(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: Hildo J K Ananias, Zilin Yu, Rudi A Dierckx, Christophe van der Wiele, Wijnand Helfrich, Fan Wang, Yongjun Yan, Xiaoyuan Chen, Igle J de Jong, Philip H Elsinga
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 8 Issue 4 Pg. 1165-73 (Aug 01 2011) ISSN: 1543-8392 [Electronic] United States
• PMID: 21699202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Contrast Media
• Organotechnetium Compounds
• Bombesin

Topics

• Animals
• Bombesin (chemistry)
• Contrast Media (chemistry)
• Humans
• Male
• Mice
• Mice, Nude
• Organotechnetium Compounds (chemistry)
• Prostatic Neoplasms (pathology)
• Radiochemistry
• Tomography, Emission-Computed, Single-Photon (methods)