Theranostics 2015; 5(8):882-889. doi:10.7150/thno.12303

Research Paper

Prospective Study of 68Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients

Zhe Wang1*, Mingru Zhang1*, Liang Wang2, Shengjun Wang1, Fei Kang1, Guoquan Li1, Orit Jacobson3, Gang Niu3, Weidong Yang1, Jing Wang1✉, Xiaoyuan Chen3✉

1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China
2. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China
3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States
* Zhe Wang and Mingru Zhang contributed equally to this article.

Abstract

Purpose: The chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, 68Ga-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.

Methods: Six healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after 68Ga-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 68Ga-NOTA-NFB and 18F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining.

Results: 68Ga-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 68Ga-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 18F-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 68Ga-NOTA-NFB uptake.

Conclusion: With a favorable radiation dosimetry profile, 68Ga-NOTA-NFB is safe for clinical imaging. Compared to 18F-FDG PET/CT, 68Ga-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients.

Keywords: 68Ga-NOTA-NFB, internal dosimetry, CXCR4, glioma, PET/CT

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How to cite this article:
Wang Z, Zhang M, Wang L, Wang S, Kang F, Li G, Jacobson O, Niu G, Yang W, Wang J, Chen X. Prospective Study of 68Ga-NOTA-NFB: Radiation Dosimetry in Healthy Volunteers and First Application in Glioma Patients. Theranostics 2015; 5(8):882-889. doi:10.7150/thno.12303. Available from http://www.thno.org/v05p0882.htm