Phenylalanine can be detected in brain tissue of healthy subjects by 1 H magnetic resonance spectroscopy J. PIETZ 1 *, T. LUTZ 2 , K. ZWYGART 3 , G. F. HOFFMANN 2 , F. EBINGER 1 , C. BOESCH 3 and R. KREIS 3 Departments of 1 Pediatric Neurology and 2 General Pediatrics, University of Heidelberg, Germany; 3 Department of Clinical Research, Division for Magnetic Resonance Spectroscopy and Methodology, University of Berne, Switzerland *Correspondence: Department of Pediatric Neurology, University of Heidelberg, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany. E-mail: joachim pietz@med.uni-heidelberg.de MS received 09.06.03 Accepted 26.08.03 Summary: Transport of phenylalanine (Phe) and the other large neutral amino acids across the blood^brain barrier plays a crucial role in the pathogenesis of phenylketonuria (PKU). Thus, investigation of Phe transport kinetics by means of proton magnetic resonance spectroscopy ( 1 H MRS) became an important research area in the mid 1990s. As 1 H MRS measurements of brain phenylalanine are restricted to tissue concentrations above 100^150 mmol/kg wet weight, this approach was possible only in PKU patients, and comparison with healthy controls was not achieved. Using standardized single-dose oral Phe loading in three healthy subjects, it was shown that Phe values increase steeply, peak at about 1 h post load, and decrease thereafter. In a single case study, repetitive Phe loading was then performed to achieve a plateau of high blood Phe concentrations for several hours. It was demonstrated that detection and monitoring of brain Phe concentrations is feasible by means of 1 H MRS. This approach constitutes a prerequisite for describing carrier kinetics in health. Brain function and development depend on the in£ux of nutrients across the blood^brain barrier (BBB). For the large neutral amino acids (LNAAs; phenyl- alanine, tryptophan, leucine, isoleucine, methionine, tyrosine, histidine and valine), uptake from blood into brain tissue is determined by the ratio of these LNAAs in blood and their af¢nity for the L-type amino acid carrier system at the BBB. Bidirectional transport via this carrier system is saturable, stereospeci¢c and sodium/energy-independent. It forms the rate-limiting step for the uptake of LNAAs from blood into brain cells and is therefore the control-point for the J.Inherit.Metab.Dis. 26 (2003) 683^691 # SSIEM and Kluwer Academic Publishers. Printedinthe Netherlands 683