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 journalArticle

52 Citations (Scopus)

Abstract

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
Volume33
Issue number4
DOIs
Publication statusPublished - May 2006
Externally publishedYes

Fingerprint

Diphosphonates
Bone and Bones
Pain
Radiopharmaceuticals
Hydroxyl Radical
Durapatite
Carbon
Rhenium
Reverse-Phase Chromatography
Citric Acid
Femur
(N-(2-((4-((4-hydroxy-4,4-diphosphonobutyl)amino)-4-oxobutyl)-2-thioethylamino)acetyl)-2-aminoethanethiolate)oxorhenium(V)
Buffers
High Pressure Liquid Chromatography
Neoplasm Metastasis
(N-(2-((3-(3,3-diphosphonopropylcarbamoyl)propyl)-2-thioethylamino)acetyl)-2-aminoethanethiolate)oxorhenium(V)

Keywords

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

ASJC Scopus subject areas

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

Cite this

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.

In: Nuclear Medicine and Biology, Vol. 33, No. 4, 05.2006, p. 513-520.

Research output: Contribution to journalArticle

Ogawa, K, Mukai, T, Arano, Y, Otaka, A, Ueda, M, Uehara, T, Magata, Y, Hashimoto, K & Saji, H 2006, 'Rhemium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation', Nuclear Medicine and Biology, vol. 33, no. 4, pp. 513-520. https://doi.org/10.1016/j.nucmedbio.2006.03.006
Ogawa, Kazuma ; Mukai, Takahiro ; Arano, Yasushi ; Otaka, Akira ; Ueda, Masashi ; Uehara, Tomoya ; Magata, Yasuhiro ; Hashimoto, Kazuyuki ; Saji, Hideo. / Rhemium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation. In: Nuclear Medicine and Biology. 2006 ; Vol. 33, No. 4. pp. 513-520.
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AU - Otaka, Akira

AU - Ueda, Masashi

AU - Uehara, Tomoya

AU - Magata, Yasuhiro

AU - Hashimoto, Kazuyuki

AU - Saji, Hideo

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N2 - 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.

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