title: Orthogonal polarisation spectral imaging as a new tool for the assessment of antivascular tumour treatment in vivo: a validation study.
abstract: Tumour angiogenesis plays a key role in tumour growth, formation of metastasis, detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour angiogenesis is an indispensable prerequisite for developing novel treatment strategies such as anti-angiogenic and antivascular treatment options. Therefore, it was our aim to establish and validate a new and versatile imaging technique, that is orthogonal polarisation spectral imaging, allowing for non-invasive quantitative imaging of tumour angiogenesis in vivo. Experiments were performed in amelanotic melanoma A-MEL 3 implanted in a transparent dorsal skinfold chamber of the hamster. Starting at day 0 after tumour cell implantation, animals were treated daily with the anti-angiogenic compound SU5416 (25 mg kg x bw(-1)) or vehicle (control) only. Functional vessel density, diameter of microvessels and red blood cell velocity were visualised by both orthogonal polarisation spectral imaging and fluorescence microscopy and analysed using a digital image system. The morphological and functional properties of the tumour microvasculature could be clearly identified by orthogonal polarisation spectral imaging. Data for functional vessel density correlated excellently with data obtained by fluorescence microscopy (y=0.99x+0.48, r2=0.97, R(S)=0.98, precision: 8.22 cm(-1) and bias: -0.32 cm(-1)). Correlation parameters for diameter of microvessels and red blood cell velocity were similar (r2=0.97, R(S)=0.99 and r2=0.93, R(S)=0.94 for diameter of microvessels and red blood cell velocity, respectively). Treatment with SU5416 reduced tumour angiogenesis. At day 3 and 6 after tumour cell implantation, respectively, functional vessel density was 4.8+/-2.1 and 87.2+/-10.2 cm(-1) compared to values of control animals of 66.6+/-10.1 and 147.4+/-13.2 cm(-1), respectively. In addition to the inhibition of tumour angiogenesis, tumour growth and the development of metastasis was strongly reduced in SU5416 treated animals. This new approach enables non-invasive, repeated and quantitative assessment of tumour vascular network and the effects of antiangiogenic treatment on tumour vasculature in vivo. Thus, quantification of tumour angiogenesis can be used to more accurately classify and monitor tumour biologic characteristics, and to explore aggressiveness of tumours.
authors.affiliation: Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. Pahernik@Urologie.Klinik.Uni-Mainz.de
authors.forename: S
authors.initials: S
authors.lastname: Pahernik
authors.forename: A G
authors.initials: AG
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Schmitt-Sody
authors.forename: S
authors.initials: S
authors.lastname: Krasnici
authors.forename: A E
authors.initials: AE
authors.lastname: Goetz
authors.forename: M
authors.initials: M
authors.lastname: Dellian
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001783:Blood Flow Velocity; D002196:Capillaries / Q000187:drug effects* / Q000648:ultrastructure; D006224:Cricetinae; D004912:Erythrocytes / Q000648:ultrastructure; D006454:Hemoglobins / Q000737:chemistry; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods*; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000648:ultrastructure; D008647:Mesocricetus; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D008859:Microscopy, Polarization / Q000295:instrumentation / Q000379:methods*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012884:Skin Window Technique
chemical_list: D020533:Angiogenesis Inhibitors; D006454:Hemoglobins; D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib