Jingjing Zhang1, Deling Li2, Lixin Lang3, Zhaohui Zhu4, Ling Wang4, Peilin Wu4, Gang Niu3, Fang Li5, Xiaoyuan Chen6. 1. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland; and. 2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland; and. 4. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 5. 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. 6. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland; and lifang@pumch.cn shawn.chen@nih.gov.
Abstract
UNLABELLED: This work was designed to study the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR)-targeting, (68)Ga-labeled bombesin (BBN) peptide derivative PET tracer, NOTA-Aca-BBN(7-14) (denoted as (68)Ga-BBN) in healthy volunteers and to assess the level of receptor expression in glioma patients. METHODS: Four healthy volunteers (2 male and 2 female) underwent whole-body PET/CT at multiple time points after a bolus injection of (68)Ga-BBN (111 ± 148 MBq). Regions of interest were drawn manually over major organs, and time-activity curves were obtained. Dosimetry was calculated using the OLINDA/EXM software. Twelve patients with glioma diagnosed by contrast-enhanced MRI underwent PET/CT at 30-45 min after (68)Ga-BBN injection. Within 1 wk afterward, the tumor was surgically removed and immunohistochemical staining of tumor samples against GRPR was performed and correlated with the PET/CT results. RESULTS: (68)Ga-BBN was well tolerated in all healthy volunteers, with no adverse symptoms being noticed or reported. (68)Ga-BBN cleared rapidly from the circulation and was excreted mainly through the kidneys and urinary tract. The total effective dose equivalent and effective dose were 0.0335 ± 0.0079 and 0.0276 ± 0.0066 mSv/MBq, respectively. In glioma patients, all MRI-identified lesions showed high signal intensity on (68)Ga-BBN PET/CT. SUVmax and SUVmean were 2.08 ± 0.58 and 1.32 ± 0.37, respectively. With normal brain tissue as background, tumor-to-background ratios were 24.0 ± 8.85 and 13.4 ± 4.54 based on SUVmax and SUVmean, respectively. The immunohistochemical staining confirmed a positive correlation between SUV and GRPR expression level (r(2) = 0.71, P < 0.001). CONCLUSION: (68)Ga-BBN is a PET tracer with favorable pharmacokinetics and a favorable dosimetry profile. It has the potential to evaluate GRPR expression in glioma patients and guide GRPR-targeted therapy of glioma.
UNLABELLED: This work was designed to study the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR)-targeting, (68)Ga-labeled bombesin (BBN) peptide derivative PET tracer, NOTA-Aca-BBN(7-14) (denoted as (68)Ga-BBN) in healthy volunteers and to assess the level of receptor expression in gliomapatients. METHODS: Four healthy volunteers (2 male and 2 female) underwent whole-body PET/CT at multiple time points after a bolus injection of (68)Ga-BBN (111 ± 148 MBq). Regions of interest were drawn manually over major organs, and time-activity curves were obtained. Dosimetry was calculated using the OLINDA/EXM software. Twelve patients with glioma diagnosed by contrast-enhanced MRI underwent PET/CT at 30-45 min after (68)Ga-BBN injection. Within 1 wk afterward, the tumor was surgically removed and immunohistochemical staining of tumor samples against GRPR was performed and correlated with the PET/CT results. RESULTS: (68)Ga-BBN was well tolerated in all healthy volunteers, with no adverse symptoms being noticed or reported. (68)Ga-BBN cleared rapidly from the circulation and was excreted mainly through the kidneys and urinary tract. The total effective dose equivalent and effective dose were 0.0335 ± 0.0079 and 0.0276 ± 0.0066 mSv/MBq, respectively. In gliomapatients, all MRI-identified lesions showed high signal intensity on (68)Ga-BBNPET/CT. SUVmax and SUVmean were 2.08 ± 0.58 and 1.32 ± 0.37, respectively. With normal brain tissue as background, tumor-to-background ratios were 24.0 ± 8.85 and 13.4 ± 4.54 based on SUVmax and SUVmean, respectively. The immunohistochemical staining confirmed a positive correlation between SUV and GRPR expression level (r(2) = 0.71, P < 0.001). CONCLUSION: (68)Ga-BBN is a PET tracer with favorable pharmacokinetics and a favorable dosimetry profile. It has the potential to evaluate GRPR expression in gliomapatients and guide GRPR-targeted therapy of glioma.
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