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METABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Nuclear Trafficking of a Gadolinium Conjugate in Nude Mice Xenografted with Human LN-229 Glioma

Departments of Neuroradiololgy (S.H.) and Pathology (U.V.), University of Tübingen, Tübingen, Germany

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.

Address correspondence to: Dr. Stefan Heckl, Department of Neuroradiology, University of Tübingen, Medical School, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. E-mail: stefan.heckl{at}med.uni-tuebingen.de