Excerpt
Angiogenesis is one of the hallmarks of cancer and is increasingly in the focus of oncological research. Judah Folkman first articulated the importance of angiogenesis for tumor growth in 1971 [
1]. He stated that the growth of solid tumors remains restricted to 2–3 mm in diameter until the onset of angiogenesis. Although this hypothesis first was strongly criticized, angiogenesis soon became one of the most important fields of research in oncology. Up to now, subsequent investigations have identified more than 20 angiogenic growth factors, their receptors and signal transduction pathways. Moreover, endogenous angiogenesis inhibitors have been discovered, and the cellular and molecular characterization of the angiogenic phenotype in human cancers has been achieved [
2,
3]. Although the results of the first clinical trials using angiogenesis inhibitors in oncology were disappointing, encouraging results have been achieved in the past few years with the vascular endothelial growth factor (VEGF) antibody Avastin® in combination with standard cytotoxic chemotherapy. This combined antiangiogenic-cytotoxic therapy has been proven to be successful first in metastasized colorectal cancer, and subsequently also in breast cancer and non-small cell lung cancer [
4‐
7]. This success of targeted antiangiogenic therapy will spur the demand for imaging modalities for assessment of the angiogenic cascade, which is the topic of this supplement “Imaging of Angiogenesis.” Imaging of angiogenic activity might on the one hand help in the process of developing novel antiangiogenic drugs in the preclinical setting. Moreover, in the clinical setting, imaging of angiogenesis might be useful for assessment of the optimum dose of new antiangiogenic agents and for early response evaluation. Up to now, clinical trials with conventional cytotoxic chemotherapeutic agents have mainly used morphological imaging to provide indices of therapeutic response, mostly computed tomography (CT) or magnetic resonance imaging (MRI). Bidimensional measurements of the maximum tumor extension are mainly used to estimate changes in response to the investigational therapy as compared with a baseline measure. Through standardization of these measurements by introducing the RECIST criteria in the year 2000, considerable progress has been achieved [
8]. However, as antiangiogenic agents lead to a stop of tumor progression rather than to tumor shrinkage, the approach of measuring tumor response by a reduction of tumor size is not applicable and might take months or years to become apparent. Therefore, there is great interest in identifying reliable biomarkers of early tumor response to noncytotoxic drugs [
9]. Imaging techniques could potentially be used as such a biomarker and could provide an early indicator of effectiveness at a functional or molecular level. Concerning morphological imaging of the vasculature, conventional X-ray angiography and digital subtraction angiography (DSA) are widely used in the clinical arena; however, they do not allow for assessment of the microvasculature and thus are not commonly used for response evaluation of antiangiogenic therapies. More promising is the assessment of changes in hemodynamic parameters such as blood flow, blood volume, or vessel permeability. They may be effective biomarkers for response evaluation, because antiangiogenic therapies are designed to affect the abnormal blood vessels found in tumors. Current clinical trials employ various imaging techniques for this purpose, mostly dynamic contrast-enhanced MRI (DCE MRI), and less often ultrasound, PET (especially with [
15O]water), and dynamic contrast-enhanced CT (DCE CT) [
10]. In the future, targeting specific molecular markers of angiogenesis might also be used for response assessment of antiangiogenic therapies like the VEGF pathway or cell surface markers like the integrin αvβ3. …
