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

By Min Yang, Haokao Gao, Yaru Zhou, Ying Ma, Qimeng Quan, Lixin Lang, Kai Chen, Gang Niu, Yongjun Yan and Xiaoyuan Chen


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

Topics: Research Paper
Publisher: Ivyspring International Publisher
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Provided by: PubMed Central

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  2. (2003). [99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging. Eur J Nucl Med Mol Imaging.
  3. (2006). 18F-labeled bombesin analogs for targeting GRP receptor-expressing prostate cancer. J Nucl Med.
  4. (2010). 18F-labeled galacto and PEGylated RGD dimers for PET imaging of αvβ3 integrin expression. Mol Imaging Biol.
  5. (2007). 18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of αvβ3 integrin expression. Eur J Nucl Med Mol Imaging.
  6. (2009). 18F, 64Cu, and 68Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer. Bioconjug Chem.
  7. A new 18F-labeled BBN-RGD peptide heterodimer with a symmetric linker for prostate cancer imaging. Amino Acids. 2010;[Epub ahead of print]
  8. A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues.
  9. (2010). A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues. Eur J Nucl Med Mol Imaging.
  10. (2008). Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J Nucl Med.
  11. (2004). Criteria for the design and biological characterization of radiolabeled peptide-based pharmaceuticals. BioDrugs.
  12. (2008). Design, synthesis, and biological evaluation of an antagonist-bombesin analogue as targeting vector. Bioconjug Chem.
  13. (2009). Dual integrin and gastrin-releasing peptide receptor targeted tumor imaging using 18F-labeled PEGylated RGD-bombesin heterodimer 18F-FB-PEG3-Glu-RGD-BBN. J Med Chem.
  14. (2005). Gastrin-releasing peptide receptors in normal and neoplastic human uterus: involvement of multiple tissue compartments. J Clin Endocrinol Metab.
  15. (1999). Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res.
  16. (2004). High expression of peptide receptors as a novel target in gastrointestinal stromal tumours. Eur J Nucl Med Mol Imaging.
  17. (2009). Improving tumor uptake and pharmacokinetics
  18. In vitro and in vivo characterization of novel 18F-labeled bombesin analogues for targeting GRPR-positive tumors.
  19. (2004). microPET and autoradiographic imaging of GRP receptor expression with 64Cu-DOTA-[Lys3]bombesin in human prostate adenocarcinoma xenografts. J Nucl Med.
  20. (2004). MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide. Eur J Nucl Med Mol Imaging.
  21. (2008). Nuclear imaging of prostate cancer with gastrin-releasing-peptide-receptor targeted radiopharmaceuticals. Curr Pharm Des.
  22. (2007). Overexpression of gastrin-releasing peptide receptors in tumor-associated blood vessels of human ovarian neoplasms. Cell Oncol.
  23. (2004). Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor αvβ3-integrin expression. J Nucl Med.
  24. (2009). Peptide receptor imaging of prostate cancer with radiolabelled bombesin analogues. Methods.
  25. (2003). Peptide targeted imaging of cancer. Cancer Biother Radiopharm.
  26. (2008). Peptide-based probes for cancer imaging.
  27. Peptide-based probes for targeted molecular imaging.
  28. Peptides and peptide hormones for molecular imaging and disease diagnosis.
  29. (2008). Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med.
  30. (2005). Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. J Med Chem.
  31. (2005). Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes. Nucl Med Biol.
  32. (2006). Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors.
  33. (2005). Species differences of bombesin analog interactions with GRP-R define the choice of animal models in the development of GRP-R-targeting drugs.
  34. Tetraamine-derived bifunctional chelators for technetium-99m labelling: synthesis, bioconjugation and evaluation as targeted SPECT imaging probes for GRP-receptor-positive tumours.
  35. (2010). Tetraamine-derived bifunctional chelators for technetium-99m labelling: synthesis, bioconjugation and evaluation as targeted SPECT imaging probes for GRP-receptor-positive tumours. Chemistry.
  36. (2000). The presence of receptors for bombesin/GRP and mRNA for three receptor subtypes in human ovarian epithelial cancers. Regul Pept.