First Whole-Body Three-Dimensional Tomographic Imaging of Alpha Particle Emitting Radium-223

Abstract

Objective: Dose optimization and pharmacokinetic evaluation of alpha emitting Radium-223 dichloride (²²³RaCl₂) by planar gamma camera or single photon emission computed tomographic (SPECT) imaging are hampered by the low photon abundance and injection activities. Here, we demonstrate SPECT of ²²³Ra using phantoms and small animal in vivo models. Methods: Line phantoms and mice bearing ²²³Ra were imaged using a next generation 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 effect determined by immunofluorescence. Results: 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. Line sources of ²²³Ra in both air and in a water scattering phantom gave linear response functions with provide 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 were correlated with DNA damage from the alpha particle emissions. Conclusions: This work demonstrates the capability to noninvasively define the distribution of ²²³Ra, a recently approved alpha emitting radionuclide. This approach allows quantitative assessment of ²²³Ra distribution and may provide radiation dose optimization strategies to improve therapeutic response and ultimately to enable personalized treatment planning.