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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

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Vascular targeting strategies using F8-SIP antibody against the ED-A domain of fibronectin in glioma angiogenesis

Meeting Abstract

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  • Marcus Czabanka - Department of Neurosurgery, Charité Universitätsmedizin Berlin, Germany
  • Gueliz Parmaksiz - Department of Neurosurgery, Charité Universitätsmedizin Berlin, Germany
  • Alessandro Palumbo - Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland
  • Axel Ullrich - Department of Biochemistry, MPI Martinsried, Germany
  • Dario Neri - Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Switzerland
  • Peter Vajkoczy - Department of Neurosurgery, Charité Universitätsmedizin Berlin, Germany

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. DocV1621

doi: 10.3205/10dgnc094, urn:nbn:de:0183-10dgnc0943

Published: September 16, 2010

© 2010 Czabanka et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Vascular targeting strategies have become a promising approach for tumor diagnostics and therapy. The alternatively spliced extra domain A (ED-A) of fibronectin represents a promising neoangiogenic marker in this concept. The aim of our study was to characterize biodistribution characteristics of an ED-A small immunoprotein (F8-SIP) during anti-angiogenesis and to analyze the microcirculatory effects of F8-SIP mediated photodynamic therapy (PDT).

Methods: SF126 glioma cells were implanted into dorsal skinfold chambers (DSC) of nude mice (n=5 per group). Microvascular and interstitial accumulation of F8-SIP, microvascular blood flow rate and preferential binding sites were analyzed after intravenous application of ALEXA555-F8-SIP using intravital microscopy. Treatment with Sunitinib (i.p., 40 mg/kg/day) was initiated on day 6 after tumor cell implantation and was applied daily for 6 days. Intravital microscopic analyses were performed on day 8 (acute phase [AP]) and on day 12 (end phase [EP]) after tumor cell implantation and compared to tumors without therapy (basic group [BG]). In PDT experiments red light irradiation (150j/cm2) was applied on tumors after i.v. administration of photosensitizer-coupled F8-SIP and microcirculatory alterations as well as tumor size were analyzed daily for 4 days.

Results: Antiangiogenic treatment increased microvascular binding (EP, t24: 102±4,9 vs. BG, t24: 85,5±6,8; p<0,05). Extravasation of F8-SIP into tumor interstitium was significantly increased in both therapy groups (AP, t24: 76,2±4,9 and EP, t24: 77,5±9,9 vs. BG, t24: 61,4±6,3; p<0,05, respectively). PDT resulted in short initial hyperperfusion followed by significantly reduced functional vessel density (Pre-PDT: 200±122 cm/cm2; Post-PDT:80±74cm/cm2), microvascular blood flow rate (Pre-PDT:42±29nl/s; Post-PDT:18±10nl/s) and perfusion index (Pre-PDT: 0,65±0,14; Post-PDT:0,38±0,32). Microcirculatory failure recovered to normal values 24-48h after single PDT. Single PDT led to short-term reduction of tumor growth 48h after treatment (PDT: 115±31mm3; Control: 205±91mm3) followed by recovery of growth rate. Only repetitive PDT induced long-term reduction of tumor growth (PDT: 139±44mm3; Control: 322±112mm3)

Conclusions: F8-SIP represents a useful tool to specifically target tumor microvessels. Our results provide insights into microvascular consequences of F8 vascular targeting strategies useful for future diagnostic and therapeutic interventions.