Coded aperture and Compton imaging for the development of ²²⁵Ac‐based radiopharmaceuticals

Abstract

BackgroundTargeted alpha‐particle therapy (TAT) has great promise as a cancer treatment. Arguably the most promising TAT radionuclide that has been proposed is 225Ac. The development of 225Ac‐based radiopharmaceuticals has been hampered due to the lack of effective means to study the daughter redistribution of these agents in small animals at the preclinical stage.PurposeThe ability to directly image the daughters, namely 221Fr and 213Bi, via their gamma‐ray emissions would be a boon for preclinical studies. That said, conventional medical imaging modalities, including single photon emission computed tomography (SPECT) based on nonmultiplexed collimation, cannot be employed due to sensitivity limitations.MethodsAs an alternative, we propose the use of both coded aperture and Compton imaging with the former modality suited to the 218‐keV gamma‐ray emission of 221Fr and the latter suited to the 440‐keV gamma‐ray emission of 213Bi.ResultsThis work includes coded aperture images of 221Fr and Compton images of 213Bi in tumor‐bearing mice injected with 225Ac‐based radiopharmaceuticals.ConclusionsThese results are the first demonstration of visualizing and quantifying the 225Ac daughters in small animals through the application of coded aperture and Compton imaging.

Actinium-225 targeted alpha particle therapy for prostate cancer

“…Traditional collimator-based SPECT imaging has challenges to image gamma emission above 300 keV, therefore utilization of 440 keV from 213 Bi is more difficult. To overcome this, a new approach to combine the coded aperture imager (for lower keV) and Compton imager (for higher keV) was utilized to visualize and quantify the daughters from 225 Ac 122 .…”

A generalization of the maximum likelihood expectation maximization (MLEM) method: Masked-MLEM

“…For experimental 3D collimatorless tomography, a fillable micro hollow sphere phantom filled with 0.53 kBq μl −1 of 225 Ac aqueous solution in its three different-sized spheres, was rotated at 8 angles separated by 45°a nd scanned by a 3D position-sensitive HPGe double-sided strip detector (DSSD) for 30 min per projection (see figure 3) (Frame et al 2022(Frame et al , 2023. The detector is part of a Compton camera and consists of 37 by 37 orthogonal stripes with an active pixel size of 2 mm × 2 mm × 15 mm (Frame et al 2022(Frame et al , 2023. The cylinder phantom has a diameter of 40 mm and a height of 82 mm, and was filled with water.…”

“…The distance from the center of the micro hollow sphere phantom to the surface of the detector was about 52.5 mm. The detailed experiment setup for measuring the micro hollow sphere phantom is shown in Frame et al (2023). Given that the 3D position-sensitive detector could record the depth of interactions, we summed the counts of the single interaction events as the projection data, whose interaction depths were within 3 mm from the surface of the first detector of Compton cameras, and energies were in the 18% energy window of the characteristic X-ray peak centering at 87 keV, the 1.1% energy window of the 218 keV photopeak of 221 Fr, and the 0.6% energy window of the 440 keV photopeak of 213 Bi.…”