18F-FDOPA kinetics in brain tumors.
L-3,4-Dihydroxy-6-(18)F-fluoro-phenyl-alanine ((18)F-FDOPA) is an amino acid analog used to evaluate presynaptic dopaminergic neuronal function. Evaluation of tumor recurrence in neurooncology is another application. Here, the kinetics of (18)F-FDOPA in brain tumors were investigated.


METHODS
A total of 37 patients underwent 45 studies; 10 had grade IV, 10 had grade III, and 13 had grade II brain tumors; 2 had metastases; and 2 had benign lesions. After (18)F-DOPA was administered at 1.5-5 MBq/kg, dynamic PET images were acquired for 75 min. Images were reconstructed with iterative algorithms, and corrections for attenuation and scatter were applied. Images representing venous structures, the striatum, and tumors were generated with factor analysis, and from these, input and output functions were derived with simple threshold techniques. Compartmental modeling was applied to estimate rate constants.


RESULTS
A 2-compartment model was able to describe (18)F-FDOPA kinetics in tumors and the cerebellum but not the striatum. A 3-compartment model with corrections for tissue blood volume, metabolites, and partial volume appeared to be superior for describing (18)F-FDOPA kinetics in tumors and the striatum. A significant correlation was found between influx rate constant K and late uptake (standardized uptake value from 65 to 75 min), whereas the correlation of K with early uptake was weak. High-grade tumors had significantly higher transport rate constant k(1), equilibrium distribution volumes, and influx rate constant K than did low-grade tumors (P < 0.01). Tumor uptake showed a maximum at about 15 min, whereas the striatum typically showed a plateau-shaped curve. Patlak graphical analysis did not provide accurate parameter estimates. Logan graphical analysis yielded reliable estimates of the distribution volume and could separate newly diagnosed high-grade tumors from low-grade tumors.


CONCLUSIONS
A 2-compartment model was able to describe (18)F-FDOPA kinetics in tumors in a first approximation. A 3-compartment model with corrections for metabolites and partial volume could adequately describe (18)F-FDOPA kinetics in tumors, the striatum, and the cerebellum. This model suggests that (18)F-FDOPA was transported but not trapped in tumors, unlike in the striatum. The shape of the uptake curve appeared to be related to tumor grade. After an early maximum, high-grade tumors had a steep descending branch, whereas low-grade tumors had a slowly declining curve, like that for the cerebellum but on a higher scale.
Schiepers
Christiaan
C
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, USA. cschiepers@mednet.ucla.edu
Chen
Wei
W
Cloughesy
Timothy
T
Dahlbom
Magnus
M
Huang
Sung-Cheng
SC
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003198:Computer Simulation; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine