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Objectives:

he aim of this study was to investigate the feasibility of using ¹⁸F-(2S, 4R) 4-fluoroglutamine (¹⁸F-GLN) PET/CT imaging as a novel amino-acid based metabolism radio-tracer. The potential of ¹⁸F-GLN for diagnosis of brain metastases (BM) was also determined.

Methods:

13 healthy volunteers (5M, 8F; age, 37~64y) underwent a 60min dynamic whole-body PET/CT after intravenous injection of ¹⁸F-GLN (292.8±49.8MBq). Ten patients (7M and 3F; age, 25~62 y) with BM diagnosed by contrast enhanced MRI, CT or pathology were enrolled. Each patient also underwent standard ¹⁸F-FDG PET/CT for comparison analysis.

Results:

¹⁸F-GLN was well tolerated in all 23 subjects, with no adverse symptoms being noticed or reported. Predominant uptake was in kidneys, pancreas and liver (SUV mean ≥5), with moderate uptake observed in heart, aorta, salivary glands, thyroid, spleen, stomach, small intestine, prostate and uterus(3≤ SUV mean <5= )in 13 healthy volunteers. No significant levels of accumulation in brain, lung, breasts, bone and muscle were observed in all scans(SUV mean ≤1). Significant wash out of radioactivity from heart, liver, pancreas, spleen and kidneys was noted. On the contrary, brain, bone and red bone marrow showed continually uptake during 2 h. Uptake in the breast was also observed and reached the plateau at about 30 min after injection. The low ¹⁸F-GLN in the muscle remained relatively constant. Variabilities between all paired organs were similar (P > 0.05). The coefficient of variation(CV) of liver was 14.7±2.6%, which was lower than the 22.1±0.7% CV previously reported for ¹⁸F-FDG PET in liver. In addition, SUVmean measured in different organs except thyroid did not differ significantly between men and women (P > 0.05). In BM patients, it was proper to deduce that 30±10 min after injection might be the optimal scan time. Specific accumulation of ¹⁸F-GLN was observed with the SUVmax of 2.66 ± 1.33 (range, 1.04~5.29) in brain lesion, which was significantly different from that of ¹⁸F-FDG (p < 0.05), with the SUVmax of 10.68± 5.57 (range, 2.3~22.92). As a result, The tumor-to-nontumor ratios (T/NTmax)of ¹⁸F-GLN (5.28±2.86, range: 2.05~12.94) was significantly higher than that of ¹⁸F-FDG (1.10± 0.34, range: 0.56~1.69) (p < 0.05).¹⁸F-GLN found 11 discordant lesions in brain, and all of them were confirmed during follow-up (MRI, CT or pathological examination) to be true-positive.

Conclusions:

¹⁸F-GLN PET/CT administered to healthy humans demonstrated a favorable biodistribution, pharmacokinetics and safety profile. This study also indicates that ¹⁸F-GLN PET/CT is useful for diagnosis of patients with brain metastases. Finical Support: Beijing Natural Science Foundation Key Program (No. 7171002). Key Words: PET imaging study; biodistribution; pharmacokinetics; ¹⁸F-(2S, 4R) 4-fluoroglutamine; positron emission tomography; SUV; brain metastases.

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References