Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts

Purpose Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the Ga-68-labelled bombesin analogue AMBA with metabolism-based targeting using F-18-methylcholine (F-18-FCH) in nude mice bearing human prostate VCaP xenografts. Methods PET and biodistribution studies were performed with both Ga-68-AMBA and F-18-FCH in all VCaP tumour-bearing mice, with PC-3 tumour-bearing mice as reference. Scanning started immediately after injection. Dynamic PET scans were reconstructed and analysed quantitatively. Biodistribution of tracers and tissue uptake was expressed as percent of injected dose per gram tissue (%ID/g). Results All tumours were clearly visualized using Ga-68-AMBA. F-18-FCH showed significantly less contrast due to poor tumour-to-background ratios. Quantitative PET analyses showed fast tumour uptake and high retention for both tracers. VCaP tumour uptake values determined from PET at steady-state were 6.7 +/- 1.4%ID/g (20-30 min after injection, N=8) for Ga-68-AMBA and 1.6 +/- 0.5%ID/g (10-20 min after injection, N=8) for F-18-FCH, which were significantly different (p<0.001). The results in PC-3 tumour-bearing mice were comparable. Biodistribution data were in accordance with the PET results showing VCaP tumour uptake values of 9.5 +/- 4.8% ID/g (N=8) for Ga-68-AMBA and 2.1 +/- 0.4% ID/g (N=8) for F-18-FCH. Apart from the GRPR-expressing organs, uptake in all organs was lower for Ga-68-AMBA than for F-18-FCH. Conclusion Tumour uptake of Ga-68-AMBA was higher while overall background activity was lower than observed for F-18-FCH in the same PC-bearing mice. These results suggest that peptide receptor-based targeting using the bombesin analogue AMBA is superior to metabolism-based targeting using choline for scintigraphy of PC.