Preparation and evaluation of rhenium-188-pamidronate as a palliative treatment in bone metastasis.

OBJECTIVE

Rhenium-188-hydroxyethylidene diphosphonate (Re-HEDP) as a first generation bisphosphonate has been widely used for bone seeking radiopharmaceutical in cases of metastatic bone disease. No study has been yet reported on preparing a complex of Re with pamidronate (3-aminohydroxypropylidene-1,1-bisphosphonic acid) (PMA) as a second generation bisphosphonate. Based on this fact, it was hypothesized that a bone-seeking Re-PMA radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases.

METHODS

Pamidronate was labeled with ReO eluted from the alumina based W/Re generator. Labeling was optimized, and radiochemical analysis was performed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Biodistribution of this radioconjugate was evaluated and verified further in mice.

RESULTS

Re-PMA was prepared successfully in a high labeling yield (˃95%) corresponding to a specific activity of 124MBq/μmol and good in vitro stability, but it is likely to consist of multiple species. In biodistribution studies selective uptake and retention of activity in the skeletal system (0.81±0.25% ID/g and 0.57±0.16 at 4 and 48h in bone post injection respectively) followed by clearance in the soft tissues were observed.

CONCLUSION

These results show that due to its biological capabilities it would be advantageous to use Re-PMA for bone pain palliation therapy.