CXCR4 – Evaluation (Eleni Gourni / Calogero D’Alessandria)

Binding studies of the new ligands to CXCR4 are performed in a competitive binding assay on Jurkat cells endogenously express CXCR4 receptor (IC50). More detailed studies are carried out for the most promising derivatives, which include determination of KD, Bmax, rate of internalization, metabolic stability. Additionally, comparative binding studies with murine and human cells are performed in order to reveal if there are species differences or species specificity. The in vivo behaviour and the pharmacokinetic profile of the new ligands are evaluated performing biodistribution studies on non-metastasizing and metastasizing-tumor bearing mice at different time points and specificity of binding is demonstrated by in vivo competition/displacement experiments. Finally, a small animal PET/CT camera is used to characterize the CXCR4 expression in several non-metastasizing tumors and in metastasizing tumor models, during tumor growth and metastasis.