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

Objective:Dose optimization and pharmacokinetic evaluation of alpha-particle emitting radium-223 dichloride ((RaCl2)-Ra-223) by planar gamma-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(223)Ra using phantoms and small animalin vivomodels. Methods:Line phantoms and mice bearing(223)Ra were imaged using a dedicated small animal SPECT by detecting the low-energy photon emissions from(223)Ra. Localization of the therapeutic agent was verified by whole-body and whole-limb autoradiography and its radiobiological effect confirmed 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 at reasonable administered activities and acquisition times. Line sources of(223)Ra 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 alpha particle emissions. Conclusions:This work demonstrates the capability to noninvasively define the distribution of(223)RaCl(2), a recently approved alpha-particle-emitting radionuclide. This approach allows quantitative assessment of(223)Ra distribution and may assist radiation-dose optimization strategies to improve therapeutic response and ultimately to enable personalized treatment planning.