### WP3: Measurement of absorbed dose from radionuclides

The absorbed dose to a volume of tissue from a radionuclide is at present evaluated by a calculation based on the activity-time integral in all relevant source volumes and the decay scheme and particle spectra for the radionuclide.

This workpackage explores both experimentally and theoretically, ways in which calculated absorbed doses can be verified against measurements using geometrical configurations and radionuclides that are relevant to MRT treatments (or used as a surrogate for dosimetry purposes): ^{177}Lu, ^{124}I, ^{111}In, ^{89} Y, ^{90}Y. As no standardised methods for absorbed dose measurements for MRT treatments have been developed thus far, this workpackage aims at the establishment of measurement procedures traceable to the existing absorbed dose standards for radiotherapy. To this aim secondary absorbed dose methods (Fricke solutions, radiochromic films, alanine) will be investigated for their suitability for absorbed dose measurements following a survey of published reports. Moreover the feasibility of developing absorbed dose primary standards for key radionuclides will be investigated with the aim of developing a more robust dosimetric chain for absorbed dose measurements in MRT.

On the basis of the feasibility studies an absorbed dose primary standard will be built and a calibration chain will be established.

A comparison of the measured and calculated absorbed dose will be done in Task 3.4 and a recommendation for preferred methods of dosimetry will be produced (e.g. techniques to be used for clinical dosimetry, best data for dose calculation, etc). The information obtained will provide an indication of how much the uncertainty can be reduced through good practice. The aim will be to reduce the uncertainty associated with the absorbed dose, estimated purely on the administered activity of around

100 %, to a clinically significant 10 %.

Furthermore, in order to explore the possibility of a new reference quantity for radiotherapy - dosimetry based on the biological effects of irradiation - the feasibility of a novel type of biological dosimeter will be investigated in Task 3.5.

#### Task 3.1: Development of absorbed dose measurement techniques and procedures for MRT dosimetry based on dosimeter calibrations against the existing absorbed dose primary standards for external beams

The aim of this task is to develop dosimetry techniques that will permit the determination of the absorbed dose to a defined volume of a medium, calculated from the time-activity integral of a radionuclide. The following dosimeters will be evaluated: radiochromic films, Fricke solutions and gels, diamond detectors, alanine pellets. All of these dosimeters are capable of measuring the dose at a point, provided that the appropriate correction factors are determined. The correction factors will be determined both experimentally and by Monte Carlo calculations. The dosimeters will be calibrated against the existing primary standards for dosimetry in radiotherapy with external beams. To be useful for verification of calculation methods the techniques adopted will aim for an uncertainty less than 5 % (k = 1), if possible after calibration under suitable reference conditions. The measurement methods will be developed for the radionuclides most commonly used for MRT (^{32}P, ^{89}Sr, ^{90}Y, ^{131}I, ^{153}Sm, ^{177}Lu).

#### Task 3.2: Feasibility study for the development of a primary absorbed dose standard for radionuclides (ENEA, NPL, VSL) (Start June 2012, End May 2013)

The aim of the task is to introduce the absorbed dose to water for a given radionuclide as a reference quantity, being the absorbed dose to water, the quantity of interest in radiotherapy, based on primary absorbed dose to water standards as recommended by the international IAEA protocol 398 [7].

Hence, the primary aim of this task is to develop suitable technologies capable of measuring the quantity absorbed dose from selected radionuclides in media and geometries relevant to MRT treatments. Absorbed dose primary standards are intended to be developed in order to achieve the traceability of absorbed dose measurements through the calibration of secondary dosimetry instruments specific for MRT. The uncertainty associated with the primary standards will not be known until a prototype is tested, however for the new standard to be useful, the uncertainty will need to be less than 10 %.

The reference geometry will be a water-filled volume where the radionuclide is distributed. Although for pure beta emitters the absorbed dose can be calculated by the decay scheme, this conversion procedure does not allow dose verification and it introduces an additional uncertainty component. The development of a primary standard is of utmost importance since: 1) molecular radiotherapy often uses non pure beta-emitting radionuclides which do not allow accurate dose calculation from activity 2) current absorbed dose measurements from radionuclides are performed using dosimeters which are calibrated against radiation sources different from the sources the dosimeter will be exposed to.

At this stage, the feasibility of the development of a primary absorbed dose standard is considered to be very likely since different NMIs, each independently, will investigate different approaches. This strategic redundancy will increase the likelihood of at least one method being successful.

#### Task 3.3: Development of prototypes based on the feasibility studies from Task 3.2

The aim of this task is to develop whichever of the candidate technologies appear promising according to the findings of Task 3.2. This will be an independent task, and as a consequence no other tasks will depend on the results elicited from it. The mechanical construction of a prototype will be carried out.

There are other ways to calibrate instruments if feasibility studies do not produce any suitable candidates for a prototype. If after 12 months from its start (May 2013) Task 3.2 shows that no suitable candidates exist for the development of an absorbed dose primary standard, the labour resources for this task will be allocated to Task 3.1, strengthening the development of absorbed dose measurement techniques and procedures for MRT dosimetry based on dosimeter calibrations against the existing absorbed dose primary standards for external beams.

#### Task 3.4: Assessment and validation of methods of obtaining absorbed dose from cumulative activity

The aim of this task is to provide a robust metrological basis for assessing and verifying different methods of calculating absorbed dose to a target volume or tissue at risk from a known cumulative activity distribution. In MRT there are a wide range of different treatment scenarios: from microscopic to macroscopic tumour size; from penetrating to non-penetrating radiations; distributions within tissues, cellular and subcellular levels that are either homogeneous or inhomogeneous relative to the particle range. There are also a range of approaches to dose estimation, from standard mathematical phantoms to full individualised Monte Carlo calculations. The task will analyse the critical dosimetric problems in terms of current state of the art methods of dose evaluation, in terms of uncertainty, with the aim of providing evidence-based advice on clinical methodology. The absorbed dose will be calculated by the product of the cumulated activity (derived from activity measurement in WP1 and WP2) and the S-factors calculated by different Monte Carlo codes. These calculated values will be compared with each other. Calculated absorbed dose values will be compared with measurements calibrated against the primary standards developed in Task 3.3, if this has been feasible, otherwise this will be done indirectly against other absorbed dose standards (high- or low-energy external beam, brachytherapy, or external beta standards).

#### Task 3.5: Feasibility of a dosimeter measuring biological outcomes of radionuclide exposure

The aim of this task is to investigate the feasibility of a novel type of dosimeter that can directly measure the biological effects of ionising radiation when immersed in a radioactive isotope solution. Rather than measuring absorbed dose, this 'dosimeter' would be used to determine the rate of strand break induction in DNA molecules.

The detection principle is based on observations of conductivity experiments on DNA which have shown that an intact DNA molecule behaves like an ohmic resistor. Defects in the DNA, such as a strand break in the backbone, lead to regions of poor conductivity. For the dosimeter, the signal to be detected would be the change in impedance across a parallel arrangement of several hundred to several thousands of DNA strands, post-irradiation.

Challenges within this task include the fabrication of a circuit consisting of a network of DNA resistors with contacts at sub-micrometre intervals along the DNA molecules, and carrying out the impedance measurements with sufficient resolution to detect individual strand breaks. These challenges can be addressed by PTB, which has facilities for electron lithography based production of electrical circuits on the sub-micrometre scale. PTB also has the competence to develop the necessary electronics for such measurements that would be based on the lock-in techniques.

**For more information:** Contact Vere Smyth