Diane S Abou1,2,3,4, Andrew Rittenbach5, Ryan E Tomlinson6, Paige A Finley7, Benjamin Tsui7, Brian W Simons8, Abhinav K Jha1,9, David Ulmert10,11, Ryan C Riddle12, Daniel L J Thorek1,2,4,9. 1. Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. 2. Program in Quantitative Molecular Therapeutics, Washington University School of Medicine, St. Louis, Missouri, USA. 3. Radiology Cyclotron Facility, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA. 4. Oncologic Imaging Program, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, USA. 5. Information Sciences Institute, University of Southern California, Los Angeles, California, USA. 6. Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. 7. Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 8. Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas, USA. 9. Department of Biomedical Engineering, Washington University, St. Louis, Missouri, USA. 10. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California, USA. 11. Division of Urological Research, Department of Clinical Sciences, Lünd University, Malmö, Sweden. 12. Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract
Objective: 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. Methods: 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. 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 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. Conclusions: 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.
Objective: 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. Methods: 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. 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 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. Conclusions: 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.
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