Investigating and Improving the Timepix Performance in Imaging Ac-225 and Daughter Nuclides

Abstract

The main objective of this research was to determine the feasibility of using the Timepix3 detector,
a novel hybrid-pixel detector developed by CERN, as a tool for imaging ex-vivo slices of tumour tissue treated with 225Ac Targeted Alpha Therapy. Targeted Alpha Therapy using 225Ac-PSMA shows
promise as a therapeutic method, as it allows direct targeting of the tumour and precise irradiation
of cancer cells while sparing healthy tissue due to the short range of α-particles (typically 50-100μm).
However, due to the recoil effect, the daughters of 225Ac can break loose from the targeting vector,
potentially diffusing away from the tumour site and harming healthy tissue resulting in unwanted side
effects. To investigate this, several experiments were conducted using the Timepix3 detector, capable
of energy, spatial and time-resolved measurements. Before experiments could be conducted, a data
processing tool was developed and an optimal bias voltage of 30V was determined. Subsequently,
the Timepix was calibrated using a γ and α calibration, which yielded energy resolutions of 4.27±0.06%
and 4.96±0.06% compared to 6.35±0.04% without calibration when measuring α-particles from 225Ac
locally. The Timepix3 was then tested using different collimators for whole surface measurements. For
a plastic collimator (L/D=2.5, ⌀=1mm) the energy resolution improved from 15.7±0.3% to 11.9% and
9.6±0.1%. For a lead-glass collimator (L/D=50, ⌀=24.8μm) the energy resolution improved to 13.5%
and 12.6±0.4%, here the uncalibrated resolution could not be determined. Finally, the spatial resolution
of the Timepix was determined using the plastic collimator, which was 310±10μm. Based on the findings, the Timepix3 detector is not suitable for the proposed application, an imaging tool to determine
nuclide distribution in 225Ac-PSMA treated tissue samples, using this particular setup. However, using
a different collimator with a more suitable L/D ratio should definitely be capable as this improves spatial
and energy resolution further.
Furthermore, the Timepix3 detector was used in a clinical test to directly measure and determine the
nuclide contents of the radio-pharmaceutical 225Ac-PSMA separated by high-performance liquid chromatography. The results indicated an initially lower amount of 213Po in the sample which grew over
time This indicates that the HPLC is capable of separating individual nuclides. This result also demonstrated the potential use of the Timepix3 detector for these types of applications.
In experiments where the Timepix3 was placed inside a 70MeV and 120MeV proton beam to test its
feasibility as a beam verification tool, the results were less successful due to the high intensity of the
proton beam. However, it was concluded that it was still possible to measure scattered protons and
secondary products.