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18 F-(2S,4R)-4-fluoroglutamine ( 18 F-FGln) is an investigational PET radiotracer for imaging tumor glutamine flux and metabolism. The aim of this study was to investigate its pharmacokinetic properties in patients with cancer. Methods: Fifty lesions from 41 patients (21 men and 20 women, aged 54 ± 14 y) were analyzed. Thirty-minute dynamic PET scans were performed concurrently with a rapid intravenous bolus injection of 232 ± 82 MBq of 18 F-FGln, followed by 2 static PET scans at 97 ± 14 and 190 ± 12 min after injection. Five patients also underwent a second 18 F-FGln study 4-13 wk after initiation of therapy with glutaminase, dual TORC1/2, or programmed death-1 inhibitors. Blood samples were collected to determine plasma and metabolite fractions and to scale the image-derived input function. Regions of interest were manually drawn to calculate SUVs. Pharmacokinetic modeling with both reversible and irreversible 1- and 2-tissue-compartment models was performed to calculate the kinetic rate constants K  1 , k  2 , k  3 , and k  4 The analysis was repeated with truncated 30-min dynamic datasets. Results : Intratumor 18 F-FGln uptake patterns demonstrated substantial heterogeneity in different lesion types. In most lesions, the reversible 2-tissue-compartment model was chosen as the most appropriate according to the Akaike information criterion. K  1 , a surrogate biomarker for 18 F-FGln intracellular transport, was the kinetic rate constant that was most correlated both with SUV at 30 min (Spearman ρ = 0.71) and with SUV at 190 min (ρ = 0.51). Only K  1 was reproducible from truncated 30-min datasets (intraclass correlation coefficient, 0.96). k  3 , a surrogate biomarker for glutaminolysis rate, was relatively low in about 50% of lesions. Treatment with glutaminase inhibitor CB-839 substantially reduced the glutaminolysis rates as measured by k  3  Conclusion:  18 F-FGln dynamic PET is a sensitive tool for studying glutamine transport and metabolism in human malignancies. Analysis of dynamic data facilitates better understanding of 18 F-FGln pharmacokinetics and may be necessary for response assessment to targeted therapies that impact intracellular glutamine pool size and tumor glutaminolysis rates.

Pharmacokinetic Assessment of 18F-(2S,4R)-4-Fluoroglutamine in Patients with Cancer

Pharmacokinetic Assessment of ¹⁸F-(2S,4R)-4-Fluoroglutamine in Patients with Cancer