Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

Abstract

There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

Subcellular Targeting of Theranostic Radionuclides

“…Its utility in detecting β-particles from a Carbon-14 ( 14 C) sample showed that Timepix was highly sensitive with a minimum detectable activity of 0.0077 Bq and with a spatial resolution of 76.9 μm at full-width at half-maximum (FWHM; Esposito et al, 2011a , b ). In another study, Timepix was used to measure α-particle emissions in tumor sections from mice treated with chemotherapy and a radiolabeled DAB4 murine monoclonal antibody [thorium-227 ( 227 Th)-APOMAB] ( Darwish et al, 2015 ). Results showed that the α-particle emissions could be visualized and quantified using the detector ( Miller, 2018 ).…”

Development of a transmission alpha particle dosimetry technique using A549 cells and a Ra‐223 source for targeted alpha therapy

“…19 The Timepix radiation detector 20 has the ability to identify individual radiation particles including photons (x-rays or gamma rays), electrons, and alpha particles. [21][22][23][24][25][26] Our previous study confirmed that Timepix could be used to detect and quantify spatial distribution of alpha particles, electrons, and x-rays resulting from thorium-227 (Th-227) decay in tumor sections from mice treated with a Th-227-labeled antibody. 26 These features along with the ability of Timepix to measure deposited energy suggest that Timepix could be used to estimate absorbed dose in targeted alpha therapy.…”

Updated developments on molecular imaging and therapeutic strategies directed against necrosis

“…The La-specific monoclonal antibody, DAB4 (also known as APOMAB ® ) was demonstrated to be able to specifically target dead tumor cells in vivo 143 , and targetability was augmented after DNA-damaging treatment81., 82., 143., 144.. A recent study further demonstrated the selectivity of DAB4 for chemotherapy-induced dead tumor cells and this postchemotherapy selectivity was related to a relative increase in the availability of DAB4-binding targets in tumor tissue rather than in normal tissues 115 , which provided further evidence to support the diagnostic use of DAB4 as a predictive marker of treatment responses.…”