Production of Holmium-166 DOTMP: A promising agent for bone marrow ablation in hematologic malignancies

  Intoduction: Therapeutic radiopharmaceuticals are radiolabeled molecules to deliver sufficient doses of ionizing radiation to specific disease sites such as bone metastases, brain and liver tumors and bone marrows malignancies including multiple myeloma. Among some therapeutic radiopharmaceuticals, 166Ho-1,4,7,10 -tetraazacyclo dodecane-1,4,7,10 tetraethylene phosphonic acid (166Ho-DOTMP) is used for delivering high doses to bone marrow. In this research production, quality control, pharmacokinetics and biodistribution studies of 166Ho-DOTMP with respect to its radiochemical and in vivo biological characteristics have been presented. Methods: Holmium-166 was produced by irradiation of holmium oxide (Ho2O3, purity > 99.8%) at a thermal neutron flux. 166Ho-DOTMP complex was obtained in very high yields (radiochemical purity > 99%) under the reaction conditions employed. Radiochemical purity and the stability of the 166Ho-DOTMP complex in human serum were assayed. Wild type rats were used for biodistribution and imaging studies of this agent. Results: 166Ho produced by irradiation of holmium-165 oxide demonstrated high radionuclide purity. 166Ho-DOTMP was obtained in very high yield (radiochemical purity > 99%) and the complex exhibited excellent in vitro stability at pH~7 when stored at room temperature and human serum. Biodistribution studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation of activity in other non-target organs. The scintigraphic image recorded in rat at 3 h after the injection of the 166Ho-DOTMP radiopharmaceutical revealed that 166Ho-DOTMP rapidly accumulated in skeleton especially in the thigh bones. Conclusion: Biodistribution, stability, imaging and pharmacokinetics studies of  166Ho-DOTMP radiopharmaceutical in this research showed favorable features such as; rapid and selective skeletal  uptake, fast clearance from blood and almost no uptake in any other major organs. Our research demonstrated that 166Ho-DOTMP has promising features suggesting good potential for efficient use of this radiopharmaceutical for bone marrow ablation in different hematologic malignancies including multiple myeloma.