Chemical Design of ^sup 99m^Tc-Labeled Probes for Targeting Osteogenic Bone Region

Radionuclide bone imaging using polynuclear ...Tc 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 ...Tc-labeled compound considering...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2013-07, Vol.24 (7), p.1248
Main Authors: Yanagi, Mashiho, Uehara, Tomoya, Uchida, Yukie, Kiyota, Sachiko, Kinoshita, Mai, Higaki, Yusuke, Akizawa, Hiromichi, Hanaoka, Hirofumi, Arano, Yasushi
Format: Article
Language:English
Subjects:
Bone cancer
Clinical medicine
Membranes
Molecules
Permeability
Rodents
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Radionuclide bone imaging using polynuclear ...Tc 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 ...Tc-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 ...Tc chelating moiety to prepare EC-[(d-Asp)5]2. The molecular size, HA binding, and pharmacokinetics of ...Tc-EC-[(d-Asp)5]2 in normal mice and model rats bearing osteogenic tumor were compared to those of ...Tc-MDP and ...Tc-EC with one (d-Asp)5 motif, ...Tc-EC-(d-Asp)5. The molecular size of ...Tc-EC-[(d-Asp)5]2 was higher than that of ...Tc-MDP and ...Tc-EC-(d-Asp)5 when determined by permeability of the ...Tc-compounds through a membrane filter (10 kDa). The HA binding of ...Tc-EC-[(d-Asp)5]2 was higher than and similar to that of ...Tc-EC-(d-Asp)5 and 99mTc-MDP. ...Tc-EC-[(d-Asp)5]2 exhibited significantly lower accumulation in normal bone of mice than did ...Tc-MDP. In osteogenic tumor bearing model rats, ...Tc-EC-[(d-Asp)5]2 accumulated in the osteogenic and normal bone region similar to and lower than ...Tc-MDP, respectively. Although further studies including the chain length of d-Asp are required, these findings indicated that the present chemical design of ...Tc-labeled probe would be applicable to develop ...Tc-labeled probes for selective imaging of osteogenic bone region as well as develop therapeutic agents using therapeutic radionuclides such as ...Y, ...Lu, ...Re, or ...Re and cytotoxic agents to osteogenic bone tumor region. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:1043-1802
1520-4812