Kumar Chandan, Sharma Rohit, Das Tapas, Korde Aruna, Sarma Haladhar, Banerjee Sharmila, Dash Ashutosh
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
J Labelled Comp Radiopharm. 2018 Sep;61(11):837-846. doi: 10.1002/jlcr.3651. Epub 2018 Jul 11.
Bone pain is the major manifestation of skeletal metastases. Although various treatment modalities are available for bone pain palliation, use of radiolabeled phosphonates is documented to be more effective. Among radionuclides available for this purpose, lutetium-177 is gaining popularity due to its moderate beta energy, theranostic capability, favorable half-life and convenient production logistics. Lu-DOTMP has shown considerable promise as a metastatic bone pain palliating agent in preliminary evaluations and recent clinical studies. Therefore, an attempt was made to elucidate the possible mechanism of in vitro cell death induced by Lu-DOTMP in MG63 cells. Lu-DOTMP binding studies were carried out in mineralized bone of MG63 cells and around 50% binding was observed. Skeletons of Wistar rats showed 1.78 ± 0.5% IA/g at a 3 h time period which was almost constant up to 7 days. MG63 cells were incubated with 3.7 and 37 MBq of Lu-DOTMP for 48 h prior to perform assays. An increase in the magnitude of cell toxicity and apoptotic DNA fragmentation was observed. Enhancement of G2/M phase cell cycle arrest and apoptosis were documented which were dose-dependent. Thus, Lu-DOTMP induced apoptotic cell death in MG63 cells, which might be one of the primary causes of pain relief in osseous metastases.
骨痛是骨转移的主要表现。尽管有多种治疗方式可用于缓解骨痛，但已证明使用放射性标记的膦酸盐更为有效。在可用于此目的的放射性核素中，镥-177因其适度的β能量、诊疗能力、良好的半衰期和便捷的生产物流而越来越受欢迎。在初步评估和近期临床研究中，镥-二甲基膦酸五甲酯（Lu-DOTMP）作为一种转移性骨痛缓解剂已显示出相当大的前景。因此，人们试图阐明Lu-DOTMP在MG63细胞中诱导体外细胞死亡的可能机制。在MG63细胞的矿化骨中进行了Lu-DOTMP结合研究，观察到约50%的结合率。在3小时时间段内，Wistar大鼠骨骼的摄取量为1.78±0.5%注射活度/克，直至7天几乎保持恒定。在进行检测之前，将MG63细胞与3.7和37MBq的Lu-DOTMP孵育48小时。观察到细胞毒性程度和凋亡性DNA片段化增加。记录到G2/M期细胞周期阻滞和凋亡增强，且呈剂量依赖性。因此，Lu-DOTMP在MG63细胞中诱导凋亡性细胞死亡，这可能是骨转移疼痛缓解的主要原因之一。
