title: Validation of 8-[123I]iodo-L-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid as an imaging agent for prostate cancer in experimental models of human prostate cancer.
abstract: BACKGROUND
  Very few tracers are currently available for the detection and staging of prostate cancer with positron emission tomography and single-photon emission computed tomography. This study evaluates the potential of 8-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid [ITIC(OH)] as an imaging agent for prostate cancer in experimental models of human prostate cancer.
  
  
  METHODS
  ITIC(OH) was prepared by the IODO-GEN method, with 82+/-7% radiochemical yield and >99% radiochemical purity after high-performance liquid chromatography. Thereafter, ITIC(OH) was examined in CD-1 nu/nu mice engrafted with human PC-3 and DU-145 prostate cancer in the flank or orthotopically in the prostate. Bioevaluation involved examination of the in vivo stability and uptake characteristics of ITIC(OH) into tumors and different organs by dynamic in vivo analysis and gamma counting of organs of interest after dissection.
  
  
  RESULTS
  ITIC(OH) showed good in vivo stability for biological investigations and was primary cleared through urine. In vivo, ITIC(OH) accumulated highly and specifically in tumors, reaching 13.6+/-2.1% to 16.2+/-2.5% injected dose per gram (ID/g) in heterotopic tumors compared with 14.8+/-2.6% and 17.6+/-3.4% ID/g in orthotopic tumor engrafts at 60 and 240 min postinjection, respectively. In contrast, radioactivity uptake in the blood, spleen, liver and gastrointestinal tract was moderate and decreased with time, resulting in marked tumor-to-background and excellent visualization of tumors.
  
  
  CONCLUSIONS
  These results suggest that ITIC(OH) is a promising candidate as radiotracer for detecting prostate cancer and warrants further studies in patients to ascertain its potential as an imaging agent for clinical use.
authors.affiliation: Department of Nuclear Medicine, Saarland University Medical Center, D-66421 Homburg, Germany. rassam@uniklinikum-saarland.de
authors.forename: Samuel
authors.initials: S
authors.lastname: Samnick
authors.forename: Ursula
authors.initials: U
authors.lastname: Nestle
authors.forename: Mathias
authors.initials: M
authors.lastname: Wagner
authors.forename: Thierry
authors.initials: T
authors.lastname: Fozing
authors.forename: Andrea
authors.initials: A
authors.lastname: Schaefer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Carl-Martin
authors.initials: CM
authors.lastname: Kirsch
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C420687:1,2,3,4-tetrahydro-7-hydroxy-8-iodoisoquinoline-3-carboxylic acid; D019275:Radiopharmaceuticals; D044005:Tetrahydroisoquinolines