Background

[PubMed]

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 ⁸⁹SrCl₂) and samarium-153 (administered as ¹⁵³Sm-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 (⁸⁹Sr has a half-life of ~50 days; E_β(max) = 1.49 MeV) or is short-lived and has to be produced in close vicinity to the treatment center (¹⁵³Sm has a half-life of ~47 h; E_β(max) = 0.81 MeV; Eγ = 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, ⁸⁹SrCl₂ 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 ([¹⁷⁷Lu]-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 [¹⁷⁷Lu]-EDTMP in rats (8). A freeze-dried kit for the preparation of [¹⁷⁷Lu]-EDTMP was developed subsequently by Garnuszek et al. (9). On the basis of these observations, there is a renewed interest to use ¹⁷⁷Lu (half-life, ~7 days; E_β(max) = 497 keV; Eγ = 113 keV (6.4%); 208 keV (11%)) as an alternative nuclide to those currently in use (⁸⁹Sr and ¹⁵³Sm) 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 ¹⁷⁷Lu 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 [¹⁷⁷Lu]-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 ¹⁷⁷Lu-labeled compounds as palliative care agents for bone pain (6).

Synthesis

[PubMed]

The synthesis of [¹⁷⁷Lu]-EDTMP has been described by Chakraborty et al. (5, 8). The radiochemical yield and purity of the labeled compound were reported to be >98% and >99.0%, respectively, as determined with paper chromatography (R_f of [¹⁷⁷Lu]-EDTMP was ~1, whereas ¹⁷⁷LuCl₃, the labeling agent, stayed at the origin) and paper electrophoresis (only [¹⁷⁷Lu]-EDTMP moved toward the anode). The specific activity of the radiochemical was not reported.

The development of a freeze-dried kit containing sodium EDTMP, stannous chloride, and ascorbic acid for the preparation of [¹⁷⁷Lu]-EDTMP was reported by Garnuszek et al. (9). The yield of the final labeled product prepared from this kit was >99% as determined with paper chromatography and paper electrophoresis. The specific activity of the radiolabeled compound varied from 3.2 GBq/mg (86 mCi/mg) to 390 GBq/mg (10.5 Ci/mg) depending on the specific activity of the ¹⁷⁷LuCl₃ used to prepare the tracer.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

The [¹⁷⁷Lu]-EDTMP complex was reported to retain its stability at room temperature for at least 14 days (8). Investigators have also reported that [¹⁷⁷Lu]-EDTMP prepared from a freeze-dried kit had a purity of >99% over a period of 10 days (9). Chakraborty et al. reported that [¹⁷⁷Lu]-EDTMP maintained a purity of >99% at room temperature for at least 30 days under in vitro conditions (5). In another study, incubation of [¹⁷⁷Lu]-EDTMP in the presence of 0.1 M hydrochloric acid was shown to reduce its purity to <70% within 24 h (10).

Animal Studies

Human Studies

[PubMed]

No publications are currently available.

Supplemental Information

[Disclaimers]

No information is currently available.

References

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