Erfani Mostafa, Rahmani Nasim, Doroudi Alireza, Shafiei Mohammad
Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), P.O.Box: 14395-836, Tehran, Iran.
School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, P.O.Box: 61357-33184, Ahvaz, Iran.
Nucl Med Biol. 2017 Jun;49:1-7. doi: 10.1016/j.nucmedbio.2017.02.001. Epub 2017 Feb 24.
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.
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.
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.
These results show that due to its biological capabilities it would be advantageous to use Re-PMA for bone pain palliation therapy.
铼-188-羟基亚乙基二膦酸盐（Re-HEDP）作为第一代双膦酸盐，已被广泛用作转移性骨病病例中的亲骨性放射性药物。尚未有关于制备铼与帕米膦酸（3-氨基羟丙基亚乙基-1,1-双膦酸）（PMA）（作为第二代双膦酸盐）的配合物的研究报道。基于这一事实，有人推测可以开发一种亲骨性的Re-PMA放射性药物，作为因骨转移引起的骨痛姑息性放疗的药物。
用从氧化铝基W/Re发生器洗脱的ReO对帕米膦酸进行标记。对标记进行了优化，并通过薄层色谱法（TLC）和高效液相色谱法（HPLC）进行放射化学分析。在小鼠中评估并进一步验证了这种放射性缀合物的生物分布。
成功制备了Re-PMA，标记产率高（>95%），比活度为124MBq/μmol，体外稳定性良好，但它可能由多种物质组成。在生物分布研究中，观察到骨骼系统中活性的选择性摄取和保留（注射后4小时和48小时骨中的摄取率分别为0.81±0.25%ID/g和0.57±0.16），随后软组织中的活性被清除。
这些结果表明，由于其生物学特性，使用Re-PMA进行骨痛姑息治疗将是有利的。
