Radiopharmaceuticals for Bone Metastasis Therapy and Beyond: A Voyage from the Past to the Present and a Look to the Future

Bone cancer can be divided into primary and secondary (metastatic) bone cancer. Osteosarcoma is the most common type of primary bone cancer, but still is a rare cancer. The development of bone metastases is a common event for the cancer patient and the main cause of treatment failure and death, being chronic pain syndrome the most important complication. There are currently several therapeutic modalities for the treatment of metastatic bone disease, including radiation therapy. Treatment with radionuclides (beta- and alpha-particle emitters and Auger electron cascades) is a safe and effective tool of medicine. There is a great deal of interest in diphosphonic acids in nuclear medicine as ligands for radiometals in bone-seeking diagnostic and therapeutic agents. Several radiopharmaceuticals have been designed with the phosphonates as ligands. A recent approach to develop an effective radiopharmaceutical for therapy of bone cancer was the design of a water-soluble polymer that would exploit the disrupted vasculature in tumors according to the enhanced permeability and retention effect. To enhance the effect of radionuclide therapy on the cancer cells, new strategies have recently been investigated, such as the combined radionuclide and chemotherapy, high-dose radionuclide therapy, and repeated radionuclide therapy.