title: 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.
abstract: OBJECTIVE
  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 (68)Ga-labelled bombesin analogue AMBA with metabolism-based targeting using (18)F-methylcholine ((18)F-FCH) in nude mice bearing human prostate VCaP xenografts.
  
  
  METHODS
  PET and biodistribution studies were performed with both (68)Ga-AMBA and (18)F-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 (68)Ga-AMBA. (18)F-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 (68)Ga-AMBA and 1.6 ± 0.5%ID/g (10-20 min after injection, N = 8) for (18)F-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 (68)Ga-AMBA and 2.1 ± 0.4%ID/g (N = 8) for (18)F-FCH. Apart from the GRPR-expressing organs, uptake in all organs was lower for (68)Ga-AMBA than for (18)F-FCH.
  
  
  CONCLUSIONS
  Tumour uptake of (68)Ga-AMBA was higher while overall background activity was lower than observed for (18)F-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.
authors: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. r.schroeder@erasmusmc.nl
authors: Rogier P J
authors: RP
authors: Schroeder
authors: W M
authors: WM
authors: van Weerden
authors: E P
authors: EP
authors: Krenning
authors: C H
authors: CH
authors: Bangma
authors: S
authors: S
authors: Berndsen
authors: C H
authors: CH
authors: Grievink-de Ligt
authors: H C
authors: HC
authors: Groen
authors: S
authors: S
authors: Reneman
authors: E
authors: E
authors: de Blois
authors: W A P
authors: WA
authors: Breeman
authors: M
authors: M
authors: de Jong
mesh_terms: D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002794:Choline / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D006801:Humans; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D018004:Receptors, Bombesin / Q000378:metabolism*
chemical_list: C512446:DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D009842:Oligopeptides; D018004:Receptors, Bombesin; C017506:methylcholine; D002794:Choline; D001839:Bombesin