Differentiation of angiogenic burden in human cancer xenografts using a perfusion-type optical contrast agent (SIDAG).

Wall A, Persigehl T, Hauff P, Licha K, Schirner M, Müller S, von Wallbrunn A, Matuszewski L, Heindel W, Bremer C

Research article (journal)

Abstract

INTRODUCTION: Use of fluorescence imaging in oncology is evolving rapidly, and nontargeted fluorochromes are currently being investigated for clinical application. Here, we investigated whether the degree of tumour angiogenesis can be assessed in vivo by planar and tomographic methods using the perfusion-type cyanine dye SIDAG (1,1'-bis- [4-sulfobutyl]indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium). METHOD: Mice were xenografted with moderately (MCF7, DU4475) or highly vascularized (HT1080, MDA-MB435) tumours and scanned up to 24 hours after intravenous SIDAG injection using fluorescence reflectance imaging. Contrast-to-noise ratio was calculated for all tumours, and fluorochrome accumulation was quantified using fluorescence-mediated tomography. The vascular volume fraction of the xenografts, serving as a surrogate marker for angiogenesis, was measured using magnetic resonance imaging, and blood vessel profile (BVP) density and vascular endothelial growth factor expression were determined. RESULTS: SIDAG accumulation correlated well with angiogenic burden, with maximum contrast to noise ratio for MDA-MB435 (P < 0.0001), followed by HT1080, MCF7 and DU4475 tumours. Fluorescence-mediated tomography revealed 4.6-fold higher fluorochrome concentrations in MDA-MB435 than in DU4475 tumours (229 +/- 90 nmol/l versus 49 +/- 22 nmol/l; P < 0.05). The vascular volume fraction was 4.5-fold (3.58 +/- 0.9% versus 0.8 +/- 0.53%; P < 0.01), blood vessel profile density 5-fold (399 +/- 36 BVPs/mm2 versus 78 +/- 16 BVPs/mm2) and vascular endothelial growth factor expression 4-fold higher for MDA-MB435 than for DU4475 tumours. CONCLUSION: Our data suggest that perfusion-type cyanine dyes allow assessment of angiogenesis in vivo using planar or tomographic imaging technology. They may thus facilitate characterization of solid tumours.

Details about the publication

JournalBreast Cancer Research
Volume10
Issue2
StatusPublished
Release year2008
Language in which the publication is writtenEnglish
DOI10.1186/bcr1875
KeywordsHumans; Vascular Endothelial Growth Factor A. Contrast Media; Neovascularization Pathologic; Animals; Adenocarcinoma; Optics; Neoplasms; Magnetic Resonance Imaging; Cell Line Tumor; Blotting Western; Fluorescence; Immunohistochemistry; Transplantation Heterologous; Melanoma; Mice; Fibrosarcoma; Breast Neoplasms; Tomography; Gene Expression Regulation Neoplastic; Carbocyanines; Humans; Vascular Endothelial Growth Factor A. Contrast Media; Neovascularization Pathologic; Animals; Adenocarcinoma; Optics; Neoplasms; Magnetic Resonance Imaging; Cell Line Tumor; Blotting Western; Fluorescence; Immunohistochemistry; Transplantation Heterologous; Melanoma; Mice; Fibrosarcoma; Breast Neoplasms; Tomography; Gene Expression Regulation Neoplastic; Carbocyanines

Authors from the University of Münster

Bremer, Christoph
Clinic of Radiology
Heindel, Walter Leonhard
Clinic of Radiology
Matuszewski, Lars
Clinic of Radiology
Persigehl, Thorsten
Clinic of Radiology