Dosimetry of Bone Seeking Beta Emitters for Bone Pain Palliation Metastases

Amongst cancer patients, bone pain due to skeletal metastases is a major cause of morbidity. A number of beta-emitting radiopharmaceuticals have been used to provide internal radiotherapy of bone metastases and provide palliative pain relief. In this article we describe the different physical characteristics of the various beta emitting radionuclides which have been used in this clinical setting and the potential impact of differences in dose-rate on radiobiological outcomes. A detailed review of the biodistribution of these treatments, based on both in-vivo clinical investigations and post mortem autoradiography assessments is provided. These treatments result in physiological delivery of radiation doses to the target disease as well as to critical healthy organs. Particular attention is paid to the radiation doses received by normal bone tissue, bone marrow as well as metastatic bone disease. The underlying models of radiation transport within bone and bone marrow are reviewed alongside the practical steps that must be taken to acquire and analyse the information require for clinical dosimetry assessments. The role of whole body measurements, blood and faecal assays as well as both planar and tomographic gamma camera imaging are considered. In addition we review the rationale for allocating measured bone uptake between trabecular and cortical bone tissue. The difference between bone volume and bone surface seeking radiopharmaceuticals are also discussed. This review also extends to the development of preclinical models of bone metastases which may inform future dosimetric calculations. Finally, we also present a comprehensive review of the dosimetry of the established treatments ⁸⁹Strontium-chloride; ³²Phosphorus; ¹⁸⁸Rhenium-hydroxyethylidine disphosphonate; ¹⁸⁶Rhenium-1,1-hydroxyethylidene disphosphonate (¹⁸⁶Re-HEDP); ¹⁵³Samarium-ethylenediaminetetramethylene phosphonate; as well as the emerging treatments ¹⁸⁸Rhenium-zoledronic acid; ¹⁸⁸Rhenium-ibedronat; ¹⁷⁷Lutetium-zoledronic acid; and ¹⁷⁷Lutetium ethylenediaminetetramethylene phosphonate. This review highlights not only the inter treatment differences in the radiation absorbed doses delivered to metastatic disease by different radiopharmaceuticals but also the intra treatment differences which result in a large range of observed doses between patients.