Radiolabelled RGD peptides and peptidomimetics for tumour targeting

Imaging techniques allowing non-invasive monitoring of tumour angiogenesis have attracted great interest over the last years. The integrin alpha(v)beta3 is overexpressed during tumour spread and metastasis and therefore is an attractive target for monitoring angiogenetic processes. This review summarizes attempts to develop radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence and related peptidomimetics with high affinity and selectivity for the alpha(v)beta3 integrin for tumour targeting. Most developments were based on cyclic RGD peptides radiolabelled with F-18, Cu-64, Ga-68 for PET, (99)mTc for SPECT or Lu-177 for therapeutic applications. To enable fast elimination from non target tissue and rapid excretion of the radiolabelled peptides pharmacokinetic modifiers such as sugar amino acids have been evaluated. Out of these developments [F-18] Galacto-RGD has shown high tumour-to-background ratios preclinically and has been evaluated in a number of clinical studies, showing the possibility for non invasive imaging of alpha(v)beta3 in tumour patients. To improve targeting efficiency multimeric constructs were reported revealing improved targeting properties in preclinical models. These developments still have to be transferred into the clinical setting.