Transport of cis- and trans-4-[18F]fluoro-L-proline in F98 glioma cells

The transport mechanisms of cis-4-[F-18]fluoro-L-proline (cis-FPro) and trans-4-[F-18]fluoro-L-proline (trans-FPro) were studied in F98 rat glioma cells in comparison to the natural parent [H-3]-L-proline. Uptake rates of cis-FPro and trans-FPro in F98 glioma cells were 50-70% lower than those of [H-3]-L-proline. The amino transport system A inhibitor MeAIB reduced the uptake of [H-3]-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 [H-3]-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. (C) 2002 Elsevier Science Inc. All rights reserved.