title: Comparison of the uptake of [123/125I]-2-iodo-D-tyrosine and [123/125I]-2-iodo-L-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo.
abstract: BACKGROUND
  Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [(123)I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[(123/125)I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats.
  
  
  METHODS
  The uptake of [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine into R1M cells was determined in appropriate buffers, allowing the study of the involved transport systems. In vivo, the biodistribution in R1M-bearing rats of [(123)I]-2-iodo-L-tyrosine and [(123)I]-2-iodo-D-tyrosine was performed by both dynamic and static planar imaging with a gamma camera.
  
  
  RESULTS
  In in vitro conditions, the uptake of both [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na(+) ions. In the absence of Na(+) ions, [(125)I]-2-iodo-D-tyrosine was taken up reversibly in the R1M cells, with an apparent accumulation, probably for the larger part by the LAT1 system. Dynamic planar imaging showed that the uptake in the tumors of [(123)I]-2-iodo-D-tyrosine was somewhat lower than that of [(123)I]-2-iodo-L-tyrosine. At 30 min postinjection, the mean differential uptake ratio values of the L- and D-enantiomers are 2.5+/-0.7 and 1.7+/-0.6, respectively. Although the uptake of the D-isomer is lower, probably due to a faster clearance from the blood, the tumor-background ratio is the same as that of the l-analogue.
  
  
  CONCLUSIONS
  A large part (75%) of [(125)I]-2-iodo-D-tyrosine in vitro and [(123)I]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in R1M tumor cells by Na(+)-independent LAT transport systems, more likely by the LAT1. The clearance from the blood of [(123)I]-2-iodo-D-tyrosine in the rats is faster than that of the L-analogue, resulting in a slightly lower tumor uptake but with the same tumor-background ratio.
authors.affiliation: Radiopharmaceutical Chemistry, BEFY, Vrije Universiteit Brussel, 1090 Brussels, Belgium. matthias.bauwens@vub.ac.be
authors.forename: Matthias
authors.initials: M
authors.lastname: Bauwens
authors.forename: Tony
authors.initials: T
authors.lastname: Lahoutte
authors.forename: Ken
authors.initials: K
authors.lastname: Kersemans
authors.forename: Carol
authors.initials: C
authors.lastname: Gallez
authors.forename: Axel
authors.initials: A
authors.lastname: Bossuyt
authors.forename: John
authors.initials: J
authors.lastname: Mertens
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D007470:Monoiodotyrosine / Q000493:pharmacokinetics*; D009374:Neoplasms, Experimental / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D012208:Rhabdomyosarcoma / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D007470:Monoiodotyrosine