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61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Specific detection of erbB receptors on glioma cells by quantum-dot (QD) nanoparticles and new superparamagnetic iron oxide nanoparticles (SPION)

Meeting Abstract

  • Sven R. Kantelhardt - Klinik für Neurochirurgie, Georg-August-Universität Göttingen, Deutschland
  • Donna Arndt-Jovin - Laboratory for Cellular Dynamics, Max Planck Institut für Biophysikalische Chemie, Göttingen, Deutschland
  • Thomas Jovin - Laboratory for Cellular Dynamics, Max Planck Institut für Biophysikalische Chemie, Göttingen, Deutschland
  • Veit Rohde - Klinik für Neurochirurgie, Georg-August-Universität Göttingen, Deutschland
  • Alf Giese - Klinik für Neurochirurgie, Georg-August-Universität Göttingen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1533

DOI: 10.3205/10dgnc010, URN: urn:nbn:de:0183-10dgnc0109

Published: September 16, 2010

© 2010 Kantelhardt et al.
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Outline

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Objective: The bright fluorescence emission and resistance to photobleaching make quantum dots (QDs) ideal for single-particle detection and permit imaging over prolonged time periods. We have used QDs in combination with targeting molecules and advanced microscopy techniques for specific staining of receptors on high-grade glioma cells. There are however further possible applications of small targeted nanoparticles. New superparamagnetic iron oxide nanoparticles (SPION) are small enough to reach glioma cells beyond the resection cavity by way of diffusion. SPIONS work as actuators of the erbB receptor tyrosine kinases and can thus be applied as vehicle for drug delivery.

Methods: Experiments were conducted on cultured human glioma cells (15 established cell lines) a glioma-mouse model (6 animals implanted with cells of 3 established cell lines) and human tumor biopsies (2 glioblastoma, 2 anaplastic astrocytoma and 1 oligodendroglioma). QDs and SPIONs were specifically targeted to cell surface receptors by coupling to EGF and monoclonal antibodies directed against extracellular portions of the erbB1- and PDGF-receptors. Staining of experimental and human glioma tissue was performed under physiological conditions. Binding was monitored by flow cytometry of erbB1-receptor postive cultured glioma cells (G-28). Imaging of glioma cells and adjacent brain tissue was performed using the Programmable Array Microscope (PAM), confocal laser scanning microscopy, and macroscopic imaging.

Results: Extensive binding of targeted nanoparticles to glioma cells was achieved after less than 30 min. Specifically targeted QDs distinguished both high-grade and low-grade glioma cells from adjacent brain tissue. Fluorescent tissue contrast between solid glioma and adjacent brain was found to be 200 in the oligodendroglioma and up to 103 in glioblastoma. QDs-EGF was internalized by glioma cells which expressed intact erbB1 receptors (25% of cell lines), wheras QDs coupled to specific monoclonal antibodies which bound to intact and mutated erbB1 remained on the cellular surface (85% of cell lines). In contrast cultured glioma cells and human glioma biopsies could be induced to internalize all bound SPIONs by simple magnetic stimultion.

Conclusions: Targeted QDs have great promise for intraoperative detection of residual glioma cells. Targeted SPIONs might additionally be used for targeted drug delivery beyond the resection cavity.