Efficient preparation and stabilization of Re-188-MDP under physiological conditions

Labeling of diphosphonate ligands such as MDP and HEDP with the generator-produced 13-emitting radioisotope Re-188 is currently of considerable interest due to the potential application of this type of therapeutic agents for pain palliation. Various methods have been proposed for the high-yield preparation of Re- 188-MDP and Re-188-HEDP, and these are all based on the use of significant amounts of stannous chloride and were carried out at very low pH values. Increasing the final pH at values acceptable for in wvo injection (5-7) usually caused a rapid decomposition of the resulting compounds with concomitant formation of large amounts of Re- 188-perrhenate. We describe here a new procedure for the efficient reduction of generator- produced Re-188-perrhenate that was applied to the quantitative preparation of Re-188-MDP under physiological conditions. This procedure is based on the reaction of Re-188-perrhenate with oxalate and stannous ions conducted in the presence of a large host molecule such as y-cyclodextrin. It was observed that the high-yield formation of Re- 188-MDP (> 97%) could be accomplished in 15-30 min, at room temperature and at pH = 5.5. No formation of Re-188-perrhanate or hydrolyzed Re-188-dioxide was observed in solution over a period of 24 hours, indicating that the stability of the resulting products remained almost unchanged. The influence of the concentrations of the various reactants ~on the yield ofRe-188-MDP were studied in detail. Biodistribution experiments have been performed in rat models with different types of bone lesions. The results showed that Re-188-MDP, prepared through the new procedure, was retained into bone tissues, and that it was able to localize selectively into bone lesions.