Systemic metabolic radiotherapy with samarium-153 EDTMP for the treatment of painful bone metastasis

Various radioisotopes conjugated to pyrophosphate analogues have been developed for systemic metabolic radiotherapy. Samarium-153-EDTMP is a 1:1 complex of radioactive Samarium-153 and a Tetraphosphonate [ethylenediamine-tetramethylene phosphonic acid (EDTMP)]. Samarium Sm-153-EDTMP has a high affinity for skeletal tissue and concentrates by chemiabsorption in areas of enhanced metabolic activity, where it associates with the hydroxyapatite crystal. Samarium-153 Lexidronam [Quadramet (R)] has been approved for routine use by the FDA. This agent offers several advantages over other agents used for palliating bone pain. Due to its half-life of 46 hours and its beta emissions, a high dose rate can be delivered to regions adjacent to enhanced osteoblastic activity over a short period of time with little residual long term activity being left in the bone marrow. This paper summarizes both animal studies and clinical studies performed with this agent. Special emphasis will be given to the pivotal Phase-III clinical studies and subsequent studies performed since its approval by the FDA. Special considerations regarding appropriate selection of patients, preparation, follow-up of patients and adjustments to the usual recommended dose [1 mCi/kg (35 Mbq/kg)] will be discussed. Current and future treatment options utilizing Sm-153-EDTMP with other pharmaceuticals appear promising and will substantially extend its use into new areas. In addition, because it also emits a 103 keV gamma ray which makes it suitable for imaging and assessment of biodistribution, dosimetric applications are possible in the future.