[Frontiers in Bioscience 14, 872-886, January 1, 2009]
Radiolabelled RGD peptides and peptidomimetics for tumour targeting

Roland Haubner1, Clemens Decristoforo1

1Clinical Department of Nuclear Medicine, Medical University Innsbruck, Austria,Anichstrasse 35, A-6020 Innsbruck, Austria


1. Abstract
2. Angiogenesis and tumour growth
3. Targeting integrin expression in tumours
4. alpha(v)beta3 antagonists for radiolabelling
5. Radiolabelling strategies 5.1 .Halogens
5.2. Technetium
5.3. Other radiometals
6. Optimizing pharmakokinetics
7. The "multimerisation" approach
8. Heteromultimers
9. Clinical evaluation
10. Perspective
11. Acknowledgement
12. References


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 18F, 64Cu, 68Ga for PET, 99mTc for SPECT or 177Lu 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 (18F)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.