Characterization of uptake of 3-[(131)I]iodo-alpha-methyl-L-tyrosine in human monocyte-macrophages.
The radiopharmaceutical 3-[(123)I]iodo-alpha-methyl-L-tyrosine ([(123)I]IMT) can be used to study amino acid transport by single-photon emission tomography (SPET). In order to evaluate the potential contribution of [(123)I]IMT accumulation in macrophages to overall uptake values measured in neoplastic lesions in vivo, we studied the mechanisms governing the uptake of this tracer by human monocyte-macrophages (HMMs). HMMs were isolated from healthy human donors by density gradient centrifugation using Ficoll methods. The human glioblastoma cell line U-138 MG (GLIOs) was obtained from American Type Culture Collection. Using multiwell dishes, cells were incubated in phosphate buffered saline or an equivalent sodium-free buffer with 50 kBq [(131)I]IMT per well. [(131)I]IMT uptake was quantified as % injected dose per mass of protein within each culture well. Several natural and artificial amino acids were used as potential transport inhibitors both in sodium-containing and sodium-free medium. [(131)I]IMT uptake was significantly lower in HMMs than in GLIOs (34 +/- 2 %/mg (40 min) vs. 507 +/- 50 %/mg at 30 minutes of incubation, respectively; p < 0.01). Endotoxin (LPS) significantly increased [(131)I]IMT uptake in HMMs by a factor of approximately 2. Transport into non-stimulated HMMs was exclusively sodium-independent and inhibitable by BCH, but not by MeAIB. Under LPS stimulation exclusively, there was in addition also a sodium-dependent inhibition of [(131)I]IMT uptake by L-arginine and MeAIB, albeit to a minor extent. [(131)I]IMT accumulation in HMMs is mainly mediated via an L-like amino acid transport system and increases on HMM activation by LPS. LPS may induce an additional Na(+)-dependent transport system in HMMs. The considerably lower [(131)I]IMT uptake in HMMs than in GLIOs suggests that overall uptake values of this tracer measured by SPET in tumors are not significantly affected by [(123)I]IMT accumulation in macrophages within the neoplastic lesion.
Prante
Olaf
O
Department of Nuclear Medicine, Laboratory of Molecular Imaging, Friedrich-Alexander University, Erlangen, Germany. olaf.prante@nuklear.imed.uni-erlangen.de
Deichen
J Thiess
JT
Hocke
Carsten
C
Kuwert
Torsten
T
D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D008781:Methyltyrosines / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D008070:Lipopolysaccharides; D008781:Methyltyrosines; D019275:Radiopharmaceuticals; C030855:3-iodo-alpha-methyltyrosine