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Labeling, characterization, and in vivo localization of a new Y-90-based phosphonate chelate 2,3-dicarboxypropane-1,1-diphosphonic acid for the treatment of bone metastases: Comparison with Tc-99m-DPD complex

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Đokić, Divna Đ.
Janković, Drina
Nikolić, Nadežda S.
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Abstract
The goal of this investigation was to examine the possibilities for yttrium-90-labeling of the 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), which is currently labeled with technetium-99m and as a Tc-99m-DPD clinically used as bone imaging agent. Analysis of the complex enclosed the radiochemical quality control methods, biodistribution studies, as well as the determination of pharmacokinetic parameters. The biological behavior of complexes Y-90-DPD, Tc-99m-DPD and Y-90-labeled DPD-kit formulation [Y-90-(Sn)-DPD] in animal model was compared. The labeling conditions were standardized to give the maximum yield, which ranged between 93% and 98%. The examined Y-90 complex could be easily prepared, with an outstanding yield and was also found to be very stable for at least 10 h after Y-90-labeling. Protein binding value was 4.6 +/- 0.7% for Y-90-DPD complex and the complex possess a hydrophilic character. The satisfactory results of Y-90- DPD biodistribution in healthy test animals wer...e obtained; the uptake in the bone was 11-13% ID/g after 24 h depending on the pH value during the preparation. With high skeletal uptake, a minimum uptake in soft tissues and rapid blood clearance the Y-90-DPD complex proved to be an excellent candidate for targeting tumor therapy. (C) 2008 Elsevier Ltd. All rights reserved.

Keywords:
phosphonates / DPD / Y-90-radiolabeling / targeted tumor therapy
Source:
Bioorganic and Medicinal Chemistry, 2008, 16, 8, 4457-4465

DOI: 10.1016/j.bmc.2008.02.062

ISSN: 0968-0896 (print)

PubMed: 18331797

WoS: 000255246100024

Scopus: 2-s2.0-42349099555
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http://vinar.vin.bg.ac.rs/handle/123456789/3240
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