The use of vascular biomarkers and imaging studies in the early clinical development of anti-tumour agents targeting angiogenesis

Recent findings about the pathomechanisms of tumour angiogenesis have led to new therapeutic options in the treatment of malignant tumours. During the development of anti-angiogenic drugs, reporting ranged from healing cancer to completely ineffective drugs. In 2003 the first anti-angiogenic drug was approved. Several anti-angiogenic drugs are still in the clinical phase of development. In contrast to identifying the maximal tolerable dose, determination of the optimal biological dose - reaching biological activity at lower doses -has become the main target in the early development of anti-angiogenic agents. This has been evaluated by different biomarker techniques. As a new standard in anti-tumour treatment, a better understanding of imaging in the treatment monitoring for anti-angiogenic agents is important. Studies of tumour angiogenesis by tissue sampling rely on invasive procedures, adequate sampling and painstaking estimation of histological microvessel density. Attempts to develop wound healing assays to correlate angiogenesis in wounds with angiogenesis in tumour have been made but are still considered invasive and correlation of healthy with malignant tissue is still of limited validity. Several soluble markers of tumour angiogenesis were detected in various malignant diseases and were evaluated for assessing their use as surrogate markers in tumour angiogenesis. Further, soluble markers were investigated for visualizing them as imaging tools. Combining both, new soluble markers and imaging techniques, developing anticancer drugs and monitoring of therapy success becomes a dynamic process in which finally the patients' individual response can be achieved soon. Time-consuming delays for anatomically based restaging procedures can be avoided. Characterization of soluble biomarkers as well as different imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging and positron emission tomography combined with or without CT are reviewed in this manuscript.