Kinetic parameters of 3-[123I]iodo-L-α-methyl tyrosine ([123I]IMT) transport in human GOS3 glioma cells

Riemanna, Burkhard; Kopka, Klaus; Stögbauer, Florian; Halfter, Hartmut; Ketteler, Sonja; Phan, T.; Franzius, Christiane; Weckesser, Matthias; Ringelstein, E. B.; Schober, Otmar

doi:10.1016/s0969-8051(01)00191-3

Cited by 16 publications

(10 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We showed, in a previous study, that system T transporter TAT1 does not transport a-methyl amino acids (29), suggesting that FAMT is not transported by system T because of its a-methyl moiety. System B 0 and B 0,1 transporters were previously suggested to somewhat transport a SPECT tracer, L-3-123 I-a-methyl tyrosine ( 123 I-IMT) (30,31). System B 0 , a Na 1 -dependent broad-scope neutral amino acid transporter, is present on the apical membrane of renal proximal tubules and small intestine and responsible for the absorption of neutral amino acids from the lumen (26).…”

Section: Discussionmentioning

confidence: 99%

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

Wiriyasermkul¹,

Nagamori²,

Tominaga³

et al. 2012

J Nucl Med

124

114

View full text Add to dashboard Cite

L-3-18 F-a-methyl tyrosine ( 18 F-FAMT) has been developed as a PET radiotracer for tumor imaging. Clinical studies have demonstrated the usefulness of 18 F-FAMT PET for the prediction of prognosis and the differentiation of malignant tumors and benign lesions. 18 F-FAMT exhibits higher cancer specificity in peripheral organs than other amino acid PET tracers and 18 F-FDG. The accumulation of 18 F-FAMT is strongly correlated with the expression of L-type amino acid transporter 1 (LAT1), an isoform of system L highly upregulated in cancers. In this study, we examined the interaction of 3-fluoro-L-a-methyltyrosine (FAMT) with amino acid transporters to assess the mechanisms of 18 F-FAMT uptake in PET. Methods: We applied in vitro assays using established mammalian cell lines stably expressing LAT1 or a non-cancer-type system L isoform LAT2. The inhibitory effect on L-14 C-leucine uptake and the induction effect on efflux of preloaded L-14 C-leucine were examined for FAMT and other amino acid tracers. FAMT transport was compared among cell lines with varied LAT1 expression level. Results: FAMT prominently inhibited LAT1-mediated L-14 C-leucine uptake in a competitive manner but had less of an effect on LAT2. In the efflux experiments, FAMT induced the efflux of preloaded L-14 C-leucine through LAT1, indicating that FAMT is transported by LAT1 and not by LAT2. Among amino acid-related compounds examined in this study, including those used for PET tracers, the compounds with an a-methyl group such as FAMT, 2-fluoro-L-a-methyl-tyrosine, 3-iodo-L-a-methyl-tyrosine, and L-a-methyl-tyrosine were well transported by LAT1 but not by LAT2. However, L-methionine, L-tyrosine, 3-fluoro-L-tyrosine, 2-fluoro-L-tyrosine, and O-(2-fluoroethyl)-L-tyrosine were transported by both LAT1 and LAT2, suggesting that the a-methyl moiety is responsible for the LAT1 selectivity of FAMT. FAMT transport rate and LAT1 protein level were well correlated, supporting the importance of LAT1 for the cellular uptake of FAMT. Conclusion: Distinct from other amino acid PET tracers, because of its a-methyl moiety, FAMT is selective to LAT1 and not transported by LAT2. This property of FAMT is proposed to contribute to highly tumorspecific accumulation of 18 F-FAMT in PET.

show abstract

Section: Discussionmentioning

confidence: 99%

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

Wiriyasermkul¹,

Nagamori²,

Tominaga³

et al. 2012

J Nucl Med

124

114

View full text Add to dashboard Cite

show abstract

“…Membrane transport of [ 123 I]IMT has been studied using cultured human 86HG-39 glioma cells [4], rat C6 glioma cells [5], human GOS3 glioma cells [6], and human Ewing's sarcoma cells [7]. The majority of transport of [ 123 I]IMT in glioma cells involves the Na ϩ -independent system L (Ͼ [4,5,6,7].…”

Section: Discussionmentioning

confidence: 99%

“…The majority of transport of [ 123 I]IMT in glioma cells involves the Na ϩ -independent system L (Ͼ [4,5,6,7]. In U266 human myeloma cells, system L contributes 39.0% of […”

Section: Discussionmentioning

confidence: 99%

“…The kinetics of [ 123 I]IMT transport have also been studied in rat C6 glioma cells [5], human GOS3 glioma cells [6] and human Ewing's sarcoma cells [7]. The studies of [ 123 I]IMT uptake in glioma cells revealed that the majority of transport takes place via the Na ϩ -independent system L (Ͼ 70%) and that relatively minor uptake takes place via the Na ϩ -dependent system B 0,ϩ (Ͻ 20%).…”

Section: -[mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of 3-[125I]iodo-α-methyl-L-tyrosine transport via human L-type amino acid transporter 1

Shikano

Kanai

Kawai

et al. 2003

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…This a three-step approach still using the Baye- The Utility values for each design are also compared. Four di¡erent kinetic systems are compared: cell transport [3], continuous culture [7], drug transport [8] and receptor binding [9].…”

Section: Cell Transport Kinetics: Using a Bayesian Experimentalmentioning

confidence: 99%

Efficient and cost‐effective experimental determination of kinetic constants and data: the success of a Bayesian systematic approach to drug transport, receptor binding, continuous culture and cell transport kinetics

2003

View full text Add to dashboard Cite

Details about the parameters of kinetic systems are crucial for progress in both medical and industrial research, including drug development, clinical diagnosis and biotechnology applications. Such details must be collected by a series of kinetic experiments and investigations. The correct design of the experiment is essential to collecting data suitable for analysis, modelling and deriving the correct information. We have developed a systematic and iterative Bayesian method and sets of rules for the design of enzyme kinetic experiments. Our method selects the optimum design to collect data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. The rules select features of the design such as the substrate range and the number of measurements. We show here that this method can be directly applied to the study of other important kinetic systems, including drug transport, receptor binding, microbial culture and cell transport kinetics. It is possible to reduce the errors in the estimated parameters and, most importantly, increase the e⁄ciency and cost-e¡ectiveness by reducing the necessary amount of experiments and data points measured.

show abstract

Kinetic parameters of 3-[123I]iodo-L-α-methyl tyrosine ([123I]IMT) transport in human GOS3 glioma cells

Cited by 16 publications

References 21 publications

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

Transport of 3-Fluoro-l-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET

Characterization of 3-[125I]iodo-α-methyl-L-tyrosine transport via human L-type amino acid transporter 1

Efficient and cost‐effective experimental determination of kinetic constants and data: the success of a Bayesian systematic approach to drug transport, receptor binding, continuous culture and cell transport kinetics

Contact Info

Product

Resources

About