Wen Jiang1, David Ulmert2, Brian W Simons3, Diane S Abou4, Daniel L J Thorek5. 1. Department of Biomedical Engineering, Johns Hopkins University, United States. 2. Department of Radiology, Memorial Sloan Kettering Cancer Center, United States. 3. Department of Molecular and Comparative Pathobiology, Johns Hopkins University, United States; Department of Urology, Johns Hopkins University School of Medicine, United States. 4. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Johns Hopkins University School of Medicine, United States. Electronic address: dabou1@jhmi.edu. 5. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Johns Hopkins University School of Medicine, United States; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, United States. Electronic address: dthorek1@jhmi.edu.
Abstract
INTRODUCTION: Radium-223 dichloride is the first alpha-particle emitting therapeutic agent approved by FDA and EMA for bone metastatic castration-resistant prostate cancer. We studied its age-dependent biodistribution in mice, and compared it with [99mTc]Tc-MDP and [18F]NaF aiming to identify a potential imaging surrogate to predict [223Ra]RaCl2 whole-body localization. METHODS: Male C57Bl/6 mice dosed with [223Ra]RaCl2 were sacrificed at different time points to explore [223Ra]RaCl2 whole-body distribution. In another experiment, mice at different ages were dosed with [223Ra]RaCl2 to evaluate the aging impact. Finally, [99mTc]Tc-MDP and [18F]NaF were administered to mice, and we compared their biodistributions with [223Ra]RaCl2. Detailed micro-localization of each tracer was visualized using autoradiography and histochemical staining. RESULTS: [223Ra]RaCl2 uptake in bone was rapid and stable. We observed persistent localization at bone epiphyses, as well as the red pulp of the spleen, while its uptake in most soft tissues cleared within 24 h. [223Ra]RaCl2 distribution in soft tissues is similar in all age groups tested, while bone activity significantly decreased with aging. Although the diagnostic tracers cleared much faster from soft tissues than the therapeutic radionuclide, [99mTc]Tc-MDP and [18F]NaF both co-localized with [223Ra]RaCl2 in the skeletal compartment. CONCLUSIONS: Radium-223 localization to the bone is dependent on age-varying factors, which implies that radium-223 dosimetry should take patient age into account. [99mTc]Tc-MDP shows a different biodistribution from [223Ra]RaCl2, both in soft tissues and in bone. [18F]NaF presents a high similarity with [223Ra]RaCl2 in skeletal uptake, which validates the potential of [18F]NaF as an imaging surrogate to predict radium-223 radiotherapeutic distribution in bone.
INTRODUCTION:Radium-223 dichloride is the first alpha-particle emitting therapeutic agent approved by FDA and EMA for bone metastatic castration-resistant prostate cancer. We studied its age-dependent biodistribution in mice, and compared it with [99mTc]Tc-MDP and [18F]NaF aiming to identify a potential imaging surrogate to predict [223Ra]RaCl2 whole-body localization. METHODS: Male C57Bl/6 mice dosed with [223Ra]RaCl2 were sacrificed at different time points to explore [223Ra]RaCl2 whole-body distribution. In another experiment, mice at different ages were dosed with [223Ra]RaCl2 to evaluate the aging impact. Finally, [99mTc]Tc-MDP and [18F]NaF were administered to mice, and we compared their biodistributions with [223Ra]RaCl2. Detailed micro-localization of each tracer was visualized using autoradiography and histochemical staining. RESULTS: [223Ra]RaCl2 uptake in bone was rapid and stable. We observed persistent localization at bone epiphyses, as well as the red pulp of the spleen, while its uptake in most soft tissues cleared within 24 h. [223Ra]RaCl2 distribution in soft tissues is similar in all age groups tested, while bone activity significantly decreased with aging. Although the diagnostic tracers cleared much faster from soft tissues than the therapeutic radionuclide, [99mTc]Tc-MDP and [18F]NaF both co-localized with [223Ra]RaCl2 in the skeletal compartment. CONCLUSIONS:Radium-223 localization to the bone is dependent on age-varying factors, which implies that radium-223 dosimetry should take patient age into account. [99mTc]Tc-MDP shows a different biodistribution from [223Ra]RaCl2, both in soft tissues and in bone. [18F]NaF presents a high similarity with [223Ra]RaCl2 in skeletal uptake, which validates the potential of [18F]NaF as an imaging surrogate to predict radium-223 radiotherapeutic distribution in bone.
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