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60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

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In vivo biodistribution and microvascular binding of a high-affinity monoclonal antibody fragment F8-SIP against the extra-domain A of fibronectin

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  • G. Parmaksiz - Klinik für Neurochirurgie, Charité - Universitätsmedizin Berlin
  • M. Czabanka - Klinik für Neurochirurgie, Charité - Universitätsmedizin Berlin
  • D. Neri - Institut für Pharmazeutische Wissenschaften, ETH Zürich
  • P. Vajkoczy - Klinik für Neurochirurgie, Charité - Universitätsmedizin Berlin

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP14-11

doi: 10.3205/09dgnc409, urn:nbn:de:0183-09dgnc4097

Published: May 20, 2009

© 2009 Parmaksiz 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: The human monoclonal antibody fragment F8-SIP (small immunoprotein) is specific to the angiogenic marker EDA domain of fibronectin. The aim of our study was to characterize microvascular binding and biodistribution characteristics of F8-SIP.

Methods: SF126 cells were implanted into dorsal skin chamber (DSC) preparations of nude mice. Microvascular and interstitial accumulation of F8-SIP and microvascular blood flow rates were analyzed at t=0h, t=2h, t=4h, and t=24h after intra-arterial application of fluorescence labeled F8-SIP (n=5 per group) by intravital microscopy. Host vasculature of mice without tumor bearing DSCs were used as control group.

Results: F8-SIP binds specifically to tumor vessels reaching its maximum binding capacity 4 hours after injection (t=0h: 26.12±10.89 vs. t=4h: 91.46±6.19; p<0.05). In control vasculature no binding was observed. Extravasation of F8-SIP into the tumor interstice was observed reaching its maximum 4 hours after injection (t=0h: 19.25±9.45 vs. t=4h: 60.41±7.77; p<0.05). Microvascular binding was flow-dependent with significantly increased binding in high flow-blood vessels (HF≥60nl/sec) compared to low flow-blood vessels (LF≤20nl/sec) by 44% at t=2h and by 22% at t=4h, respectively. F8-SIP binding preferentially occurred in angiogenic sprouts (AS) compared to remaining tumor vasculature (RTV) 2 hours after injection (AS: 115.14±12.38 vs. RTV: 77.86±11.25; p<0.05).

Conclusions: F8-SIP represents a useful tool to specifically target tumor microvessels. Microvascular binding occurs in a time- and blood flow dependent manner with preferential binding sites. Our results provide biodistribution characteristics that might be used for future clinical applications.