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Download Hi-Res ImageDownload to MS-PowerPointCite This:Mol. Pharmaceutics 2011, 8, 4, 1165-1173
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99mTechnetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7–14) as a Targeted Imaging Agent with MicroSPECT in a PC-3 Prostate Cancer Xenograft Model

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† Department of Urology, University Medical Center Groningen, Groningen, The Netherlands
‡ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
§ Department of Nuclear Medicine, University Hospital Ghent, Ghent, Belgium
∥ Surgical Research Laboratory, University Medical Center Groningen, Groningen, The Netherlands
⊥ Medical Isotopes Research Center, Peking University, Peking, China
# Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, United States
Hanzeplein 1, 9712 RB Groningen, The Netherlands. E-mail: [email protected]. Phone: 0031503612380. Fax: 0031503619607.
Cite this: Mol. Pharmaceutics 2011, 8, 4, 1165–1173
Publication Date (Web):June 23, 2011
https://doi.org/10.1021/mp200014h
Copyright © 2011 American Chemical Society
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    Abstract

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    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 99mtechnetium-HYNIC(tricine/TPPTS)-Aca-BN(7–14) (99mTc-HABN) and evaluated its GRPR targeting properties in vitro and in a xenograft tumor model for human prostate cancer in athymic mice. 99mTc-HABN was synthesized, and its lipophilicity and stability were investigated. The IC50, internalization and efflux properties were determined in vitro using the GRPR expressing human prostate cancer cell line PC-3. 99mTc-HABN biodistribution and microSPECT imaging were performed in PC-3 tumor-bearing athymic mice. 99mTc-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. 99mTc-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 99mTc-HABN demonstrated rapid cellular internalization and a long intracellular retention time. When mice were injected with 99mTc-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. 99mTc-HABN microSPECT imaging resulted in clear delineation of the tumor. 99mTc-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.

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