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Rhemium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation

Ogawa, Kazuma*; Mukai, Takahiro*; Arano, Yasushi*; Otaka, Akira*; Ueda, Masashi*; Uehara, Tomoya*; Magata, Yasuhiro*; Hashimoto, Kazuyuki; Saji, Hideo*

To develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we synthesized a bisphosphonate derivative labeled with rhenium-186 ($$^{186}$$Re) that contains a hydroxyl group at the central carbon of its bisphosphonate structure and attached a stable $$^{186}$$Re-MAMA chelate to the amino group of a 4-amino-butylidene-bisphosphonate derivative, $$^{186}$$Re-MAMA-HBP, and investigated the effect of a hydroxyl group at the central carbon of its bisphosphonate structure on the affinity for hydroxyapatite and biodistribution by conducting a comparative study with $$^{186}$$Re-MAMA-BP. $$^{186}$$Re-MAMA-HBP was prepared by a reaction with $$^{186}$$ReO$$_{4}$$$$^{-}$$ and SnCl$$_{2}$$ in citrate buffer after the deprotection of trityl groups of Tr-MAMA-HBP. After reversed phase HPLC, $$^{186}$$Re-MAMA-HBP had a radiochemical purity of over 95 %. Compared with $$^{186}$$Re-MAMA-BP, $$^{186}$$Re-MAMA-HBP showed a greater affinity for hydroxyapatite beads in vitro and accumulated a significantly higher level in the femur in vivo. Thus, the introduction of a hydroxyl group into $$^{186}$$Re complex-conjugated bisphosphonates would be effective in enhancing accumulation in bone. These findings provide useful information on the design of bone-seeking therapeutic radiopharmaceuticals.

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Category:Radiology, Nuclear Medicine & Medical Imaging

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