scholarly journals Effects of Large Neutral Amino Acid Concentrations on 6-[F-18]Fluoro-L-DOPA Kinetics

1998 ◽  
Vol 18 (1) ◽  
pp. 43-51 ◽  
Author(s):  
David B. Stout ◽  
Sung-Cheng Huang ◽  
William P. Melega ◽  
Michael J. Raleigh ◽  
Michael E. Phelps ◽  
...  

6-[F-18]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) has been used to measure the central dopaminergic function in many species, including humans and monkeys. For transport across the blood brain barrier (BBB), FDOPA competes with plasma large neutral amino acids (LNAA). In this article we evaluate the effects of normal physiological LNAA concentration variation on BBB transport (K1) and the FDOPA uptake measurement, Ki. We also investigate a method for reducing the dependency of FDOPA quantitation on LNAA. Adult vervet monkeys ( Cercopithecus aethiops sabaeus, n = 19) were fasted overnight before FDOPA positron emission tomography scans. Blood samples were drawn for LNAA determination, metabolite analysis, and compartmental modeling. The estimated K1 and Ki were both negatively correlated with LNAA concentrations (r2 = 0.51 and 0.62, respectively). Using an adjustment to K1 and Ki based on these correlations, the LNAA dependency was reduced (SD of the data for K1 was reduced by 33%, for Ki by 40%). Experiments with amino acid loading on an additional six animals indicate that BBB transport can be described using Michaelis-Menten kinetics. Results show a clear dependence of FDOPA uptake on plasma LNAA concentrations, which can be removed to increase the precision of FDOPA quantitation.

2000 ◽  
Vol 20 (12) ◽  
pp. 1717-1724 ◽  
Author(s):  
David B. Stout ◽  
Sung-Cheng Huang ◽  
Mohammad Namavari ◽  
Nagichettiar Satyamurthy ◽  
Randa E. Yee ◽  
...  

The distribution volume (DY) of 6-[F-18]fluoro-L-DOPA (FDOPA) in the cerebellum recently has been linked using positron emission tomography (PET) to plasma large neutral amino acid (LNAA) concentrations in monkeys. In this article the authors provide additional experimental support for this relation by directly measuring the DY as the steady-state tissue to plasma radioactivity ratio in rats using a labeled LNAA analog 3-O-methyl-6-[F-18]FDOPA (OMFD), a compound that has no known specific enzyme or receptor interactions in brain tissue. The measured DY for OMFD (tissue OMFD concentration/plasma OMFD concentration) was found to be inversely related to plasma LNAA concentrations. The relation (DY = 1.5−0.00094* [LNAA], R^2 = 0.79) resulted in an 8% DY decrease per 100 nmol/mL plasma LNAA increase within the observed range of 330 to 510 nmol/mL. This was similar to recent noninvasive observations with FDOPA PET in vervet monkeys and with 6-[F-18]Fluoro-m-tyrosine PET in squirrel monkeys. The OMFD striatum to cerebellum (Str/Cb) ratio was greater than 1.0 for all measurements, averaging 1.09 ± 0.04, and was approximately equal to the Str/Cb LNAA ratio of 1.12 ± 0.05. This current study verifies the variation of DV of OMFD or FDOPA as a function of plasma LNAA concentrations and suggests the possibility of using OMFD for measuring cerebral LNAA noninvasively with PET.


1980 ◽  
Vol 15 (5) ◽  
pp. 380
Author(s):  
C Leon Partain ◽  
Karl F. Hubner ◽  
M. Stephen Mahaley ◽  
F. David Rollo ◽  
Ronald R. Price ◽  
...  

Methods ◽  
2017 ◽  
Vol 130 ◽  
pp. 124-134 ◽  
Author(s):  
Karl-Josef Langen ◽  
Gabriele Stoffels ◽  
Christian Filss ◽  
Alexander Heinzel ◽  
Carina Stegmayr ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2252 ◽  
Author(s):  
Danique van Vliet ◽  
Els van der Goot ◽  
Wiggert G. van Ginkel ◽  
Martijn H. J. R. van Faassen ◽  
Pim de Blaauw ◽  
...  

Many phenylketonuria (PKU) patients cannot adhere to the severe dietary restrictions as advised by the European PKU guidelines, which can be accompanied by aggravated neuropsychological impairments that, at least in part, have been attributed to brain monoaminergic neurotransmitter deficiencies. Supplementation of large neutral amino acids (LNAA) to an unrestricted diet has previously been shown to effectively improve brain monoamines in PKU mice of various ages. To determine the additive value of LNAA supplementation to a liberalized phenylalanine-restricted diet, brain and plasma monoamine and amino acid concentrations in 10 to 16-month-old adult C57Bl/6 PKU mice on a less severe phenylalanine-restricted diet with LNAA supplementation were compared to those on a non-supplemented severe or less severe phenylalanine-restricted diet. LNAA supplementation to a less severe phenylalanine-restricted diet was found to improve both brain monoamine and phenylalanine concentrations. Compared to a severe phenylalanine-restricted diet, it was equally effective to restore brain norepinephrine and serotonin even though being less effective to reduce brain phenylalanine concentrations. These results in adult PKU mice support the idea that LNAA supplementation may enhance the effect of a less severe phenylalanine-restricted diet and suggest that cerebral outcome of PKU patients treated with a less severe phenylalanine-restricted diet may be helped by additional LNAA treatment.


Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 153 ◽  
Author(s):  
Philipp Lohmann ◽  
Jan-Michael Werner ◽  
N. Shah ◽  
Gereon Fink ◽  
Karl-Josef Langen ◽  
...  

Imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) provide valuable information about brain tumor patients. Particularly amino acid PET, advanced MRI techniques, and combinations thereof are of great interest for the non-invasive assessment of biological characteristics in patients with primary or secondary brain cancer. A methodological innovation that potentially advances research in patients with brain tumors is the increasing availability of hybrid PET/MRI systems, which enables the simultaneous acquisition of both imaging modalities. Furthermore, the advent of ultra-high field MRI scanners operating at magnetic field strengths of 7 T or more will allow further development of metabolic MR imaging at higher resolution. This review focuses on the combination of amino acid PET with MR spectroscopic imaging, perfusion- and diffusion-weighted imaging, as well as chemical exchange saturation transfer in patients with high-grade gliomas, especially glioblastomas.


2010 ◽  
Vol 18 (21) ◽  
pp. 7338-7347 ◽  
Author(s):  
Dinesh Shetty ◽  
Jae Min Jeong ◽  
Chang Hwan Ju ◽  
Young Ju Kim ◽  
Ji-Youn Lee ◽  
...  

2010 ◽  
Vol 37 (8) ◽  
pp. 893-902 ◽  
Author(s):  
Dinesh Shetty ◽  
Jae Min Jeong ◽  
Chang Hwan Ju ◽  
Yun-Sang Lee ◽  
Seo Young Jeong ◽  
...  

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