[Tm]-Labeled ethylenediamine tetramethylene phosphonic acid

Due to the metastases of cancer in the skeletal tissue, severe bone pain affects the quality of life of most patients suffering from malignancies of the breast, prostate, lungs, thyroid, or kidneys (2, 3). Although several interventions such as analgesics, bisphosphonates, hormone therapy, and systemic radionuclide therapy are available to manage the pain, these treatments are known to have many undesirable secondary effects (3). Radiopharmaceuticals that contain nuclides, such as strontium-89 (as SrCl) and samarium-153 (administered as Sm-ethylenediamine tetramethylene phosphonic acid (EDTMP)), which are commonly used for palliative care of pain in the bones of these cancer patients, have been approved by the United States Food and Drug Administration (FDA) for the treatment of this condition (3). However, these are not the most ideal agents to treat pain due to bone metastases because the radionuclide either has a long half-life and generates high-energy β particles (Sr has a half-life of ~50 days and = 1.49 MeV) or is short-lived and has to be produced in close vicinity to the treatment center (Sm has a half-life of ~47 h, = 0.81 MeV, and γ = 103 keV (28%)) (2). In addition, both of these bone pain palliative agents are known to produce myelotoxicity in some patients (4). Between the two labeled compounds, SrCl appears to be the agent of choice for clinical applications because of its longer half-life, which provides the flexibility to develop a suitable treatment regimen for the patient. There is much interest to develop alternative radiolabeled compounds that do not suppress the bone marrow but are suitable to treat pain resulting from osseous metastases as discussed by Jansen et al. (4). Recently, Das et al. evaluated the use of thulium-170 (Tm has a half-life of ~128 days, = 968 keV, and γ = 84 keV (3.26%)) as an alternative to SrCl for the development of a bone pain palliative (2). According to these investigators, Tm would probably exhibit low myelosupression because it emits β particles of lower energy than those emitted by Sr, and the γ-photons generated by the nuclide can be used for scintigraphy to detect the accumulation and location of the radiolabel in the organs of an animal. This chapter describes the biodistribution of Tm-labeled EDTMP (Tm-EDTMP) in normal Wistar rats (2).