Sharma Rohit, Kumar Chandan, Mallia Madhava B, Kameswaran Mythili, Sarma Haladhar D, Banerjee Sharmila, Dash Ashutosh
1 Radiopharmaceuticals Division, Bhabha Atomic Research Centre , Mumbai, India .
2 Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre , Mumbai, India .
Cancer Biother Radiopharm. 2017 Jun;32(5):184-191. doi: 10.1089/cbr.2017.2200. Epub 2017 Jun 9.
Skeletal metastasis is common in advanced stages of various cancers, particularly of the prostate and breast carcinoma. Re-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 Re-HEDP in osteosarcoma cells and biodistribution studies in mice.Re-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 Re-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.
骨转移在各种癌症的晚期很常见，尤其是前列腺癌和乳腺癌。Re-HEDP（1-羟基乙烷-1,1-二膦酸）是一种临床上已确立的用于缓解骨转移骨痛的放射性药物，它利用了高骨亲和力。目前的工作旨在阐明Re-HEDP在骨肉瘤细胞中杀伤细胞的可能机制以及在小鼠中的生物分布研究。Re-HEDP复合物是使用内部制备的冻干HEDP试剂盒制备的。发现在矿化骨基质中的体外细胞摄取率在2小时时为13.41%±0.46%，在存在过量未标记HEDP配体的情况下降至2.44%±0.12%。Re-HEDP在正常瑞士小鼠体内的骨骼和体外矿化骨中的摄取表明其对骨基质具有亲和力。该研究还表明，细胞毒性和G2/M细胞周期阻滞呈剂量依赖性。在较高剂量下，观察到G2/M细胞周期阻滞，这可能是细胞死亡的主要原因以及缓解骨痛的可能机制。
