Title:Evaluating the Diagnostic and Chemotherapeutic Potential of Vancomycin- Derived Imaging Conjugates
VOLUME: 8 ISSUE: 6
Author(s):Sumbla Sheikh, Alexander Sturzu, Uwe Klose, Hartmut Echner, Martin Deeg, Thomas Nagele, Marius Horger, Christian Schwentner, Ulrike Ernemann, Wolfgang Voelter and Stefan Heckl
Affiliation:Department of Neuroradiology, University of Tubingen, Hoppe-Seyler-Str. 3, 72076 Tubingen, Germany.
Keywords:Vancomycin conjugates, Magnetic resonance imaging, Fluorescence imaging
Abstract:The main use of glycopeptide antibiotics is treatment of infections which are resistant to the commonly used -
lactam antibiotics. Antitumor activity has also been reported for some glycopeptide antibiotics like bleomycin. In the present
study we investigated the chemotherapeutic and diagnostic potential of two imaging agent derivatives of the glycopeptide
antibiotic vancomycin. For the first conjugate, vancomycin was coupled to the fluorescent dye rhodamine, used in
confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). The second conjugate consisted
of vancomycin coupled to gadolinium-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (GdDOTA), a
magnetic resonance imaging (MRI) contrast agent. The cellular uptake, specificity, and the accessibility by imaging
methods of the two vancomycin conjugates was evaluated on 8 human cell lines (one benign, 7 malignant) by CLSM,
FACS, and MRI experiments. Cytotoxicity of both vancomycin conjugates was determined in the FACS experiments with
the annexin test indicating disrupted cell membranes. Some of the malignant cell lines showed clearly stronger uptake
than the others and the benign cell line was among the cell lines with the lowest uptake. In the annexin test the cytotoxicity
could be correlated to the conjugate uptake for all cell lines. The intracellular uptake of the vancomycin conjugates and
the increased uptake into some of the malignant cell lines were interesting findings which should be further pursued.
