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

Objectives ⁶⁸Ga-NOTA-NFB, a specific imaging agent of CXCR4, was investigated its safety, biodistribution and dosimetric 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, 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. Eight patients with glioma were enrolled and performed with both ⁶⁸Ga-NOTA-NFB and ¹⁸F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues were determined by immunohistochemical staining.

Results ⁶⁸Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance was observed in the blood circulation. 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 (SUV_max) and the maximum target to non-target ratios (T/NT_max) 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.

Conclusions 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 value in diagnosing and treatment planning for CXCR4 positive patients.