Sodium Fluoride-18 and Radium-223 Dichloride Uptake Colocalize in Osteoblastic Mouse Xenograft Tumors

Patients with osteoblastic bone metastases are candidates for radium-223 (²²³RaCl₂) therapy and may undergo sodium fluoride-18 (¹⁸F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. ¹⁸F-NaF has been shown to predict ²²³RaCl₂ uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of ¹⁸F-NaF and ²²³RaCl₂ in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. ¹⁸F-NaF and ²²³RaCl₂ were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from in vivo biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. ¹⁸F and ²²³Ra accumulated in proportional amounts in whole Hu09-H3 tumors (r² = 0.82) and in microcalcified regions within these tumors (r² = 0.87). Intratumor distributions of ¹⁸F and ²²³Ra were spatially congruent in these microcalcified regions. ¹⁸F-NaF and ²²³RaCl₂ uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of ¹⁸F is predictive of ²²³Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered ²²³Ra dose and therapeutic effect.