Amino acid uptake in the skeletal muscle measured using [11C]methylaminoisobutyrate (MEAIB) and PET.
An amino acid analogue, [(11)C]MeAIB, recently introduced for oncological positron emission tomography (PET) studies, is a highly selective substrate for insulin-sensitive amino acid transport system A. The aim of this study was to study the uptake kinetics of [(11)C]MeAIB in skeletal muscle in the fasting state and during insulin stimulation. Two dynamic PET studies were carried out in 11 healthy subjects, once in the fasting state and once during euglycaemic hyperinsulinaemia (serum insulin 67+/-12 mU l(-1)). Graphical analysis was used to calculate the fractional [(11)C]MeAIB uptake rate ( K(i)). Amino acid uptake was estimated by multiplying K(i) by the serum amino acid concentration. After tracer injection, rapid uptake in muscle tissue was detected both in the fasting state and during insulin stimulation and femoral muscles were clearly visualised in both studies. In the graphical analysis, the volume of distribution of [(11)C]MeAIB plotted against normalised plasma time yielded a linear curve (the slope of which = K(i)). The fractional [(11)C]MeAIB uptake rate ( K(i)) in the femoral muscle regions increased from 0.0070+/-0.0018 min(-1) (mean+/-SD) in the fasting state to 0.0079+/-0.0020 min(-1) ( P<0.05) during insulin stimulation. When compared with the fasting state, serum total amino acid concentration decreased from 2.49+/-0.22 to 2.16+/-0.18 mmol l(-1) ( P<0.0001) and the serum concentration of six amino acids typically using system A for their transport decreased from 0.72+/-0.1 to 0.63+/-0.07 mmol l(-1) ( P=0.0001) during hyperinsulinaemia. The calculated skeletal muscle total amino acid uptake and the uptake of the six amino acids typically using system A were similar in the fasting state and during insulin clamp (17.1+/-3.2 vs 17.7+/-3.7 micro mol kg(-1) min(-1), NS, and 5.0+/-1.3 vs 5.0+/-1.4 micro mol kg(-1) min(-1), NS, respectively). The uptake rates correlated with perfusion both in the fasting state and during hyperinsulinaemia ( P<0.05). [(11)C]MeAIB PET appears to be a feasible method for measurement of amino acid uptake in human skeletal muscle. As a tracer that is not metabolised in the tissues, [(11)C]MeAIB provides simple modelling and robust data analysis and thus provides a means to investigate amino acid uptake into muscle tissue in various disease conditions known to affect protein metabolism.
Asola
Markku R
MR
Turku PET Centre, University of Turku, Finland. markku.asola@tyks.fi
Virtanen
Kirsi A
KA
Peltoniemi
Pauliina
P
Någren
Kjell
K
Yu
Meixiang
M
Mattila
Kari
K
Jyrkkiö
Sirkku
S
Metsärinne
Kaj
K
Nuutila
Pirjo
P
Knuuti
Juhani
J
D000596:Amino Acids / Q000097:blood / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013848:Thigh / Q000000981:diagnostic imaging; D014055:Tomography, Emission-Computed / Q000379:methods*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
D000596:Amino Acids; D002250:Carbon Radioisotopes; D007328:Insulin; D019275:Radiopharmaceuticals; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine