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Comprehensive treatment for vertebral metastatic lesions commonly involves vertebral augmentation (vertebroplasty or kyphoplasty) to relieve pain and stabilize the spine followed by multiple sessions of radiotherapy. We propose to combine vertebral augmentation and radiotherapy into a single treatment by adding32P, aβ-emitting radionuclide, to bone cement, thereby enabling spinal brachytherapy to be performed without irradiating the spinal cord. The goal of this study was to address key dosimetry and safety questions prior to performing extensive animal studies. The32P was in the form of hydroxyapatite powder activated by neutron bombardment in a nuclear reactor. We performedex vivodosimetry experiments to establish criteria for safe placement of the cement within the sheep vertebral body. In anin vivostudy, we treated three control ewes and three experimental ewes with brachytherapy cement containing 2.23-3.03 mCi32P ml-1to identify the preferred surgical approach, to determine if32P leaches from the cement and into the blood, urine, or feces, and to identify unexpected adverse effects. Ourex vivoexperiments showed that cement with 4 mCi32P ml-1could be safely implanted in the vertebral body if the cement surface is at least 4 mm from the spinal cord in sheep and 5 mm from the spinal cord in humans.In vivo, a lateral retroperitoneal surgical approach, ventral to the transverse processes, was identified as easy to perform while allowing a safe distance to the spinal cord. The blood, urine, and feces of the sheep did not contain detectable levels of32P, and the sheep did not experience any neurologic or other adverse effects from the brachytherapy cement. These results demonstrate, on a preliminary level, the relative safety of this brachytherapy cement and support additional development and testing.