Autoradiography imaging in targeted alpha therapy with Timepix detector

Area of Science:

• Nuclear Medicine
• Medical Physics
• Radiotherapy Research

Background:

• Targeted alpha therapy (TAT) requires detailed activity uptake and particle track distribution data for accurate cellular absorbed dose estimation.
• Alpha particles have a short range, necessitating precise tracking for dosimetry.
• The Timepix semiconductor radiation detector offers potential for individual alpha particle tracking.

Purpose of the Study:

• To investigate the feasibility of imaging alpha particle emissions in mouse tumor sections using the Timepix detector.
• To assess Thorium-227 (Th-227) uptake and distribution in tumors treated with APOMAB, with and without prior chemotherapy.
• To evaluate the Timepix detector's sensitivity in monitoring tumor uptake variations related to necrotic tissue volume.

Main Methods:

• Utilized the Timepix semiconductor radiation detector to image alpha particle emissions in mouse tumor sections.
• Administered Th-227 labeled APOMAB to mice, with and without prior chemotherapy.
• Employed a compartmental analysis model based on imaging data to quantify Th-227 uptake.

Main Results:

• The Timepix detector successfully detected and resolved tracks from alpha particles, photons, electrons, and muons.
• Individual alpha particle emissions from TAT were visualized and quantified.
• Tumors pretreated with chemotherapy showed a fourfold higher Th-227 uptake compared to tumors without chemotherapy, correlating with necrotic tissue volume.

Conclusions:

• The Timepix detector is a feasible tool for visualizing and quantifying individual alpha particle emissions in targeted alpha therapy.
• Chemotherapy pretreatment significantly enhances Th-227 uptake in tumors, suggesting a potential strategy for improving TAT efficacy.
• Accurate dosimetry and understanding of uptake variations are crucial for optimizing cellular-level absorbed doses in TAT.