SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation

Tony Lahoutte, Vicky Caveliers, Simone M R Camargo, Raffaella Franca, Tamara Ramadan, Emilija Veljkovic, John Mertens, Axel Bossuyt, François Verrey

Research output: Contribution to journalArticlepeer-review

Abstract

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-α-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.

Original languageEnglish
Pages (from-to)1591-1596
Number of pages6
JournalJournal of Nuclear Medicine
Volume45
Issue number9
Publication statusPublished - Sep 1 2004

Keywords

  • Amino acids
  • Membrane transport
  • Xenopus laevis

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Fingerprint Dive into the research topics of 'SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation'. Together they form a unique fingerprint.

Cite this