Microvascular biodistribution of L19-SIP in angiogenesis targeting strategies

• Verfasst von: Czabanka, Marcus Alexander [VerfasserIn]
• Verfasst von: Parmaksiz, Güliz [VerfasserIn]
• Verfasst von: Bayerl, Simon H. [VerfasserIn]
• Verfasst von: Nieminen, Melina [VerfasserIn]
• Verfasst von: Trachsel, Eveline [VerfasserIn]
• Verfasst von: Menssen, Hans D. [VerfasserIn]
• Verfasst von: Erber, Ralf [VerfasserIn]
• Verfasst von: Neri, Dario [VerfasserIn]
• Verfasst von: Vajkoczy, Peter [VerfasserIn]
• Titel: Microvascular biodistribution of L19-SIP in angiogenesis targeting strategies
• Verf.angabe: Marcus Czabanka, Güliz Parmaksiz, Simon H. Bayerl, Melina Nieminen, Eveline Trachsel, Hans D. Menssen, Ralf Erber, Dario Neri, Peter Vajkoczy
• E-Jahr: 2011
• Jahr: 9 March 2011
• Umfang: 9 S.
• Fussnoten: Gesehen am 25.04.2022
• Titel Quelle: Enthalten in: European journal of cancer
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1965
• Jahr Quelle: 2011
• Band/Heft Quelle: 47(2011), 8, Seite 1276-1284
• ISSN Quelle: 1879-0852
• DOI: doi:10.1016/j.ejca.2011.02.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Angiogenesis
• Sach-SW: Anti-angiogenic therapy
• Sach-SW: Antibody-based vascular targeting
• Sach-SW: Extra domain B of fibronectin
• Sach-SW: L19-SIP
• K10plus-PPN: 1800095163

Abstract

Introduction - Various strategies using L19-mediated fibronectin targeting have become useful clinical tools in anti-tumour therapy and diagnostics. The aim of our study was to characterise the microvascular biodistribution and binding process during tumour angiogenesis and after anti-angiogenic therapy. - Materials and methods - SF126 glioma and F9 teratocarcinoma cells were implanted into dorsal skin fold chambers (SF126: n=4; F9: n=6). Using fluorescence and confocal intravital microscopy the biodistribution process was assessed at t=0h, t=4h and t=24h after intravenous application of Cy3-L19-SIP. Sunitinib treatment was applied for six days and microscopy was performed 2 and 6days after treatment initiation. Analysed parameters included: vascular and interstitial binding, preferential binding sites of L19-SIP, microvascular blood flow rate, microvascular permeability. Histological analysis included CD31 and DAPI. - Results - L19-SIP showed a specific and time-dependent neovascular binding with a secondary extravasation process reaching optimal vascular/interstitial binding ratio 4hours after iv administration (F9: L19-SIP: vascular binding: 74.6±14.5; interstitial binding: 46.8±12.1; control vascular: 22,2±16.6). Angiogenic sprouts were preferred binding sites (F9: L19-SIP: 188±15.5; RTV: 90.6±13.5). Anti-angiogenic therapy increased microvascular hemodynamics (SF126: Su: 106.6±13.3μl/sec; Untreated: 19.7±9.1μl/sec) and induced increased L19-SIP accumulation (SF 126: t24; Su: 92.6±2.7; Untreated: 71.9±5.9) in therapy resistant tumour vessels. - Conclusion - L19-SIP shows a time and blood-flow dependent microvascular biodistribution process with angiogenic sprouts as preferential binding sites followed by secondary extravasation of the antibody. Microvascular biodistribution is enhanced in anti-angiogenic-therapy resistant tumour vessels.