Feasibility of labeled alpha-acetamido-aminoisobutyric acid as new tracer compound for kinetic labeling of neutral amino acid transport: preparation of alpha-(N-[1-11C]acetyl)- and alpha-(N-[1-14C]acetyl)-aminoisobutyric acid.
The nonphysiological, nonracemic, branched-chain alpha-acetamido-aminoisobutyric acid was labeled with the carbon isotope 11C with the intention to use it in conjunction with positron emission tomography (PET) to measure the kinetics of amino acid transport in vivo. It was produced by the reaction of the novel 11C-precursor N-[1-11C]acetylpyridinium chloride with alpha-aminoisobutyric acid. Typically, 2 GBq of alpha-(N-[1-11C]acetyl)-aminoisobutyric acid were isolated with a specific activity of 12 to 20 GBq. mumol-1 at the time of application, and with a radiochemical purity of > 98%. The chemical identity of alpha-(N-[1-11C]acetyl)-aminoisobutyric acid was confirmed by comparison with alpha-(N-[1-14C]acetyl)-aminoisobutyric acid that was independently prepared by a standard acetylation procedure of alpha-aminoisobutyric acid using [1-14C]acetic anhydride. In vivo, both labeled substrates were not metabolized. In cell-culture experiments, 84% of the substrate entered the cells by the sodium-dependent amino acid transport system A, whereas 16% was taken up by the sodium-independent system. The uptake of the radiotracer was measured 20 min and 40 min postinjection in tumor-bearing male Copenhagen rats for assessment of its in vivo biodistribution.
Prenant
C
C
Deutsches Krebsforschungszentrum, Abteilung Radiochemie, Heidelberg, Germany.
Theobald
A
A
Haberkorn
U
U
Bellemann
M E
ME
Weber
K
K
Oberdorfer
F
F
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism*; D000613:Aminobutyrates / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002460:Cell Line; D005240:Feasibility Studies; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000613:Aminobutyrates; D002250:Carbon Radioisotopes; D007202:Indicators and Reagents; C102275:alpha-(N-acetylamino)isobutyric acid