Chemical design of 99mTc-labeled probes for targeting osteogenic bone region

Mashiho Yanagi, Tomoya Uehara, Yukie Uchida, Sachiko Kiyota, Mai Kinoshita, Yusuke Higaki, Hiromichi Akizawa, Hirofumi Hanaoka, Yasushi Arano

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9 Citations (Scopus)


Radionuclide bone imaging using polynuclear 99mTc complexes of bisphosphonates is the most common clinical practice in nuclear medicine. However, the improvement in the contrast between normal and osteogenic bone regions has been required. Herein we reported a new 99mTc-labeled compound considering the increased vascular permeability of osteogenic region. We selected penta-d-Asp as both a targeting motif to hydroxyapatite (HA) and a molecular size modifier, and two penta-d-Asp molecules were conjugated with the two carboxylate residues of ethylene dicysteine (EC) selected as the 99mTc chelating moiety to prepare EC-[(d-Asp)5] 2. The molecular size, HA binding, and pharmacokinetics of 99mTc-EC-[(d-Asp)5]2 in normal mice and model rats bearing osteogenic tumor were compared to those of 99mTc-MDP and 99mTc-EC with one (d-Asp)5 motif, 99mTc-EC-(d- Asp)5. The molecular size of 99mTc-EC-[(d-Asp) 5]2 was higher than that of 99mTc-MDP and 99mTc-EC-(d-Asp)5 when determined by permeability of the 99mTc-compounds through a membrane filter (10 kDa). The HA binding of 99mTc-EC-[(d-Asp)5]2 was higher than and similar to that of 99mTc-EC-(d-Asp)5 and 99mTc-MDP. 99mTc-EC-[(d-Asp)5]2 exhibited significantly lower accumulation in normal bone of mice than did 99mTc-MDP. In osteogenic tumor bearing model rats, 99mTc-EC-[(d-Asp)5]2 accumulated in the osteogenic and normal bone region similar to and lower than 99mTc- MDP, respectively. Although further studies including the chain length of d-Asp are required, these findings indicated that the present chemical design of 99mTc-labeled probe would be applicable to develop 99mTc-labeled probes for selective imaging of osteogenic bone region as well as develop therapeutic agents using therapeutic radionuclides such as 90Y, 177Lu, 186Re, or 188Re and cytotoxic agents to osteogenic bone tumor region.

Original languageEnglish
Pages (from-to)1248-1255
Number of pages8
JournalBioconjugate Chemistry
Issue number7
Publication statusPublished - Jul 17 2013

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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