title: In vivo characterization of 123/125I-2-iodo-L-phenylalanine in an R1M rhabdomyosarcoma athymic mouse model as a potential tumor tracer for SPECT.
abstract: The application of 123I-3-iodo-alpha-methyltyrosine is limited to diagnosis of brain tumors due to its marked long-term uptake in kidneys. In vitro evaluation of 125I-2-iodo-L-phenylalanine showed high uptake in R1M cells by L-type amino acid transport system 1 (LAT1). This study evaluates 123I-2-iodo-L-phenylalanine as a new specific tumor tracer for SPECT.
  
  
  METHODS
  123/125I-2-Iodo-L-phenylalanine is prepared as a one-pot kit using the Cu1+-assisted isotopic exchange method. The characteristics of 125I-2-iodo-L-phenylalanine were examined in vivo in R1M tumor-bearing athymic mice and in acute inflammation-bearing NMRI mice. The uptake of 123/125I-2-iodo-L-phenylalanine in tumor and other organs of interest was measured by dynamic planar imaging (DPI) and gamma-counting after dissection. Displacement of 123I-2-iodo-L-phenylalanine radioactivity by L-phenylalanine, L-methionine, and L-cysteine was measured. 123I-Iodo-human serum albumin planar imaging was performed to correct for blood-pool activity and MRI was performed to delineate the tumor in DPI. 18F-FDG uptake was measured with an animal PET scanner. 125I-2-Iodo-L-phenylalanine and 18F-FDG uptake in inflamed muscle were compared.
  
  
  RESULTS
  123/125I-2-Iodo-L-phenylalanine showed a high and fast tumor uptake and followed a reversible first-order pattern allowing calculation of the half-life and the time to reach equilibrium (t(R)). Net tumor-to-background ratios up to 6.7 at 60 min were obtained. This radioactivity was significantly displaced by L-phenylalanine, L-methionine, and L-cysteine, pointing to reversible LAT transport. When plotting t(R) of the tumor uptake as a function of tumor volume, a rectangular hyperbolic curve was obtained. The almost constant t(R) values at higher tumor volumes (>4 mL) could be linked to increased necrotic tissue. Fast blood clearance of the tracer through the kidneys to the bladder and low tracer activity in the abdomen and brain were observed. The inflamed muscle showed only a slight increase of 125I-2-iodo-L-phenylalanine uptake (inflammation-to-background ratio, RIB = 1.30 +/- 0.02), in contrast to the high 18F-FDG uptake (RIB = 11.1 +/- 1.7). The in vivo stability of 123/125I-2-iodo-L-phenylalanine was good: Only 7% of free radioiodide and no other labeled metabolites were observed after 90 min.
  
  
  CONCLUSIONS
  123/125I-2-Iodo-L-phenylalanine is quickly taken up by the overexpressed LAT1 system in R1M tumors with high tumor specificity. The availability of a kit and the specificity of the tracer make 123I-2-iodo-L-phenylalanine a promising tool for oncologic SPECT.
authors.affiliation: Laboratory for Radiopharmacy, Universiteit Gent, Gent, Belgium. veerle.kersemans@ugent.be
authors.forename: Veerle
authors.initials: V
authors.lastname: Kersemans
authors.forename: Bart
authors.initials: B
authors.lastname: Cornelissen
authors.forename: Ken
authors.initials: K
authors.lastname: Kersemans
authors.forename: Matthias
authors.initials: M
authors.lastname: Bauwens
authors.forename: Erik
authors.initials: E
authors.lastname: Achten
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.forename: John
authors.initials: J
authors.lastname: Mertens
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005240:Feasibility Studies; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C496694:2-iodophenylalanine; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D010649:Phenylalanine