title: Tryptophane-based biphenylsulfonamide matrix metalloproteinase inhibitors as tumor imaging agents.
abstract: OBJECTIVE
  As a part of our efforts to use small organic matrix metalloproteinase (MMP) inhibitors with improved characteristics for the diagnosis and treatment of different kinds of tumor tissues, biphenylsulfonamide analogues were synthesized. This study reports on the in vivo biodistribution of iodine-123-labeled biphenylsulfonide and analogues in A549 lung carcinoma inoculated into athymic mice and the evaluation of their suitability as imaging agents using a single photon emission computed tomography (SPECT) camera.
  
  
  METHODS
  The radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'- [(123)I]iodobiphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (1') and 2-(4'-[(123)I]iodobiphenyl-4- sulfonylamino)-3-(1H-indol-3-yl)-propionamide (2') were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives. Planar gamma camera imaging was performed in nu/nu athymic mice bearing an A549 tumor using a Toshiba GCA-9300A/hg SPECT camera in planar mode equipped with a high-resolution, parallel-hole collimator.
  
  
  RESULTS
  Radiosynthesis of (1') and (2') resulted in radiochemical yields of 60 +/- 5% (n +/- 3) and 70 +/- 5% (n = 6), respectively. Evaluation of tumors induced in athymic mice by the inoculation of non-small cell lung A549 carcinoma cells, showed a tumor uptake of 0.27-0.01 percent injected dose per gram (%ID/g) (3 hours-48 hours p.i.), a tumor-blood ratio of 0.7, a tumor-muscle ratio of 1.6, and a tumor-fat ratio of 0.5 at 24 hours (p.i.) for compound 1'. For compound 2' a tumor uptake of 0.7-0.04 %ID/g (3 hours-48 hours p.i.), a postinjection tumor-blood ratio of 1.2, a tumor-muscle ratio of 3.2, and a tumor-fat ratio of 2.4 at 48 hours p.i. was observed. SPECT evaluation confirmed the results obtained from biodistribution.
  
  
  CONCLUSIONS
  In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that they do not appear suitable as tumor-imaging agents.
authors.affiliation: Laboratory of Radiopharmacy, Ghent University, Ghent, Belgium. ruth.oltenfreiter@Ugent.be
authors.forename: Ruth
authors.initials: R
authors.lastname: Oltenfreiter
authors.forename: Ludovicus
authors.initials: L
authors.lastname: Staelens
authors.forename: Soraya
authors.initials: S
authors.lastname: Labied
authors.forename: Veerle
authors.initials: V
authors.lastname: Kersemans
authors.forename: Francis
authors.initials: F
authors.lastname: Frankenne
authors.forename: Agnes
authors.initials: A
authors.lastname: Noël
authors.forename: Christophe
authors.initials: C
authors.lastname: Van de Wiele
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging; D045744:Cell Line, Tumor; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging*; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D013449:Sulfonamides / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014364:Tryptophan
chemical_list: D001713:Biphenyl Compounds; D007457:Iodine Radioisotopes; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013449:Sulfonamides; D014364:Tryptophan