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Imaging Brain Metastasis Patients With 18F-(2S,4R)-4-Fluoroglutamine

Xu, Xiaoxia, PhD*; Zhu, Hua, PhD*; Liu, Fei, PhD*; Zhang, Yan, PhD; Yang, Jianhua, BS*; Zhang, Lifang, PhD; Zhu, Lin, PhD; Li, Nan, MD*; Kung, Hank F., PhD‡§; Yang, Zhi, PhD*

doi: 10.1097/RLU.0000000000002257
Original Articles

Purpose There is a need for an alternative PET probe, which does not show normal brain tissue uptake in the evaluation of metastasis to the brain. Therefore, we investigate the feasibility of 18F-labeled glutamine analog, 18F-(2S,4R)-4-fluoroglutamine (18F-FGln), as a new metabolic probe to detect brain metastasis.

Methods Patients (7 men and 7 women; age, 25–67 years) with suspected brain metastasis were enrolled for this study. All patients were imaged first with 18F-FGln PET (3 patients for 1-hour dynamic whole-body PET/CT scans, and 11 patients for static whole-body scans at 30 ± 10 minutes after injection), followed by a whole-body 18F-FDG PET performed in the same week. The characteristics of 18F-FGln PET imaging in brain metastasis patients were compared with that of 18F-FDG PET and/or contrast-enhanced MRI patient-by-patient. A composite of all functional and anatomic imaging studies served as the imaging comparator.

Results Initial study in 3 patients using 1-hour dynamic scan showed that 30 ± 10 minutes after injection is optimal for identifying brain metastasis with a high-contrast ratio. All patients were positive for brain metastasis on this studies that demonstrated 38 lesions in 6 anatomic regions on the imaging comparator. The per-lesion detection rates for 18F-FGln PET and 18F-FDG PET were 81.6% and 36.8%, respectively. The average tumor-to-normal brain ratio of 18F-FGln PET was significantly better than that of 18F-FDG PET in all patients (4.97 ± 2.23 vs 1.22 ± 0.69, P < 0.05). Furthermore, our results suggest that 18F-FGln uptake in brain metastasis appeared to be independent of tumor size and peripheral edema. In addition, in 14 brain metastatic lesions visualized by both 18F-FDG PET and 18F-FGln PET imaging, a positive correlation of SUVmax was observed (r = 0.780, P < 0.01). As to the extracranial metastasis, both tracers showed a concordant increased radioactive uptake except in liver and bone.

Conclusions The initial imaging of 18F-FGln presenting a promising new PET radiotracer for patients with brain metastasis and its utility in the liver and bone metastatic lesions may require more caution due to uptake in normal structures.

From the *Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute;

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China;

Department of Radiology, University of Pennsylvania, Philadelphia, PA; and

§Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.

Received for publication May 16, 2018; revision accepted July 18, 2018.

Conflicts of interest and sources of funding: This work was supported in part by grants from Beijing Natural Science Foundation Key Program (no. 7171002). None declared to all authors.

Correspondence to: Zhi Yang, PhD, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd, Beijing, 100142, China. E-mail:

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