Definition of the “Drug-Angiogenic-Activity-Index” that Allows the Quantification of the Positive and Negative Angiogenic Active Drugs: A Study Based on the Chorioallantoic Membrane Model

Abstract

Since the introduction of the angiogenic therapy by Folkman et al. in the 1970’ies many antiangiogenic drugs were identified. Only few of them are still now in clinical use. Also the Vascular Endothelial Growth Factor (VEGF), the cytokine with the highest angiogenic activity, has been identified. Its antagonist, Bevacizumab, is produced and admitted for the angiogenic therapy in first line for metastatic colorectal cancer. When we look at preclinical studies, they fail of in vivo models that define the “Drug-AngiogenicActivity-Index” of angiogenic or antiangiogenic drugs. This work proposes a possible standardized procedure to define the “Drug Angiogenic Activity Index” by counting the vascular intersections (VIS) on the Chorioallantoic Membrane after drug application. The equation was defined as follows: {ΔVIS[Drug]−ΔVIS[Control]} / Δ VIS[Control]. For VEGF a Drug-Angiogenic-Activity-Index of 0.92 was found and for Bevacizumab a −1. This means almost that double of the naturally angiogenic activity was achieved by VEGF on the Chorioallantoic membrane. A complete blocking of naturally angiogenic activity was observed after Bevacizumabs application. Establishing the “Drug-Angiogenic-Activity-Index” in the preclinical phase will give us an impact of effectivness for the new constructed antiangiogenic drugs like the impact of effectiveness in the cortisone family.