Introduction:: Actinium-225 (Ac-225) is a very promising and popular alpha-emitting radionuclide in targeted alpha therapy (TAT), which has demonstrated an excellent efficacy in the treatment of solid and liquid tumors. The decay chain of Ac-225 includes imageable photon emissions, enabling alpha theranostics using quantitative single photon emission tomography (SPECT). However, in vivo imaging of Ac-225 is extremely challenging primarily because of the ultra-low injection activities [1]. This presents a particular challenge for preclinical studies with mice when novel alpha theranostics is developed for which the activities are often sub-microcurie (uCi, or sub-37 kBq) levels. Therefore, it is important to have an imaging method that allows Ac-225 imaging at such low activities especially. Imaging Ac-225 has been demonstrated using a preclinical SPECT before; however, it was based on very high activities and scan time [1, 2]. In this study, we characterize the limitation of a preclinical SPECT/CT system (VECTor4CT, MILabs) for imaging Ac-225. We will present the characterization of the system’s sensitivity for the dominant Ac-225 emissions (x-rays, and gamma rays from Fr-221 and Bi-213) and its imaging performance as a function of activity and scan time.
Materials and Methods:: We performed a series of scans of Ac-225 using a preclinical SPECT/CT scanner (VECTor4CT) using a high-energy, general-purpose multi-pinhole collimator designed for rats and mice (HE-GP-RM). To characterize the performance of SPECT/CT, we used a 3D-printed mouse-sized phantom (BIOEMTECH). The phantom’s cavities (representing the brain, thyroid, upper tumor, left and right lungs, heart, liver, left and right kidneys, bladder, and flank tumor) were filled with a total of 1.10 MBq (29.6 uCi) of Ac-225 in 4.2 mL (all cavities) and imaged for 24 hours in the scanner. CT was acquired prior to SPECT for anatomical segmentations of cavities and attenuation correction for SPECT reconstruction. Both SPECT and CT reconstructions were performed using vendor-provided software, and both scatter and attenuation corrections were applied for SPECT reconstruction.
We first calibrated the SPECT/CT system by imaging an Ac-225 vial containing 2.12 MBq (57.4 uCi) in 1.07 mL for 24 hours. For the initial analysis, we used the Fr-221 energy window (150-250 keV). The analysis using other energy windows (60-100 keV for x-ray and 400-500 keV for Bi-213) will be completed and presented at the conference. In order to emulate shorter scan times (i.e., lower activities), we applied count reductions in reconstruction. Finally, we computed the activity concentration in each organ from the SPECT images by defining regions of interest (ROI) for each organ. We compared the measured concentrations to the true activity concentration by computing the recovery coefficient (RC), which equals to the ratio of measured divided by true activity concentration.
Results, Conclusions, and Discussions:: The SPECT images for 24hr, 12hr, 6hr, 3hr, and 1.5hr scan times, emulated for approximately 1100, 548, 274, 127, and 68.5 kBq, respectively if the scan time is fixed for 24 hours, are shown in Figure 1. At the scan time of 3 hours, the SPECT images of mouse phantom showed drastic decrease in uniformity due to the poorer signal to noise ratio introduced by lower number of counts. The measured activity concentrations were quantitatively compared for each organ and scan time in Figure 2. The quantitative results for 1.5 hours hours are very similar to those of 24 hours, suggesting that exposure time can be reduced by more than an order of magnitude without significantly affecting the organ activity measurements. In terms of activity, it is still 68.5 kBq for 24 hours of scan time, impractical for in vivo mouse imaging for both the activity and the scan time. In addition, as Figure 3 shows, the recovery coefficient for almost all organs in the phantom except liver and heart reached a ratio of 0.8 and above at an exposure of 1.5 hours. As a sanity check, we also monitored the measured activity in a background region where no activity was injected (Figure 4).
In summary, a commercial preclinical SPECT/CT system can image much lower activities of Ac-225 than those presented in the previous study [1]. However, the activity level we tested is still much higher than the typical level used in therapy studies in mice. We will also compute activity concentration as a function of scan time as well as recovery coefficients in images reconstructed in the energy window of x-ray (60-100) keV and Bi-213 (400-500 keV). This would allow us to study the performance of VECTor4 SPECT/CT in imaging Ac-225 at all three relevant energy windows.
Acknowledgements (Optional): : This work was supported in part by National Institute of Biomedical Imaging and Bioengineering under grants R01EB026331 and R01EB032324, and Simon Memorial Fund awarded by UCSF Research and Allocation Committee.
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3. A. Morgenstern, C. Apostolidis, C. Kratochwil, M. Sathekge, L. Krolicki, and F. Bruchertseifer, “An overview of targeted alpha therapy with 225actinium and 213bismuth,” Current Radiopharmaceuticals, vol. 11, no. 3, pp. 200–208, 2018.
