Influx rate of 18 F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts.

Autor: Pitman KE; Department of Physics, University of Oslo, P.O. Box 1048 Blindern, 0316, Oslo, Norway.; Department of Medical Physics, Oslo University Hospital, Oslo, Norway., Alluri SR; Department of Chemistry, University of Oslo, P.O. Box 1048 Blindern, 0316, Oslo, Norway., Kristian A; Department of Tumour Biology, Oslo University Hospital, Oslo, Norway., Aarnes EK; Department of Radiation Biology, Oslo University Hospital, Oslo, Norway., Lyng H; Department of Radiation Biology, Oslo University Hospital, Oslo, Norway., Riss PJ; Department of Chemistry, University of Oslo, P.O. Box 1048 Blindern, 0316, Oslo, Norway., Malinen E; Department of Physics, University of Oslo, P.O. Box 1048 Blindern, 0316, Oslo, Norway. eirik.malinen@fys.uio.no.; Department of Medical Physics, Oslo University Hospital, Oslo, Norway. eirik.malinen@fys.uio.no.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2019 Sep; Vol. 46 (10), pp. 2190-2198. Date of Electronic Publication: 2019 Jul 01.
DOI: 10.1007/s00259-019-04375-8
Abstrakt: Purpose: 18 F-fluoroaminosuberic acid ( 18 F-FASu) is a recently developed amino acid tracer for positron emission tomography (PET) of oxidative stress that may offer improved tumour assessment over the conventional tracer 18 F-fluorodeoxyglucose ( 18 F-FDG). Our aim was to evaluate and relate dynamic 18 F-FASu and 18 F-FDG uptake with pharmacokinetic modelling to transporter protein expression levels in a panel of diverse tumour xenograft lines.
Methods: Four different tumour xenograft lines were implanted in female athymic nude mice: MAS98.12 and HBCx3 (breast), TPMX (osteosarcoma) and A549 (lung). Dynamic PET over 60 min was performed on a small animal unit. The time-activity curves (TACs) for 18 F-FASu and 18 F-FDG in individual tumours were used to extract early (SUV E ; 2 min p.i.) and late (SUV L ; 55 min p.i.) standardised uptake values. Pharmacokinetic two-tissue compartment models were applied to the TACs to estimate rate constants K 1 -k 4 and blood volume fraction v B . Relative levels of cystine/glutamate antiporter subunit xCT were assessed by western blotting, and expression of GLUT1 and CD31 by immunohistochemistry.
Results: 18 F-FASu showed higher SUV E , whilst 18 F-FDG exhibited higher SUV L . Influx rate K 1 for 18 F-FASu was significantly correlated with xCT levels (p = 0.001) and was significantly higher than K 1 for 18 F-FDG (p < 0.001). K 1 for 18 F-FDG was significantly correlated with GLUT1 levels (p = 0.002). v B estimated from 18 F-FASu and 18 F-FDG TACs was highly consistent and significantly correlated (r = 0.85, p < 0.001). Two qualitatively different 18 F-FASu uptake profiles were identified: type α with low xCT expression and low K 1 (A549 and HBCx3), and type β with high xCT expression and high K 1 (MAS98.12 and TPMX).
Conclusion: The influx rate of 18 F-FASu reflects xCT activity in tumour xenografts. Dynamic PET with pharmacokinetic modelling is needed to fully appraise 18 F-FASu distribution routes.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje