UMMS Affiliation

Center for Molecular Imaging Research; Department of Radiology

Date

10-19-2005

Document Type

Article

Subjects

Adenocarcinoma; Animals; Cell Line, Tumor; Colonic Neoplasms; Erythrocyte Volume; Humans; Indazoles; Magnetic Resonance Angiography; Mice; Mice, Nude; Neovascularization, Pathologic; imaging; Phosphorylation; Protein Kinase Inhibitors; Vascular Endothelial Growth Factor Receptor-2; inhibitors; Xenograft Model Antitumor Assays

Disciplines

Radiology

Abstract

Antiangiogenesis is emerging as efficient strategy for targeting and potentially eliminating neoplastic tumor vessels. The main goal of this study was to establish whether absolute tumor blood volume (V(b)) change could be used as an early predictor of antiangiogenesis in ectopic and orthotopic colon carcinomas. To assess therapy-induced changes of V(b), we did comparative analysis of signal intensities in tumors and muscle using steady-state magnetic resonance imaging (MRI) assisted with an intravascular paramagnetic contrast agent [gadolinium-labeled protected graft copolymer (PGC-Gd)]. Athymic mice with implanted human MV522 tumors were treated with vascular endothelial growth factor type 2 receptor tyrosine kinase inhibitor (VEGFR2-TKI) that has been shown to inhibit VEGFR2 phosphorylation and tumor growth in vivo. Animals were imaged either after a single day or after a 1-week course of treatments. The measured V(b) in ectopic tumors was 2.5 +/- 1.5% of total tissue volume 1 week after the implantation (n = 8). Two doses of VEGFR2-TKI (25 mg/kg, p.o., b.i.d.) resulted in a decrease of V(b) to 1.3 +/- 0.3%. In orthotopic tumors, the measured V(b) was initially higher (11.9 +/- 2.0%); however, VEGFR2-TKI treatment also resulted in a statistically significant decrease of V(b). The absolute V(b) was not affected in the muscle as a result of treatments. MRI measurements were corroborated by using isotope and correlative histology experiments. Our results show that steady-state MRI is highly sensitive to early antiangiogenic effects caused by small molecule drugs.

Rights and Permissions

Citation: Cancer Res. 2005 Oct 15;65(20):9253-60. Link to article on publisher's site

DOI of Published Version

10.1158/0008-5472.CAN-03-2619

Related Resources

Link to article in PubMed

Journal Title

Cancer research

PubMed ID

16230386

Included in

Radiology Commons

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