title: (99m)technetium-HYNIC(tricine/TPPTS)-Aca-bombesin(7-14) as a targeted imaging agent with microSPECT in a PC-3 prostate cancer xenograft model.
abstract: The peptide bombesin (BN) and derivates thereof show high binding affinity for the gastrin-releasing peptide receptor (GRPR), which is highly expressed in primary and metastasized prostate cancer. We have synthesized a new BN-based radiopharmaceutical (99m)technetium-HYNIC(tricine/TPPTS)-Aca-BN(7-14) ((99m)Tc-HABN) and evaluated its GRPR targeting properties in vitro and in a xenograft tumor model for human prostate cancer in athymic mice. (99m)Tc-HABN was synthesized, and its lipophilicity and stability were investigated. The IC(50), internalization and efflux properties were determined in vitro using the GRPR expressing human prostate cancer cell line PC-3. (99m)Tc-HABN biodistribution and microSPECT imaging were performed in PC-3 tumor-bearing athymic mice. (99m)Tc-HABN was prepared with high labeling yield (>90%), high radiochemical purity (>95%) and a specific activity of ~19.8 MBq/nmol. The partition coefficient log D value was -1.60 ± 0.06. (99m)Tc-HABN proved to be stable in human serum for 6 h. The IC50 of HYNIC-Aca-BN(7-14) was 12.81 ± 0.14 nM. Incubation of PC-3 cells with (99m)Tc-HABN demonstrated rapid cellular internalization and a long intracellular retention time. When mice were injected with (99m)Tc-HABN, the activity was predominantly cleared via the kidneys. Uptake in the tumor was 2.24 ± 0.64% ID/g after 30 min, with a steady decrease during the 4 h study period. In vivo experiments with a blocking agent showed GRPR mediated uptake. (99m)Tc-HABN microSPECT imaging resulted in clear delineation of the tumor. (99m)Tc-HABN is a novel BN-based radiopharmaceutical that proved to be suitable for targeted imaging of prostate cancer with microSPECT using the human prostate cancer cell line PC-3 in a xenograft mouse model.
authors.affiliation: Department of Urology, University Medical Center Groningen, Groningen, The Netherlands. h.j.k.ananias@uro.umcg.nl
authors.forename: Hildo J K
authors.initials: HJ
authors.lastname: Ananias
authors.forename: Zilin
authors.initials: Z
authors.lastname: Yu
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Christophe
authors.initials: C
authors.lastname: van der Wiele
authors.forename: Wijnand
authors.initials: W
authors.lastname: Helfrich
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yan
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Igle J
authors.initials: IJ
authors.lastname: de Jong
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
mesh_terms: D000818:Animals; D001839:Bombesin / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015609:Organotechnetium Compounds / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000473:pathology*; D011854:Radiochemistry; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D003287:Contrast Media; D015609:Organotechnetium Compounds; D001839:Bombesin