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SPECT and PET Amino Acid Tracer Influx via System L (h4F2hc-hLAT1) and Its Transstimulation

¹ Department of Nuclear Medicine, Academic Hospital Free University Brussels, Brussels, Belgium
² Institute of Physiology, University of Zürich, Zürich, Switzerland

System L amino acid transport is increased in various types of cancer. The tracer ¹²³I-2-iodotyrosine (2IT), which is accumulated via system L, could thus serve to allow visualization of cancer in vivo. Here, we studied the transport of ¹²⁵I-2IT by h4F2hc-hLAT1, the major transporter subserving system L in growing cells, using the Xenopus laevis oocyte expression system. We compared the apparent affinity of ¹²⁵I-2IT with that of tyrosine, tested the influence of intracellular methionine availability on the influx rate of this substrate, and then compared the transport of 2IT with that of the other tracers—iodo--methyltyrosine (IMT), fluoroethyltyrosine (FET), and 2-fluorotyrosine (2FT)—by measuring their transstimulating effect on phenylalanine efflux. Methods: Transport experiments were performed with Xenopus laevis oocytes expressing h4F2hc-hLAT1 (the functional transporter) and oocytes expressing only h4F2hc (negative control). The values obtained for the functional transporter were corrected for endogenous background transport by subtracting the values for the negative controls. Results: The apparent affinity for ¹²⁵I-2IT and ³H-tyrosine was 29.3 ± 9.3 µmol/L and 21.2 ± 4.2 µmol/L, respectively. The influx rate of ¹²⁵I-2IT was, similarly to that of ³H-phenylalanine, transstimulated by a factor of 3 when the oocytes were preinjected with methionine or phenylalanine. The proportion of preinjected ³H-phenylalanine that effluxed within 90 s in the presence of an extracellular 2IT concentration of 0.1 mmol/L was 4.1% ± 0.5%, compared with 3.3% ± 0.4% for extracellular IMT, 1.3% ± 0.3% for FET, 9.3% ± 0.8% for 2FT, and 9.1% ± 0.5% for phenylalanine. Conclusion: 2IT has a high affinity for h4F2hc-hLAT1, comparable to that of natural tyrosine, and its influx rate is transstimulated by intracellular amino acids. The 2IT influx rate is comparable to that of IMT but lower than that of phenylalanine. In contrast to FET, which is only poorly transported, 2FT displays a high influx rate equal to that of phenylalanine.

Key Words: amino acids • membrane transport • Xenopus laevis

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