Giuseppe graduated in Nuclear Physics at the University of Naples (Italy) in 1994 and obtained his PhD from King’s College London (UK) (X-ray diffraction group) in 1999 working on the development of ultrasoft X-ray microbeams for radiobiological applications.
Following two postdoctoral experiences at the Gray Cancer Institute in the UK (2000-2004) (Low dose hypersensitivity response project) and the Center for Radiological Research at the Columbia University in New York (2004-2007) (High throughput biodosimeter project), he worked as Lecturer at the Centre for Cancer Research and Cell Biology (CCRCB) in the School of Medicine for Queen’s University Belfast from 2007 to 2013.
In 2013, Giuseppe joined the Medical Radiation Group at the National Physical Laboratory (NPL) as Principal Research Scientist. He also covered the role of Head of Science for the Medical Physics area from 2015 to 2018.
In 2018, he become Professor of Medical Physics at the University of Surrey with a joint position with the National Physical Laboratory.
He is also Honorary Senior Lecturer for the Queen’s University Belfast and the University College London.
My main research interest is in radiation biology, advanced radiotherapy and dosimetry. It includes detection and calculation of nano- and micro-scale dose distribution, DNA damage induction by ionising radiation and its repair, radiobiological modelling, cell signalling and the resulting lethal and sub-lethal effects in normal and tumor in vitro and in vivo models.
Current ongoing research activities are focused on dosimetry and radiobiology for MRI-based radiotherapy, biological effectiveness of proton and ion beams, use of gold nanoparticle as radio-sensitizers, definition of new dosimetry quantities closely related to biological response and biological optimization of treatment plans.
I am also leading UK activities for standardization of dosimetry and QA processes for pre-clinical radiotherapy & radiobiology research. This program is sponsored by the UK government through the Innovate UK agency and supported by the UK Clinical and Translational Radiotherapy Research Working Group (CTRad) and Cancer Research UK (CRUK).
The clinical introduction of magnetic resonance imaging guided radiotherapy has
prompted consideration of the potential impact of the static magnetic field on biological
responses to radiation. This review provides an introduction to the mechanisms of
biological interaction of radiation and magnetic fields individually, in addition to a
description of the magnetic field effects on megavoltage photon beams at the
macroscale, microscale and nanoscale arising from the Lorentz force on secondary
A relatively small number of scientific studies have measured the impact of combined
static magnetic fields and ionising radiation on biological endpoints of relevance to
radiotherapy. Approximately half of these investigations found that static magnetic
fields in combination with ionising radiation produced a significantly different outcome
compared with ionising radiation alone. MRI strength static magnetic fields appear to
modestly influence the radiation response via a mechanism distinct from modification
to the dose distribution. This review intends to serve as a reference for future biological
studies, such that understanding of static magnetic field plus ionising radiation
synergism may be improved, and if necessary, accounted for in magnetic resonance
imaging guided radiotherapy treatment planning.
Significant improvements in radiotherapy are likely to come from biological rather than technical optimization, for example increasing tumour radiosensitivity via combination with targeted therapies. Such paradigms must first be evaluated in preclinical models for efficacy, and recent advances in small animal radiotherapy research platforms allow advanced irradiation protocols, similar to those used clinically, to be carried out in orthotopic models. Dose assessment in such systems is complex however, and a lack of established tools and methodologies for traceable and accurate dosimetry is currently limiting the capabilities of such platforms and slowing the clinical uptake of new approaches. Here we report the creation of an anatomically correct phantom, fabricated from materials with tissue-equivalent electron density, into which dosimetry detectors can be incorporated for measurement as part of quality control (QC). The phantom also allows training in preclinical radiotherapy planning and cross-institution validation of dose delivery protocols for small animal radiotherapy platforms without the need to sacrifice animals, with high reproducibility.
Mouse CT data was acquired and segmented into soft tissue, bone and lung. The skeleton was fabricated using 3D printing, whilst lung was created using computer numerical control (CNC) milling. Skeleton and lung were then set into a surface-rendered mould and soft tissue material added to create a whole-body phantom. Materials for fabrication were characterized for atomic composition and attenuation for x-ray energies typically found in small animal irradiators. Finally cores were CNC milled to allow intracranial incorporation of bespoke detectors (alanine pellets) for dosimetry measurement.
