sigma below the average dose per cell ([Formula: see text]15.4 Gy). One possible implication of this is that the efficacy of cell kill in alpha particle therapy need not rely solely on ionization clustering on DNA but possibly also on indirect DNA damage through the production of free radicals and ensuing intracellular signaling.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2021
DOI: 10.1186/S40658-021-00362-X
Abstract: SPECT-derived dose estimates in tissues of diameter less than 3× system resolution are subject to significant losses due to the limited spatial resolution of the gamma camera. Incorporating resolution modelling (RM) into the SPECT reconstruction has been proposed as a possible solution however, the images produced are prone to noise lification and Gibbs artefacts. We propose a novel approach to SPECT reconstruction in a theranostic setting, which we term SPECTRE (single photon emission computed theranostic reconstruction) using a diagnostic PET image, with its superior resolution, to guide the SPECT reconstruction of the therapeutic equivalent. This report demonstrates a proof in principle of this approach. We have employed the hybrid kernelised expectation maximisation (HKEM) algorithm implemented in STIR, with the aim of producing SPECT images with PET-equivalent resolution. We demonstrate its application in both a dual 68 Ga/ 177 Lu IEC phantom study and a clinical ex le using 64 Cu/ 67 Cu. SPECTRE is shown to produce images comparable in accuracy and recovery to PET with minimal introduction of artefacts and lification of noise. The SPECTRE approach to image reconstruction shows improved quantitative accuracy with a reduction in noise lification. SPECTRE shows great promise as a method of improving SPECT radioactivity concentrations, directly leading to more accurate dosimetry estimates in small structures and target lesions. Further investigation and optimisation of the algorithm parameters is needed before this reconstruction method can be utilised in a clinical setting.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2021
DOI: 10.1038/S41598-021-81910-4
Abstract: Positron (β + ) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a β + emitter fluorine-18 ( 18 F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, 18 F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of β + emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of β + emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of 18 F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for β + emitters. These results may also have implications for emerging cancer theranostic strategies, where β + emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2018
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.IJROBP.2017.07.031
Abstract: To develop a Monte Carlo model for patient-specific dosimetry of Spherical tumor geometries and a pancreatic phantom were modeled, as well as different 3-dimensional non-uniform clinical pancreatic geometries based on patient-specific ultrasound images. The dosimetry simulations modeled the dose distribution due to the energy spectrum of emitted beta particles. The average dose for small (3-cm diameter) and large (6-cm diameter) spherical tumors was 111 Gy (for 7.6 MBq administered activity) and 128 Gy (for 58 MBq), respectively. For the clinical 3-dimensional geometries, on the basis of patient data, the mean doses delivered to the tumor were calculated to be in the range 102 to 113 Gy, with negligible dose to the pancreas for the smallest tumor volumes. The calculated dose distributions are highly non-uniform. For the largest tumor studied, the pancreas received approximately 6% of the tumor dose (5.7 Gy). Importantly, we found that because the smallest tumor studied exhibited the most dynamic changes in volume in response to the treatment, the dose to tumor and pancreas is significantly underestimated if a static tumor volume is assumed. These results demonstrate the dosimetry of
Publisher: IOP Publishing
Date: 22-10-2020
Publisher: Springer Science and Business Media LLC
Date: 30-07-2022
DOI: 10.1186/S40658-022-00479-7
Abstract: The prediction of response is one of the major challenges in radiation-based therapies. Although the selection of accurate linear–quadratic model parameters is essential for the estimation of radiation response and treatment outcome, there is a limited knowledge about these radiobiological parameters for liver tumours using radionuclide treatments. The “clinical radiobiological” parameters ( $$T_{{\\text{p}}}$$ T p , $$T_{{\\text{k}}}$$ T k , $$\\alpha$$ α , $$\\alpha {/}\\beta$$ α / β ) for twenty-five patients were derived using the generalised linear–quadratic model, the diagnostic ([ 18 F] FDG PET/CT) and therapeutic ([ 90 Y]-SIR-Spheres PET/CT) images to compute the biological effective dose and tumour control probability (TCP) for each patient. It was estimated that the values for $$\\alpha$$ α and $$\\alpha {/}\\beta$$ α / β parameters range in ≈ 0.001–1 Gy −1 and ≈ 1–49 Gy, respectively. We have demonstrated that the time factors, $$T_{{\\text{p}}}$$ T p , $$T_{{\\text{k}}}$$ T k and $$T_{{{\\text{critic}}}}$$ T critic are the key parameters when evaluating liver malignancy lesional response to [ 90 Y]SIR-Spheres treatment. Patients with cholangiocarcinoma have been shown to have the longest average $$T_{{\\text{p}}}$$ T p (≈ 236 ± 67 d), highest TCP (≈ 53 ± 17%) and total liver lesion glycolysis response ( $$\\Delta {\\text{TLG}}_{{{\\text{liver}}}}$$ Δ TLG liver ≈ 64%), while patients with metastatic colorectal cancer tumours have the shortest average $$T_{{\\text{p}}}$$ T p (≈ 129 ± 19 d), lowest TCP (≈ 28 ± 13%) and $$\\Delta {\\text{TLG}}_{{{\\text{liver}}}}$$ Δ TLG liver ≈ 8%, respectively. Tumours with shorter $$T_{{\\text{k}}}$$ T k have shown a shorter $$T_{{{\\text{critic}}}}$$ T critic and thus poorer TCP and $$\\Delta {\\text{TLG}}_{{{\\text{liver}}}}$$ Δ TLG liver . Therefore, these results suggest for such tumours the [ 90 Y]SIR-Spheres will be only effective at higher initial dose rate (e.g. 50 Gy/day).
Publisher: IOP Publishing
Date: 15-06-2020
Start Date: 1979
End Date: 1979
Funder: University of Sydney
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