Preliminary studies on 177Lu-labeled sodium pyrophosphate (177Lu-PYP) as a potential bone-seeking radiopharmaceutical for bone pain palliation

Objective99mTc-Sn-PYP (Technetium-99m labeled tin pyrophosphate) has been widely used as a radiopharmaceutical for bone scanning as well as in nuclear cardiology. It is also found in the body in trace amounts. 177Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. PYP is an analogue of MDP and MDP has been labeled with 177Lu. No study on preparing a complex of 177Lu with PYP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking 177Lu-PYP (Lutetium-177 labeled Pyrophosphate) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases.Methods177Lu was produced by irradiating lutetium foil (11 mg) natural target at a flux ∼ 1.0 × 1014n/cm2/s for 12 h in the swimming pool type reactor. 177Lu in the form of 177LuCl3 was labeled with PYP. The radiochemical purity and labeling efficiencies were determined by paper chromatography. Labeling of 177Lu with PYP was optimized and a labeled sample was subjected to HPLC analysis. To determine the charge on the 177Lu-PYP complex, radio-electrophoresis was conducted for 1 h under a voltage of 300 V and 45 mA current using 0.025 M phosphate buffer (pH 6.9). Bioevaluation studies with rabbit under γ-camera were also performed to verify the skeletal uptake.ResultsThe quality control using paper radio-chromatography has shown > 99% radiochemical purity of 177Lu-PYP complex. Radio-chromatography also showed maximum labeling at ligand/metal ratio = 60:1. HPLC analysis showed 1.42 ± 0.01 min retention time of 177Lu-PYP complex. No decrease in labeling was observed at higher temperatures. Gamma-camera images of 177Lu-PYP in normal rabbit at 24 h post injection also showed high skeletal uptake.ConclusionThe study demonstrated that sodium pyrophosphate could be labeled with 177Lu with high radiochemical yields (> 99%). Negatively charged 177Lu-PYP complex retained stability for a day and at high temperatures too. Gamma-camera images of 177Lu-PYP in normal rabbit at 24 h post injection showed high skeletal uptake, suggesting that it may be useful as a bone-pain palliation agent for the treatment of bone metastases.