Radiopharmaceutical therapy for palliation of bone pain from osseous metastases

Abstract

Bone metastasis occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. The process is mediated by parathyroid hormones, cytokines, and tumor-derived factors. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. Pain associated with osseous metastasis is thought to be distinct from neuropathic or inflammatory pain. Several mechanisms-such as invasion of tumor cells, spinal cord astrogliosis, and sensitization of nervous system-have been postulated to cause pain. Pharmaceutical therapy of bone pain includes nonsteroidal analgesics and opiates. These drugs are associated with side effects, and tolerance to these agents necessitates treatment with other modalities. Bisphosphonates act by inhibiting osteoclast-mediated resorption and have been increasingly used in treatment of painful bone metastasis. While external beam radiation therapy remains the mainstay of pain palliation of solitary lesions, bone-seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. (32)P has been used for >3 decades in the treatment of multiple osseous metastases. The myelosuppression caused by this agent has led to the development of other bone-seeking radiopharmaceuticals, including (89)SrCl, (153)Sm-ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP), (179m)SnCl, and (166)Ho-Labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonate ((166)Ho-DOTMP). (89)Sr is a bone-seeking radionuclide, whereas (153)Sm-EDTMP is a bone-seeking tetraphosphonate; both have been approved by the Food and Drug Administration for the treatment of painful osseous metastases. While both agents have been shown to have efficacy in the treatment of painful osseous metastases from prostate cancer, they may also have utility in the treatment of painful osseous metastases from breast cancer and perhaps from non-small cell lung cancer. This article illustrates the salient features of these radiopharmaceuticals, including the approved dose, method of administration, and indications for use. We conclude with recommended guidelines for therapy and follow-up.