A feasibility study on L-[1-carbon-11]tyrosine and L-[methyl-carbon-11]methionine to assess liver protein synthesis by PET.
We studied the potential of L-[1-11C]tyrosine ([1-11C]Tyr) and L-[methyl-11C]methionine ([Me-11C]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models.


METHODS
In the liver and plasma of control and cycloheximide-treated mice injected with [1-14C]Tyr and [Me-3H]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with 11C-labeled analogs and PET.


RESULTS
In mice, liver uptake of [Me-3H]Met was over twice as large as that of [1-14C]Tyr. Similar uptake patterns of the 11C-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, approximately 69%-73% of the 14C was detected in the protein fraction, whereas approximately 65%-70% of the 3H was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were approximately 73%-76% for 14C and approximately 36%-46% for 3H. Gel-filtration analysis suggested that 80% of the 14C-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide, the liver uptake of the [1-14C]Tyr and the protein-incorporation of 14C in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-3H]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction.


CONCLUSIONS
[1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-11C]Met mainly reflects phospholipid synthesis through the transmethylation process.
Ishiwata
K
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Enomoto
K
K
Sasaki
T
T
Elsinga
P H
PH
Senda
M
M
Okazumi
S
S
Isono
K
K
Paans
A M
AM
Vaalburg
W
W
D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis; D002250:Carbon Radioisotopes; D003513:Cycloheximide / Q000494:pharmacology; D005240:Feasibility Studies; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051379:Mice; D008815:Mice, Inbred Strains; D010743:Phospholipids / Q000096:biosynthesis; D014176:Protein Biosynthesis; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D014055:Tomography, Emission-Computed / Q000379:methods*; D014443:Tyrosine / Q000493:pharmacokinetics
D001798:Blood Proteins; D002250:Carbon Radioisotopes; D010743:Phospholipids; D014443:Tyrosine; D003513:Cycloheximide; D008715:Methionine; C038344:methionine methyl ester