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

摘要

Objective: 99mTc-Sn-PYP (Technetium-99 m 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. Methods: 177Lu was produced by irradiating lutetium foil (11mg) natural target at a flux ~1.0×10 14n/cm 2/s for 12h in the swimming pool type reactor. 177Lu in the form of 177LuCl 3 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 300V and 45mA current using 0.025M phosphate buffer (pH 6.9). Bioevaluation studies with rabbit under γ-camera were also performed to verify the skeletal uptake. Results: The 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±0.01min 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 24h post injection also showed high skeletal uptake. Conclusion: The 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 24h post injection showed high skeletal uptake, suggesting that it may be useful as a bone-pain palliation agent for the treatment of bone metastases.