We introduce a methodology to calculate the microdosimetric quantity dose-mean lineal energy for input into the microdosimetric kinetic model (MKM) to model the relative biological effectiveness (RBE) of proton irradiation experiments.
Methods and Materials
The data from 7 individual proton RBE experiments were included in this study. In each experiment, the RBE at several points along the Bragg curve was measured. Monte Carlo simulations to calculate the lineal energy probability density function of 172 different proton energies were carried out with use of Geant4 DNA. We calculated the fluence-weighted lineal energy probability density function , based on the proton energy spectra calculated through Monte Carlo at each experimental depth, calculated the dose-mean lineal energy for input into the MKM, and then computed the RBE. The radius of the domain (rd) was varied to reach the best agreement between the MKM-predicted RBE and experimental RBE. A generic RBE model as a function of dose-averaged linear energy transfer (LETD) with 1 fitting parameter was presented and fit to the experimental RBE data as well to facilitate a comparison to the MKM.
Both the MKM and LETD-based models modeled the RBE from experiments well. Values for rd were similar to those of other cell lines under proton irradiation that were modeled with the MKM. Analysis of the performance of each model revealed that neither model was clearly superior to the other.
Our 3 key accomplishments include the following: (1) We developed a method that uses the proton energy spectra and lineal energy distributions of those protons to calculate dose-mean lineal energy. (2) We demonstrated that our application of the MKM provides theoretical validation of proton irradiation experiments that show that RBE is significantly greater than 1.1. (3) We showed that there is no clear evidence that the MKM is better than LETD-based RBE models.
Lack of standardization and inaccurate dosimetry assessment in preclinical research is hampering translational opportunities for new radiation therapy interventions. The aim of this work was to develop and implement an end-to-end dosimetry test for small animal radiation research platforms to monitor and help improve accuracy of dose delivery and standardization across institutions.
Methods and Materials
The test is based on a bespoke zoomorphic heterogeneous mouse and WT1 Petri dish phantoms with alanine as a reference detector. Alanine measurements within the mouse phantom were validated with Monte Carlo simulations at 0.5 mm Cu x-ray reference beam. Energy dependence of alanine in medium x-ray beam qualities was taken into consideration. For the end-to-end test, treatment plans considering tissue heterogeneities were created in Muriplan treatment planning systems (TPS) and delivered to the phantoms at 5 institutions using Xstrahl's small animal irradiation platforms. Mean calculated dose to the pellets were compared with alanine measured dose.
Monte Carlo simulations and in phantom alanine measurements in NPL's reference beam were in excellent agreement, validating the experimental approach. At 1 institute, initial measurements showed a larger than 12% difference between calculated and measured dose caused by incorrect input data. The physics data used by the calculation engine were corrected, and the TPS was recommissioned. Subsequent end-to-end test measurements showed differences Conclusions
An end-to-end dosimetry test was developed and implemented for dose evaluation in preclinical irradiation with small animal irradiation research platforms. The test was capable of detecting treatment planning commissioning errors and highlighted critical elements in dose calculation. Absolute dosimetry with alanine in relevant preclinical irradiation conditions showed reasonable levels of accuracy compared with TPS calculations. This work provides an independent and traceable dosimetric validation in preclinical research involving small animal irradiation.
Ricketts, K., R. Ahmad, L. Beaton, B. Cousins, K. Critchley, M. Davies, S. Evans, I. Fenuyi, A. Gavriilidis, Q.J. Harmer, D. Jayne, M. Jefford, M. Loizidou, A. Macrobert, S. Moorcroft, I. Naasani, Z.Y. Ong, K.M. Prise, S. Rannard, T. Richards, G. Schettino, R.A. Sharma, O. Tillement, G. Wakefield, N.R. Williams, E. Yaghini, and G. Royle, Recommendations for clinical translation of nanoparticle-enhanced radiotherapy. Br J Radiol, 2018: p. 20180325.
Ghita, M., C. Fernandez-Palomo, H. Fukunaga, P.M. Fredericia, G. Schettino, E. Brauer-Krisch, K.T. Butterworth, S.J. McMahon, and K.M. Prise, "Microbeam evolution: From single cell irradiation to preclinical studies", (2018) Int J Radiat Biol. p.1-32.
