This article reports the syntheses and evaluation of ⁶⁸Ga‐ and ¹⁵³Sm‐complexes of a new DOTA (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid)‐conjugated geminal bisphosphonate, DOTA‐Bn‐SCN‐BP, for their potential uses in the early detection of skeletal metastases by imaging and palliation of pain arising from skeletal metastases, respectively. The conjugate was synthesized in high purity following an easily adaptable three‐step reaction scheme. Gallium‐68‐ and ¹⁵³Sm‐complexes were prepared in high yield (>98%) and showed excellent in vitro stability in phosphate‐buffered saline (PBS) and human serum. Both the complexes showed high affinity for hydroxyapatite particles in in vitro binding study. In biodistribution studies carried out in normal Wistar rats, both the complexes exhibited rapid skeletal accumulation with almost no retention in any other major organ. The newly synthesized molecule DOTA‐Bn‐SCN‐BP would therefore be a promising targeting ligand for the development of radiopharmaceuticals for both imaging skeletal metastases and palliation of pain arising out of it in patients with cancer when radiolabeled with ⁶⁸Ga and ¹⁵³Sm, respectively. A systematic comparative evaluation, however, showed that there was no significant improvement of skeletal accumulation of the ¹⁵³Sm‐DOTA‐Bn‐SCN‐BP complex over ¹⁵³Sm‐DOTMP (1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethylenephosphonic acid) as the later itself demonstrated optimal properties required for an agent for bone pain palliation.

中文翻译：

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68Ga和153Sm标记的DOTA共轭双膦酸酯配体的合成和评估，可潜在地用于检测骨骼转移和管理由骨骼转移引起的疼痛

本文报告了新的DOTA（1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸）-共轭双膦酸酯双膦酸酯（DOTA-Bn）的⁶⁸ Ga-和¹⁵³ Sm-配合物的合成和评估。‐SCN-BP，分别用于通过成像和缓解因骨骼转移引起的疼痛而在早期检测骨骼转移中的潜在用途。按照易于适应的三步反应方案，以高纯度合成了结合物。镓68和¹⁵³Sm复合物的制备产率高（> 98％），并且在磷酸盐缓冲液（PBS）和人血清中显示出出色的体外稳定性。在体外结合研究中，两种复合物均对羟基磷灰石颗粒显示出高亲和力。在正常Wistar大鼠中进行的生物分布研究中，两种复合物均显示出快速的骨骼积累，几乎没有保留在任何其他主要器官中。因此，新合成的DOTA-Bn-SCN-BP分子将成为有前途的靶向配体，可用于放射性药物的开发，用于在用⁶⁸ Ga和^153进行放射性标记的癌症患者中成像骨骼转移和减轻因疼痛引起的疼痛Sm，分别。然而，系统的比较评估表明，与¹⁵³ Sm-DOTMP相比，¹⁵³ Sm-DOTA-Bn-SCN-BP复合物的骨架积累没有明显改善（1、4、7、10-四氮杂环十二烷-1,4， 7,10-四亚甲基膦酸）后来证明了骨痛缓解剂所需的最佳性能。