title: Transport of cis- and trans-4-[(18)F]fluoro-L-proline in F98 glioma cells.
abstract: The transport mechanisms of cis-4-[(18)F]fluoro-L-proline (cis-FPro) and trans-4-[(18)F]fluoro-L-proline (trans-FPro) were studied in F98 rat glioma cells in comparison to the natural parent [(3)H]-L-proline. Uptake rates of cis-FPro and trans-FPro in F98 glioma cells were 50-70% lower than those of [(3)H]-L-proline. The amino transport system A inhibitor MeAIB reduced the uptake of [(3)H]-L-proline by 30% and uptake of cis-FPro by 46% while uptake of trans-FPro was not significantly changed. BCH inhibited the uptake of all tracers by 35-44%, serine by 70-90% and L-proline by 60 -80%. Absence of Na(+) reduced uptake of all tracers significantly but no further inhibitory effect could be observed which suggests a component of unspecific uptake. Radioactivity of cis- and trans-FPro in the acid precipitable fraction was < 1% after 120 min incubation time while [(3)H]-L-proline exhibited a 20% incorporation into protein. Whole body PET scans in humans demonstrated a retention of cis-FPro in the renal cortex, liver and the pancreas while trans-FPro was retained particularly in muscles. We conclude that system A amino acid transport appears to be selectively relevant for cis-FPro which may contribute to the observed differences in whole body distribution of cis-FPro and trans-FPro in humans.
authors.affiliation: Institute of Medicine, Research Centre Jülich, Jülich, Germany. k.j.langen@fz-juelich.de
authors.forename: Karl-J
authors.initials: KJ
authors.lastname: Langen
authors.forename: Heinz
authors.initials: H
authors.lastname: Mühlensiepen
authors.forename: Sven
authors.initials: S
authors.lastname: Schmieder
authors.forename: Kurt
authors.initials: K
authors.lastname: Hamacher
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
authors.forename: Anne R
authors.initials: AR
authors.lastname: Börner
authors.forename: Frank H A
authors.initials: FH
authors.lastname: Schneeweiss
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Coenen
mesh_terms: D000005:Abdomen / Q000000981:diagnostic imaging; D000328:Adult; D000818:Animals; D001415:Back / Q000000981:diagnostic imaging; D001693:Biological Transport, Active; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D011392:Proline / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D051381:Rats; D012016:Reference Values; D012680:Sensitivity and Specificity; D013909:Thorax / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured; D014915:Whole-Body Counting
chemical_list: D019275:Radiopharmaceuticals; C431803:fluoro-proline; D011392:Proline