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Purpose: We explored the imaging of bombesin receptors and evaluated the clinical use of [Tc]Demobesin 4 ([Tc]DB4) in prostate cancer patients. Procedures: [Tc]DB4 was prepared according to Good Manufacturing Practice. Patients with prostate cancer underwent serial planar and SPECT imaging up to 3 h after administration. Blood and urine samples were taken to assess pharmacokinetics. Results: [Tc]DB4 is safe and clears rapidly from the bloodstream via the kidneys resulting in low background activity. The tracer binds strongly to the gastrin-releasing peptide receptor (GRPR) in vivo as indicated by the high uptake in the pancreas seen in all patients. In patients who had undergone hormone therapy, [Tc]DB4 did not efficiently image metastatic prostate cancer. In contrast, in newly diagnosed patients local disease was visualised. Conclusions: The GRPR is an unsuitable target for imaging refractory prostate cancer but may be useful in untreated disease. [Tc]DB4 is a promising radiopharmaceutical which merits further exploration in this specific group of patients. [ABSTRACT FROM AUTHOR]