Samarium-153-ethylene diamine tetramethylene phosphonate, known as 153Sm-EDTMP and sold under the trade name Quadramet, is a radiopharmaceutical used in the palliation of metastatic bone pain. Bone metastases are unfortunately common in patients with solid malignant tumors. About half of breast cancer patients and 80% of prostate cancer patients develop bone metastases, and nearly half of these patients suffer from bone pain.  By the late 1990s, 153Sm-EDTMP was approved for use in the United States, Europe, Canada, and Australia.  Radioisotopes such as 153Sm are therapeutically useful due to their emission of beta particles. The cytotoxic irradiation delivered by the beta decay of 153Sm kills malignant cells in the bone and thus can relieve pain for as long as four months. 
Samarium is a member of the lanthanide series with atomic number 62. 153Sm is formed by neutron capture of 152Sm2O3.  The reaction is high yielding (>99%) and creates only trace amounts of byproduct 152Eu and 154Eu.  The therapeutic potential of 153Sm stems from the radioisotope's desirable particle emission and short half-life. 153Sm emits a beta particle, an electron, at a maximum energy of 810 keV, suitable for killing malignant cells. It also releases gamma photons of 103 keV, allowing physicians to easily image the biodistribution of the radionuclide using a gamma camera. [2,3] Moreover, the half-life of 153Sm is short at 46.7 hours, allowing for rapid clearance.  While other radioisotopes, such as 32P and 89Sr, have been administered to relieve the pain associated skeletal metastases, their biochemical and nuclear properties are not as ideal as those of 153Sm for a therapeutic.
EDTMP, a polydentate ligand, chelates 153Sm 1:1 by forming four O-153Sm bonds and two N-153Sm bonds, as shown in Figure 1.  153Sm-EDTMP is administered intravenously as a pentasodium salt with molecular mass 696 gmol-1.  Importantly, 153Sm-EDTMP is bone-seeking. EDTMP contains four phosphonate moieties and is structurally similar to biphosphonates, bone-specific agents often linked to other drugs.  The ability of biphosphonates and similar agents to target bone is due to their great affinity for hydroxyapatite, the inorganic material that composes much of the skeleton.  Moreover, the skeletal uptake of 153Sm-EDTMP is superior to that of 111In-EDTMP and 99mTc-EDTMP. Thus, when chelated by EDTMP, the samarium radionuclide also plays a role in bone targeting. 
153Sm-EDTMP has a high affinity for bone, and is also largely selective to malignant cells. The adsorption of 153Sm-EDTMP is found to be about four times higher in the metastatic region of the bone than in unaffected regions.  This selectivity may be explained by the enhanced metabolic activity of metastatic regions of bone. As 153Sm-EDTMP readily chelates calcium cations, the compound will accumulate in the metastatic sites where metabolism and thus calcium levels are highest. 
There are two major sources of toxicity from 153Sm-EDTMP treatment: unchelated samarium and the targeting of sites other than bone by 153Sm-EDTMP. Sm3+ metal has been found to distribute to the liver, lungs, and spleen. Thus, it is imperative during the formulation process that 153Sm-EDTMP contain as little unchelated Sm3+ as possible to avoid uptake by liver and hepatotoxicity.  Additionally, bone marrow toxicity is often observed during 153Sm-EDTMP therapy. Interestingly, if a radionuclide could be used that emitted beta particles with a shorter range than 153Sm, more of the energy would be delivered to the bone tissue and less would be deposited in the adjacent bone marrow.  Moreover, significant radiation from 153Sm is often delivered to the bladder wall and kidneys.
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