Chemical Design of 99mTc-Labeled Probes for Targeting Osteogenic Bone Region

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• 作者：Mashiho Yanagi ; Tomoya Uehara ; Yukie Uchida ; Sachiko Kiyota ; Mai Kinoshita ; Yusuke Higaki ; Hiromichi Akizawa ; Hirofumi Hanaoka ; Yasushi Arano
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：July 17, 2013
• 年：2013
• 卷：24
• 期：7
• 页码：1248-1255
• 全文大小：349K
• 年卷期：v.24,no.7(July 17, 2013)
• ISSN：1520-4812

文摘

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.