Transport of cis- and trans-4-[�8F]fluoro-L-proline in F98 glioma cells
Date
2002
Authors
Langen, Karl-Josef
Muhlensiepen, Heinz
Schmieder, Sven
Hamacher, Kurt
Broer, Stefan
Borner, Anne R
Schneeweiss, Frank
Coenen, Heinz
Journal Title
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Volume Title
Publisher
Elsevier
Abstract
The transport mechanisms of cis-4-[18F]fluoro-L-proline (cis-FPro) and trans-4-[18F]fluoro-L-proline (trans-FPro) were studied in F98 rat glioma cells in comparison to the natural parent [3H]-L-proline. Uptake rates of cis-FPro and trans-FPro in F98 glioma cells were 50-70% lower than those of [3H]-L-proline. The amino transport system A inhibitor MeAIB reduced the uptake of [3H]-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 [3H]-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.
Description
Keywords
Keywords: 4 aminobutyric acid; 4 fluoroproline f 18; diacetylsplenopentin; proline derivative; tracer; unclassified drug; acid precipitation; adult; amino acid transport; animal cell; article; controlled study; drug distribution; drug retention; drug transport; dru Amino acid transport; Cis- and trans-4-[18F]fluoro-L-proline; Glioma cells; PET; Whole body distribution
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Source
Nuclear Medicine and Biology
Type
Journal article
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2037-12-31