Dataset Information

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

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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5242342 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeThe chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, (68)Ga-NOTA-NFB was investigated in this study to assess its safety, biodistribution and dosimetry properties in healthy volunteers, and to preliminarily evaluate its application in glioma patients.MethodsSix healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after (68)Ga-NOTA-NFB injection (mean dose, 182.4 ± 3.7 MBq (4.93 ± 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the injection. The estimated radiation doses were calculated by OLINDA/EXM software. Eight patients with glioma were enrolled and underwent both (68)Ga-NOTA-NFB and (18)F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining.Results(68)Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance from the blood circulation was observed. The organs with the highest absorbed doses were spleen (193.8 ± 32.5 μSv/MBq) and liver (119.3 ± 25.0 μSv/MBq). The mean effective dose was 25.4 ± 6.1 μSv/MBq. The maximum standardized uptake values (SUVmax) and the maximum target to non-target ratios (T/NTmax) of (68)Ga-NOTA-NFB PET/CT in glioma tissues were 4.11 ± 2.90 (range, 0.45-8.21) and 9.21 ± 8.75 (range, 3.66-24.88), respectively, while those of (18)F-FDG PET/CT were 7.34 ± 2.90 (range, 3.50-12.27) and 0.86 ± 0.41 (range, 0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake.ConclusionWith a favorable radiation dosimetry profile, (68)Ga-NOTA-NFB is safe for clinical imaging. Compared to (18)F-FDG PET/CT, (68)Ga-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients.