H-CRRETAWAC-OH, a Lead Structure for the Development of Radiotracer Targeting Integrin α (5) β (1)?

Imaging of angiogenic processes is of great interest in preclinical research as well as in clinical settings. The most commonly addressed target structure for imaging angiogenesis is the integrin α (v) β (3). Here we describe the synthesis and evaluation of [(18)F]FProp-Cys(*)-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys(*)-OH, a radiolabelled peptide designed to selectively target the integrin α (5) β (1). Conjugation of 4-nitrophenyl-(RS)-2-[(18)F]fluoropropionate provided [(18)F]FProp-Cys(*)-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys(*)-OH in high radiochemical purity (>95%) and a radiochemical yield of approx. 55%. In vitro evaluation showed α (5) β (1) binding affinity in the nanomolar range, whereas affinity to α (v) β (3) and α (IIb) β (3) was >50 μM. Cell uptake studies using human melanoma M21 (α (v) β (3)-positive andα (5) β (1)-negative), human melanoma M21-L (α (v) β (3)-negative and α (5) β (1)-negative), and human prostate carcinoma DU145 (α (v) β (3)-negative and α (5) β (1)-positive) confirmed receptor-specific binding. The radiotracer was stable in human serum and showed low protein binding. Biodistribution studies showed tumour uptake ranging from 2.5 to 3.5% ID/g between 30 and 120 min post-injection. However, blocking studies and studies using mice bearing α (5) β (1)-negative M21 tumours did not confirm receptor-specific uptake of [(18)F]FProp-Cys(*)-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys(*)-OH, although this radiopeptide revealed high affinity and substantial selectivity to α (5) β (1) in vitro. Further experiments are needed to study the in vivo metabolism of this peptide and to develop improved radiopeptide candidates suitable for PET imaging of α (5) β (1) expression in vivo.