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Evaluation of the feasibility of in vivo Ac-225 imaging

Abstract

Targeted alpha therapy (TAT) is showing promise in the treatment of solid and liquid tumors. TAT uses alpha particles that have small effective range and high linear energy transfer (LET) to achieve high killing in tumor cells and spare normal tissues around the tumor cells. Currently, Actinium-225 (Ac-225) is the most sought-after alpha-emitter. To study the biodistribution of any Ac-225 labeled radiopharmaceuticals, we need to image Ac-225 in vivo in small animals at a sub-Ci activity level. With this research question, we investigate the feasibility of using a commercial preclinical single photon emission computed tomography scanner (SPECT) to quantitatively image a mouse-like phantom at low Ac-225 activity. We first developed an Ac-225 imaging protocol with the SPECT scanner. The protocol consisted of calibrating the scanner for two imageable photon emissions from the Ac-225 decay to Fr-221 and Bi-213 (218 keV and 440 keV). Then, we selected regions of interests (ROIs) from phantom images and characterized the quantitative accuracy of the resulting images as a function of activity in Ci equivalent to 1-hour exposure. For both energy windows, with three ROI methods, the recovery coefficients (RCs) showed consistent quantitative accuracy of SPECT images at an activity level as low as 3.36 Ci with 1-hour exposure. 20% or more deviation of RCs from the ground truth as well as increasing variations of RC values measured between phantom cavities were found at activities below 3.36 Ci. Additional phantom studies, at lower activity levels, and animal studies are being prepared for further investigation on the preclinical scanner’s limit of detection of Ac-225.

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