PET imaging of $alpha$v$beta$₃ integrin expression in tumours with �?��?�Ga-labelled mono-, di- and tetrameric RGD peptides

I. Dijkgraaf, C. Yim, G. Franssen, R. Schuit, G. Luurtsema, S. Liu, W. Oyen and O. Boerman

Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Jan, 2011



Due to the restricted expression of α(v)β(3) in tumours, α(v)β(3) is considered a suitable receptor for tumour targeting. In this study the α(v)β(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their (111)In-labelled counterparts.A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)](2)) and a tetrameric (EE[c(RGDfK)](2)(2)) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with (68)Ga. In vitro α(v)β(3)-binding characteristics were determined in a competitive binding assay. In vivo α(v)β(3)-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner.The IC(50) values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)](2) and DOTA-EE[c(RGDfK)](2)(2) were 23.9 ± 1.22, 8.99 ± 1.20 and 1.74 ± 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 ± 1.15, 3.34 ± 1.16 and 1.80 ± 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the (68)Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 ± 0.30, 5.24 ± 0.27 and 7.11 ± 0.67\%ID/g, respectively) was comparable to that of their (111)In-labelled counterparts (2.70 ± 0.29, 5.61 ± 0.85 and 7.32 ± 2.45\%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised.The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The (68)Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of α(v)β(3) expression with PET.