Add time:08/14/2019         Source:sciencedirect.com

The radiopharmaceutical 3-[123I]iodo-α-methyl-L-tyrosine ([123I]IMT) can be used to study amino acid transport by single-photon emission tomography (SPET). In order to evaluate the potential contribution of [123I]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 [131I]IMT per well. [131I]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. [131I]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 [131I]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 [131I]IMT uptake by L-arginine and MeAIB, albeit to a minor extent. [131I]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 [131I]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 [123I]IMT accumulation in macrophages within the neoplastic lesion.

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