68Ga-NOTA-Aca-BBN(7-14) PET/CT in Healthy Volunteers and Glioma Patients

J Nucl Med. 2016 Jan;57(1):9-14. doi: 10.2967/jnumed.115.165316. Epub 2015 Oct 8.

Abstract

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.

Keywords: 68Ga-BBN; BBN peptide; PET/CT; gastrin-releasing peptide receptor (GRPR); glioma.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bombesin / analogs & derivatives*
  • Bombesin / chemistry
  • Bombesin / pharmacokinetics
  • Child
  • Child, Preschool
  • Female
  • Gallium Radioisotopes*
  • Gene Expression Regulation, Neoplastic
  • Glioma / diagnostic imaging*
  • Glioma / metabolism
  • Healthy Volunteers*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds, 1-Ring
  • Humans
  • Male
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacokinetics
  • Positron-Emission Tomography / adverse effects
  • Positron-Emission Tomography / methods*
  • Receptors, Bombesin / metabolism
  • Safety
  • Tissue Distribution
  • Tomography, X-Ray Computed / adverse effects
  • Tomography, X-Ray Computed / methods*
  • Young Adult

Substances

  • Gallium Radioisotopes
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • Peptide Fragments
  • Receptors, Bombesin
  • bombesin (7-14)
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • Bombesin