title: Clinical Translation of a Dual Integrin αvβ3- and Gastrin-Releasing Peptide Receptor-Targeting PET Radiotracer, 68Ga-BBN-RGD.
abstract: This study aimed to document the first-in-human application of a68Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin αvβ3and gastrin-releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnostic value of68Ga-BBN-RGD PET/CT in prostate cancer patients in comparison with68Ga-BBN.
  
  
  
  Five healthy volunteers (4 men and 1 woman; age range, 28-53 y) were enrolled to validate the safety of68Ga-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 of68Ga-BBN-RGD and also accepted68Ga-BBN PET/CT within 2 wk for comparison.
  
  
  
  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 of68Ga-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 of 4 primary tumors, 14 metastatic lymph nodes, and 20 bone lesions with an SUVmaxof 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 on68Ga-BBN PET/CT, with the SUVmaxof 2.98 ± 1.24, 4.17 ± 1.89, and 3.61 ± 1.85, respectively.
  
  
  
  This study indicates the safety and efficiency of a new type of dual integrin αvβ3- and GRPR-targeting PET radiotracer in prostate cancer diagnosis and staging.
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China lifang@pumch.cn shawn.chen@nih.gov.|Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
authors: Jingjing
authors: J
authors: Zhang
authors: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
authors: Gang
authors: G
authors: Niu
authors: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
authors: Lixin
authors: L
authors: Lang
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China lifang@pumch.cn shawn.chen@nih.gov.
authors: Fang
authors: F
authors: Li
authors: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; and.
authors: Xinrong
authors: X
authors: Fan
authors: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland.
authors: Xuefeng
authors: X
authors: Yan
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Shaobo
authors: S
authors: Yao
authors: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; and.
authors: Weigang
authors: W
authors: Yan
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Li
authors: L
authors: Huo
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Libo
authors: L
authors: Chen
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Zhiyuan
authors: Z
authors: Li
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Zhaohui
authors: Z
authors: Zhu
authors: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland lifang@pumch.cn shawn.chen@nih.gov.
authors: Xiaoyuan
authors: X
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D001839:Bombesin / Q000493:pharmacokinetics*; D005260:Female; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D057054:Molecular Imaging; D009842:Oligopeptides / Q000493:pharmacokinetics*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018004:Receptors, Bombesin / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; C047981:arginyl-glycyl-aspartic acid; D001839:Bombesin
keywords: BBN-RGD; GRPR; PET; first-in-human; integrin αvβ3; prostate cancer