title: Preferred transport of O-(2-[18F]fluoroethyl)-D-tyrosine (D-FET) into the porcine brain.
abstract: Amino acids are valuable tracers for brain tumor imaging with positron emission tomography (PET). In this study the transport of O-(2-[(18)F]fluoroethyl)-D-tyrosine (D-FET) across the blood-brain barrier (BBB) was studied with PET in anesthetized piglets and patients after subtotal resection of brain tumors and compared with O-(2-[(18)F]fluoroethyl)-L-tyrosine (L-FET) and 3-O-methyl-6-[(18)F]fluoro-L-DOPA (L-OMFD). In piglets, compartmental modeling of PET data was used to calculate the rate constants for the blood-brain (K(1)) and the brain-blood (k(2)) transfer of D-FET, L-FET and L-OMFD. In patients standardized uptake values (SUVs) were calculated in brain cortex and lesions. Additionally, affinity determinations on various amino acid transporters (LAT1, LAT2, PAT1, XPCT) were performed in vitro using unlabeled D-FET, L-FET and L-OMFD. The initial brain uptake of D-FET in piglets was more than two-fold higher than that of l-FET, whereas the initial brain uptake of D-FET in patients was similar to that of L-FET. Calculation of K(1) and k(2) from the brain uptake curves and the plasma input data in piglets revealed about 4- and 2-fold higher values for D-FET compared to L-FET and L-OMFD, respectively. The distribution volume of D-FET in the piglet brain was slightly higher than that of L-FET as it was also found for most other organs. In brain tumor patients, initial D-FET uptake in the brain was similar to that of L-FET but showed faster tracer washout. L-FET uptake remained rather constant and provided a better delineation of residual tumor than D-FET. In conclusion, our data indicate considerable differences of stereoselective amino acid transport at the BBB in different species. Therefore, the results from animal experiments concerning BBB amino acid transport may not be transferable to humans.
authors.affiliation: Institute of Physiology, University of Zurich, Switzerland.
authors.forename: Victoria
authors.initials: V
authors.lastname: Makrides
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weber
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Steffen
authors.initials: S
authors.lastname: Fischer
authors.forename: Rainer
authors.initials: R
authors.lastname: Hinz
authors.forename: Katja
authors.initials: K
authors.lastname: Huggel
authors.forename: Thomas
authors.initials: T
authors.lastname: Opfermann
authors.forename: Michael
authors.initials: M
authors.lastname: Herzau
authors.forename: Vadivel
authors.initials: V
authors.lastname: Ganapathy
authors.forename: Francois
authors.initials: F
authors.lastname: Verrey
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
mesh_terms: D000328:Adult; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000601:surgery; D003287:Contrast Media / Q000493:pharmacokinetics; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D013237:Stereoisomerism; D013552:Swine; D014018:Tissue Distribution; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D003287:Contrast Media; D005462:Fluorine Radioisotopes; C117289:O-(2-fluoroethyl)tyrosine; C055151:3-O-methyl-6-fluoro-dopa; D014443:Tyrosine; D004295:Dihydroxyphenylalanine