Abstract
We synthesized a novel fluorescein isothiocyanate-labeled gadolinium-diethylenetriamine pentaacetic acid (DTPA) conjugate in which the commonly used gadolinium-DTPA complex is flanked by the nuclear localization sequences of the simian virus-40 T antigen and the acute lymphatic leukemia-1 (ALL-1) protein. The distribution of the conjugate after i.p. or i.v. injection in nude mice bearing human LN-229 glioma xenografts was confirmed by magnetic resonance imaging, with an increase in signal intensity in all the organs and tumors except for healthy brain parenchyma with an intact blood-brain barrier. Nuclear uptake and efflux of the conjugate was demonstrated by confocal laser scanning microscopy. Such gadolinium conjugates may therefore be of value in the development of novel diagnostic and therapeutic agents.
Footnotes
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This work was supported by the Hertie Foundation for Brain Research.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.109868.
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ABBREVIATIONS: Gd-DTPA, gadolinium-diethylenetriamine pentaacetic acid; MRI, magnetic resonance imaging; NLS, nuclear localization sequence; FITC, fluorescein isothiocyanate; SV, simian virus; Fmoc, 9-fluorenylmethoxycarbonyl-t-butyl; Boc, t-butyloxy-carbonyl; ivDde, 4,4-dimethyl-2,6-dicyclohexyl-1-xylidine-3-methylbutyl; CLSM, confocal laser scanning microscopy; TR, time to repetition; TE, time to echo; ALL-1, acute lymphatic leukemia.
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↵ The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.
- Received June 23, 2006.
- Accepted August 18, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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