title: A comparative study of radiolabeled bombesin analogs for the PET imaging of prostate cancer.
abstract: Radiolabeled bombesin (BBN) analogs that bind to the gastrin-releasing peptide receptor (GRPR) represent a topic of active investigation for the development of molecular probes for PET or SPECT of prostate cancer (PCa). RM1 and AMBA have been identified as the 2 most promising BBN peptides for GRPR-targeted cancer imaging and therapy. In this study, to develop a clinically translatable BBN-based PET probe, we synthesized and evaluated (18)F-AlF- (aluminum-fluoride) and (64)Cu-radiolabeled RM1 and AMBA analogs for their potential application in PET imaging of PCa.
  
  
  METHODS
  1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)-conjugated RM1 and AMBA were synthesized and tested for their GRPR-binding affinities. The NODAGA-RM1 and NODAGA-AMBA probes were further radiolabeled with (64)Cu or (18)F-AlF and then evaluated in a subcutaneous PCa xenograft model (PC3) by small-animal PET imaging and biodistribution studies.
  
  
  RESULTS
  NODAGA-RM1 and NODAGA-AMBA can be successfully synthesized and radiolabeled with (64)Cu and (18)F-AlF. (64)Cu- and (18)F-AlF-labeled NODAGA-RM1 demonstrated excellent serum stability and tumor-imaging properties in the in vitro stability assays and in vivo imaging studies. (64)Cu-NODAGA-RM1 exhibited tumor uptake values of 3.3 ± 0.38, 3.0 ± 0.76, and 3.5 ± 1.0 percentage injected dose per gram of tissue (%ID/g) at 0.5, 1.5, and 4 h after injection, respectively. (18)F-AlF-NODAGA-RM1 exhibited tumor uptake values of 4.6 ± 1.5, 4.0 ± 0.87, and 3.9 ± 0.48 %ID/g at 0.5, 1, and 2 h, respectively.
  
  
  CONCLUSIONS
  The high-stability, efficient tumor uptake and optimal pharmacokinetic properties highlight (18)F-AlF-NODAGA-RM1 as a probe with great potential and clinical application for the PET imaging of prostate cancer.
authors.affiliation: Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Center of Excellence in Medical Molecular Imaging of Zhejiang State, Hangzhou, China; and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.forename: Hongguang
authors.initials: H
authors.lastname: Liu
authors.forename: Lihong
authors.initials: L
authors.lastname: Bu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.forename: Jinbo
authors.initials: J
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Tian
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003301:Copper Radioisotopes; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D011854:Radiochemistry
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D003301:Copper Radioisotopes; D005462:Fluorine Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D001839:Bombesin
keywords: 18F-AlF; GRPR; PET; bombesin; prostate cancer