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

Abstract

(99m)Tc-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. (177)Lu 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 (177)Lu. No study on preparing a complex of (177)Lu with PYP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking (177)Lu-PYP (Lutetium-177 labeled Pyrophosphate) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. (177)Lu was produced by irradiating lutetium foil (11mg) natural target at a flux ∼1.0×10(14)n/cm(2)/s for 12h in the swimming pool type reactor. (177)Lu in the form of (177)LuCl(3) was labeled with PYP. The radiochemical purity and labeling efficiencies were determined by paper chromatography. Labeling of (177)Lu with PYP was optimized and a labeled sample was subjected to HPLC analysis. To determine the charge on the (177)Lu-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. The quality control using paper radio-chromatography has shown >99% radiochemical purity of (177)Lu-PYP complex. Radio-chromatography also showed maximum labeling at ligand/metal ratio=60:1. HPLC analysis showed 1.42±0.01min retention time of (177)Lu-PYP complex. No decrease in labeling was observed at higher temperatures. Gamma-camera images of (177)Lu-PYP in normal rabbit at 24h post injection also showed high skeletal uptake. The study demonstrated that sodium pyrophosphate could be labeled with (177)Lu with high radiochemical yields (>99%). Negatively charged (177)Lu-PYP complex retained stability for a day and at high temperatures too. Gamma-camera images of (177)Lu-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.