Lu-Labeled ethylenediamine tetramethylene phosphonic acid

Most patients with malignancies of the breast, prostate, lungs, thyroid, or kidneys suffer from severe bone pain due to metastases of the cancer to the skeletal tissue (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 on the patient (3). Radiopharmaceuticals containing nuclides such as strontium-89 (as SrCl) and samarium-153 (administered as Sm-labeled ethylenediamine tetramethylene phosphonic acid (EDTMP)), which have been approved by the United States Food and Drug Administration for the treatment of bone pain due to metastases, are commonly used for palliative care of pain in the bones of cancer patients (3). However, these are not ideal agents to treat bone pain because the radionuclide either has a long half-life and generates high-energy β particles (Sr has a half-life of ~50 days; = 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; γ = 103 keV (28%)) (2). A major limitation of using these bone pain palliative agents is that they produce myelotoxicity in some patients (4). Between the two labeled compounds, SrCl appears to be the agent of choice for clinical applications because its longer half-life allows some flexibility to develop a suitable treatment regimen for the patient. There is great interest in the development of alternative radiolabeled compounds that can be used to treat pain resulting from osseous metastases (3). An important characteristic of this labeled compound is that it must have the ability to be targeted specifically to the cancerous lesions on the skeleton and should be minimally toxic to the bone marrow as discussed elsewhere (4-6). In an earlier study with healthy rats, it was reported that EDTMP labeled with lutetium-177 ([Lu]-EDTMP) was cleared rapidly from blood circulation, showed little uptake in the soft tissues, and accumulated primarily in the bones of these animals (7). Chakraborty et al. made similar observations when they investigated the biodistribution of [Lu]-EDTMP in rats (8). A freeze-dried kit for the preparation of [Lu]-EDTMP was developed subsequently by Garnuszek et al. (9). On the basis of these observations, there is a renewed interest to use Lu (half-life, ~7 days; = 497 keV; γ = 113 keV (6.4%); 208 keV (11%)) as an alternative nuclide to those currently in use (Sr and Sm) in the development of a palliative care agent for pain due to the metastases of cancer to the skeletal tissue (5, 6). The main advantages of using Lu are that it can be easily transported to places where it is not available and the low-energy gamma photons emitted by the nuclide allow detection of the bone lesions with scintigraphy. The biodistribution of [Lu]-EDTMP was studied recently in mice, rats, and rabbits, and scintigraphic imaging was performed on rodents, rabbits, and dogs (5, 6). In addition, the International Atomic Energy Agency has initiated projects to develop Lu-labeled compounds as palliative care agents for bone pain (6).