We evaluated a 3D-positioning Compton camera based on cadmium-zinc-telluride (CZT) detectors in the context of imaging of 225Ac.225Ac, an alpha-emitting radionuclide, shows strong potential for targeted alpha therapy (TAT) of cancer. Its decay chain includes emission of 440 keV gamma rays (from 213Bi), which enables Compton imaging. Due to the extremely low injected activities of TAT radiopharmaceuticals, especially for225Ac-based ones, the ability to measure gamma rays with high sensitivity is critical, and Compton cameras can provide higher sensitivities than collimated cameras. In Compton cameras, precise angular resolution is essential to provide good spatial resolution for accurate localization of radiopharmaceuticals. For this purpose, we customized the GDS-100 CZT camera (IDEAS) with two layers of CZT crystals in order to compare single- and double-layer Compton imaging. We measured and compared the key performance metrics for imaging of225Ac, sensitivity and angular resolution, in order to determine the performance of single- and double-layer CZT cameras for imaging of225Ac. For comparison, we also characterized the camera at higher energies with a137Cs source that emits 662 keV gamma rays. We optimized the depth of interaction and center-of-gravity methods for 3D positioning, followed by 3D voxel-based energy calibration. Our results show that a double-layer configuration can improve the angular resolution measure (ARM) more than a factor of three from 14.0° to 4.3° for137Cs (662 keV), and from 15.8° to 8.9° for225Ac (440 keV). On the other hand, we measured a sensitivity approximately 40 times higher for the single-layer setup with respect to the double-layer setup. This is due to the small size and absorption of scattered photons in scatterer layer. A larger double-layer Compton camera implementing more detector area is expected to provide an equivalent sensitivity with the advantage of a much better angular resolution.
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