Ghita, M., S.J. McMahon, H.F. Thompson, C.K. McGarry, R. King, S.O.S. Osman, J.L. Kane, A. Tulk, G. Schettino, K.T. Butterworth, A.R. Hounsell, and K.M. Prise, "Small field dosimetry for the small animal radiotherapy research platform (SARRP)", (2017) Radiat Oncol. 12 (1); p.204.
Kokurewicz, K., G.H. Welsh, E. Brunetti, S.M. Wiggins, M. Boyd, A. Sorensen, A. Chalmers, G. Schettino, A. Subiel, C. DesRosiers, and D.A. Jaroszynski, "Laser-plasma generated very high energy electrons (VHEEs) in radiotherapy", (2017) Proc. SPIE. Conference Volume 10239 (Medical Applications of Laser-Generated Beams of Particles IV: Review of Progress and Strategies for the Future);
Ghita, M., S.J. McMahon, L.E. Taggart, K.T. Butterworth, G. Schettino, and K.M. Prise, "A mechanistic study of gold nanoparticle radiosensitisation using targeted microbeam irradiation", (2017) Sci Rep. 7 p.44752.
Dummott, L.M., G. Schettino, P. Seller, M.D. Wilson , M.C. Veale, and S. Pani, "Effects of dead time on quantitative dual-energy imaging using a position-sensisitve spectroscopic detector", (2017) Proc. SPIE. 10132 (Medical Imaging 2017: Physics of Medical Imaging); p.1-9.
O'Keeffee, S., L. Chen, E. Lewis, M. Grattan, A.R. Hounsell, G. Whitten, and G. Schettino, "Effects of Magnetic Field on an Optical Fibre Radiation Dosimeter", (2017) Sensors IEEE. p.1-3.
Rosa, S., C. Connolly, G. Schettino, K.T. Butterworth, and K.M. Prise, "Biological mechanisms of gold nanoparticle radiosensitization", (2017) Cancer Nanotechnol. 8 (1); p.2.
Acheva, A., G. Schettino, and K.M. Prise, "Pro-inflammatory Signaling in a 3D Organotypic Skin Model after Low LET Irradiation-NF-kappaB, COX-2 Activation, and Impact on Cell Differentiation", (2017) Front Immunol. 8 p.82.
Subiel, A., Ashmore R., and Schettino G., "Standards and Methodologies for Characterizing Radiobiological Impact of High-Z Nanoparticles", (2016) Theranostics. 6 (10); p.1651-1671.
Marshall, T.I., P. Chaudhary, A. Michaelidesova, J. Vachelova, M. Davidkova, V. Vondracek, G. Schettino, and K.M. Prise, "Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak", (2016) Int J Radiat Oncol Biol Phys. 95 (1); p.70-7.
Taggart, L.E., S.J. McMahon, K.T. Butterworth, F.J. Currell, G. Schettino, and K.M. Prise, "Protein disulphide isomerase as a target for nanoparticle-mediated sensitisation of cancer cells to radiation", (2016) Nanotechnology. 27 (21); p.215101.
McQuaid, H.N., M.F. Muir, L.E. Taggart, S.J. McMahon, J.A. Coulter, W.B. Hyland, S. Jain, K.T. Butterworth, G. Schettino, K.M. Prise, D.G. Hirst, S.W. Botchway, and F.J. Currell, "Imaging and radiation effects of gold nanoparticles in tumour cells", (2016) Sci Rep. 6 p.19442.
Chaudhary, P., T.I. Marshall, F.J. Currell, A. Kacperek, G. Schettino, and K.M. Prise, "Variations in the Processing of DNA Double-Strand Breaks Along 60-MeV Therapeutic Proton Beams", (2015) Int J Radiat Oncol Biol Phys. 95 p.86-94.
Ghita, M., C.B. Coffey, K.T. Butterworth, S.J. McMahon, G. Schettino, and K.M. Prise, "Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields", (2015) Phys Med Biol. 61 (2); p.515-526.
Palmans, H., H. Rabus, A.L. Belchior, M.U. Bug, S. Galer, U. Giesen, G. Gonon, G. Gruel, G. Hilgers, D. Moro, H. Nettelbeck, M. Pinto, A. Pola, S. Pszona, G. Schettino, P.H. Sharpe, P. Teles, C. Villagrasa, and J.J. Wilkens, "Future development of biologically relevant dosimetry", (2015) Br J Radiol. 88 (1045).