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 (
Re) that contains a hydroxyl group at the central carbon of its bisphosphonate structure and attached a stable
Re-MAMA chelate to the amino group of a 4-amino-butylidene-bisphosphonate derivative,
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
Re-MAMA-BP.
Re-MAMA-HBP was prepared by a reaction with
ReO
and SnCl
in citrate buffer after the deprotection of trityl groups of Tr-MAMA-HBP. After reversed phase HPLC,
Re-MAMA-HBP had a radiochemical purity of over 95 %. Compared with
Re-MAMA-BP,
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
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.