In-vivo visualization of tumor microvessel density and response to anti-angiogenic treatment by high resolution MRI in mice.

Purpose: Inhibition of angiogenesis has shown clinical success in patients with cancer. Thus, imaging approaches that allow for the identification of angiogenic tumors and the detection of response to anti-angiogenic treatment are of high clinical relevance.

Experimental Design: We established an in vivo magnetic resonance imaging (MRI) approach that allows us to simultaneously image tumor microvessel density and tumor vessel size in a NSCLC model in mice.

Systemic coagulation parameters in mice after treatment with vascular targeting agents.

Background: Vascular targeting of malignant tumors has become a clinically validated new treatment approach with clear patient benefit. However clinical studies have also revealed that some types of vascular targeting agents (VTAs) are prone to coagulation system side effects. It is therefore essential to predetermine coagulation parameters in preclinical studies.

Specific occlusion of murine and human tumor vasculature by VCAM-1-targeted recombinant fusion proteins.

Background: The tumor vasculature is increasingly recognized as a target for cancer therapy. We developed and evaluated recombinant fusion proteins targeting the coagulation-inducing protein soluble tissue factor (sTF) to the luminal tumor endothelial antigen vascular cell adhesion molecule 1 (VCAM-1, CD106).

Methods: We generated fusion proteins consisting of sTF fused to antibody fragments directed against mouse or human VCAM-1 and characterized them in vitro by flow cytometry, surface plasmon resonance, and two-stage coagulation assays.

Soluble tissue factor induces coagulation on tumor endothelial cells in vivo if coadministered with low-dose lipopolysaccharides.

Objective: This study was performed to evaluate the mechanisms leading to tumor vessel occlusion by tissue factor-based drugs, which are used in vascular targeting approaches for the treatment of malignant tumors.

Methods And Results: The effects of nontargeted soluble tissue factor were evaluated in vitro and in vivo. Tumor-bearing mice were treated with (1) the extracellular portion of tissue factor (soluble tissue factor), (2) low nontoxic doses of lipopolysaccharides, or (3) a combination thereof.