In Vitro Evaluation of 188Re-HEDP: A Mechanistic View of Bone Pain Palliations.

Skeletal metastasis is common in advanced stages of various cancers, particularly of the prostate and breast carcinoma. 188Re-HEDP (1-hydroxyethane 1, 1-diphosphonic acid) is a clinically established radiopharmaceutical for bone pain palliation of osseous metastasis, and it takes advantage of high bone affinity. The present work aims at elucidating the possible mechanisms of cell killing by 188Re-HEDP in osteosarcoma cells and biodistribution studies in mice.188Re-HEDP complex was prepared by using lyophilized HEDP kits prepared in-house. In vitro cellular uptake in mineralized bone matrix was found to be 13.41% ± 0.46% (at 2 hours), which was reduced to 2.44% ± 0.12% in the presence of excess amounts of unlabeled HEDP ligand. Uptake of 188Re-HEDP in bones of normal Swiss mice in vivo and mineralized bone in vitro indicated its affinity toward the bone matrix. The study also revealed that cellular toxicity and G2/M cell cycle arrest were dose dependent. At higher doses, G2/M cell cycle arrest was observed, which might be the major cause of cell death and a possible mechanism of bone pain relief.