title: In vivo evaluation and dosimetry of 123I-2-iodo-D-phenylalanine, a new potential tumor-specific tracer for SPECT, in an R1M rhabdomyosarcoma athymic mouse model.
abstract: Earlier reports described the preferential uptake of d-amino acids in tumor-bearing mice. Moreover, it was shown that in tumor cells in vitro the L-amino acid transporter system seemed to lack stereospecificity. Because of the successful results with 123/125I-2-iodo-L-phenylalanine, 123/125I-2-iodo-D-phenylalanine was developed, and its tumor-detecting characteristics were evaluated in vivo.
  
  
  METHODS
  123I labeling of 2-iodo-D-phenylalanine was performed with a kit formulation by use of Cu1+-assisted nucleophilic exchange. 123I-2-Iodo-D-phenylalanine was evaluated in R1M tumor-bearing athymic mice by dynamic planar imaging (DPI) and dissection. The in vivo stability of the tracer was tested by high-performance liquid chromatography. Tumor tracer retention and tracer contrast were evaluated as a function of time. Two-compartment blood modeling from DPI results and dosimetric calculations from biodistribution results were carried out. Moreover, 125I-2-iodo-D-phenylalanine and 18F-FDG uptake in acute inflammation was investigated.
  
  
  RESULTS
  123I-2-Iodo-D-phenylalanine was metabolically stable. Fast, high, and specific tumor retention was observed. Two-compartment modeling confirmed the fast clearance of the tracer through the kidneys to the bladder, as observed by DPI and dissection. Moreover, compared with the L-isomer, 123I-2-iodo-D-phenylalanine demonstrated faster clearance and faster uptake in the peripheral compartment. No accumulation in the abdomen or in the brain was noted. Dosimetry revealed that 123I-2-iodo-D-phenylalanine demonstrated a low radiation burden comparable to those of 123I-2-iodo-L-phenylalanine and 123I-2-iodo-L-tyrosine. Although 123I-2-iodo-D-phenylalanine showed a tumor retention of only 4%, the tumor contrast was increased up to 350% at 19 h after injection.
  
  
  CONCLUSIONS
  123I-2-Iodo-D-phenylalanine is a promising tracer for diagnostic oncologic imaging because of its high, fast, and specific tumor uptake and fast clearance from blood.
authors.affiliation: Laboratory for Radiopharmacy, Universiteit Gent, Gent, Belgium. veerle.kersemans@utoronto.ca
authors.forename: Veerle
authors.initials: V
authors.lastname: Kersemans
authors.forename: Bart
authors.initials: B
authors.lastname: Cornelissen
authors.forename: Klaus
authors.initials: K
authors.lastname: Bacher
authors.forename: Ken
authors.initials: K
authors.lastname: Kersemans
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
authors.forename: John
authors.initials: J
authors.lastname: Mertens
mesh_terms: D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000000981:diagnostic imaging; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C496694:2-iodophenylalanine; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D010649:Phenylalanine