Studies on the labeling of Ethylenediaminetetramethylene phosphonic acid, Methylene Diphosphonate, Sodium pyrophosphate and Hydroxyapatite with Lutetium-177 for use in nuclear medicine

For the treatment of skeletal metastasis, a therapeutic radionuclide tagged with a bone seeking ligand is required, while for radiation synovectomy (RS), a therapeutic radionuclide irreversibly attached to pre-formed particles of appropriate size is required. Radio lanthanides are mostly therapeutic, and ligands containing phosphate groups are predominantly bone seekers. Exploiting these facts, number of new therapeutic radiopharmaceuticals could be developed. Labeling of four phosphate containing materials was pursued in the present study. It was hypothesized that various ¹⁷⁷ Lu-labeled bone-seeking complexes such as ¹⁷⁷ Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP), ¹⁷⁷ Lu-methylene diphosphonate (MDP) and ¹⁷⁷ Lu-pyrophosphate (PYP) could be developed as agents for palliative radiotherapy of bone pain due to skeletal metastases, and ¹⁷⁷ Lu-Hydroxyapatite (HA) could be developed as an agent for radiosynovectomy of small joints. Lyophilized kit vials of EDTMP, MDP and sodium pyrophosphate (Na-PYP) were formulated. HA particles were synthesized locally and purity was checked by high-performance liquid chromatography (HPLC). ¹⁷⁷ Lu was labeled with EDTMP, MDP, PYP, and HA and the behavior of all was studied by radio-thin layer chromatography (TLC) radio-HPLC and radio-electrophoresis. Radio-TLC confirmed the labeling. HPLC analysis too verified the labeling. Radio-electrophoresis results depicted peaks for ¹⁷⁷ Lu-MDP, ¹⁷⁷ Lu-EDTMP and ¹⁷⁷ Lu-PYP at 3.37 ΁ 0.06 cm, 5.53 ΁ 0.15 cm and 7.03 ΁ 0.06 cm respectively confirming negative charge on each specie as all migrated toward positive anode. All 3 methods verified the labeling. The study demonstrated that EDTMP, MDP and PYP form stable complexes with ¹⁷⁷ Lu in injectable solution form. HA particulates could too be labeled with ¹⁷⁷ Lu with high radiochemical yields (>98%) in suspension form. Former three could be utilized as bone-pain palliation agents for the treatment of bone metastases, and the later could be applied for the treatment of Rheumatoid arthritis of small joints. The study has also indicated the possibility of developing other numerous radiolanthanide analogs with the potentials of possible use in radiation therapy.

Keywords

¹⁷⁷ Lu-labeled methylene diphosphonate - bone-pain palliation - radiation synovectomy - radio-labeling

Publication History

Article published online:
21 May 2022