Clinical translation of a dual integrin αvβ3 and GRPR targeting PET radiotracer ⁶⁸Ga-NOTA-BBN-RGD

Abstract

This study aims to document the first-in-human application of a ⁶⁸Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin αvβ3 and gastrin releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnosis value of ⁶⁸Ga- BBN-RGD positron emission tomography (PET)/x-ray computed tomography (CT) in prostate cancer patients in comparison with ⁶⁸Ga-BBN. Methods: Five healthy volunteers (M 4, F 1, 28–53 y) were enrolled to validate the safety of ⁶⁸Ga-BBN-RGD. Dosimetry was calculated using the OLINDA/EXM software. A total of 13 patients with prostate cancer (4 newly diagnosed and 9 post-therapy) were enrolled. All the patients underwent PET/CT scans 15–30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram body weight of ⁶⁸Ga-BBN-RGD, and also accepted ⁶⁸Ga-BBN PET/CT within 2 weeks 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 weeks follow-up, demonstrating the safety of ⁶⁸Ga-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, ⁶⁸Ga-BBN-RGD PET/CT detected 3 out of 4 primary tumors, 14 metastatic lymph nodes and 20 bone lesions with maximum standardized uptake values (SUV_max) of 4.46 ± 0.50, 6.26 ± 2.95, and 4.84 ± 1.57, respectively. Only 2/4 primary tumors, 5 lymph nodes and 12 bone lesions were positive on ⁶⁸Ga-BBN PET/CT with the SUV_max of 2.98 ± 1.24, 4.17 ± 1.89, and 3.61 ± 1.85, respectively. Conclusion: This study indicates the safety and the efficiency of a new type of dual integrin αvβ3 and GRPR targeting PET radiotracer in prostate cancer diagnosis and staging.