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Structure-Activity Relationships of ^sup 111^In- and ^sup 99m^TcLabeled Quinolin-4-one Peptidomimetics as Ligands for the Vitronectin Receptor: Potential Tumor Imaging Agents

The integrin receptor α^sub v^ß^sub 3^ is overexpressed on the endothelial cells of growing tumors and on some tumor cells themselves. Radiolabeled α^sub v^ß^sub 3^ antagonists have demonstrated potential application as tumor imaging agents and as radiotherapeutic agents. This report describes the t...

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Bibliographic Details
Published in:Bioconjugate chemistry 2006-09, Vol.17 (5), p.1294
Main Authors: Harris, Thomas D, Kalogeropoulos, Shirley, Nguyen, Tiffany, Dwyer, Gregory
Format: Article
Language:English
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Summary:The integrin receptor α^sub v^ß^sub 3^ is overexpressed on the endothelial cells of growing tumors and on some tumor cells themselves. Radiolabeled α^sub v^ß^sub 3^ antagonists have demonstrated potential application as tumor imaging agents and as radiotherapeutic agents. This report describes the total synthesis of eight new HYNIC and DOTA conjugates of receptor α^sub v^ß^sub 3^ antagonists belonging to the quinolin-4-one class of peptidomimetics, and their radiolabeling with Tc (for HYNIC) and ^sup 99m^In (for DOTA). Tethering of the radionuclide-chelator complexes was achieved at two different sites on the quinolin-4-one molecule. All such derivatives maintained high affinity for receptor α^sub v^ß^sub 3^ and high selectivity versus receptors ß^sub 3^, α^sub v^ß^sub 5^, α^sub 5^ß^sub 1^. Biodistribution of the radiolabeled compounds was evaluated in the c-neu Oncomouse mammary adenocarcinoma model. DOTA conjugate ^sup 111^In-TA138 presented the best biodistribution profile. Tumor uptake at 2 h postinjection was 9.39% of injected dose/g of tissue (%ID/g). Activity levels in selected organs was as follows: blood, 0.54% ID/g; liver, 1.94% ID/g; kidney, 2.33% ID/g; lung, 2.74% ID/g; bone, 1.56% ID/g. A complete biodistribution analysis of ^sup 111^In-TA138 and the other radiolabeled compounds of this study are presented and discussed. A scintigraphic imaging study with ...In-TA138 showed a clear delineation of the tumors and rapid clearance of activity from nontarget tissues. [PUBLICATION ABSTRACT]
ISSN:1043-1802
1520-4812