Publication

(99m)Technetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) as a Targeted Imaging Agent with MicroSPECT in a PC-3 Prostate Cancer Xenograft Model

Ananias, H. J. K., Yu, Z., Dierckx, R. A., van der Wiele, C., Helfrich, W., Wang, F., Tan, Y., Chen, X., de Jong, I. J. & Elsinga, P. H., 2011, In : Molecular pharmaceutics. 8, 4, p. 1165-1173 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

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) (Tc-99m-HABN) and evaluated its GRPR targeting properties in vitro and in a xenograft tumor model for human prostate cancer in athymic mice. Tc-99m-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. Tc-99m-HABN biodistribution and microSPECT imaging were performed in PC-3 tumor-bearing athymic mice. Tc-99m-HABN was prepared with high labeling yield (>90%), hip radiochemical purity (>95%) and a specific activity of similar to 19.8 MBq/nmol. The partition coefficient log D value was -1.60 +/- 0.06. Tc-99m-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 Tc-99m-HABN demonstrated rapid cellular internalization and a long intracellular retention time. When mice were injected with Tc-99m-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. Tc-99m-HABN microSPECT imaging resulted in clear delineation of the tumor. Tc-99m-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.

Original languageEnglish
Pages (from-to)1165-1173
Number of pages9
JournalMolecular pharmaceutics
Volume8
Issue number4
Publication statusPublished - 2011

    Keywords

  • bombesin, prostate, cancer, imaging, SPECT, microSPECT, GRPR, GRP, GASTRIN-RELEASING-PEPTIDE, RADIOLABELED BOMBESIN ANALOGS, PELVIC LYMPH-NODES, RECEPTOR ANTAGONIST, POSITIVE TUMORS, BONE METASTASES, IN-VITRO, GRP, RADIOPHARMACEUTICALS, DIAGNOSIS

ID: 5375285