The Need for Accurate Dosimetry in
Pre-Clinical Radiobiology Studies
The needs
Dose measurements in pre-clinical and radiobiology studies are frequently inadequate, thus undermining the reliability and reproducibility of the published findings. These concerns
have already been emphasized by NIST in 2011 [1]. According to ICRU Report 24 [2] a change of 7-10% in dose to target volume results in clinically significant change in tumour control
probability (TCP). Therefore, it has been agreed that there is a requirement for an accuracy of 5% in the delivery of absorbed dose to a tumour volume. This criterion should be also
applied to the pre-clinical studies as inadequate dosimetry can impair the significance or cause misinterpretation of the radiobiological findings. Recent survey on verification of
radiobiological irradiator dose [3] have shown that only one out of five laboratories, which took part in this study, delivered the output within 5% of the target dose. This project aims to
develop tools, dosimetry protocols, guidelines and quality assurance (QA) procedures for pre-clinical and radiobiological studies.
Reference dosimetry
Existing national and international guidelines and Code
of Practice are often not suitable for the irradiators used
in radiobiological investigators due to geometrical
limitations and non-reference conditions.
Recommendations on best practice and methodologies
guidelines will be drafted based on technical
specification of common radiobiological units.
As part of the process, a capability map for the
radiobiological units and their dosimetry traceability will
be drafted.
UK radiobiological capability map. Work ongoing (http://j.mp/2dwKjwo)
Dosemeters
Radiobiological investigations use a wide range of
irradiators with the radiation quality of these beams
strongly depending on filtration, cabinet geometry and
set-up. The half value layer (HVL) is commonly used for
determining radiation quality in the kV energy range
and it should be reported for each study together with
absorbed dose values.
In order to establish robust dosimetry protocols, it is
necessary to characterize the response of a series of
detectors as a function of HVL.
Passive detectors that will be employed for the
development for traceable pre-clinical dosimetry:
Alanine
Glass beads
Radiochromic films
Alanine dosemetetrs and EPR spectrometer at NPL.
Alanine is well characterized for MV X-ray beams [4],
however, further measurements are needed to extend
the energy range of this reference dosimeter to kV beams
with a minimal impact on the overall 1% uncertainty.
Acknowledgements
We would like to acknowledge
DrShakardokht Jafari, who contributed
to this work. This work is supported by
InnovateUK, grant no. 102524.
Anna Subiel1, Amanda Tulk2, Chris Cawthorne3, Georgios Soultanidis3,
John Greenman3, Vicky Green3 and Giuseppe Schettino1
Tube potential
90 kv
Alanine
Inherent filtration
3 mm Be
Additional filtration
0.85 mm Cu
Relative dose
difference
1%
Irradiation set up or response of the alanine dosemeter
to two X-ray beams with distinct energy spectra but the
same HVL (0.5 mm Cu) indicates that HVL could be a
suitable parameter for the dosemeter response.
In parallel, we are investigating the use of silica glass
beads as potential reference dosimeters. Previous work
[5] showed that commercially available glass beads have
a great potential for dosimetry with clinical MV X-rays.
These detectors exhibit thermo-luminescent properties
and can be used for radiotherapy dosimetry. Glass beads
could easily be injected/inserted in the animal before
the irradiation and retrieved post-irradiation for dose
verification, thus their small size and biocompatibility
offers opportunity for in vivo dose monitoring.
Response of glass bead dosemeters as a function of HVL
Additionally, radiochromic films will be employed to
assess 2D dose distributions of the delivered treatment.
1 mm glass beads used for in-vivo dosimetry and the associated TLD
readout system
Multipurpose phantom
Multipurpose phantom for assessment of accuracy in
dose delivery during animal radiobiology experiments
is currently under development. 3D printing and
conventional milling and moulding are being considered
as the phantom manufacturing options. Materials
mimicking tissue equivalent materials (lung, bone and
soft tissue) have been identified. This work is supported
by Monte Carlo (MC) calculations allowing to study
dosimetric properties of tested materials. The phantom
will be used to audit radiobiological centres.
References
1 Desrosiers, M., et al., The Importance of Dosimetry Standardization in Radiobiology.
Journal of Research of the National Institute of Standards and Technology, 2013. 118.
2 ICRU, Determination of Absorbed Dose in a Patient Irradiated by Beams of X or Gamma
Rays in Radiotherapy, in ICRU REPORT 24. 1976, International Commission on Radiation
Units and Measurements: Bethesa, MD.
3 Pedersen, K.H., et al., Radiation Biology Irradiator Dose Verification Survey. Radiation
Research, 2016. 185(2): p. 163-168.
1
National Physical Laboratory, Hampton Road, Teddington, Middlesex, TW11 0LW, UK
2
Xstrahl Ltd, Riverside Way, Camberley, Surrey, GU15 3YL UK
3
University of Hull, Cottingham Road, Hull, East Riding of Yorkshire, HU6 7RX, UK
Tube potential
135 kv
Inherent filtration
3 mm Be
Additional filtration
0.27 mm Cu
1.2 mm Al
Realistic representation of the mouse skeleton
Complex bone and soft tissue structures
Extracted by a CT and post segmented into bone,
lung and soft tissue
3D printing or moulding
Simplified skeleton
A size equivalent representation of the animal.
Simplified, modular bone and lung structures
Milling, 3D printing or moulding
The phantom will be segmented into slices. This
will enable incorporation of passive detectors and a
microfluidic device.
Small animal phantom with incorporated inserts for passive detectors and
microfluidic device
Microfluidic device
Microfluidic device, fabricated from material of tumour
tissue-specific density, is designed for maintaining live
tissues. It will allow controlled delivery of medium and
drugs to tumour slices derived from patients or 3D
cultures. This technology, integrated with small animal
phantom, will enable in vivo like radiobiological studies.
Small animal phantom with incorporated inserts for passive detectors and
microfluidic device
Future work
Guidelines for characterization of radiation output
and radiation quality from radiobiological cabinets
Full characterization of passive detectors in keV
energy range
Monte Carlo calculations will be employed to support
11801/0816
this work
NPL Management Limited, 2016.
National audit
Provision of dosimetry traceable to Standard Laboratories
4 Sharpe, P.H.G., K. Rajendran, and J.P. Sephton, Progress towards an alanine/ESR therapy
level reference dosimetry service at NPL. Applied Radiation and Isotopes, 1996. 47(11-
12): p. 1171-1175.
5 Jafari, S.M., et al., Low-cost commercial glass beads as dosimeters in radiotherapy.
Radiation Physics and Chemistry, 2014. 97: p. 95-101.