UNLABELLED: This study aimed to document the first-in-human application of a Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin αβ and gastrin-releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnostic value of Ga-BBN-RGD PET/CT in prostate cancer patients in comparison with Ga-BBN. METHODS: Five healthy volunteers (4 men and 1 woman; age range, 28-53 y) were enrolled to validate the safety of Ga-BBN-RGD. Dosimetry was calculated using the OLINDA/EXM software. Thirteen patients with prostate cancer (4 newly diagnosed and 9 posttherapy) were enrolled. All the patients underwent PET/CT scans 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of Ga-BBN-RGD and also accepted Ga-BBN PET/CT within 2 wk for comparison. RESULTS: With a mean injected dose of 107.3 ± 14.8 MBq per patient, no side effect was found during the whole procedure and 2 wk follow-up, demonstrating the safety of Ga-BBN-RGD. A patient would be exposed to a radiation dose of 2.90 mSv with an injected dose of 129.5 MBq (3.5 mCi), which is much lower than the dose limit set by the Food and Drug Administration. In 13 patients with prostate cancer diagnosed by biopsy, Ga-BBN-RGD PET/CT detected 3 of 4 primary tumors, 14 metastatic lymph nodes, and 20 bone lesions with an SUV of 4.46 ± 0.50, 6.26 ± 2.95, and 4.84 ± 1.57, respectively. Only 2 of 4 primary tumors, 5 lymph nodes, and 12 bone lesions were positive on Ga-BBN PET/CT, with the SUV of 2.98 ± 1.24, 4.17 ± 1.89, and 3.61 ± 1.85, respectively. CONCLUSION: This study indicates the safety and efficiency of a new type of dual integrin αβ- and GRPR-targeting PET radiotracer in prostate cancer diagnosis and staging.