Theranostics 2011; 1:220-229. doi:10.7150/thno/v01p0220 This volume

Research Paper

18F-Labeled GRPR Agonists and Antagonists: A Comparative Study in Prostate Cancer Imaging

Min Yang1,2*, Haokao Gao2, 3*, Yaru Zhou4, Ying Ma2, Qimeng Quan2, Lixin Lang2, Kai Chen2, Gang Niu2, Yongjun Yan2✉, Xiaoyuan Chen2✉

1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China
2. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892, USA
3. Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an, 710032, China
4. Department of Endocrinology, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, 050051, China
* These authors contributed equally in this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Yang M, Gao H, Zhou Y, Ma Y, Quan Q, Lang L, Chen K, Niu G, Yan Y, Chen X. 18F-Labeled GRPR Agonists and Antagonists: A Comparative Study in Prostate Cancer Imaging. Theranostics 2011; 1:220-229. doi:10.7150/thno/v01p0220. Available from

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Radiolabeled bombesin analogs are promising probes for cancer imaging of gastrin-releasing peptide receptor (GRPR). In this study, we developed 18F-labeled GRPR agonists and antagonists for positron emission tomography (PET) imaging of prostate cancer. GRPR antagonists ATBBN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH2CH3) and MATBBN (Gly-Gly-Gly-Arg-Asp-Asn-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH2CH3), and agonists AGBBN (Gln-Trp-Ala-Val-Gly-His-Leu-MetNH2) and MAGBBN (Gly-Gly-Gly-Arg-Asp-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-MetNH2) were radiolabeled with 18F via 4-nitrophenyl 2-18F-fluoropropionate. The in vitro receptor binding, cell uptake, and efflux properties of the radiotracers were studied on PC-3 cells. An in vivo PET study was performed on mice bearing PC-3 tumors. Direct 18F-labeling of known GRPR antagonist ATBBN and agonist AGBBN did not result in good tumor targeting or appropriate pharmacokinetics. Modification was made by introducing a highly hydrophilic linker Gly-Gly-Gly-Arg-Asp-Asn. Higher receptor binding affinity, much higher cell uptake and slower washout were observed for the agonist 18F-FP-MAGBBN over the antagonist 18F-FP-MATBBN. Both tracers showed good tumor/background contrast, with the agonist 18F-FP-MAGBBN having significantly higher tumor uptake than the antagonist 18F-FP-MATBBN (P < 0.01). In conclusion, Gly-Gly-Gly-Arg-Asp-Asn linker significantly improved the pharmacokinetics of the otherwise hydrophobic BBN radiotracers. 18F-labeled BBN peptide agonists may be the probes of choice for prostate cancer imaging due to their relatively high tumor uptake and retention as compared with the antagonist counterparts.

Keywords: gastrin-releasing peptide receptor (GRPR), bombesin (BBN), agonist, antagonist, positron emission tomography (PET), 18F