Quantitative SPECT Imaging of the Alpha-Emitter ${ }^{225}$ Ac in Hepatocellular Carcinoma

Hepatocellular carcinoma is the most common primary liver cancer and the fifth most frequently diagnosed malignancy worldwide. Advanced-stage presentation in most patients restricts management to non-surgical palliative therapies. Alpha-emitter radiopharmaceutical therapy ($\alpha$ RPT) has emerged as a highly effective targeted therapy for liver cancer. Accurate quantification of $\alpha \text{RPT}$ in vivo remains a major hurdle for dosimetry optimization. In this study, we evaluated a quantitative reconstruction framework, QSPECT for simultaneous quantitative SPECT/CT imaging of ${ }^{225} \text{Ac}$ and its daughter radionuclides in an orthotopic rabbit VX2 liver tumor model. Longitudinal SPECT/CT data were acquired at 24, 72, and 144 h post-injection using an energy window centered at 218 keV for ${ }^{221} \text{Fr}$ and 440 keV for ${ }^{213} \text{Bi}$. QSPECT reconstruction substantially reduced contamination from scatter and crosstalk compared to Siemens Flash3D OSEM and increased lesion contrast. QSPECT also yielded higher tumor-to-liver and tumor-to-kidney ratios at each time point. We also observed that the tumor-to-liver and tumor-to-kidney ratio for ${ }^{221} \text{Fr}$ consistently exceeded that of ${ }^{213} \text{Bi}$, which reflects differences in kinetics between the parent and long half-life daughter radionuclides. These findings highlight the critical role of quantitative SPECT imaging for accurately characterizing both parent and daughter radionuclide distributions.