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

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

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)


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 (186Re) that contains a hydroxyl group at the central carbon of its bisphosphonate structure, we attached a stable 186Re-MAMA chelate to the amino group of a 4-amino butylidene-bisphosphonate derivative [N-[2-[[4-[(4-hydroxy-4,4-diphosphonobutyl)amino]-4-oxobutyl]-2-thioethylamino]acetyl]-2-aminoethanethiolate] oxorhenium (V) (186Re-MAMA-HBP) and we investigated the effect of a hydroxyl group at the central carbon of its bisphosphonate structure on affinity for hydroxyapatite and on biodistribution by conducting a comparative study with [N-[2-[[3-(3,3-diphosphonopropylcarbamoyl)propyl]-2-thioethylamino]acetyl]-2-aminoethanethiolate] oxorhenium (V) (186Re-MAMA-BP). The precursor of 186Re-MAMA-HBP, trityl (Tr)-MAMA-HBP, was obtained by coupling a Tr-MAMA derivative to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. 186Re-MAMA-HBP was prepared by a reaction with 186ReO4- and SnCl2 in citrate buffer after the deprotection of the Tr groups of Tr-MAMA-HBP. After reversed-phase high-performance liquid chromatography, 186Re-MAMA-HBP had a radiochemical purity of over 95%. Compared with 186Re-MAMA-BP, 186Re-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 186Re complex-conjugated bisphosphonates would be effective in enhancing accumulation in bones. These findings provide useful information on the design of bone-seeking therapeutic radiopharmaceuticals.

Original languageEnglish
Pages (from-to)513-520
Number of pages8
JournalNuclear Medicine and Biology
Issue number4
Publication statusPublished - May 2006
Externally publishedYes


  • Bisphosphonate
  • Bone
  • Monoaminemonoamidedithiols
  • Palliation
  • Rhenium-186

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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