Preclinical Single Photon Emission Computed Tomography of Alpha Particle-Emitting Radium-223

Dose optimization and pharmacokinetic evaluation of α-particle emitting radium-223 dichloride (²²³RaCl₂) by planar γ-camera or single photon emission computed tomography (SPECT) imaging are hampered by the low photon abundance and injected activities. In this study, we demonstrate SPECT of ²²³Ra using phantoms and small animal in vivo models. Line phantoms and mice bearing ²²³Ra were imaged using a dedicated small animal SPECT by detecting the low-energy photon emissions from ²²³Ra. Localization of the therapeutic agent was verified by whole-body and whole-limb autoradiography and its radiobiological effect confirmed by immunofluorescence. A state-of-the-art commercial small animal SPECT system equipped with a highly sensitive collimator enables collection of sufficient counts for three-dimensional reconstruction at reasonable administered activities and acquisition times. Line sources of ²²³Ra in both air and in a water scattering phantom gave a line spread function with a full-width-at-half-maximum of 1.45 mm. Early and late-phase imaging of the pharmacokinetics of the radiopharmaceutical were captured. Uptake at sites of active bone remodeling was correlated with DNA damage from the α particle emissions. This work demonstrates the capability to noninvasively define the distribution of ²²³RaCl₂, a recently approved α-particle-emitting radionuclide. This approach allows quantitative assessment of ²²³Ra distribution and may assist radiation-dose optimization strategies to improve therapeutic response and ultimately to enable personalized treatment planning.