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

Autor: Grkovski M; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York., Goel R; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Krebs S; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Staton KD; Radiochemistry and Molecular Imaging Probe Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York., Harding JJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; and., Mellinghoff IK; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York., Humm JL; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York., Dunphy MPS; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York dunphym@mkscc.org.
Jazyk: angličtina
Zdroj: Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2020 Mar; Vol. 61 (3), pp. 357-366. Date of Electronic Publication: 2019 Oct 10.
DOI: 10.2967/jnumed.119.229740
Abstrakt: 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.
(© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze: MEDLINE
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